Updated on 2025/02/01

写真a

 
FUJIYA Mikihiro
 
Organization
President /Vice-President
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Degree

  • Reduced Expression of Syndecan-1 Affects Metastatic Potential and Clinical Outcome in Patients with Colorectal Cancer ( 2001.12   Asahikawa Medical College )

Research Interests

  • Oncology

  • -Gastroenterology

  • Comensal bacteria

  • Gaseroenterology

Research Areas

  • Life Science / Gastroenterology

Education

  • Asahikawa Medical College   Faculty of Medicine   Medical Course

    - 1989.3

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    Country: Japan

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  • Asahikawa Medical College   Faculty of Medicine

    - 1989

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Research History

  • Asahikawa Medical College   Division of Gastroenterology, Department of Internal Medicine   Professor

    2023.10

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  • Asahikawa Medical College   Vice President

    2023.7

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  • Asahikawa Medical College

    2021.7

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  • Asahikawa Medical College   Professor

    2021.6 - 2023.9

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  • Asahikawa Medical College   Research Professor

    2024.4

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  • Asahikawa Medical College   Manager(Dean)

    2024.4

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  • Asahikawa Medical College   Manager(Dean)

    2024.4

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  • Asahikawa Medical College   Research Professor

    2024.4

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  • Asahikawa Medical College   Research Professor

    2024.4

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  • 旭川医科大学消化器疾患病態学講座   特任教授

    2023.5

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  • Asahikawa Medical College   Manager(Dean)

    2021.7 - 2023.6

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  • Asahikawa Medical College   Manager(Dean)

    2021.4 - 2021.6

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  • Asahikawa Medical College   Professor

    2020.6

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  • Asahikawa Medical College   Research Professor

    2018.5

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  • Asahikawa Medical College   Department of Gastroenterology and Advanced Medical Science   Professor

    2018.5

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  • Asahikawa Medical University   Join Research Department of Telemedicine and Telecare   Professor

    2018.4 - 2022.3

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  • 京都大学大学院医学研究科   非常勤講師

    2017.8 - 2019.3

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  • Asahikawa Medical University   School of Medicine

    2008.4

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  • Asahikawa Medical University   School of Medicine

    2007.11 - 2008.3

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  • シカゴ大学(米国)   研究員

    2004.2 - 2006.5

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  • シカゴ大学医学部消化器科(米国)

    2004.2 - 2006.5

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  • Asahikawa Medical University   School of Medicine

    2000.5 - 2007.10

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  • 岩内協会病院   職員(医療系)

    2000.4 - 2002.3

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  • Asahikawa Medical University

    1998.4 - 2000.4

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  • 市立旭川病院   職員(医療系)

    1996.4 - 1998.3

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  • 市立旭川病院 内科医長

    1996.4 - 1998.3

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  • 町立中標津病院   職員(医療系)

    1995.7 - 1996.3

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  • 町立中標津病院 内科医長

    1995.7 - 1996.3

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  • 早期胃癌検診協会(東京)   研究員

    1992.4 - 1995.6

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  • (財)早期胃癌検診協会 (東京) 研究生

    1992.4 - 1995.6

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  • 岩内協会病院 医師

    1990.4 - 1992.3

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  • Asahikawa Medical University   School of Medicine

    1989.4 - 1990.3

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  • Asahikawa Medical College

    1989

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Professional Memberships

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Committee Memberships

  • 日本消化器がん検診学会北海道支部   支部長  

    2021.6   

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    Committee type:Academic society

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  • 日本消化器がん検診学会   理事  

    2021.6   

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    Committee type:Academic society

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  • 日本内科学会北海道支部   大学評議員  

    2021.4   

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    Committee type:Academic society

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  • 日本消化器内視鏡学会   社団評議員  

    2020.9   

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    Committee type:Academic society

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  • 日本消化器病学会   財団評議員  

    2018.3   

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    Committee type:Academic society

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  • 日本消化器がん検診学会   企画・広報委員会 委員長  

    2021.6   

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    Committee type:Academic society

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  • 日本炎症性腸疾患学会   総務委員  

    2021.4   

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    Committee type:Academic society

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  • 日本消化器免疫学会   広報委員  

    2021.1   

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    Committee type:Academic society

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  • 日本消化器がん検診学会   認定医・専門医制度委員会委員  

    2017.8 - 2021.6   

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    Committee type:Academic society

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  • 日本消化器がん検診学会   幹事  

    2017.6 - 2021.6   

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    Committee type:Academic society

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  • 日本小腸学会   評議員  

    2017.1   

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    Committee type:Academic society

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  • 日本消化器免疫学会   広報委員会副委員長  

    2017.1 - 2020.12   

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    Committee type:Academic society

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  • 日本消化器内視鏡学会   機関誌編集委員会委員(英文誌)  

    2016.2   

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    Committee type:Academic society

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  • 日本内科学会   支部評議員  

    2016.1 - 2021.6   

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    Committee type:Academic society

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  • 日本癌治療学会   代議員  

    2015.7   

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    Committee type:Academic society

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  • 日本消化器病学会   機関誌編集委員会(英文誌)  

    2015.5 - 2021.5   

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    Committee type:Academic society

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  • 日本炎症性腸疾患学会   学術委員  

    2015.4 - 2021.3   

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    Committee type:Academic society

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  • 厚生労働科学研究費補助金(厚生労働科学特別研究事業)「薬価算定基準(原価計算方式)における平均的利益率の補正率の定量的算出法及び特定保険医療材料の保険償還価格算定の基準における定量的評価に係る研究」   分担研究者  

    2015.4 - 2016.3   

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    Committee type:Government

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  • 日本消化器内視鏡学会   卒後教育委員会委員  

    2015.2   

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    Committee type:Academic society

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  • IBD日本語版   編集委員  

    2015.1   

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    Committee type:Other

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  • 日本消化器病学会   学術研究助成金選考委員会委員  

    2015.1 - 2021.5   

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    Committee type:Academic society

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  • 日本消化器免疫学会   評議員  

    2014.7   

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    Committee type:Academic society

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  • 日本消化器がん検診学会   専門医制度委員  

    2014.4 - 2017.8   

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    Committee type:Academic society

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  • 分子消化器病   編集委員  

    2014.1 - 2015.12   

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    Committee type:Other

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  • 日本医療安全調査機構   「診療行為に関連した死亡の調査分析モデル事業」 北海道ブロック地域推薦窓口担当者  

    2013.8 - 2015.9   

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    Committee type:Government

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  • 日本医療安全調査機構「診療行為に関連した死亡の調査分析モデル事業」   北海道ブロック地域推薦窓口担当者  

    2013.6 - 2015.9   

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    Committee type:Government

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  •   日本医療安全調査機構「診療行為に関連した死亡の調査分析モデル事業」 北海道ブロック地域推薦窓口担当者  

    2013.6 - 2014.5   

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  • 北海道腸疾患研究会   代表世話人  

    2013.4 - 2017.3   

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    Committee type:Academic society

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  •   独立行政法人日本学術振興会 科学研究費委員会専門委員  

    2012.12 - 2013.11   

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  • 日本消化器内視鏡学会   北海道支部財団評議員選考委員会委員  

    2012.12   

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    Committee type:Academic society

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  • 日本消化器内視鏡学会   北海道支部例会会長選考委員  

    2012.12   

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    Committee type:Academic society

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  • 日本がん分子標的治療学会   評議員  

    2012.6   

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    Committee type:Academic society

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  •   医学系CBT実施小委員会ブラッシュアップ専門部会 委員  

    2012.6   

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  • 独立行政法人日本学術振興会   科学研究費委員会専門委員  

    2011.12 - 2013.11   

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    Committee type:Academic society

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  •   独立行政法人日本学術振興会 科学研究費委員会専門委員  

    2011.12 - 2012.11   

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  • 日本消化器病学会   専門医研修カリキュラム改訂ワーキング委員会委員  

    2011.7 - 2013.9   

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    Committee type:Academic society

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  • International Scholarly Research Network Pathology   Editor  

