2022/12/01 更新

写真a

アベ ヒロユキ
阿部 寛幸
ABE Hiroyuki
所属
教育研究院 医歯学系 医学系列 助教
医歯学総合研究科 分子細胞医学専攻 細胞機能 助教
職名
助教
外部リンク

学位

  • 医学博士 ( 2016年3月   新潟大学 )

研究分野

  • ライフサイエンス / 消化器内科学  / 肝臓

経歴(researchmap)

  • 新潟大学大学院医歯学総合研究科   消化器内科学分野   特任助教

    2020年4月 - 現在

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  • ヨハネスグーテンベルク大学   Institute of Translational Immunology   客員研究員

    2018年4月 - 2020年3月

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    国名:ドイツ連邦共和国

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  • 佐渡総合病院   消化器内科   医長

    2016年4月 - 2018年3月

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  • 済生会新潟第二病院   消化器内科   医員

    2011年4月 - 2012年3月

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  • 済生会新潟第二病院   研修医

    2009年4月 - 2011年3月

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経歴

  • 新潟大学   教育研究院 医歯学系 医学系列   助教

    2022年2月 - 現在

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 細胞機能   助教

    2022年2月 - 現在

  • 新潟大学   医歯学総合病院 消化器内科   特任助教

    2020年4月 - 2022年1月

学歴

  • 新潟大学   大学院医歯学総合研究科   分子細胞生物学

    2012年4月 - 2016年3月

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  • 新潟大学   医学部   医学科

    2003年4月 - 2009年3月

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論文

  • β-arrestin: Dr Jekyll and Mr Hyde in NASH and fibrosis. 査読 国際誌

    Hiroyuki Abe, Detlef Schuppan

    Journal of hepatology   72 ( 5 )   813 - 815   2020年5月

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  • Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model. 査読 国際誌

    Hiroyuki Abe, Kenya Kamimura, Yuji Kobayashi, Masato Ohtsuka, Hiromi Miura, Riuko Ohashi, Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

    Molecular therapy. Nucleic acids   5   e276   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Liver fibrosis is the final stage of liver diseases that lead to liver failure and cancer. While various diagnostic methods, including the use of serum marker, have been established, no standard therapy has been developed. The objective of this study was to assess the approach of overexpressing matrix metalloproteinase-13 gene (MMP13) in rat liver to prevent liver fibrosis progression. A rat liver fibrosis model was established by ligating the bile duct, followed by liver-targeted hydrodynamic gene delivery of a MMP13 expression vector, containing a CAG promoter-MMP13-IRES-tdTomato-polyA cassette. After 14 days, the serum level of MMP13 peaked at 71.7 pg/ml in MMP13-treated group, whereas the nontreated group only showed a level of ~5 pg/ml (P < 0.001). These levels were sustained for the next 60 days. The statistically lower level of the hyaluronic acids in treated group versus the nontreated group (P < 0.05) reveals the therapeutic effect of MMP13 overexpression. Quantitative analysis of tissue stained with sirius red showed a statistically larger volume of fibrotic tissue in the nontreated group compared to that of MMP13-treated rats (P < 0.05). These results suggest that the liver-targeted hydrodynamic delivery of MMP13 gene could be effective in the prevention of liver fibrosis.

    DOI: 10.1038/mtna.2015.49

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  • HBx and YAP expression could promote tumor development and progression in HBV-related hepatocellular carcinoma. 国際誌

    Chiyumi Oda, Kenya Kamimura, Osamu Shibata, Shinichi Morita, Yuto Tanaka, Toru Setsu, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Satoshi Kofuji, Toshifumi Wakai, Hiroshi Nishina, Shuji Terai

    Biochemistry and biophysics reports   32   101352 - 101352   2022年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) accounts for 10%-20% of the total HCC numbers. Its clinical features include the occurrence in the younger generation, large tumors, and poor prognosis. The contribution of hepatitis B virus X (HBx) protein in hepatocytes during activation of various oncogenic pathways has been reported. We aimed to assess the possible association between HBx and Yes-associated protein (YAP) expression in the liver tissue and the clinical features of HBV-related HCC. Methods: The relationship between HBx and YAP expression was examined in vivo using HCC tumor and peritumor tissues (n = 55). The clinical information including tumor size, marker, and the prognosis was assessed with protein expressions. The in vitro gene expression analyses were conducted using HBx- and YAP-overexpressing HCC cell lines. Results: Among 19 cases of HBV-related, 17 cases of hepatitis C virus (HCV)-related, and 19 cases of nonviral-related HCC, the HBV-related tumor showed the largest size. The HBx-stained area in the tumor and peritumor tissue showed a significant correlation with tumor size and serum α-fetoprotein level. YAP expression was higher in HBV-related tumor tissue than in the peritumor tissue and HCV-related tumor. Additionally, HBx and YAP protein expressions are correlated and both expressions in the tumor contributed to the poor prognosis. An in vitro study demonstrated that HBx and YAP overexpression in the hepatocytes activate the various oncogenic signaling pathways. Conclusions: Our study demonstrated that YAP expression in the liver of HBV-infected patients might be the key factor in HBV-related HCC development and control of tumor-related features.

    DOI: 10.1016/j.bbrep.2022.101352

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  • Effects of a selective PPARα modulator, sodium-glucose cotransporter 2 inhibitor, and statin on the myocardial morphology of medaka nonalcoholic fatty liver disease model. 国際誌

    Marina Ohkoshi-Yamada, Kenya Kamimura, Atsushi Kimura, Yuto Tanaka, Itsuo Nagayama, Shunta Yakubo, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Shuji Terai

    Biochemical and biophysical research communications   625   116 - 121   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic dysregulation and is linked with various cardiovascular complications, which often lead to poor prognostic outcomes. To develop a standard therapy for NAFLD and to urgently address its complications, the current study aimed to investigate the mechanisms of NAFLD-related heart disease and the therapeutic effects of drugs targeting various metabolic pathways. METHODS: To explore the mechanism of NAFLD-related heart disease, a medaka model of high-fat diet-induced NAFLD was utilized. The gross structural, histological, and inflammatory changes in the myocardium were evaluated in a time-dependent manner. In addition, the therapeutic effects of medicines used for NAFLD treatment including, selective peroxisome proliferator-activated receptor α modulator (SPPARMα, pemafibrate), sodium-glucose cotransporter 2 (SGLT2) inhibitor (tofogliflozin), and statin (pitavastatin), and their combinations on heart pathology were evaluated. To determine the mechanisms underlying the therapeutic effects, the expression of genes related to liver inflammation was assessed via whole transcriptome sequencing analysis. RESULTS: The fish with NAFLD-related heart injury presented with cardiomyocyte hypertrophy, which led to cardiac hypertrophy. This morphological change was caused by the infiltration of inflammatory cells, including macrophages and CD4- and CD8-positive lymphocytes, in the cardiac wall and the expression of transforming growth factor beta 1 in the cardiomyocytes. Further, the livers of the fish had upregulated expressions of senescence-associated secretory phenotype-related genes. Treatment with pemafibrate, tofogliflozin, and pitavastatin reduced these changes and, consequently, cardiomyopathy. CONCLUSION: Our results demonstrated that NAFLD-related heart disease was attributed to the senescence-associated secretory phenotype-induced inflammatory activity in the cardiac wall, which resulted in myocardial hypertrophy. Moreover, the effects of SPPARMα, SGLT2 inhibitor, and statin on NAFLD-related heart disease were evident in the medaka NAFLD model.

    DOI: 10.1016/j.bbrc.2022.07.117

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  • Cumulative risk of developing a new symptom in patients with primary biliary cholangitis and its impact on prognosis. 国際誌

    Naruhiro Kimura, Toru Setsu, Yoshihisa Arao, Norihiro Sakai, Yusuke Watanabe, Hiroyuki Abe, Hiroteru Kamimura, Akira Sakamaki, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Akihiko Osaki, Kentarou Igarashi, Nobuo Waguri, Masahiko Yanagi, Toru Takahashi, Soichi Sugitani, Yuka Kobayashi, Masaaki Takamura, Akira Yoshikawa, Toru Ishikawa, Toshiaki Yoshida, Toshiaki Watanabe, Hitoshi Bannai, Tomoyuki Kubota, Kazuhiro Funakoshi, Hiroto Wakabayashi, So Kurita, Norio Ogata, Masashi Watanabe, Yuhsaku Mita, Shigeki Mori, Motoya Sugiyama, Toru Miyajima, Sumio Takahashi, Shuichi Sato, Kisei Ishizuka, Hironobu Ohta, Yutaka Aoyagi, Shuji Terai

    JGH open : an open access journal of gastroenterology and hepatology   6 ( 8 )   577 - 586   2022年8月

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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: Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods: This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan-Meier analysis with propensity score matching and logistic progression analysis. Results: The cumulative risk of developing a new symptom after 10 and 20 years of follow-up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033-1.165; P = 0.002), the serum D-Bil level (HR, 6.262; 95% CI, 2.522-15.553, P < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183-1.036; P = 0.037) were significant independent predictors of a new symptom. Kaplan-Meier analysis showed that the overall survival and liver-related death were not significant between patients with and without a new symptom. Conclusion: The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D-Bil level, and Paris II criteria.