    2011.3   

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    Committee type:Other

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  • Journal of Gastrointestinal and Digestive Systems   Editor  

    2011.2   

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    Committee type:Other

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  • World Journal of Gastrointestinal Pathophysiology   Editor  

    2011.1   

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    Committee type:Other

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  • 日本消化器がん検診学会   学会評議員  

    2009.6   

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    Committee type:Academic society

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  • 日本消化器がん検診学会   全国集計委員  

    2009.6 - 2021.6   

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    Committee type:Academic society

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  • 日本消化器がん検診学会   認定委員  

    2009.6 - 2021.6   

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    Committee type:Academic society

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  •   北海道保険福祉部 生活習慣病検診管理指導協議会 大腸がん部会  

    2009.4 - 2011.3   

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  • 北海道保健福祉部 生活習慣病検診管理指導協議会   大腸がん部会委員  

    2009.4 - 2011.3   

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    Committee type:Government

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  • 日本消化器内視鏡学会   北海道支部長選出規約制定委員  

    2008.11 - 2009.10   

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    Committee type:Academic society

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  • 厚生労働省特定疾患「難治性炎症性腸管障害」に関する調査研究   癌サーベイランスプロジェクト研究 プロジェクト委員  

    2008.10 - 2010.9   

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    Committee type:Government

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  • 日本内科学会   北海道支部幹事  

    2008.4   

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    Committee type:Academic society

    日本内科学会

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  • 日本消化器がん検診学会   北海道支部幹事  

    2008.4 - 2021.6   

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    Committee type:Academic society

    日本消化器癌検診学会

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  • 日本消化器内視鏡学会   北海道支部専門医制度審議会施設認定委員  

    2008.4 - 2014.3   

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    Committee type:Academic society

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  • 日本消化器内視鏡学会   北海道支部内視鏡セミナー実行委員  

    2008.4 - 2012.3   

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    Committee type:Academic society

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  • 日本消化器病学会   学術評議員  

    2007.1 - 2018.3   

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    Committee type:Academic society

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  • 日本消化器内視鏡学会   学術評議員  

    2002.4 - 2020.9   

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    Committee type:Academic society

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  •   COMMITTEE RESPONSIBILITIES:  

       

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Studying abroad experiences

  • 2004.2 - 2006.5   シカゴ大学   postdoctoral fellow

Papers

  • Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway Reviewed

    Hiroaki Konishi, Shotaro Isozaki, Shin Kashima, Kentaro Moriichi, Satoshi Ichikawa, Kazuki Yamamoto, Chikage Yamamura, Katsuyoshi Ando, Nobuhiro Ueno, Hiroaki Akutsu, Naoki Ogawa, Mikihiro Fujiya

    SCIENTIFIC REPORTS   11 ( 1 )   11070 - 11070   2021.5

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    Authorship:Last author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE RESEARCH  

    Intake of probiotics or fermented food produced by some probiotic bacteria is believed to exert anti-tumor functions in various cancers, including pancreatic cancer, because several studies have demonstrated the anti-tumor effects of probiotic bacteria in vitro and in vivo in animal carcinogenesis models. However, the mechanisms underlying the anticancer effects of probiotics on pancreatic cancer have not been clarified. In this study, we assessed the anti-tumor effects of probiotic bacteria against pancreatic cancer cells. Among the known probiotic bacteria, Aspergillus oryzae exhibited a strong pancreatic tumor suppression effect. The culture supernatant of A. oryzae was separated by HPLC. Heptelidic acid was identified as an anti-tumor molecule derived from A. oryzae by LC-MS and NMR analysis. The anti-tumor effect of heptelidic acid was exhibited in vitro and in vivo in a xenograft model of pancreatic cancer cells. The anti-tumor effect of heptelidic acid was exerted by the p38 MAPK signaling pathway. Heptelidic acid traverses the intestinal mucosa and exerts anti-tumor effects on pancreatic cancer cells. This is a novel anti-tumor mechanism induced by beneficial bacteria against pancreatic cancer in which bacterial molecules pass through the intestinal tract, reach the extra-intestinal organs, and then induce apoptosis via an inducible signaling pathway.

    DOI: 10.1038/s41598-021-90707-4

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  • Bacteria-derived ferrichrome inhibits tumor progression in sporadic colorectal neoplasms and colitis-associated cancer Reviewed

    Takuya Iwama, Mikihiro Fujiya, Hiroaki Konishi, Hiroki Tanaka, Yuki Murakami, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura

    CANCER CELL INTERNATIONAL   21 ( 1 )   2021.1

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:BMC  

    BackgroundColorectal cancers develop through several pathways, including the adenoma-carcinoma sequence and colitis-associated carcinogenesis. An altered intestinal microflora has been reported to be associated with the development and progression of colorectal cancer via these pathways. We identified Lactobacillus casei-derived ferrichrome as a mediator of the bacterial anti-tumor effect of colorectal cancer cells through the upregulation of DDIT3. In this study, we investigated the anti-tumor effects of ferrichrome on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer.MethodsSRB and MTT assays were performed to assess growth inhibition in vitro. Eighteen organoids were prepared from biopsy specimens obtained by colonoscopy. An AOM-DSS carcinogenesis model and xenograft model of colorectal cancer cells were generated for the assessment of the tumor suppressive effect of ferrichrome in vivo.ResultsFerrichrome inhibited the cell growth of colorectal cancer cells in vitro and in in vivo xenograft models. Ferrichrome exerted a strong tumor-suppressive effect that was superior to that of currently available anti-tumor agents, including 5-FU and cisplatin, both in vitro and in vivo. The tumor-suppressive effect of the combination of ferrichrome and 5-FU was superior to that of single treatment with either drug. The tumor suppressive effects of ferrichrome were confirmed through the upregulation of DDIT3 in patient-derived organoids of adenoma and carcinoma. Ferrichrome inhibited the tumor progression in the AOM-DSS model while exhibiting no anti-inflammatory effect in the DSS-colitis model, suggesting that ferrichrome inhibited cancer cells, but not a precancerous condition, via the colitis-associated pathway.ConclusionsFerrichrome exerts a tumor suppressive effect on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer. The anti-tumor effect of ferrichrome was mediated by the upregulation of DDIT3, and was superior to that of 5-FU or cisplatin. These results suggest that Lactobacillus brevis-derived ferrichrome may be a candidate anti-tumor drug for the treatment of colorectal neoplasms.

    DOI: 10.1186/s12935-020-01723-9

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  • A tumor-specific modulation of heterogeneous ribonucleoprotein A0 promotes excessive mitosis and growth in colorectal cancer cells

    Hiroaki Konishi, Mikihiro Fujiya, Shin Kashima, Aki Sakatani, Tatsuya Dokoshi, Katsuyoshi Ando, Nobuhiro Ueno, Takuya Iwama, Kentaro Moriichi, Hiroki Tanaka, Toshikatsu Okumura

    CELL DEATH & DISEASE   11 ( 4 )   2020.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    RNA regulation mediating RNA-binding proteins (RBPs) have been shown to be related to the maintenance of homeostasis as well as cancer progression. However, the tumor-associated functions as well as the detailed mechanisms underlying the anti-tumor effects of most RBPs have yet to be explored. We herein report that the phosphorylated heterogeneous ribonucleoprotein (hnRNP) A0 promotes mitosis through the RAS-associated protein 3 GTPase-activating protein catalytic subunit 1 (RAB3GAP1)-Zeste white 10 interactor (ZWINT1) cascade. The downregulation assay of 20 representative hnRNPs, a major family of RNA-binding proteins, in colorectal cancer cells revealed that hnRNPA0 is a strong regulator of cancer cell growth. The tumor promotive function of hnRNPA0 was confirmed in gastrointestinal cancer cells, including pancreatic, esophageal, and gastric cancer cells, but not in non-cancerous cells. Flow cytometry and Western blotting analyses revealed that hnRNPA0 inhibited the apoptosis through the maintenance of G2/M phase promotion in colorectal cancer cells. A comprehensive analysis of mRNAs regulated by hnRNP A0 and immunostaining revealed that mitotic events were regulated by the hnRNPA0-RAB3GAP1 mRNA-mediated ZWINT-1 stabilization in colorectal cancer cells, but not in non-tumorous cells. The interaction of hnRNP A0 with mRNAs was dramatically changed by the deactivation of its phosphorylation site in cancer cells, but not in non-tumorous cells. Therefore, the tumor-specific biological functions characterized by the abnormal phosphorylation of RBPs are considered to be an attractive target for tumor treatment.

    DOI: 10.1038/s41419-020-2439-7

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  • Long-Chain Polyphosphate Is a Potential Agent for Inducing Mucosal Healing of the Colon in Ulcerative Colitis Reviewed International journal

    Mikihiro Fujiya, Nobuhiro Ueno, Shin Kashima, Kazuyuki Tanaka, Aki Sakatani, Katsuyoshi Ando, Kentaro Moriichi, Hiroaki Konishi, Naoya Kamiyama, Yoshikazu Tasaki, Tomohiro Omura, Kazuo Matsubara, Masaki Taruishi, Toshikatsu Okumura

    CLINICAL PHARMACOLOGY & THERAPEUTICS   107 ( 2 )   452 - 461   2020.2

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    The goal of ulcerative colitis (UC) treatment has recently been shown to be "mucosal healing," as no drug directly induces mucosal healing. Probiotics possess sufficient safety, but their efficacy in the treatment of UC remains controversial because of the influence of intestinal conditions. It is believed that the identification of bioactive molecules produced by probiotics and their application will help to solve this issue. We therefore identified a probiotic-derived long-chain polyphosphate as a molecule enhancing the intestinal barrier function. This study demonstrated that long-chain polyphosphate exhibited antiinflammatory effects in a human macrophage and interleukin-10 knockout transfusion mouse model. The first-in-human trial showed that 7 of the 10 enrolled patients acquired clinical remission, 4 of whom achieved endoscopic remission despite a history of treatment with anti-tumor necrosis factor (TNF)-alpha agents. No adverse reactions were observed. Long-chain polyphosphate might be useful for the treatment of refractory UC, even in patients with failure or intolerance to anti-TNF-alpha therapy.

    DOI: 10.1002/cpt.1628

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  • Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis Reviewed

    Hiroaki Konishi, Mikihiro Fujiya, Hiroki Tanaka, Nobuhiro Ueno, Kentaro Moriichi, Junpei Sasajima, Katsuya Ikuta, Hiroaki Akutsu, Hiroki Tanabe, Yutaka Kohgo

    NATURE COMMUNICATIONS   7   12365   2016.8

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Previous reports have suggested that some probiotics inhibit tumorigenesis and cancer progression. However, the molecules involved have not yet been identified. Here, we show that the culture supernatant of Lactobacillus casei ATCC334 has a strong tumour-suppressive effect on colon cancer cells. Using mass spectrometry, we identify ferrichrome as a tumour-suppressive molecule produced by L. casei ATCC334. The tumour-suppressive effect of ferrichrome is greater than that of cisplatin and 5-fluorouracil, and ferrichrome has less of an effect on non-cancerous intestinal cells than either of those agents. A transcriptome analysis reveals that ferrichrome treatment induces apoptosis, which is mediated by the activation of c-jun N-terminal kinase (JNK). Western blotting indicates that the induction of apoptosis by ferrichrome is reduced by the inhibition of the JNK signalling pathway. This we demonstrate that probiotic-derived ferrichrome exerts a tumour-suppressive effect via the JNK signalling pathway.

    DOI: 10.1038/ncomms12365

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  • Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis Reviewed

    Shin Kashima, Mikihiro Fujiya, Hiroaki Konishi, Nobuhiro Ueno, Yuhei Inaba, Kentaro Moriichi, Hiroki Tanabe, Katsuya Ikuta, Takaaki Ohtake, Yutaka Kohgo

    TRANSLATIONAL RESEARCH   166 ( 2 )   163 - 175   2015.8

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE INC  

    Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis. To clarify the mechanism responsible for the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with transforming growth factor beta 1 (TGF-beta 1) to induce fibrosis. The expression levels of fibrosis- and inflammation-associated molecules were evaluated by both a Western blotting analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The histologic inflammation and fibrosis were significantly improved in the group administered poly P in both the DSS and TNBS colitis models. The levels of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (INF-alpha) were significantly decreased by poly P treatment. The expression levels of TGF-beta 1 and collagens in the colitis mice were decreased by poly P. The LPS-induced expressions of IL-1 beta and TGF-beta 1 in Caco-2/BBE cells and of TNF-alpha in THP-1 cells were reduced by poly P treatment. Poly P did not affect the expression of collagens and connective tissue growth factor in the CCD-18 cells. In conclusion, poly P suppresses intestinal inflammation and fibrosis by downregulating the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium. The administration of poly P is therefore a novel option to treat fibrosis because of chronic intestinal inflammation.

    DOI: 10.1016/j.trsl.2015.02.002

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  • Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection Reviewed

    Mikihiro Fujiya, Kazuyuki Tanaka, Tatsuya Dokoshi, Motoya Tominaga, Nobuhiro Ueno, Yuhei Inaba, Takahiro Ito, Kentaro Moriichi, Yutaka Kohgo

    GASTROINTESTINAL ENDOSCOPY   81 ( 3 )   583 - 595   2015.3

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    Background: EMR and endoscopic submucosal dissection (ESD) are used frequently to remove colon neoplasms. However, the predominance of these procedures has not yet been thoroughly explored.Objective: To compare the efficacy and adverse events related to EMR with those related to ESD for colon neoplasms.Design: A meta-analysis of 8 studies published between 2005 and 2013.Setting: Multicenter review.Patients: Patients from 8 studies yielding 2299 lesions.Interventions: EMR or ESD. Main Outcome Measurements: En bloc resection, curative resection, recurrence, and adverse events.Results: The pooled odds ratios (OR) (OR [95% confidence interval]) for the tumor size, length of the procedure, en bloc resection, curative resection, recurrence, additional surgery, delayed bleeding, and perforation by ESD versus EMR were 7.38 (6.42-8.34), 58.07 (36.27-79.88), 6.84 (3.30-14.18), 4.26 (3.77-6.57), 0.08 (0.04-0.17), 2.16 (1.16-4.03), 0.85 (0.45-1.60), and 4.96 (2.79-8.85), respectively.Limitations: This analysis included only nonrandomized studies.Conclusion: The size of the tumor and rate of en bloc resection and curative resection were higher, and the rate of recurrence was lower in the ESD group versus the EMR group. However, in the ESD group, the procedure was longer, and the rate of additional surgery and perforation was higher, suggesting that the indications for ESD should therefore be rigorously determined in order to avoid such problems.

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  • Decreased numbers of vascular networks and irregular vessels on narrow-band imaging are useful findings for distinguishing intestinal lymphoma from lymphoid hyperplasia Reviewed

    Mikihiro Fujiya, Shin Kashima, Katsuya Ikuta, Tatsuya Dokoshi, Aki Sakatani, Kazuyuki Tanaka, Katsuyoshi Ando, Nobuhiro Ueno, Motoya Tominaga, Yuhei Inaba, Takahiro Ito, Kentaro Moriichi, Hiroki Tanabe, Yusuke Saitoh, Yutaka Kohgo

    GASTROINTESTINAL ENDOSCOPY   80 ( 6 )   1064 - 1071   2014.12

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    Background: No method for sufficiently making the differential diagnosis of intestinal lymphoma resembling lymphoid hyperplasia (LH) on endoscopy has yet been established.Objective: The aim of this study was to evaluate the usefulness of narrow-band imaging (NBI) in diagnosing intestinal lymphoma.Design: Prospective study.Setting: Single-center study.Patients: Sixty-one patients with primary or systemic lymphoma were enrolled in this study.Interventions: The terminal ileum and entire colon were observed by using conventional endoscopy. NBI was subsequently performed when small polypoid lesions were detected. A decrease in the number of vascular networks (DVNs) and the presence of irregular vessels on the surface of the epithelia were defined as characteristic findings of intestinal lymphoma. The diagnostic accuracy of these 2 findings in distinguishing intestinal lymphoma from LH was examined.Main Outcome Measurements: The ability to use NBI to distinguish intestinal lymphoma from LH.Results: Two hundred ninety-four small polypoid lesions, including 59 lymphomas and 235 LH lesions, were detected. The rates of detecting DVNs and the presence of irregular vessels were significantly higher in the lymphoma samples (81.4% and 62.7%) than in the LH samples (25.5% and 4.7%). Based on these findings, the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values for differentiating intestinal lymphoma from LH were 88.8%, 62.7%, 95.3%, 77.1%, and 91.1%, respectively, which are significantly higher than those of conventional endoscopy.Limitations: Single-center study.Conclusion: DVNs and the presence of irregular vessels on NBI are thus considered to be useful findings for differentiating intestinal lymphoma from benign LH.