    DOI: 10.1002/jgh3.12789

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  • 『高齢者(75歳以上)の非アルコール性脂肪性肝疾患の現状と課題』非アルコール性脂肪性肝炎を背景とした高齢者肝硬変に対する非侵襲的スコアリングシステムの有用性の検討

    坂牧 僚, 酒井 規裕, 阿部 寛幸, 横尾 健, 上村 顕也, 寺井 崇二

    日本高齢消化器病学会誌   25 ( 1 )   74 - 74   2022年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本高齢消化器病学会  

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  • Daisaikoto improves fatty liver and obesity in melanocortin-4 receptor gene-deficient mice via the activation of brown adipose tissue. 国際誌

    Shinichi Morita, Akira Sakamaki, Kyutaro Koyama, Osamu Shibata, Takashi Owaki, Chiyumi Oda, Atsushi Kimura, Taiki Nakaya, Katsuya Ohbuchi, Miwa Nahata, Naoki Fujitsuka, Norihiro Sakai, Hiroyuki Abe, Kenya Kamimura, Shuji Terai

    Scientific reports   12 ( 1 )   10105 - 10105   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Melanocortin 4 receptor gene-knockout (MC4R-KO) mice are known to develop obesity with a high-fat diet. Meanwhile, daisaikoto, one of Kampo medicines, is a drug that is expected to have therapeutic effects on obesity. Here, we report the efficacy of daisaikoto in MC4R-KO mice. Eight-week-old MC4R-KO male mice (n = 12) were divided into three groups as follows: the SD group, which is fed with a standard diet; the HFD group, fed a high-fat diet; and the DSK group, fed with a high-fat diet containing 10% of daisaikoto. After the four-week observation period, mice in each group were sacrificed and samples were collected. The body weights at 12 weeks were significantly higher in the HFD group than in the other groups, indicating that daisaikoto significantly reduced body weight gain and fat deposition of the liver. The metabolome analysis indicated that degradation of triglycerides and fatty acid oxidation in the liver were enhanced by daisaikoto administration. In MC4R-KO mice, the cytoplasm and uncoupling protein 1 expression of brown adipose tissue was decreased; however, it was reversed in the DSK group. In conclusion, daisaikoto has potentially improved fatty liver and obesity, making it a useful therapeutic agent for obesity and fatty liver.

    DOI: 10.1038/s41598-022-14371-y

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  • Establishment of a pancreatic cancer animal model using the pancreas-targeted hydrodynamic gene delivery method. 国際誌

    Osamu Shibata, Kenya Kamimura, Yuto Tanaka, Kohei Ogawa, Takashi Owaki, Chiyumi Oda, Shinichi Morita, Atsushi Kimura, Hiroyuki Abe, Satoshi Ikarashi, Kazunao Hayashi, Takeshi Yokoo, Shuji Terai

    Molecular therapy. Nucleic acids   28   342 - 352   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This research developed an easy-to-use, reproducible pancreatic cancer animal model utilizing pancreas-targeted hydrodynamic gene delivery to deliver human pancreatic cancer-related genes to the pancreas of wild-type rats. KRAS G12D -induced pancreatic intraepithelial neoplasia lesions showed malignant transformation in the main pancreatic duct at 4 weeks and developed acinar-to-ductal metaplasia, which led to pancreatic ductal adenocarcinoma within 5 weeks, and the gene combination of KRAS G12D and YAP enhanced these effects. The repeat hydrodynamic gene delivery of KRAS G12D  + YAP combination at 4 weeks showed acinar-to-ductal metaplasia in all rats and pancreatic ductal adenocarcinoma in 80% of rats 1 week later. Metastatic tumors in the liver, lymph nodes, and subcutaneous lesions and nervous invasion were confirmed. KRAS G12D and YAP combined transfer contributes to the E- to N-cadherin switch in pancreatic ductal adenocarcinoma cells and to tumor metastases. This pancreatic cancer model will speed up pancreatic cancer research for novel treatments and biomarkers for early diagnosis.

    DOI: 10.1016/j.omtn.2022.03.019

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  • Effects of Atezolizumab and Bevacizumab on Adrenal Gland Metastasis of Hepatocellular Carcinoma: A Case Report and Review of Literature.

    Natsuki Ishikawa, Kenya Kamimura, Saori Endo, Soichi Ishii, Kazuya Ogawa, Norihiro Sakai, Hiroyuki Abe, Masayoshi Ko, Osamu Shibata, Youhei Koseki, Junji Yokoyama, Akira Sakamaki, Shuji Terai

    Internal medicine (Tokyo, Japan)   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Regarding the prognosis of cases with advanced-stage hepatocellular carcinoma (HCC), a recent clinical study showed that the immune checkpoint inhibitors atezolizumab plus bevacizumab have superior efficacy to sorafenib. However, only a few reports have focused on their effects on extrahepatic metastases. We herein report a case of HCC in a 59-year-old man with intrahepatic lesions treated successfully by hepatic arterial chemoembolization, radiotherapy, and sorafenib; the extrahepatic lesion in the adrenal gland was treated by atezolizumab plus bevacizumab. The patient showed a tumor-free condition for one year. We have summarized the clinical course and reviewed the literature to underscore the efficacy of atezolizumab plus bevacizumab for treating extrahepatic lesions of HCC.

    DOI: 10.2169/internalmedicine.9341-22

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  • Relative Dose Intensityに基づく高齢者レンバチニブ投与における全生存期間の検討

    横尾 健, 酒井 規裕, 渡邉 雄介, 荒生 祥尚, 木村 成宏, 阿部 寛幸, 薛 徹, 上村 博輝, 坂牧 僚, 上村 顕也, 土屋 淳紀, 寺井 崇二

    肝臓   63 ( Suppl.1 )   A302 - A302   2022年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Effects of a novel selective PPARα modulator, statin, sodium-glucose cotransporter 2 inhibitor, and combinatorial therapy on the liver and vasculature of medaka nonalcoholic steatohepatitis model. 国際誌

    Atsushi Kimura, Kenya Kamimura, Marina Ohkoshi-Yamada, Yoko Shinagawa-Kobayashi, Ryo Goto, Takashi Owaki, Chiyumi Oda, Osamu Shibata, Shinichi Morita, Norihiro Sakai, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Shuji Terai

    Biochemical and biophysical research communications   596   76 - 82   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a disease entity with an increasing incidence, with involvement of several metabolic pathways. Various organs, including the liver, kidneys, and the vasculature, are damaged in NASH, indicating the urgent need to develop a standard therapy. Therefore, this study was conducted to investigate the effects of drugs targeting various metabolic pathways and their combinations on a high-fat diet (HFD)-induced NASH medaka model. METHODS: To investigate the effects of drugs on vascular structures, the NASH animal model was developed using the fli::GFP transgenic medaka fed with HFD at 20 mg/fish daily. The physiological changes, histological changes in the liver, vascular structures in the fin, and serum biochemical markers were evaluated in a time-dependent manner after treatment with selective peroxisome proliferator-activated receptor α modulator (pemafibrate), statin (pitavastatin), sodium-glucose cotransporter 2 inhibitor (tofogliflozin), and their combinations. Furthermore, to determine the mechanisms underlying the effects, whole transcriptome sequencing was conducted using medaka liver samples. RESULTS: Histological analyses revealed significant suppression of fat accumulation and fibrotic changes in the liver after treatment with drugs and their combinations. The expression levels of steatosis- and fibrosis-related genes were modified by the treatments. Moreover, the HFD-induced vascular damages in the fin exhibited milder changes after treatment with the drugs. CONCLUSION: The effects of treating various metabolic pathways on the medaka body, liver, and vascular structures of the NASH medaka model were evidenced. Moreover, to our knowledge, this study is the first to report whole genome sequence and gene expression evaluation of medaka livers, which could be helpful in clarifying the molecular mechanisms of drugs.

    DOI: 10.1016/j.bbrc.2022.01.086

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  • Cyclin D1 Binding Protein 1 Responds to DNA Damage through the ATM-CHK2 Pathway. 国際誌

    Yusuke Niwa, Kenya Kamimura, Kohei Ogawa, Chiyumi Oda, Yuto Tanaka, Ryoko Horigome, Masato Ohtsuka, Hiromi Miura, Koichi Fujisawa, Naoki Yamamoto, Taro Takami, Shujiro Okuda, Masayoshi Ko, Takashi Owaki, Atsushi Kimura, Osamu Shibata, Shinichi Morita, Norihiro Sakai, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Shuji Terai

    Journal of clinical medicine   11 ( 3 )   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cyclin D1 binding protein 1 (CCNDBP1) is considered a tumor suppressor, and when expressed in tumor cells, CCNDBP1 can contribute to the viability of cancer cells by rescuing these cells from chemotherapy-induced DNA damage. Therefore, this study focused on investigating the function of CCNDBP1, which is directly related to the survival of cancer cells by escaping DNA damage and chemoresistance. Hepatocellular carcinoma (HCC) cells and tissues obtained from Ccndbp1 knockout mice were used for the in vitro and in vivo examination of the molecular mechanisms of CCNDBP1 associated with the recovery of cells from DNA damage. Subsequently, gene and protein expression changes associated with the upregulation, downregulation, and irradiation of CCNDBP1 were assessed. The overexpression of CCNDBP1 in HCC cells stimulated cell growth and showed resistance to X-ray-induced DNA damage. Gene expression analysis of CCNDBP1-overexpressed cells and Ccndbp1 knockout mice revealed that Ccndbp1 activated the Atm-Chk2 pathway through the inhibition of Ezh2 expression, accounting for resistance to DNA damage. Our study demonstrated that by inhibiting EZH2, CCNDBP1 contributed to the activation of the ATM-CHK2 pathway to alleviate DNA damage, leading to chemoresistance.

    DOI: 10.3390/jcm11030851

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  • Simultaneous muscular hemorrhages in two regions three years after successfully controlling refractory ascites using transjugular intrahepatic portosystemic shunt treatment: a case report.

    Hiroteru Kamimura, Michitaka Imai, Hiroyuki Abe, Aiko Yoshioka, Kanae Hirose, Noriko Ishihara, Toru Ishikawa, Shuji Terai

    Clinical journal of gastroenterology   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Various therapies and drugs have been developed to extend the life expectancy of patients with liver cirrhosis. The prolonged prognosis of cirrhotic patients may change the final cause of death in the future. Deep bleeding into the muscle is an uncommon but potentially life-threatening complication of liver cirrhosis. CASE REPORT: A 53-year-old man had undergone transjugular intrahepatic portosystemic shunt treatment for refractory ascites, which successfully controlled it for three years. However, he had started drinking again and experienced acute-on-chronic liver failure. He also had severe back pain. Abdominal computed tomography showed hyperdensities in the retroperitoneum and right pleural cavity. Despite blood infusion, he died from acute-on-chronic liver failure. A pathological autopsy revealed bleeding from the iliopsoas and right diaphragmatic muscle simultaneously, evident from the presence of red blood cells located between the muscle sheaths. Disruption of the small vessels in the skeletal muscle fibers was inferred. CONCLUSION: This is a critical case that underscores the significance of improving available knowledge based on the cause of final death of the patients with cirrhosis, who now have a good long-term prognosis owing to the latest medical developments.