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  • microRNA-18a induces apoptosis in colon cancer cells via the autophagolysosomal degradation of oncogenic heterogeneous nuclear ribonucleoprotein A1 Reviewed

    M. Fujiya, H. Konishi, M. K. Mohamed Kamel, N. Ueno, Y. Inaba, K. Moriichi, H. Tanabe, K. Ikuta, T. Ohtake, Y. Kohgo

    ONCOGENE   33 ( 40 )   4847 - 4856   2014.10

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    It is well known that microRNAs (miRs) are abnormally expressed in various cancers and target the messenger RNAs (mRNAs) of cancer-associated genes. While (miRs) are abnormally expressed in various cancers, whether miRs directly target oncogenic proteins is unknown. The present study investigated the inhibitory effects of miR-18a on colon cancer progression, which was considered to be mediated through its direct binding and degradation of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). An MTT assay and xenograft model demonstrated that the transfection of miR-18a induced apoptosis in SW620 cells. A binding assay revealed direct binding between miR-18a and hnRNP A1 in the cytoplasm of SW620 cells, which inhibited the oncogenic functions of hnRNP A1. A competitor RNA, which included the complementary sequence of the region of the miR-18a-hnRNP A1 binding site, repressed the effects of miR-18a on the induction of cancer cell apoptosis. In vitro single and in vivo double isotope assays demonstrated that miR-18a induced the degradation of hnRNP A1. An immunocytochemical study of hnRNP A1 and LC3-II and the inhibition of autophagy by 3-methyladenine and ATG7, p62 and BAG3 siRNA showed that miR-18a and hnRNP A1 formed a complex that was degraded through the autophagolysosomal pathway. This is the first report showing a novel function of a miR in the autophagolysosomal degradation of an oncogenic protein resulting from the creation of a complex consisting of the miR and a RNA-binding protein, which suppressed cancer progression.

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  • Image-enhanced endoscopy for the diagnosis of colon neoplasms Reviewed

    Mikihiro Fujiya, Yutaka Kohgo

    GASTROINTESTINAL ENDOSCOPY   77 ( 1 )   111 - U288   2013.1

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    DOI: 10.1016/j.gie.2012.07.031

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  • Probiotic-Derived Polyphosphate Enhances the Epithelial Barrier Function and Maintains Intestinal Homeostasis through Integrin-p38 MAPK Pathway Reviewed

    Shuichi Segawa, Mikihiro Fujiya, Hiroaki Konishi, Nobuhiro Ueno, Naoyuki Kobayashi, Tatsuro Shigyo, Yutaka Kohgo

    PLOS ONE   6 ( 8 )   e23278   2011.8

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    Probiotics exhibit beneficial effects on human health, particularly in the maintenance of intestinal homeostasis in a complex manner notwithstanding the diversity of an intestinal flora between individuals. Thus, it is highly probable that some common molecules secreted by probiotic and/or commensal bacteria contribute to the maintenance of intestinal homeostasis and protect the intestinal epithelium from injurious stimuli. To address this question, we aimed to isolate the cytoprotective compound from a lactobacillus strain, Lactobacillus brevis SBC8803 which possess the ability to induce cytoprotective heat shock proteins in mouse small intestine. L. brevis was incubated in MRS broth and the supernatant was passed through with a 0.2-mu m filter. Caco2/bbe cells were treated with the culture supernatant, and HSP27 expression was evaluated by Western blotting. HSP27-inducible components were separated by ammonium sulfate precipitation, DEAE anion exchange chromatography, gel filtration, and HPLC. Finally, we identified that the HSP27-inducible fraction was polyphosphate (poly P), a simple repeated structure of phosphates, which is a common product of lactobacilli and other bacteria associated with intestinal microflora without any definitive physiological functions. Then, poly P was synthesized by poly P-synthesizing enzyme polyphosphate kinase. The synthesized poly P significantly induced HSP27 from Caco2/BBE cells. In addition, Poly P suppressed the oxidant-induced intestinal permeability in the mouse small intestine and pharmacological inhibitors of p38 MAPK and integrins counteract its protective effect. Daily intrarectal administration of poly P (10 mu g) improved the inflammation grade and survival rate in 4% sodium dextran sulfate-administered mice. This study, for the first time, demonstrated that poly P is the molecule responsible for maintaining intestinal barrier actions which are mediated through the intestinal integrin beta 1-p38 MAPK.

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  • Cytokine Regulation of OCTN2 Expression and Activity in Small and Large Intestine Reviewed

    Mikihiro Fujiya, Yuhei Inaba, Mark W. Musch, Shien Hu, Yutaka Kohgo, Eugene B. Chang

    INFLAMMATORY BOWEL DISEASES   17 ( 4 )   907 - 916   2011.4

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    Background: The organic cation transporter OCTN2 is located on the IBD5 risk allele and has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). OCTN2 is expressed in the apical membrane and transports many solutes including bacteria-derived mediators that may be involved in host-microbial interactions. To explore its role further, we examined potential regulatory factors in human IBD and in experimental models of OCTN2 expression.Methods: Human colonic epithelial cells (Caco2BBE) were used to investigate the effects of inflammatory mediators on OCTN2 activity and expression. Apical membrane expression of OCTN2 was assessed by surface biotinylation. Rag-1(-/-)-deficient mice were used to determine the potential role of adaptive immune cells in the regulation of OCTN2 expression. C57Bl/6 mice were treated with the cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) to determine the effects on OCTN2 expression and activity. OCTN2 expression in human IBD specimens was assessed by Western blotting and immunohistochemistry.Results: OCTN2 activity and expression are regulated by the state of intestinal inflammation. OCTN2 expression in colonic tissues of Rag-1(-/-)-deficient mice was reduced. Treatment with IFN-gamma and TNF-alpha increased intestinal OCTN2 expression, particularly in the colon. IFN-gamma increased both total and apical membrane expression of Caco2BBE OCTN2, whereas TNF-alpha stimulated apical expression. Colonic epithelial OCTN2 expression was increased in actively inflamed areas of both Crohn's disease and ulcerative colitis.Conclusions: Intestinal epithelial OCTN2 expression is increased by intestinal inflammation, most likely through increased levels of proinflammatory cytokines. These findings suggest that OCTN2 may participate to restoration of intestinal homeostasis under conditions of inflammation-associated stress.

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  • Translational Inhibition of Colonic Epithelial Heat Shock Proteins by IFN-γ and TNF-α in Intestinal Inflammation Reviewed

    Shien Hu, Mae J. Ciancio, Maor Lahav, Mikihiro Fujiya, Lev Lichtenstein, Shrikant Anant, Mark W. Musch, Eugene B. Chang

    Gastroenterology   133 ( 6 )   1893 - 1904   2007.12

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    Background & Aims: Inducible heat shock proteins (iHsp), Hsp25/27 and Hsp70, play essential roles in protecting cells against stress and, in intestinal mucosal inflammation, potentially lessening the extent and severity of injury. We examined the expression and regulation of iHsp in human and experimental inflammatory bowel diseases (IBD) and in vitro. Methods: iHsp expression and regulation were assessed in normal and IBD colonic biopsy specimens, IL-10-/- mice, and young adult mouse colonic epithelial cells by immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR). Phosphorylation of double-stranded RNA-dependent protein kinase (PKR) and eukaryotic initiation factor-2α (eIF-2α) was determined by Western blot. Results: Hsp25/27 and Hsp70 levels were selectively reduced in areas of active mucosal inflammation associated with human IBD and IL-10-/- mice with colitis. Wild-type mice treated in vivo with interferon (IFN)-γ + tumor necrosis factor (TNF)-α also demonstrated reduced colonic Hsp25/27 and Hsp70. In young adult mouse colonic epithelial cells, IFN-γ+TNF-α inhibited heat induction of Hsp25/27 and Hsp70, an effect not associated with changes in iHsp messenger RNA or protein half-lives but caused by suppressed de novo iHsp synthesis. IFN-γ+TNF-α cotreatment activated PKR, resulting in phosphorylation and inactivation of eIF-2α, an essential factor in protein translation. These effects were not due to induced apoptosis and could be negated by PKR-inhibitor and short interfering RNA to PKR. Increased phosphorylation of PKR and eIF-2α were also observed in active IBD tissues. Conclusions: Mucosal inflammation is associated with iHsp down-regulation, an effect that appears mediated by translational down-regulation by proinflammatory cytokines. In the context of IBD, we propose that this mechanism contributes to the severity, extent, and persistence of inflammation-induced mucosal injury. © 2007 AGA Institute.

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  • The Bacillus subtilis Quorum-Sensing Molecule CSF Contributes to Intestinal Homeostasis via OCTN2, a Host Cell Membrane Transporter Reviewed

    Mikihiro Fujiya, Mark W. Musch, Yasushi Nakagawa, Shien Hu, John Alverdy, Yutaka Kohgo, Olaf Schneewind, Bana Jabri, Eugene B. Chang

    Cell Host & Microbe   1 ( 4 )   299 - 308   2007.6

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  • hsa_circ_0015388 Reduces Macrophage Derived Reactive Oxygen Species in Crohn's Disease. International journal

    Yuya Sugiyama, Hiroaki Konishi, Tatsuya Dokoshi, Hiroki Tanaka, Yu Kobayashi, Takahiro Sasaki, Koji Yamamoto, Aki Sakatani, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura, Mikihiro Fujiya

    Inflammatory bowel diseases   2025.1

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    BACKGROUND: Crohn's disease (CD) is a refractory inflammatory bowel disease with an unclear etiology. CircularRNA (circRNA) has been highlighted as a novel class of functional noncoding RNAs associated with the pathogenesis of various diseases. However, the functions of circRNA in CD remain unclear. METHODS: Biopsies were obtained from noninflammatory sites in the terminal ileum of the CD group (n = 4) and non-CD group (n = 4) and analyzed for circRNA expression using RNA sequencing. The significantly altered circRNAs were validated in the CD group (n = 45) and non-CD group (n = 15) using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Transcriptome analysis was conducted using circRNA-downregulated macrophage-like THP-1 cells. Reactive oxygen species (ROS) levels, cytokine mRNA expression, phagocytosis, and migration were evaluated in circRNA-downregulated THP-1 cells. RESULTS: CircularRNA sequencing analysis revealed significant differences in 31 circRNAs between the CD group and non-CD group. Quantitative reverse transcriptase-polymerase chain reaction analysis for each circRNA demonstrated significant upregulation of hsa_circ_0015388 in the CD group. Hsa_circ_0015388 was expressed in THP-1 cells, but not in HCEC-1CT and Caco-2/bbe. Transcriptome analysis in THP-1 cells transfected with scramble or hsa_circ_0015388 siRNA (small interfering RNA) showed a significant alteration in innate immune response related pathway. Reactive oxygen species production was significantly increased in the hsa_circ_0015388 downregulated THP-1 cells. Reactive oxygen species induction in the hsa_circ_0015388 knocked down THP-1 was diminished by the inhibition of TNFSF10. CONCLUSION: A comprehensive analysis of circRNA expression revealed that 31 circRNAs were dysregulated in the CD group. Hsa_circ_0015388 is expressed in macrophages and negatively regulates ROS function inhibiting the TNFSF10 pathway. This study first revealed that hsa_circ_0015388 plays a role in the pathogenesis of CD by suppressing ROS production in macrophages.

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  • Cognitive and ataxic adverse events following entrectinib treatment in NTRK1 fusion gene-positive intrahepatic cholangiocarcinoma: a case report.

    Kazuya Koyama, Hidetaka Iwamoto, Kenji Takahashi, Tetsuhiro Okada, Hidemasa Kawabata, Yohei Kitano, Hiroki Tanabe, Mikihiro Fujiya, Toshikatsu Okumura, Yusuke Mizukami

    Clinical journal of gastroenterology   2024.12

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    We report the rare case of severe cognitive disorder and ataxia caused by entrectinib in a patient with NTRK1 fusion gene-positive intrahepatic cholangiocarcinoma. The case was a 56-year-old woman after nine courses of GCS therapy. The patient experienced grade 1 muscle weakness on day 4 and grade 3, cognitive disorder on day 7 after receiving entrectinib, which led to hospitalization. The symptoms were reversible and tended to improve after withdrawal of entrectinib. It is crucial to increase awareness of TRKi-specific adverse events and their proper management.

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  • High-resolution genetic analysis of whole APC gene deletions: a report of two cases and patient characteristics

    Hiroki Tanabe, Yasuyuki Koshizuka, Kazuyuki Tanaka, Kenji Takahashi, Masami Ijiri, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Takeo Sarashina, Kentaro Moriichi, Kenrokuro Mitsube, Yusuke Mizukami, Mikihiro Fujiya, Yoshio Makita

    Human Genome Variation   11 ( 1 )   2024.12

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    Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by germline variants in the APC gene, leading to the development of numerous colorectal polyps and significantly increases the risk of colorectal cancer. A diagnosis is typically made using colonoscopy, and genetic testing can assist in patient surveillance and carrier identification. Recent advances include the use of whole-genome array comparative genomic hybridization (a-CGH), which provides better resolution of genetic imbalances. We aimed to explore the specific features of FAP patients with whole APC gene deletions using high-resolution a-CGH and to compare patient characteristics. Two polyposis patients with whole APC deletions were identified, and the lost genetic sizes ranged from 0.3–1.1 Mb. Nervous abnormalities were a characteristic symptom in a patient with a 1.1 Mb loss. A patient with an approximately 0.3 Mb loss, which included the entire APC gene, presented a polyposis phenotype without intellectual disability. The comparison of genetic losses, with or without intellectual disability, revealed 7 genetic changes. Consequently, EPB41L4A is a candidate gene associated with the neurogenic phenotype.

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  • Unresectable Ulcerative Colitis Associated Colon Cancer in a Young Japanese Patient: A Case Report.

    Ryunosuke Hayashi, Nobuhiro Ueno, Hiromu Watanabe, Yu Kobayashi, Aki Sakatani, Keitaro Takahashi, Sayaka Yuzawa, Katsuyoshi Ando, Chikayoshi Tani, Shin Kashima, Tatsuya Shonaka, Kentaro Moriichi, Hiroki Tanabe, Mishie Tanino, Mikihiro Fujiya

    Internal medicine (Tokyo, Japan)   2024.10

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    We herein present the case of a 30-year-old Japanese male patient with ulcerative colitis (UC) who was admitted to our hospital because of significant ascites. Upon evaluation, the patient was diagnosed with unresectable UC-associated cancer (UCAC), localized in the transverse colon. Using gene profiling of the tumor tissue, anti-epidermal growth factor receptor (EGFR) antibody combination chemotherapy was selected. Subsequently, the patient exhibited a temporary response to this regimen, with an enhancement in his quality of life and he was able to survive for 12 months. This case underscores the potential benefits of aggressive chemotherapy tailored to the gene profile in UCAC treatment, offering insights into potential avenues for improving the patient prognosis.