    DOI: 10.1007/s12328-022-01591-y

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  • Longitudinal increase in albumin-bilirubin score is associated with non-malignancy-related mortality and quality of life in patients with liver cirrhosis. 国際誌

    Akira Sakamaki, Masaaki Takamura, Norihiro Sakai, Yusuke Watanabe, Yoshihisa Arao, Naruhiro Kimura, Toru Setsu, Hiroyuki Abe, Takeshi Yokoo, Hiroteru Kamimura, Shunsuke Tsubata, Nobuo Waguri, Toru Ishikawa, Hirokazu Kawai, Soichi Sugitani, Tomomi Sato, Kazuhiro Funakoshi, Masashi Watanabe, Kentarou Igarashi, Kenya Kamimura, Atsunori Tsuchiya, Yutaka Aoyagi, Shuji Terai

    PloS one   17 ( 2 )   e0263464   2022年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Due to the developments in the treatment for hepatitis, it is possible to prevent the progression of liver fibrosis and improve patients' prognosis even if it has already led to liver cirrhosis (LC). Consequently, a two-step study was conducted. To begin with, a retrospective study was conducted to identify the potential predictors of non-malignancy-related mortality from LC. Then, we prospectively analyzed the validity of these parameters as well as their association with patients' quality of life. In the retrospective study, 89 cases were included, and the multivariate Cox regression analysis indicated that age (P = 0.012), model for end-stage liver disease (MELD) score (P = 0.012), and annual rate of change of the albumin-bilirubin (ALBI) score (P < 0.001) were significantly associated with LC prognosis. In the prospective study, 70 patients were included, and the patients were divided into cirrhosis progression and non-progression groups. The univariate logistic regression analysis indicated the serum procollagen type III N-terminal peptide level (P = 0.040) and MELD score (P = 0.010) were significantly associated with the annual rate of change of the ALBI score. Furthermore, the mean Chronic Liver Disease Questionnaire score worsened from 5.3 to 4.9 in the cirrhosis progression group (P = 0.034). In conclusion, a longitudinal increase in the ALBI score is closely associated with non-malignancy-related mortality and quality of life.

    DOI: 10.1371/journal.pone.0263464

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  • Hydrogen-producing small intestinal bacterial overgrowth is associated with hepatic encephalopathy and liver function. 国際誌

    Kunihiko Yokoyama, Akira Sakamaki, Kazuya Takahashi, Takumi Naruse, Chihiro Sato, Yuzo Kawata, Kentaro Tominaga, Hiroyuki Abe, Hiroki Sato, Atsunori Tsuchiya, Kenya Kamimura, Masaaki Takamura, Junji Yokoyama, Shuji Terai

    PloS one   17 ( 2 )   e0264459   2022年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Overt hepatic encephalopathy (HE) is one of the complications of liver cirrhosis (LC), which negatively affects the prognosis and quality of life of patients. Small intestinal bacterial overgrowth (SIBO) is significantly associated with LC and its complications, including HE. We investigated the relationship between SIBO and LC, and the difference between hydrogen-producing and methane-producing SIBO (H-SIBO and M-SIBO, respectively). This is a prospective cohort study of 107 cases. Breath measurements of hydrogen and methane concentrations were performed for the diagnosis of SIBO. The study cohort included 81 males with a median age of 70 (40-86) years, and SIBO was detected in 31 cases (29.0%). There were no significant differences between the SIBO positive and SIBO negative groups. Reclassification into H-SIBO (16 cases) and others (91 cases) was performed, and the Child-Pugh score was only derived in the multivariate logistic analysis (P = 0.028, odds ratio 1.39, 95% confidence interval 1.04-1.85). Furthermore, H-SIBO was significantly associated with covert HE in chi-square test (50.0% vs. 24.2%, P = 0.034). In addition, we evaluated the therapeutic response on SIBO of rifaximin in eight covert HE patients. 20% patients with M-SIBO and 67% patients with H-SIBO showed an improvement of the breath test. In conclusion, H-SIBO, but not M-SIBO, is significantly associated with liver function, and rifaximin might be more effective for covert HE with H-SIBO. Therefore, the diagnosis of SIBO, including the classification as H-SIBO and M-SIBO, might help to determine the choice of treatment for HE.

    DOI: 10.1371/journal.pone.0264459

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  • アルコール性肝硬変におけるB型肝炎ウイルス感染の発癌と予後に対する関与についての検討

    坂牧 僚, 小山 究太郎, 森田 真一, 阿部 寛幸, 上村 顕也, 高村 昌昭, 寺井 崇二

    アルコールと医学生物学   40   47 - 49   2021年12月

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    記述言語:日本語   出版者・発行元:梵天書房  

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  • 原発性胆汁性胆管炎患者の予後を最もよく予想する治療反応性判定Criteriaについて

    木村 成宏, 高村 昌昭, 武田 信峻, 荒生 祥尚, 高綱 将史, 渡邉 雄介, 竹内 卓, 阿部 寛幸, 薛 徹, 上村 博輝, 坂牧 僚, 上村 顕也, 土屋 淳紀, 寺井 崇二

    日本消化器病学会雑誌   118 ( 臨増大会 )   A698 - A698   2021年10月

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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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  • 有症化した症候性巨大肝嚢胞に対して、ミノサイクリン硬化療法が著効した一例

    木南 佳也, 小川 和也, 石井 壮一, 遠藤 沙織, 石川 夏生, 阿部 寛幸, 佐藤 裕樹, 坂牧 僚, 上村 顕也, 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   69回・91回   93 - 93   2021年10月

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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-甲信越支部  

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  • 原発性胆汁性胆管炎患者の予後を最もよく予想する治療反応性判定Criteriaについて

    木村 成宏, 高村 昌昭, 武田 信峻, 荒生 祥尚, 高綱 将史, 渡邉 雄介, 竹内 卓, 阿部 寛幸, 薛 徹, 上村 博輝, 坂牧 僚, 上村 顕也, 土屋 淳紀, 寺井 崇二

    日本消化器病学会雑誌   118 ( 臨増大会 )   A698 - A698   2021年10月

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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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  • 有症化した症候性巨大肝嚢胞に対して、ミノサイクリン硬化療法が著効した一例

    木南 佳也, 小川 和也, 石井 壮一, 遠藤 沙織, 石川 夏生, 阿部 寛幸, 佐藤 裕樹, 坂牧 僚, 上村 顕也, 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   69回・91回   93 - 93   2021年10月

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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-甲信越支部  

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  • Advances in the Treatment of Gastrointestinal Bleeding: Safety and Efficiency of Transnasal Endoscopy. 国際誌

    Hiroyuki Abe, Kenya Kamimura, Yoshihisa Arao, Junji Kohisa, Shuji Terai

    Medicines (Basel, Switzerland)   8 ( 9 )   2021年9月

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    記述言語:英語  

    Acute upper gastrointestinal bleeding (UGIB) is a common disorder and a gastroenterological emergency. With the development of new techniques and devices, the survivability after gastrointestinal bleeding is improving. However, at the same time, we are facing the difficulty of severely complicated cases with various diseases. For example, while endoscopic examination with a normal diameter endoscope is essential for the diagnosis and treatment of UGIB, there are several cases in which it cannot be used. In these cases, transnasal endoscopy (TNE) may be a viable treatment option. This report reviews current hemostatic devices for endoscopic treatment and the safety and efficiency of using TNE in complicated cases. The latter will be demonstrated in a case report where TNE was employed in a patient with severe esophageal stenosis. This review summarizes the advances made in the devices used and will provide further ideas for the physician in terms of combining these devices and TNE.

    DOI: 10.3390/medicines8090053

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  • 【膵癌研究最前線】膵臓選択的ハイドロダイナミック遺伝子導入法

    柴田 理, 上村 顕也, 田中 裕登, 小川 光平, 阿部 寛幸, 五十嵐 聡, 横尾 健, 寺井 崇二

    消化器・肝臓内科   10 ( 3 )   342 - 346   2021年9月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

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  • 門脈圧亢進症と臓器相関 心、肝、肺、腎、脾 当院における心不全に伴う肝臓への影響(Cardiac Hepatopathy)の解析

    上村 博輝, 寺井 崇二, 猪又 孝文, 三井田 秀, 山崎 文紗子, 柏村 健, 藤木 信也, 渡邊 雄介, 荒生 祥尚, 木村 成宏, 阿部 寛幸, 薛 徹, 坂牧 僚, 横尾 健

    日本門脈圧亢進症学会雑誌   27 ( 3 )   109 - 109   2021年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • BRTO中に出血を来し、NBCAによるEISを併用し治療を完遂した十二指腸静脈瘤の1例

    前田 悠一郎, 荒生 祥尚, 小島 雄一, 川田 雄三, 渡邉 雄介, 薛 徹, 阿部 寛幸, 坂牧 僚, 上村 博輝, 横尾 健, 土屋 淳紀, 上村 顕也, 横山 純二, 寺井 崇二

    日本門脈圧亢進症学会雑誌   27 ( 3 )   134 - 134   2021年8月

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • 高齢者消化器がん化学療法〜高齢者のがん治療を安全・効果的に遂行するための取り組み 高齢肝細胞癌症例における分子標的治療薬の生存期間延長効果と予測因子の検討

    横尾 健, 酒井 規裕, 渡邉 雄介, 荒生 祥尚, 木村 成宏, 阿部 寛幸, 薛 徹, 上村 博輝, 坂牧 僚, 上村 顕也, 土屋 淳紀, 寺井 崇二

    日本高齢消化器病学会誌   24 ( 1 )   115 - 115   2021年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本高齢消化器病学会  

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  • Effect of Lenvatinib on a Hepatocellular Carcinoma with Fibroblast Growth Factor Receptor 4 Expression: A Case Report and Review of the Literature.

    Osamu Shibata, Kenya Kamimura, Masayoshi Ko, Norihiro Sakai, Hiroyuki Abe, Shinichi Morita, Takeshi Mizusawa, Hiroki Sato, Akira Sakamaki, Shuji Terai

    Internal medicine (Tokyo, Japan)   60 ( 11 )   1709 - 1715   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Basic and clinical research have shown that the expression of molecules involved in the hepatocellular carcinoma (HCC) cell signaling pathway is related to the sensitivity to molecular-targeted agents. We herein report a case of HCC that was effectively treated with lenvatinib after a poor response to sorafenib. The tumor showed a high expression of fibroblast growth factor receptor 4, which is reportedly related to the sensitivity to lenvatinib in vitro. The information obtained from this case and from our literature review highlights the importance of assessing the expression of the molecules involved in tumors for effective precision medicine.

    DOI: 10.2169/internalmedicine.6580-20

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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

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    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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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Relationship between detection of hepatitis B virus in saliva and periodontal disease in hepatitis B virus carriers in Japan. 国際誌

    Hiroteru Kamimura, Jun Watanabe, Tomoyuki Sugano, Junji Kohisa, Hiroyuki Abe, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Shogo Okoshi, Yoshinari Tanabe, Ritsuo Takagi, Hirofumi Nonaka, Shuji Terai

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   27 ( 3 )   492 - 496   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Although hepatitis B virus infection is well-described, the additional risk posed by oral bleeding in individuals with chronic hepatitis B virus infection has not been determined. This study aimed to determine the quantity of hepatitis B virus in the saliva of carriers in Japan, as a means of understanding the potential risk for horizontal transmission. METHODS: Saliva samples from 48 confirmed hepatitis B virus carriers were included in the analysis. Hepatitis B virus concentrations and the presence of occult blood as periodontal disease were evaluated in each sample. RESULTS: Hepatitis B surface antigen was identified in 46 of the 48 samples (98%), with hepatitis B virus DNA identified in 19 of the 48 saliva samples (40%). Occult blood was detected in 32 (67%) samples with the prevalence increasing as a function of age (r = 0.413; P = 0.003). There was a significantly positive correlation between hepatitis B virus DNA levels in the serum and saliva specimens (r = 0.895; P < 0.001). CONCLUSIONS: Occult blood in saliva was detected in most participants. The detection of hepatitis B virus DNA correlated positively with hepatitis B virus in the serum and occult blood in the saliva. Therefore, improved care of periodontal disease among older people is important for preventing horizontal transmission of hepatitis B virus.

    DOI: 10.1016/j.jiac.2020.10.028

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  • 【肝硬変診療ガイドラインの改正をめぐって】肝腎症候群

    坂牧 僚, 薛 徹, 阿部 寛幸, 上村 顕也, 高村 昌昭, 寺井 崇二

    消化器・肝臓内科   9 ( 2 )   155 - 159   2021年2月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

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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

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 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

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    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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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本門脈圧亢進症学会  

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  • 【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

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    記述言語:日本語   出版者・発行元:医学図書出版(株)  

    肝腎症候群は肝硬変や末期肝疾患患者に発症した可逆的な腎機能障害である。薬物治療の基本は、アルブミン製剤投与下に血管収縮薬を投与することであり、欧米ではテルリプレシンが最も一般的に使用されている。また、経頸静脈的肝内門脈大循環短絡術や血液透析も考慮されるが、肝移植が根治的な治療として位置付けられている。治療方針の決定においては、個々の症例の状況を慎重に検討のうえ、最新のガイドラインなどを参考にしつつ行う必要がある。(著者抄録)

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  • EUS-FNAが術前診断に有用であった十二指腸Brunner腺過誤腫出血の1切除例

    荒生 祥尚, 小林 正明, 池見 雅俊, 塩路 和彦, 清野 智, 阿部 寛幸, 岩城 孝和, 田口 貴博, 谷 優佑, 寺井 崇二

    Gastroenterological Endoscopy   62 ( 7 )   778 - 784   2020年7月

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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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  • EUS-FNAが術前診断に有用であった十二指腸Brunner腺過誤腫出血の1切除例

    荒生 祥尚, 小林 正明, 池見 雅俊, 塩路 和彦, 清野 智, 阿部 寛幸, 岩城 孝和, 田口 貴博, 谷 優佑, 寺井 崇二

    Gastroenterological Endoscopy   62 ( 7 )   778 - 784   2020年7月

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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75歳男性.黒色便を認め,内視鏡検査で十二指腸球部後面に無茎性腫瘤性病変(25mm)を認め,頂部に微小な露出血管を伴ったびらんがあり止血処置を行った.EUS-FNAを施行しBrunner腺の過形成を認め悪性の可能性は極めて低いと判断したが,出血を繰り返し治療適応と判断した.局在や大きさ,形態から内視鏡的切除困難なため外科的局所切除を施行した.病理はBrunner腺の他に導管や平滑筋の増生も認めBrunner腺過誤腫と診断した.Brunner腺過誤腫が内視鏡切除できない場合,病変の局在によっては膵頭十二指腸切除など侵襲的な手術が選択された報告もあるが,EUS-FNAは診断に有用であった.(著者抄録)

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  • Effect of Diphtheria Toxin-Based Gene Therapy for Hepatocellular Carcinoma. 査読 国際誌

    Kenya Kamimura, Takeshi Yokoo, Hiroyuki Abe, Norihiro Sakai, Takuro Nagoya, Yuji Kobayashi, Masato Ohtsuka, Hiromi Miura, Akira Sakamaki, Hiroteru Kamimura, Norio Miyamura, Hiroshi Nishina, Shuji Terai

    Cancers   12 ( 2 )   2020年2月

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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) is a major global malignancy, responsible for >90% of primary liver cancers. Currently available therapeutic options have poor performances due to the highly heterogeneous nature of the tumor cells; recurrence is highly probable, and some patients develop resistances to the therapies. Accordingly, the development of a novel therapy is essential. We assessed gene therapy for HCC using a diphtheria toxin fragment A (DTA) gene-expressing plasmid, utilizing a non-viral hydrodynamics-based procedure. The antitumor effect of DTA expression in HCC cell lines (and alpha-fetoprotein (AFP) promoter selectivity) is assessed in vitro by examining HCC cell growth. Moreover, the effect and safety of the AFP promoter-selective DTA expression was examined in vivo using an HCC mice model established by the hydrodynamic gene delivery of the yes-associated protein (YAP)-expressing plasmid. The protein synthesis in DTA transfected cells is inhibited by the disappearance of tdTomato and GFP expression co-transfected upon the delivery of the DTA plasmid; the HCC cell growth is inhibited by the expression of DTA in HCC cells in an AFP promoter-selective manner. A significant inhibition of HCC occurrence and the suppression of the tumor marker of AFP and des-gamma-carboxy prothrombin can be seen in mice groups treated with hydrodynamic gene delivery of DTA, both 0 and 2 months after the YAP gene delivery. These results suggest that DTA gene therapy is effective for HCC.

    DOI: 10.3390/cancers12020472

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  • Rare Brain Metastasis From a Pancreatobiliary Subtype of Intraductal Papillary Mucinous Neoplasm. 査読 国際誌

    Yoshihisa Arao, Kenya Kamimura, Masatoshi Ikemi, Kazunao Hayashi, Masayuki Takaki, Shunsaku Takahashi, Satoshi Seino, Hiroyuki Abe, Shintaro Tsuboguchi, Yutaka Otsu, Kazuhiro Sanpei, Junji Kohisa, Shuhei Kondo, Yusuke Tani, Junko Ito, Yasuko Toyoshima, Akiyoshi Kakita, Yoichi Ajioka, Shuji Terai

    Pancreas   49 ( 1 )   e8-e11   2020年1月

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  • Obesity and accumulation of subcutaneous adipose tissue are poor prognostic factors in patients with alcoholic liver cirrhosis. 国際誌

    Akira Sakamaki, Kunihiko Yokoyama, Kyutaro Koyama, Shinichi Morita, Hiroyuki Abe, Kenya Kamimura, Masaaki Takamura, Shuji Terai

    PloS one   15 ( 11 )   e0242582   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004-1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042-1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943-0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan-Meier curve (67.1 vs 21.2 vs 65.3, P<0.001) of a 5-year survival rate. Propensity score matching analysis of the SAT and VAT groups was performed to adjust the patient's background, but no significant differences were found between them; however, the prognosis was poorer (21.2 vs 66.3, P<0.001), and hemostatic factors were still at a lower level in the SAT group. These findings suggest that SAT accumulation type of obesity is a poor prognostic factor in alcoholic LC patients without HCC, and the hemorrhagic tendency might worsen the poor prognosis in such cases.

    DOI: 10.1371/journal.pone.0242582

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  • Pulmonary tumor thrombotic microangiopathy of hepatocellular carcinoma: A case report and review of literature. 査読 国際誌

    Shinichi Morita, Kenya Kamimura, Hiroyuki Abe, Yukari Watanabe-Mori, Chiyumi Oda, Takamasa Kobayashi, Yoshihisa Arao, Yusuke Tani, Riuko Ohashi, Yoichi Ajioka, Shuji Terai

    World journal of gastroenterology   25 ( 48 )   6949 - 6958   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare condition in patients with hepatocellular carcinoma (HCC); to date, few cases have been reported. While hepatic dysfunction has been focused on the later stages of HCC, the management of symptoms in PTTM is important for supportive care of the cases. For the better understanding of PTTM in HCC, the information of our recent case and reported cases have been summarized. CASE SUMMARY: A patient with HCC exhibited acute and severe respiratory failure. Radiography and computed tomography of the chest revealed the multiple metastatic tumors and a frosted glass-like shadow with no evidence of infectious pneumonia. We diagnosed his condition as acute respiratory distress syndrome caused by the lung metastases and involvement of the pulmonary vessels by tumor thrombus. Administration of prednisolone to alleviate the diffuse alveolar damages including edematous changes of alveolar wall caused by the tumor cell infiltration and ischemia showed mild improvement in his symptoms and imaging findings. An autopsy showed the typical pattern of PTTM in the lung with multiple metastases. CONCLUSION: PTTM is caused by tumor thrombi in the arteries and thickening of the pulmonary arterial endothelium leading to the symptoms of dyspnea in terminal staged patients. Therefore, supportive management of symptoms is necessary in the cases with PTTM and hence we believe that the information presented here is of great significance for the diagnosis and management of symptoms of PTTM with HCC.