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  • 食道ESD後潰瘍底の白苔による術後狭窄リスク因子の検討

    小林 裕, 高橋 慶太郎, 坂谷 慧, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    潰瘍   51   70 - 70   2024.9

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  • Oral breathing facilitates endoscopic operability compared to nasal breathing in peroral endoscopy: a randomized controlled trial. International journal

    Keitaro Takahashi, Takuya Iwama, Momotaro Muto, Kazuyuki Tanaka, Yu Kobayashi, Katsuyoshi Ando, Shin Kashima, Nobuhiro Ueno, Kentaro Moriichi, Hiroki Tanabe, Kazumichi Harada, Takashi Teramoto, Mikihiro Fujiya

    The American journal of gastroenterology   2024.8

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    INTRODUCTION: Unsedated peroral endoscopy, including ultrathin endoscopy (UE) and conventional endoscopy (CE), is feasible in clinical practice but requires improved endoscopic operability and patient tolerance. Currently, the impact of breathing method on these factors remains unclear. We conducted the first randomized controlled trial comparing oral breathing (OB) and nasal breathing (NB) during both UE and CE to assess their influence. METHODS: 252 eligible patients undergoing CE or UE were randomly assigned to OB or NB groups. Endoscopists and patients rated endoscopic operability and patient tolerance using a 100-mm visual analog scale (VAS). Visibility from the oral cavity to the middle pharynx was recorded. RESULTS: OB led to a higher rate of improved visibility from the oral cavity to the middle pharynx compared to NB, ranging from 79.3% to 81.0%. Multivariate correlation analyses showed significantly lower VAS scores for endoscopic operability with OB compared to NB in both UE and CE groups (p < 0.05). No significant differences were found in the overall evaluation of patient tolerance between OB and NB groups in UE and CE, while the smaller diameter of UE exhibited better patient tolerance compared to CE. Discriminant analysis comparing endoscope types and breathing methods revealed that UE with OB outperformed other combinations in the overall evaluation of endoscopic operability and patient tolerance (p < 0.05). CONCLUSIONS: OB facilitates endoscopic operability compared to NB in peroral endoscopy. UE with OB is recommended as the preferred choice for unsedated peroral endoscopy in daily practice.

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  • The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn's disease: A multicenter retrospective pilot study. International journal

    Nobuhiro Ueno, Seisuke Saito, Masahiro Sato, Yuya Sugiyama, Yu Kobayashi, Yuki Murakami, Kohjiro Sugimura, Takahiro Sasaki, Aki Sakatani, Keitaro Takahashi, Kazuyuki Tanaka, Shinya Serikawa, Katsuyoshi Ando, Shin Kashima, Momotaro Muto, Yuhei Inaba, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura, Mikihiro Fujiya

    Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy   28 ( 3 )   442 - 452   2024.6

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    INTRODUCTION: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) was given to patients with Crohn's disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with CD remains unclear. METHODS: This study evaluated the clinical efficacy and subsequent clinical progression after GMA in patients with CD who underwent GMA in seven independent institutions in Japan from 2010 to 2023. RESULTS: Sixteen patients were enrolled. The overall remission and response rates were 25.0% and 68.8%, respectively. All patients responding to GMA received biologics that were continuously used and 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to biologics. CONCLUSION: GMA may exhibit effectiveness even in cases with refractory CD. Moreover, it represents a potential novel therapeutic option for refractory CD with loss of response to biologics.

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  • The white ring sign is useful for differentiating between fundic gland polyps and gastric adenocarcinoma of the fundic gland type. International journal

    Keitaro Takahashi, Takahiro Sasaki, Nobuhiro Ueno, Haruka Maguchi, Shion Tachibana, Ryunosuke Hayashi, Yu Kobayashi, Yuya Sugiyama, Aki Sakatani, Katsuyoshi Ando, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Kazumichi Harada, Sayaka Yuzawa, Shin Ichihara, Toshikatsu Okumura, Mikihiro Fujiya

    Endoscopy international open   12 ( 6 )   E723-E731   2024.6

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    Background and study aims Gastric adenocarcinoma of the fundic gland type (GA-FG) is characterized by an elevated lesion with vessel dilation exhibiting branching architecture (DVBA). However, this feature is also found in fundic gland polyps (FGPs), posing a challenge in their differentiation. In this study, we aimed to investigate the clinicopathological features of gastric elevated lesions with DVBA and assess the efficacy of the white ring sign (WRS) as a novel marker for distinguishing between FGPs and GA-FGs. Methods We analyzed 159 gastric elevated lesions without DVBA and 51 gastric elevated lesions with DVBA, further dividing the latter into 39 in the WRS-positive group and 12 in the WRS-negative group. The clinicopathological features, diagnostic accuracy, and inter-rater reliability were analyzed. Results Univariate and multivariate analyses for gastric elevated lesions with DVBA identified the histological type consistent with FGPs and GA-FGs, along with the presence of round pits in the background gastric mucosa, as independent predictors. FGPs were present in 92.3% (36/39) of the WRS-positive group and GA-FGs were observed in 50.0% (6/12) of the WRS-negative group. WRS positivity and negativity exhibited high diagnostic accuracy, with 100% sensitivity, 80.0% specificity, and 94.1% accuracy for FGPs, and 100% sensitivity, 86.7% specificity, and 88.2% accuracy for GA-FGs. Kappa values for WRS between experts and nonexperts were 0.891 and 0.841, respectively, indicating excellent agreement. Conclusions WRS positivity and negativity demonstrate high diagnostic accuracy and inter-rater reliability for FGPs and GA-FGs, respectively, suggesting that WRS is a useful novel marker for distinguishing between FGPs and GA-FGs.

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  • 大腸検査からみた感染性腸炎 炎症性腸疾患の診断と感染性腸炎との鑑別

    坂谷 慧, 佐藤 允洋, 安藤 勝祥, 上野 伸展, 藤谷 幹浩

    日本大腸検査学会雑誌   40 ( 2 )   122 - 122   2024.6

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  • Risk Factors for Post-Colorectal Endoscopic Submucosal Dissection Bleeding and Efficacy of Carbazochrome Sodium Sulfonate: A Multicenter Retrospective Cohort Study. International journal

    Keitaro Takahashi, Takuya Iwama, Kazuyuki Tanaka, Yuki Miyazawa, Shohei Kuroda, Masashi Horiuchi, Seisuke Saito, Momotaro Muto, Aki Sakatani, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura, Mikihiro Fujiya

    Digestion   1 - 10   2024.5

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    INTRODUCTION: Carbazochrome sodium sulfonate (CSS) is a hemostatic agent that reduces capillary permeability and enhances capillary resistance. However, its specific effects on colorectal endoscopic submucosal dissection (ESD) outcomes remain uncertain. This study aimed to assess the risk factors for post-ESD bleeding and the effect of CSS on colorectal ESD outcomes. METHODS: First, we retrospectively analyzed the risk factors for post-ESD bleeding using data from 1,315 lesions in 1,223 patients who underwent ESD for superficial colorectal neoplasms at eight institutions. Second, patients were divided into CSS and non-CSS groups using propensity score matching, and their outcomes from colorectal ESD were analyzed. RESULTS: The risk factors for post-colorectal ESD bleeding were identified as age of ≥70 years, tumor located in the rectum, tumor size of ≥40 mm, and post-ESD defect unclosure in both univariate and multivariate analyses. The CSS and non-CSS groups each consisted of 423 lesions after propensity score matching. The post-colorectal ESD bleeding rate was 3.5% (15/423) and 3.3% (14/423) in the CSS and non-CSS groups, respectively, indicating no significant differences. Among patients with the high-risk factors for post-ESD bleeding, the administration of CSS also did not demonstrate a significant reduction in the post-ESD bleeding rate compared to the non-CSS group. CONCLUSION: CSS administration is ineffective in preventing post-colorectal ESD bleeding in both the general population and individuals at a high risk for such bleeding. Our results indicate the necessity to reconsider the application of CSS for preventing post-colorectal ESD bleeding.