    DOI: 10.3748/wjg.v25.i48.6949

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  • Gene Therapy for Liver Cancers: Current Status from Basic to Clinics. 査読 国際誌

    Kenya Kamimura, Takeshi Yokoo, Hiroyuki Abe, Shuji Terai

    Cancers   11 ( 12 )   2019年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The liver is a key organ for metabolism, protein synthesis, detoxification, and endocrine function, and among liver diseases, including hepatitis, cirrhosis, malignant tumors, and congenital disease, liver cancer is one of the leading causes of cancer-related deaths worldwide. Conventional therapeutic options such as embolization and chemotherapy are not effective against advanced-stage liver cancer; therefore, continuous efforts focus on the development of novel therapeutic options, including molecular targeted agents and gene therapy. In this review, we will summarize the progress toward the development of gene therapies for liver cancer, with an emphasis on recent clinical trials and preclinical studies.

    DOI: 10.3390/cancers11121865

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  • A Rare Duodenal Carcinosarcoma: A Case Report and Literature Review. 査読

    Yoshihisa Arao, Kenya Kamimura, Masatoshi Ikemi, Masayuki Takaki, Shunsaku Takahashi, Satoshi Seino, Hiroyuki Abe, Junji Kohisa, Takashi Kato, Yoichi Ajioka, Shuji Terai

    Internal medicine (Tokyo, Japan)   58 ( 9 )   1273 - 1278   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Carcinosarcoma is a biphasic malignant tumor comprising both carcinomatous and sarcomatous components; its occurrence in the duodenum is very rare. We herein report the case of a 96-year-old woman with duodenal carcinosarcoma showing rapid growth within the past year. The tumor was found to be bulging into the lumen and predominantly comprised sarcomatoid components with focal positive staining for cytokeratin. Therefore, the tumor was diagnosed as duodenal carcinosarcoma. The clinical information of the present case and our literature review of the 12 cases reported to date will help physicians diagnose and treat this rare tumor.

    DOI: 10.2169/internalmedicine.2094-18

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  • 術後胆汁中膵酵素値とERCP後膵炎の関連

    河久 順志, 五十嵐 聡, 林 和直, 荒生 祥尚, 阿部 寛幸, 高橋 一也, 渡邉 順, 横山 純二, 寺井 崇二

    Gastroenterological Endoscopy   60 ( Suppl.2 )   2156 - 2156   2018年10月

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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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  • Efficacy and Safety of Pancreas-Targeted Hydrodynamic Gene Delivery in Rats. 査読 国際誌

    Kohei Ogawa, Kenya Kamimura, Yuji Kobayashi, Hiroyuki Abe, Takeshi Yokoo, Norihiro Sakai, Takuro Nagoya, Akira Sakamaki, Satoshi Abe, Kazunao Hayashi, Satoshi Ikarashi, Junji Kohisa, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

    Molecular therapy. Nucleic acids   9   80 - 88   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Development of an effective, safe, and convenient method for gene delivery to the pancreas is a critical step toward gene therapy for pancreatic diseases. Therefore, we tested the possibility of applying the principle of hydrodynamic gene delivery for successful gene transfer to pancreas using rats as a model. The established procedure involves the insertion of a catheter into the superior mesenteric vein with temporary blood flow occlusion at the portal vein and hydrodynamic injection of DNA solution. We demonstrated that our procedure achieved efficient pancreas-specific gene expression that was 2,000-fold higher than that seen in the pancreas after the systemic hydrodynamic gene delivery. In addition, the level of gene expression achieved in the pancreas by the pancreas-specific gene delivery was comparable to the level in the liver achieved by a liver-specific hydrodynamic gene delivery. The optimal level of reporter gene expression in the pancreas requires an injection volume equivalent to 2.0% body weight with flow rate of 1 mL/s and plasmid DNA concentration at 5 μg/mL. With the exception of transient expansion of intercellular spaces and elevation of serum amylase levels, which recovered within 3 days, no permanent tissue damage was observed. These results suggest that pancreas-targeted hydrodynamic gene delivery is an effective and safe method for gene delivery to the pancreas and clinically applicable.

    DOI: 10.1016/j.omtn.2017.08.009

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  • HHMはDNA損傷ストレスに対する応答機構を介して肝発癌抑制に寄与する

    小川 光平, 上村 顕也, 後藤 諒, 井上 良介, 品川 陽子, 阿部 寛幸, 阿部 聡司, 坂牧 僚, 横尾 健, 川合 弘一, 山際 訓, 高見 太郎, 山本 直樹, 坂井田 功, 寺井 崇二

    肝臓   58 ( Suppl.1 )   A448 - A448   2017年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Drug-eluting beads in hepatocellular carcinoma. 査読 国際誌

    Hiroyuki Abe, Kenya Kamimura, Shuji Terai

    Therapeutic advances in gastroenterology   10 ( 3 )   337 - 338   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1177/1756283X16681710

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  • Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment. 査読 国際誌

    Kenya Kamimura, Yuji Kobayashi, Yoshifumi Takahashi, Hiroyuki Abe, Daisuke Kumaki, Takeshi Yokoo, Hiroteru Kamimura, Norihiro Sakai, Akira Sakamaki, Satoshi Abe, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

    Cancer biology & therapy   18 ( 2 )   79 - 84   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately <1 y of survival from the time of diagnosis. A molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time. However, the therapeutic benefit for the brain metastasis remains unclear, since it causes intratumor bleeding leading to the severe brain damage. No guidelines for the brain metastasis of HCC have been developed to date due to the shortage of the experiences and evidences. Therefore, the development of standard therapy for brain metastasis following the early diagnosis is essential by accumulating the information of clinical courses and evidences. For this purpose, we reviewed cases of HCC brain metastasis reported to date and analyzed additional 8 cases from our hospital, reviewing 592 advanced HCC cases to estimate the possible metastatic lesions in the brain. With careful review of cases and literature, we suggest that the cases with lung metastasis with increase tendency of tumor markers within recent 3-6 months have higher risks of brain metastasis. Therefore, they should be carefully followed by imaging modalities. In addition, the loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.

    DOI: 10.1080/15384047.2016.1276134

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  • Case of severe alcoholic hepatitis treated with granulocytapheresis. 査読 国際誌

    Yukari Watanabe, Kenya Kamimura, Tomohiro Iwasaki, Hiroyuki Abe, Shunsaku Takahashi, Ken-Ichi Mizuno, Manabu Takeuchi, Atsushi Eino, Ichiei Narita, Shuji Terai

    World journal of clinical cases   4 ( 11 )   369 - 374   2016年11月

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    記述言語:英語  

    Severe alcoholic hepatitis (AH) has a high mortality, and it is associated with encephalopathy, acute renal failure, sepsis, gastrointestinal bleeding, and endotoxemia. The 28-d mortality remains poor (34%-40%), because no effective treatment has been established. Recently, corticosteroids (CS) have been considered effective for significantly improving the prognosis of those with AH, as it prevents the production of pro-inflammatory cytokines. However, CS are not always appropriate as an initial therapeutic option, such as in cases with an infection or resistance to CS. We describe a patient with severe AH complicated by a severe infection caused by the multidrug resistance bacteria (Pseudomonas aeruginosa), and was successfully treated with granulocytapheresis monotherapy without using CS. The experience of this case will provide understanding of the disease and information treating cases without using CS.

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  • Liver-targeted hydrodynamic gene therapy: Recent advances in the technique. 査読 国際誌

    Takeshi Yokoo, Kenya Kamimura, Hiroyuki Abe, Yuji Kobayashi, Tsutomu Kanefuji, Kohei Ogawa, Ryo Goto, Masafumi Oda, Takeshi Suda, Shuji Terai

    World journal of gastroenterology   22 ( 40 )   8862 - 8868   2016年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    One of the major research focuses in the field of gene therapy is the development of clinically applicable, safe, and effective gene-delivery methods. Since the first case of human gene therapy was performed in 1990, a number of gene-delivery methods have been developed, evaluated for efficacy and safety, and modified for human application. To date, viral-vector-mediated deliveries have shown effective therapeutic results. However, the risk of lethal immune response and carcinogenesis have been reported, and it is still controversial to be applied as a standard therapeutic option. On the other hand, delivery methods for nonviral vector systems have been developed, extensively studied, and utilized in in vivo gene-transfer studies. Compared to viral-vector mediated gene transfer, nonviral systems have less risk of biological reactions. However, the lower gene-transfer efficiency was a critical hurdle for applying them to human gene therapy. Among a number of nonviral vector systems, our studies focus on hydrodynamic gene delivery to utilize physical force to deliver naked DNA into the cells in the living animals. This method achieves a high gene-transfer level by DNA solution injections into the tail vein of rodents, especially in the liver. With the development of genome editing methods, in vivo gene-transfer therapy using this method is currently the focus in this research field. This review explains the method principle, efficiency, safety, and procedural modifications to achieve a high level of reproducibility in large-animal models.

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  • Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery. 査読 国際誌

    Yuji Kobayashi, Kenya Kamimura, Hiroyuki Abe, Takeshi Yokoo, Kohei Ogawa, Yoko Shinagawa-Kobayashi, Ryo Goto, Ryosuke Inoue, Masato Ohtsuka, Hiromi Miura, Tsutomu Kanefuji, Takeshi Suda, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

    Molecular therapy. Nucleic acids   5 ( 8 )   e359   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hydrodynamic gene delivery is a common method for gene transfer to the liver of small animals, and its clinical applicability in large animals has been demonstrated. Previous studies focused on functional analyses of therapeutic genes in animals with normal livers and little, however, is known regarding its effectiveness and safety in animals with liver fibrosis. Therefore, this study aimed to examine the effects of liver fibrosis on hydrodynamic gene delivery efficiency using a rat liver fibrosis model. We demonstrated for the first time, using pCMV-Luc plasmid, that this procedure is safe and that the amount of fibrotic tissue in the liver decreases gene delivery efficiency, resulting in decrease in luciferase activity depending on the volume of fibrotic tissue in the liver and the number of hepatocytes that are immunohistochemically stained positive for transgene product. We further demonstrate that antifibrotic gene therapy with matrix metalloproteinase-13 gene reduces liver fibrosis and improves efficiency of hydrodynamic gene delivery. These results demonstrate the negative effects of fibrotic tissue on hydrodynamic gene delivery and its recovery by appropriate antifibrotic therapy.

    DOI: 10.1038/mtna.2016.63

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  • [Effective Prevention of Hand-Foot Syndrome by the Consumption of Dried Bonito Broth]. 査読

    Kenya Kamimura, Yoko Shinagawa, Kohei Ogawa, Yuji Kobayashi, Hiroyuki Abe, Takeshi Yokoo, Hiroteru Kamimura, Hirokazu Kawai, Takeshi Suda, Satoshi Yamagiwa, Hiroshi Baba, Shuji Terai

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 4 )   463 - 5   2016年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    To examine whether the consumption of dried bonito both is effective for the prevention of hand-foot syndrome(HFS), concentrated bonito broth was administered to 10 patients with HCC who were treated with sorafenib. Among the 10 patients, seven showed an increase in peripheral blood flow, as observed on Doppler ultrasonography. Only one patient showed Grade 1 HFS on day 14 after the initiation of sorafenib (10%); this incidence rate of HFS was significantly lower than that obtained in our previous studies and reported data. These results suggest that consumption of dried bonito broth contributes to the prevention of HFS by maintaining peripheral blood flow.

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  • The Combination Therapy of Dissolution Using Carbonated Liquid and Endoscopic Procedure for Bezoars: Pragmatical and Clinical Review. 査読 国際誌

    Kohei Ogawa, Kenya Kamimura, Ken-Ichi Mizuno, Yoko Shinagawa, Yuji Kobayashi, Hiroyuki Abe, Yukari Watanabe, Shunsaku Takahashi, Kazunao Hayashi, Junji Yokoyama, Manabu Takeuchi, Masaaki Kobayashi, Satoshi Yamagiwa, Yuichi Sato, Shuji Terai

    Gastroenterology research and practice   2016   7456242 - 7456242   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Bezoars are relatively rare foreign bodies of gastrointestinal tract and often cause ileus and ulcerative lesions in the stomach and subsequent bleeding and perforation due to their size and stiffness. Therefore, the removal of bezoars is essential and recent development of devices, the endoscopic removal procedure, is often applied. However, due to their stiffness, simple endoscopic removal failed in not a few cases, and surgical removal has also been used. Recently, the efficacy of a combination therapy of endoscopic procedure and dissolution using carbonated liquid has been reported. To develop the safe and effective removal procedure, we carefully reviewed a total of 55 reported cases in this study including our 3 additional cases, successfully treated with dissolution with endoscopic fragmentation. In summary, the data showed the efficiency in the combination therapy, treating the larger size of bezoar and reducing the length of hospital stay. To the best of our knowledge, this is the largest pragmatical and clinical review for the combination therapy of dissolution and endoscopic treatment for bezoars. This review should help physicians to manage bezoars more efficiently.

    DOI: 10.1155/2016/7456242

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  • 最近経験した胃石症の3例 成因および内視鏡的処置法の検討

    小川 光平, 水野 研一, 品川 陽子, 林 和直, 上村 顕也, 阿部 寛幸, 竹内 学, 小林 正明, 小林 英之, 津野 吉裕, 寺井 崇二

    ENDOSCOPIC FORUM for digestive disease   31 ( 2 )   172 - 172   2015年11月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

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  • First case of bacteremia caused by Helicobacter cinaedi in a patient with liver cirrhosis: a case report and literature review. 査読

    Kenya Kamimura, Daisuke Kumaki, Masashi Arita, Yuji Kobayashi, Ken-Ichi Mizuno, Fumiko Kusama, Megumi Kobayashi, Hiroyuki Abe, Yoshifumi Takahashi, Kohei Ogawa, Yoko Shinagawa, Manabu Takeuchi, Yuichi Sato, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

    Clinical journal of gastroenterology   8 ( 5 )   306 - 17   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Patients with liver cirrhosis are known to be immunocompromised hosts due to the dysfunction of the cellular and humoral immune systems, allowing easier bacterial translocation from the intestine to the systemic circulation via the portal vein. Sepsis can often be seen in these patients; however, approximately 10 % of patients show negative results with the standard culture period (3-4 days) and their pathogens remain undiagnosed. Here we report the first case of a patient with liver cirrhosis diagnosed with bacteremia due to Helicobacter cinaedi after gastrointestinal symptoms and review 62 cases of H. cinaedi infection in patients with other diseases. The patient showed positive results for H. cinaedi after 10 days of culture. Administration of a carbapenem was effective and clinical symptoms recovered 20 days after admission. H. cinaedi is an enterohepatic bacterial species that causes bacteremia in immunocompromised patients. Due to the difficulty of detection, few cases have been reported to date and to the best of our knowledge, this is the first published case of bacteremia due to H. cinaedi infection in a patient with liver cirrhosis. Since bacteremia in patients with liver cirrhosis can result in fatality, we recommend vigilance for H. cinaedi infection, longer periods of blood culture, polymerase chain reaction analysis, and empirical antibiotic therapy to help improve prognosis.

    DOI: 10.1007/s12328-015-0600-0

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  • Diagnostic imaging of hepatic lymphoma. 査読 国際誌

    Hiroyuki Abe, Kenya Kamimura, Hirokazu Kawai, Hiroteru Kamimura, Koji Domori, Yuji Kobayashi, Minoru Nomoto, Yutaka Aoyagi

    Clinics and research in hepatology and gastroenterology   39 ( 4 )   435 - 42   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hepatic lymphoma is a rare disease with poor prognosis because of delayed diagnosis. The disease comprises primary, metastatic, and intravascular hepatic lymphomas. The pathological characteristics of lymphomas differ contributing to difficulty in early diagnosis. Early diagnosis and appropriate treatment result in improved prognosis; therefore, diagnostic radiology and its development with various contrast agents are critical for improving disease outcomes. Herein, we review hepatic lymphomas and summarize the results of imaging studies in correlation with pathological characteristics. The information provided will help physicians in early diagnosis and thereby improving prognosis.

    DOI: 10.1016/j.clinre.2014.11.001

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  • Image-Guided Hydrodynamic Gene Delivery: Current Status and Future Directions. 査読 国際誌

    Kenya Kamimura, Takeshi Yokoo, Hiroyuki Abe, Yuji Kobayashi, Kohei Ogawa, Yoko Shinagawa, Ryosuke Inoue, Shuji Terai

    Pharmaceutics   7 ( 3 )   213 - 23   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hydrodynamics-based delivery has been used as an experimental tool to express transgene in small animals. This in vivo gene transfer method is useful for functional analysis of genetic elements, therapeutic effect of oligonucleotides, and cancer cells to establish the metastatic cancer animal model for experimental research. Recent progress in the development of image-guided procedure for hydrodynamics-based gene delivery in large animals directly supports the clinical applicability of this technique. This review summarizes the current status and recent progress in the development of hydrodynamics-based gene delivery and discusses the future directions for its clinical application.

    DOI: 10.3390/pharmaceutics7030213

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  • Advances in understanding and treating liver diseases during pregnancy: A review. 査読 国際誌

    Kenya Kamimura, Hiroyuki Abe, Hirokazu Kawai, Hiroteru Kamimura, Yuji Kobayashi, Minoru Nomoto, Yutaka Aoyagi, Shuji Terai

    World journal of gastroenterology   21 ( 17 )   5183 - 90   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Liver disease in pregnancy is rare but pregnancy-related liver diseases may cause threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia; haemolysis, elevated liver enzymes, and low platelets syndrome; acute fatty liver of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy. Recent basic researches have shown the various etiologies involved in this disease entity. With these advances, rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival. The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention. Therefore, correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis. Therefore, here we review and summarized recent advances in understanding the etiologies, clinical courses and management of liver disease in pregnancy. This information will contribute to physicians for diagnosis of disease and optimum management of patients.

    DOI: 10.3748/wjg.v21.i17.5183

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  • Late onset post-transfusion hepatitis E developing during chemotherapy for acute promyelocytic leukemia. 査読

    Kyoko Fuse, Yuichi Matsuyama, Masato Moriyama, Shukuko Miyakoshi, Yasuhiko Shibasaki, Jun Takizawa, Tatsuo Furukawa, Ichiro Fuse, Hiro Matsumura, Shigeharu Uchida, Yoshifumi Takahashi, Kenya Kamimura, Hiroyuki Abe, Takeshi Suda, Yutaka Aoyagi, Hirohito Sone, Masayoshi Masuko

    Internal medicine (Tokyo, Japan)   54 ( 6 )   657 - 61   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We herein report the case of a leukemia patient who developed hepatitis E seven months after undergoing a transfusion with contaminated blood products. The latency period in this case was significantly longer than that of typical hepatitis E. Recently, chronic infection with hepatitis E virus (HEV) genotype 3 has been reported in immunocompromised patients. There is a possibility that our patient was unable to eliminate the virus due to immunosuppression following chemotherapy and the administration of steroids. The prevalence of HEV in healthy Japanese individuals is relatively high and constitutes a critical source of infection via transfusion. Hepatitis E is an important post-transfusion infection, and immunocompromised patients may exhibit a long latency period before developing the disease.