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  • 便潜血反応陽性を契機に発見された成人Peutz-Jeghers症候群の一例

    坂谷 慧, 上野 伸展, 小林 裕, 高橋 慶太郎, 安藤 勝祥, 嘉島 伸, 盛一 健太郎, 藤谷 幹浩

    日本消化器がん検診学会雑誌   62 ( Suppl総会 )   348 - 348   2024.5

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  • 全大腸内視鏡検査における適切な検査間隔 内視鏡後大腸癌の検討から

    盛一 健太郎, 田中 一之, 野村 好紀, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 藤谷 幹浩

    日本消化器がん検診学会雑誌   62 ( 3 )   240 - 249   2024.5

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    【目的】全大腸内視鏡検査(TCS)による大腸がん検診実施にむけ,適切な検査間隔や大腸腫瘍の取り扱いを検討する。【方法】当院と関連施設でTCSを複数施行し大腸癌を認めた120例について,1)癌進行度別のTCS間隔とROC解析によるcut-off値,得られたcut-off値による他病死は除外した疾患特異的生存期間(以下,生存期間),2)大腸腫瘍のマネージメントと生存期間,について検討した。【結果】1-1)早期69例,進行大腸癌51例のTCS間隔は47.0±33.1ヵ月,78.2±45.5ヵ月で有意に進行群が長く,cut-off値は54ヵ月であった。1-2)転移なし群99例,転移群21例のTCS間隔は54.5±38.6ヵ月,87.5±45.8ヵ月で転移群が有意に長く,cut-off値は56ヵ月であった。1-3)TCS間隔5年未満群(66例)と5年以上群(54例)で癌発見後の生存期間を比較すると5年未満群が有意に長かった。2)TCSで6mm以上の腫瘍が3個以上遺残した場合,有意に生存期間が短かった。【結論】大腸癌ハイリスク群のTCS間隔は5年が妥当であり,6mm以上の腫瘍を複数認める場合は積極的に切除することが妥当である可能性が示唆された。(著者抄録)

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  • 先進的手法を用いた消化器がん検診の可能性 核酸解析によるリキッドバイオプシーの膵癌診断臨床応用への可能性

    高橋 賢治, 水上 裕輔, 藤谷 幹浩

    日本消化器がん検診学会雑誌   62 ( Suppl総会 )   331 - 331   2024.5

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  • Comparison of diagnostic accuracy between linked color imaging and autofluorescence imaging in patients with ulcerative colitis: A prospective observational study. International journal

    Yuya Sugiyama, Keitaro Takahashi, Takahiro Sasaki, Nobuhiro Ueno, Hiromu Watanabe, Kohei Iribe, Shunya Sekiguchi, Shion Tachibana, Yu Kobayashi, Katsuyoshi Ando, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Sayaka Yuzawa, Mikihiro Fujiya

    Journal of gastroenterology and hepatology   2024.4

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    BACKGROUND AND AIM: Image enhancement endoscopy techniques, such as linked color imaging (LCI) and autofluorescence imaging (AFI), have shown promise in diagnosing mucosal inflammation in ulcerative colitis (UC). However, no studies have directly compared the diagnostic efficacy of LCI and AFI. This prospective observational study aimed to compare their diagnostic accuracy for histological healing in UC. METHODS: This study included 81 UC patients, resulting in a total of 204 endoscopic images captured using LCI and AFI, respectively. Spearman's rank correlation coefficients assessed the correlation between LCI and AFI coloration and Geboes histopathology score (GHS). Six endoscopists, who were blinded to clinicopathological features, evaluated these images, and subsequently, the diagnostic accuracy was evaluated. RESULTS: Spearman's rank correlation coefficients between LCI index, AFI index (reverse gamma value), and GHS were 0.324 and -0.428, respectively (P < 0.001), indicating a significant correlation between LCI and AFI coloration and histological healing. In LCI and AFI classifications, mean values for diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 76.3 ± 2.2 versus 77.8 ± 2.7, 91.8 ± 4.0 versus 83.2 ± 7.6, 53.4 ± 10.0 versus 70.0 ± 5.3, 74.0 ± 3.5 versus 80.0 ± 1.6, and 82.9 ± 5.2 versus 75.5 ± 7.5, respectively. No significant difference in diagnostic accuracy existed between LCI and AFI classifications. However, LCI displayed higher sensitivity than AFI while AFI showed higher specificity compared with LCI (P < 0.05). CONCLUSIONS: LCI and AFI offer comparable diagnostic accuracy for histological healing. Clinically, it is necessary to recognize diagnostic features characterized by higher sensitivity in LCI and greater specificity in AFI.

    DOI: 10.1111/jgh.16586

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  • Synthesis and biological evaluation of echinomycin analogues as potential colon cancer agent

    Keita Kojima, Hiroaki Konishi, Kyoka Momosaki, Yuya Komatani, Akira Katsuyama, Koji Nakagawa, Kayoko Kanamitsu, Fumika Yakushiji, Mikihiro Fujiya, Satoshi Ichikawa

    Scientific Reports   14 ( 1 )   2024.4

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    Abstract

    Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death, thus a novel chemotherapeutic agent for colon cancer therapy is needed. In this study, analogues of echinomycin, a cyclic peptide natural product with potent toxicity to several human cancer cell lines, were synthesized, and their biological activities against human colon cancer cells were investigated. Analogue 3 as well as 1 inhibit HIF-1α-mediated transcription. Notably, transcriptome analysis indicated that the cell cycle and its regulation were involved in the effects on cells treated with 3. Analogue 3 exhibited superior in vivo efficacy to echinomycin without significant toxicity in mouse xenograft model. The low dose of 3 needed to be efficacious in vivo is also noteworthy and our data suggest that 3 is an attractive and potentially novel agent for the treatment of colon cancer.

    DOI: 10.1038/s41598-024-58196-3

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    Other Link: https://www.nature.com/articles/s41598-024-58196-3

  • 視神経脊髄炎に対するステロイドパルス療法により再活性化をきたしたC型慢性肝炎の1例

    田村 ゆき穂, 澤田 康司, 室 和希, 大竹 晋, 林 秀美, 太田 雄, 長谷部 拓夢, 中嶋 駿介, 岡田 充巧, 麻生 和信, 藤谷 幹浩

    肝臓   65 ( Suppl.1 )   A298 - A298   2024.4

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  • Effectiveness and Persistency of Ustekinumab Treatment for Ulcerative Colitis: A Phoenix retrospective Cohort Study. International journal

    Katsuyoshi Ando, Mikihiro Fujiya, Nobuhiro Ueno, Takahiro Ito, Atsuo Maemoto, Masanao Nasuno, Hiroki Tanaka, Kensuke Sakurai, Takehiko Katsurada, Fumika Orii, Toshifumi Ashida, Satoshi Motoya, Tomoe Kazama, Yoshihiro Yokoyama, Daisuke Hirayama, Hiroshi Nakase

    Crohn's & colitis 360   6 ( 2 )   otae024   2024.4

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    BACKGROUND: Real-world data regarding ustekinumab (UST) for ulcerative colitis (UC) particularly in biologics-naïve patients is currently limited. This study aimed to elucidate the real-world effectiveness and safety of UST for UC. METHODS: Overall, 150 patients with UC treated with UST from March 2020 to January 2023 were enrolled across 7 referral hospitals. To assess the clinical efficacy and persistence of UST, retrospective analyses were conducted from weeks 8 to 56. Predictive factors concerning the response and persistence of UST were examined through univariate and multivariate analyses. RESULTS: Of the 150 patients, 125 received UST for remission induction, including 36% biologics-naïve. The response and remission rates were 72.8% and 56.0% at week 8 and 73.2% and 63.4% at week 56, respectively. Biologics-naïve patients represented higher response and remission rates at week 8 (84.4% and 73.3%) than those with biologics exposure (66.2% and 46.2%). Patients with prior antitumor necrosis factor (anti-TNF) and vedolizumab (VDZ) exposure had relatively lower response and remission rates (34.5% and 24.1%, respectively). The 1-year cumulative persistence rate was 84.0%. Multivariate analysis revealed that the chronic continuous type and prior anti-TNF and VDZ exposure were negative predictive factors for week 8 responsiveness. Clinical response at week 8 was a predictor of 1-year persistence. Adverse event incidence remained notably low at 6.4%. CONCLUSIONS: This study highlights the safety and effectiveness of UST as an induction and maintenance therapy for UC. Chronic continuous type and previous anti-TNF and VDZ exposure negatively contributed to short-term effectiveness, whereas short-term effectiveness provided good persistency.