    DOI: 10.2169/internalmedicine.54.2332

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  • Successful management of severe intrahepatic cholestasis of pregnancy: report of a first Japanese case. 査読 国際誌

    Kenya Kamimura, Hiroyuki Abe, Naomi Kamimura, Masayuki Yamaguchi, Maiko Mamizu, Kanna Ogi, Yoshifumi Takahashi, Ken-Ichi Mizuno, Hiroteru Kamimura, Yuji Kobayashi, Manabu Takeuchi, Kunihiko Yoshida, Kyoko Yamada, Takayuki Enomoto, Koichi Takakuwa, Minoru Nomoto, Miki Obata, Yoshinori Katsuragi, Yukio Mishima, Ryo Kominami, Tomoteru Kamimura, Yutaka Aoyagi

    BMC gastroenterology   14   160 - 160   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a cholestasis condition caused by elevated levels of serum bile acids that mainly occurs in the third trimester of pregnancy. Maternal symptoms include pruritus; elevation of transaminases, biliary enzymes, and bilirubin levels; and abnormal liver function tests. Fetal symptoms include spontaneous preterm labor, fetal distress, and intrauterine death. It is more prevalent in the Caucasians and is rarely found in Asian countries, including Japan. The etiology of ICP has been reported as involving various factors such as, environmental factors, hormone balance, and genetic components. The genetic factors include single-nucleotide polymorphisms (SNPs) in the genes of canalicular transporters, including ABCB4 and ABCB11. It has also been reported that the combination of these SNPs induces severe cholestasis and liver dysfunction. CASE PRESENTATION: Here, we report for the first time a 24-year Japanese case of severe ICP diagnosed by typical symptoms, serum biochemical analysis, and treated with the administration of ursodeoxycholic acid which improved cholestasis and liver injury and prevented fetal death. The sequence analysis showed SNPs reported their association with ICP in the ABCB11 (rs2287622, V444A) and ABCB4 (rs1202283, N168N) loci. CONCLUSION: The risk of ICP has been reported to be population-specific, and it is rare in the Japanese population. Our case was successfully treated with ursodeoxycholic acid and the genetic sequence analysis has supported the diagnosis. Because genetic variation in ABCB4 and ABCB11 has also been reported in the Japanese population, we need to be aware of potential ICP cases in pregnant Japanese women although further studies are necessary.

    DOI: 10.1186/1471-230X-14-160

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  • Safety assessment of liver-targeted hydrodynamic gene delivery in dogs. 査読 国際誌

    Kenya Kamimura, Tsutomu Kanefuji, Takeshi Yokoo, Hiroyuki Abe, Takeshi Suda, Yuji Kobayashi, Guisheng Zhang, Yutaka Aoyagi, Dexi Liu

    PloS one   9 ( 9 )   e107203   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Evidence in support of safety of a gene delivery procedure is essential toward gene therapy. Previous studies using the hydrodynamics-based procedure primarily focus on gene delivery efficiency or gene function analysis in mice. The current study focuses on an assessment of the safety of computer-controlled and liver-targeted hydrodynamic gene delivery in dogs as the first step toward hydrodynamic gene therapy in clinic. We demonstrate that the impacts of the hydrodynamic procedure were limited in the injected region and the influences were transient. Histological examination and the hepatic microcirculation measurement using reflectance spectrophotometry reveal that the liver-specific impact of the procedure involves a transient expansion of the liver sinusoids. No systemic damage or toxicity was observed. Physiological parameters, including electrocardiogram, heart rate, blood pressure, oxygen saturation, and body temperature, remained in normal ranges during and after hydrodynamic injection. Body weight was also examined to assess the long-term effects of the procedure in animals who underwent 3 hydrodynamic injections in 6 weeks with 2-week time interval in between. Serum biochemistry analysis showed a transient increase in liver enzymes and a few cytokines upon injection. These results demonstrate that image-guided, liver-specific hydrodynamic gene delivery is safe.

    DOI: 10.1371/journal.pone.0107203

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  • Early diagnosis of hepatic intravascular lymphoma: a case report and literature review. 査読

    Hiroyuki Abe, Kenya Kamimura, Maiko Mamizu, Yasuhiko Shibazaki, Takanobu Ishiguro, Shin-ichi Katada, Yu-ki Nishiyama, Yoshifumi Takahashi, Yu-ya Hatano, Ken-ichi Mizuno, Yukari Watanabe, Aiko Nagashima, Jun Takizawa, Manabu Takeuchi, Hirokazu Kawai, Minoru Nomoto, Hirohito Sone, Masatoyo Nishizawa, Yutaka Aoyagi

    Internal medicine (Tokyo, Japan)   53 ( 6 )   587 - 93   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hepatic intravascular large B-cell lymphoma (IVL) is a rare disease entity that involves invasion into various organs. Due to the aggressive behavior and poor prognosis of the disease and the difficulty in making an early diagnosis, some cases are diagnosed at autopsy. Early suspicion and the use of imaging studies and liver biopsies are key for diagnosing IVL; however, no reports have described the results of imaging studies due to the limited number of cases. We herein report the results of imaging studies of hepatic IVL, including the findings PET-CT, dynamic-CT, EOB-MRI and CEUS. These results may help physicians to make an early diagnosis and improve the prognosis.

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  • Hemodynamics of a hydrodynamic injection. 査読 国際誌

    Tsutomu Kanefuji, Takeshi Yokoo, Takeshi Suda, Hiroyuki Abe, Kenya Kamimura, Dexi Liu

    Molecular therapy. Methods & clinical development   1   14029 - 14029   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The hemodynamics during a hydrodynamic injection were evaluated using cone beam computed tomography (CBCT) and fluoroscopic imaging. The impacts of hydrodynamic (5 seconds) and slow (60 seconds) injections into the tail veins of mice were compared using 9% body weight of a phase-contrast medium. Hydrodynamically injected solution traveled to the heart and drew back to the hepatic veins (HV), which led to liver expansion and a trace amount of spillover into the portal vein (PV). The liver volumes peaked at 165.6 ± 13.3% and 165.5 ± 11.9% of the original liver volumes in the hydrodynamic and slow injections, respectively. Judging by the intensity of the CBCT images at the PV, HV, right atrium, liver parenchyma (LP), and the inferior vena cava (IVC) distal to the HV conjunction, the slow injection resulted in the higher intensity at PV than at LP. In contrast, a significantly higher intensity was observed in LP after hydrodynamic injection in comparison with that of PV, suggesting that the liver took up the iodine from the blood flow. These results suggest that the enlargement speed of the liver, rather than the expanded volume, primarily determines the efficiency of hydrodynamic delivery to the liver.

    DOI: 10.1038/mtm.2014.29

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  • Case of cerebral lipiodol embolism after repeated transcatheter arterial chemoembolization of hepatocellular carcinoma. 査読 国際誌

    Toru Ishikawa, Tomoyuki Kubota, Hiroyuki Abe, Yuichiro Toduka, Ryoko Horigome, Yuhsuke Watanabe, Naruhiro Kimura, Hiroki Honda, Akito Iwanaga, Keiichi Seki, Terasu Honma, Toshiaki Yoshida, Masahisa Sato

    Hepatology research : the official journal of the Japan Society of Hepatology   43 ( 11 )   1251 - 2   2013年11月

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    記述言語:英語  

    DOI: 10.1111/hepr.12074

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  • Surfactant protein-D is more useful than Krebs von den Lungen 6 as a marker for the early diagnosis of interstitial pneumonitis during pegylated interferon treatment for chronic hepatitis C. 査読 国際誌

    Toru Ishikawa, Tomoyuki Kubota, Hiroyuki Abe, Kanae Hirose, Aiko Nagashima, Tadayuki Togashi, Keiichi Seki, Terasu Honma, Toshiaki Yoshida, Tomoteru Kamimura

    Hepato-gastroenterology   59 ( 119 )   2260 - 3   2012年10月

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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 examine the usefulness of serum Krebs von den Lungen 6 (KL-6) and surfactant protein-D (SP-D) as markers of interstitial pneumonitis. Many antiviral therapies have become available for chronic hepatitis C, including pegylated interferon (PEGIFN) plus ribavirin. Since interstitial pneumonitis is a serious adverse drug reaction during interferon therapy, interferon treatment requires caution in respiratory disease patients. Hence, the predictors of interstitial pneumonitis have not been elucidated. METHODOLOGY: Fifty-two chronic hepatitis C patients who received PEG-IFN plus ribavirin were studied; 14 patients received PEGIFN-α 2a, and 38 received PEG-IFN-α 2b. Serum KL-6 and SP-D levels were measured during treatment. Time changes in serum KL-6 and SP-D levels, as well as the presence of interstitial pneumonitis, were investigated. RESULTS: No cases of pneumonitis in which both markers were below the standard values were seen. Interstitial pneumonitis developed in 1 of the 5 patients in whom both markers were above standard values. Patients whose KL-6 levels alone exceeded the standard value had bacterial pneumonia and emphysema, not interstitial pneumonitis. Though no correlation between SP-D and KL-6 levels was observed, KL-6 levels tended to increase after interstitial pneumonitis was detected on imaging, but SP-D levels increased before imaging detection. CONCLUSIONS: It is important to monitor changes in levels of serum markers and other factors to avoid interstitial pneumonitis during PEG-IFN therapy. SP-D in particular may be important for early detection of interstitial pneumonitis.

    DOI: 10.5754/hge10868

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  • Efficacy of the regimen using twice-daily β-interferon followed by the standard of care for chronic hepatitis C genotype 1b with high viral load. 査読 国際誌

    Toru Ishikawa, Tomoyuki Kubota, Hiroyuki Abe, Aiko Nagashima, Kanae Hirose, Tadayuki Togashi, Keiichi Seki, Terasu Honma, Toshiaki Yoshida, Tomoteru Kamimura

    Hepatology research : the official journal of the Japan Society of Hepatology   42 ( 9 )   864 - 9   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM:   In patients with refractory genotype 1b chronic hepatitis C with high viral loads, we retrospectively compared the efficacy of standard of care treatment (SOC: combined PEG-IFN-α-2b/ribavirin for 48 weeks) and a regimen in which 2 weeks of SOC induction was replaced by twice-daily β-interferon alone (IFN-β induction therapy). METHODS:   Seventeen patients received the IFN-β induction therapy plus SOC (IFN-β induction group) and 13 patients received SOC alone (SOC group). RESULTS:   In the IFN-β induction group and SOC group, early virological response (EVR) rates were 88.2% and 53.8%, respectively. The end of treatment rates were 100.0% and 92.3%, and sustained virological response (SVR) rates were 70.6% and 53.8%, respectively. By induction with IFN-β, even in refractory cases, the high virus negative conversion rate in the early treatment phase and actions of pegylated IFN-α-2b and ribavirin in the maintenance treatment phase led to an additive effect. In the analysis of contributing factors, only the achievement of EVR was associated with a significant difference in SVR (P = 0.0011). The univariate logistic regression analysis showed that only IFN-β treatment was associated with a significant difference in EVR (P = 0.0492, odds ratio = 6.248, 95% confidence interval = 1.026-40.252), whereas no significant factors were found in the multivariate analysis due to small samples. CONCLUSION:   IFN-β induction therapy with higher EVR might be beneficial for protease inhibitor-refractory chronic hepatitis C patients.

    DOI: 10.1111/j.1872-034X.2012.00995.x

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  • Histopathology of the tissue adhering to the multiple tine expandable electrodes used for radiofrequency ablation of hepatocellular carcinoma predicts local recurrence. 査読

    Toru Ishikawa, Tomoyuki Kubota, Hiroyuki Abe, Aiko Nagashima, Kanae Hirose, Tadayuki Togashi, Keiichi Seki, Terasu Honma, Toshiaki Yoshida, Tomoteru Kamimura, Takeo Nemoto, Keiko Takeda, Noriko Ishihara

    Internal medicine (Tokyo, Japan)   51 ( 19 )   2683 - 8   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: To assess the ability to predict the local recurrence of hepatocellular carcinoma by analyzing tissues adhering to the radiofrequency ablation probe after complete ablation. METHODS: From May 2002 to March 2011, tissue specimens adhering to the radiofrequency ablation probe from 284 radiofrequency ablation sessions performed for hepatocellular carcinomas ≤3 cm in size were analyzed. The specimens were classified as either viable tumor tissue or complete necrosis, and the local recurrence rates were calculated using the Kaplan-Meier method. RESULTS: From the tumors ≤3 cm in size, viable tissue was present in 6 (2.1%) of 284 specimens, and the local recurrence rates after 1 and 2 years of follow-up were 6.7% and 11.2%, respectively. Local recurrence developed significantly earlier in the viable tissue group. The recurrence rate was not significantly different based on whether transcatheter arterial chemoembolization was performed. CONCLUSION: The histopathology of the tissue adhering to the radiofrequency ablation probes used for hepatocellular carcinoma treatment can predict local recurrence. Additional aggressive treatment for patients with viable tissue can therefore improve the overall survival.

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  • ハイドロダイナミック遺伝子導入法による肝線維化・肝癌に対する遺伝子治療研究

    上村顕也, 横尾健, 阿部寛幸, 三浦浩美, 大塚正人, 尾田雅文, 仁科博史, 寺井崇二

    肝細胞研究会プログラム・抄録集   27th   2020年

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  • Multiple Endocrine Neoplasia Type 1-Related Acute Pancreatitis

    Shunsaku Takahashi, Kenya Kamimura, Hiroyuki Abe, Yukari Watanabe, Kazunao Hayashi, Kenichi Mizuno, Takashi Yamamoto, Manabu Takeuchi, Masaaki Natsui, Shuji Terai

    PANCREAS   48 ( 5 )   E35 - E38   2019年5月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1097/MPA.0000000000001267

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  • 9年間の経過観察を行った、全大腸に潰瘍性大腸炎類似のびまん性発赤粘膜を呈したCrohn病の1例

    阿部 寛幸, 本間 照, 石川 達, 堀米 亮子, 阿部 聡司, 土屋 淳紀, 横山 純二, 西倉 健, 石原 紀子, 加藤 卓, 味岡 洋一, 寺井 崇二

    ENDOSCOPIC FORUM for digestive disease   34 ( 1 )   82 - 82   2018年6月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

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  • Human Homologue of Maid contributes to DNA damage response pathway in HCC.

    Kohei Ogawa, Kenya Kamimura, Ryo Goto, Ryosuke Inoue, Yoko Shinagawa, Yuji Kobayashi, Hiroyuki Abe, Satoshi Abe, Akira Sakamaki, Takeshi Yokoo, Hirokazu Kawai, Satoshi Yamagiwa, Taro Takami, Naoki Yamamoto, Isao Sakaida, Shuji Terai

    HEPATOLOGY   66   373A - 373A   2017年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY  

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  • Long-term Gene Expression and Effective Prevention of Liver Fibrosis by Liver-Specific Delivery of Oligonucleotide Therapeutics

    Kenya Kamimura, Takeshi Yokoo, Hiroyuki Abe, Yuji Kobayashi, Norihiro Sakai, Takuro Nagoya, Ryo Goto, Akira Sakamaki, Satoshi Abe, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

    HEPATOLOGY   66   368A - 369A   2017年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY  

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  • Development of Image-guided, Liver Lobe-specific Hydrodynamic Gene Delivery Method for Gene Therapy in Liver Diseases

    Kenya Kamimura, Takeshi Yokoo, Hiroyuki Abe, Yuji Kobayashi, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

    HEPATOLOGY   64   271A - 271A   2016年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY  

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  • ソラフェニブによる手足症候群に対する"濃厚鰹だし"の予防効果

    上村 顕也, 品川 陽子, 小川 光平, 阿部 寛幸, 小林 雄司, 横尾 健, 坂牧 僚, 阿部 聡司, 上村 博輝, 土屋 淳紀, 高村 昌昭, 川合 弘一, 山際 訓, 寺井 崇二

    肝臓   57 ( Suppl.1 )   A218 - A218   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 鰹だしの末梢血流増加作用を利用した手足症候群の予防効果の検証

    上村 顕也, 品川 陽子, 小川 光平, 小林 雄司, 阿部 寛幸, 横尾 健, 上村 博輝, 川合 弘一, 須田 剛士, 山際 訓, 馬場 洋, 寺井 崇二

    癌と化学療法   43 ( 4 )   463 - 465   2016年4月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

    鰹だしの末梢血流増加作用を利用した手足症候群(HFS)の予防効果について検討した。ソラフェニブ(SFN)内服開始のために入院した肝細胞癌症例10例を対象とした。濃厚鰹だしを飲用せず、SFNを内服した対照群3例では、足底血管のtime averaged mean blood flow velocity(TAMEAN)の平均値はSFN内服開始1週後に前値に比較して低下を認め、2例にGrade 1、2のHFSを認めた。濃厚鰹だしを飲用した10例中7例でTAMEAN値が内服開始前後(1週)で上昇を認め、2例では33.5%の低下を認め、1例では著変を認めなかった。各症例における濃厚鰹だし飲用前後の血流変化は、飲用群で対照群に比較して有意に血流増加を認めた。血流増加を認めた症例ではサーモグラフィを施行すると手足末梢温が維持、改善していた。血流低下を認めたうちの1例のみでGrade 1のHFSを内服開始14日目に発症した(発症率10%)。経過中、濃厚鰹だしによる副作用を認めなかった。

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  • ハイドロダイナミック細胞内遺伝子送達システムの開発

    上村 顕也, 阿部 寛幸, 小林 雄司, 兼藤 努, 横尾 健, 須田 剛士, 上村 博輝, 土屋 淳紀, 高村 昌昭, 川合 弘一, 山際 訓, 寺井 崇二

    肝臓   56 ( Suppl.2 )   A776 - A776   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • Image-Guided, Liver-Targeted Hydrodynamic Gene Delivery in Dogs - Preclinical Assessment of Effectiveness and Safety of the Procedure

    Kenya Kamimura, Hiroyuki Abe, Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Yuji Kobayashi, Guisheng Zhang, Masafumi Oda, Yutaka Aoyagi, Shuji Terai, Dexi Liu

    MOLECULAR THERAPY   23   S106 - S107   2015年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:NATURE PUBLISHING GROUP  

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  • Impact of Injection Volume on Hydrodynamic Delivery To the Liver in Mice

    Tsutomu Kanefuji, Takeshi Yokoo, Takeshi Suda, Kunihiko Sawada, Yoshinori Arai, Hiroyuki Abe, Kenya Kamimura, Dexi Liu, Shuji Terai

    MOLECULAR THERAPY   23   S144 - S144   2015年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:NATURE PUBLISHING GROUP  

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  • 11 当院で経験した肝細胞癌脳転移症例の検討(Ⅰ.一般演題, 第38回リバーカンファレンス)

    小林 雄司, 上村 顕也, 高橋 祥史, 阿部 寛幸, 熊木 大輔, 水野 研一, 竹内 学, 田村 康, 高村 昌昭, 五十嵐 正人, 川合 弘一, 山際 訓, 須田 剛士, 野本 実, 青柳 豊, 八木 琢也, 小林 真, 加藤 俊幸

    新潟医学会雑誌   128 ( 9 )   473 - 473   2014年9月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    CiNii Article

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    その他リンク: http://search.jamas.or.jp/link/ui/2015093990

  • 4 遅延性に輸血後E型肝炎を発症した急性前骨髄球性白血病の1例(Ⅰ.一般演題, 第37回リバーカンファレンス)

    高橋 祥史, 上村 顕也, 阿部 寛幸, 水野 研一, 竹内 学, 須田 剛士, 野本 実, 青柳 豊, 布施 香子, 森山 雅人, 増子 正義, 曽根 博仁

    新潟医学会雑誌   127 ( 10 )   568 - 568   2013年10月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    CiNii Article

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    その他リンク: http://search.jamas.or.jp/link/ui/2014161035

  • 多彩な画像所見を呈し肝生検で診断しえた血管内リンパ腫の1例

    岩瀬 麻以子, 阿部 寛幸, 上村 顕也, 高橋 祥史, 水野 研一, 竹内 学, 川合 弘一, 野本 実, 青柳 豊, 畠野 雄也, 石黒 敬信, 堅田 慎一, 西澤 正豊, 岡塚 貴世志, 瀧澤 淳, 曽根 博仁, 高野 徹

    新潟医学会雑誌   127 ( 7 )   389 - 390   2013年7月

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    記述言語:日本語   出版者・発行元:新潟医学会  

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