    DOI: 10.1093/crocol/otae024

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  • B細胞性悪性リンパ腫診療における内視鏡検査の有用性と患者予後の関連の検討

    嘉島 伸, 佐藤 允洋, 小林 裕, 杉山 雄哉, 坂谷 慧, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩

    Gastroenterological Endoscopy   66 ( Suppl.1 )   989 - 989   2024.4

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  • 【十二指腸・小腸疾患アトラス】腫瘍,腫瘍様病変 リンパ増殖性病変 形質細胞腫瘍・骨髄腫

    安藤 勝祥, 藤谷 幹浩

    消化器内視鏡   36 ( 4 )   492 - 493   2024.4

  • Probiotic-derived ferrichrome induces DDIT3-mediated antitumor effects in esophageal cancer cells. International journal

    Takehito Kunogi, Hiroaki Konishi, Aki Sakatani, Kentaro Moriichi, Chikage Yamamura, Koji Yamamoto, Shin Kashima, Katsuyoshi Ando, Nobuhiro Ueno, Hiroki Tanaka, Toshikatsu Okumura, Mikihiro Fujiya

    Heliyon   10 ( 6 )   e28070   2024.3

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    Esophageal cancer, which is common among the elderly, has the poorest prognosis among gastrointestinal cancers. Previously, we demonstrated that ferrichrome, produced by the probiotic Lactobacillus casei, exhibited anti-tumor effects in various gastrointestinal cancers, including colorectal and gastric cancers, with minimal effects on non-cancerous intestinal cells. However, it remains unclear whether ferrichrome exerts anti-tumor effects in esophageal cancer. A sulforhodamine B assay revealed that ferrichrome suppressed esophageal adenocarcinoma (OE33, OE19) and squamous cell carcinoma (KYSE70) cells. Ki-67 staining indicated that ferrichrome inhibited the proliferation of esophageal cancer cells. Cell cycle analysis showed that ferrichrome inhibited the DNA synthesis. TUNEL staining revealed that ferrichrome-induced DNA fragmentation. We also confirmed the cleavage of caspase-9 and PARP in ferrichrome-treated cells. Reverse transcription polymerase chain reaction demonstrated an increase in the mRNA of DNA damage-inducible transcript 3 (DDIT-3), a key regulator of programmed cell death, in ferrichrome-treated OE33 cells. In an in vivo OE33 xenograft model, intraperitoneal administration of 5-mg/kg ferrichrome for 14 days resulted in an almost complete inhibition of tumor growth. However, 14 days of intraperitoneal administration of 20-mg/kg 5-fluorouracil (5-FU), but not 20-mg/kg ferrichrome, induced weight loss and myelosuppression in both young and aged mice. Our findings indicate that ferrichrome induces DNA damage-inducible transcript-3, thereby producing anti-tumor effects, including cell cycle arrest and apoptosis, with minimal adverse effects in esophageal cancer cells. This illustrates the high potential of ferrichrome as an anti-tumor drug against esophageal carcinoma.

    DOI: 10.1016/j.heliyon.2024.e28070

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  • New gel immersion endoscopic ultrasonography technique for accurate periampullary evaluation. International journal

    Hiroki Sato, Hidemasa Kawabata, Hidetaka Iwamoto, Tetsuhiro Okada, Shugo Fujibayashi, Kenji Takahashi, Yohei Kitano, Takuma Goto, Yusuke Mizukami, Toshikatsu Okumura, Mikihiro Fujiya

    Surgical endoscopy   2024.3

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    BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.

    DOI: 10.1007/s00464-024-10762-6

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  • Small Insulinoma Followed-up as an Indolent Pancreatic Tumor: A Case Report.

    Hiroki Sato, Shozaburo Fujii, Tetsuhiro Okada, Hidemasa Kawabata, Yuki Kamikokura, Mikihiro Fujiya

    Internal medicine (Tokyo, Japan)   2024.3

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    A woman in her 60s presented with a small pancreatic head tumor. Imaging studies revealed a 13-mm well-defined pancreatic head tumor. A neuroendocrine neoplasm was suspected, and the patient opted for observation at that time. After 8 months, the patient began experiencing sweating while fasting, and blood tests during regular follow-up visits showed hypoglycemia. Hypoglycemia was induced during fasting test. The tumor exhibited clear features of an insulinoma during follow-up observation. While small neuroendocrine neoplasms are often managed through observation, caution should be exercised regarding their transformation into functional neuroendocrine tumors.

    DOI: 10.2169/internalmedicine.3194-23

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  • イピリムマブ+ニボルマブ投与中に多彩な免疫関連有害事象を呈したMSI-high大腸癌の1例

    松永 滉平, 安藤 勝祥, 立花 史音, 佐藤 允洋, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   64 - 64   2024.3

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  • 膵癌に対するEUS-FNB後、胃壁穿刺部位からデスモイド腫瘍が生じた1例

    小山 一也, 河端 秀賢, 梶浦 麻未, 佐藤 裕基, 岡田 哲弘, 岩本 英孝, 高橋 賢治, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   73 - 73   2024.3

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  • 非拡張膵管に対するEUS-PD re-puncture techniqueの有用性

    石黒 達也, 河端 秀賢, 後藤 聖樹, 小山 一也, 関口 峻也, 梶浦 麻未, 佐藤 裕基, 岡田 哲弘, 岩本 英孝, 高橋 賢治, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   73 - 73   2024.3

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  • 感染性大動脈瘤への人工血管置換術後に発症した膵液瘻に対して、経乳頭的処置が著効した1例

    関口 竣也, 梶浦 麻未, 石黒 達也, 後藤 聖樹, 小山 一也, 岡田 哲弘, 河端 秀賢, 岩本 英孝, 高橋 賢治, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   73 - 73   2024.3

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  • 切除可能な胆道癌におけるN因子の予後への影響

    後藤 聖樹, 岡田 哲弘, 佐藤 裕基, 梶浦 麻未, 河端 秀賢, 岩本 英孝, 高橋 賢治, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   64 - 64   2024.3

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  • 当院における神経内分泌腫瘍に対するPRRTの初期治療経験

    梶浦 麻未, 佐藤 裕基, 石黒 達也, 関口 竣也, 小山 一也, 後藤 聖樹, 岡田 哲弘, 河端 秀賢, 岩本 英孝, 高橋 賢治, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   57 - 57   2024.3

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  • 保存的加療にて改善した分節性動脈中膜融解症による腹腔内出血の1例

    久住 悠梨子, 関口 竣也, 安藤 勝祥, 立花 史音, 佐藤 允洋, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   75 - 75   2024.3

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  • IBD患者の診療において通院距離が重症度、入院や治療に及ぼす影響の解析

    佐藤 允洋, 嘉島 伸, 立花 史音, 小林 裕, 杉山 雄哉, 坂谷 慧, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   71 - 71   2024.3

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  • 免疫チェックポイント阻害剤併用化学療法を施行中の肺癌患者にみられた慢性下痢の1例

    ム・チル, 嘉島 伸, 立花 史音, 佐藤 允洋, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 勝利

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   44 - 44   2024.3

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  • 経鼻内視鏡検査時の鼻呼吸は内視鏡の挿入性および患者の忍容性を改善する

    高橋 慶太郎, 盛一 健太郎, 藤谷 幹浩

    日本消化器がん検診学会雑誌   62 ( 2 )   129 - 129   2024.3

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  • 当院におけるPET-CTによる悪性リンパ腫消化管病変の診断能の解析

    嘉島 伸, 小林 裕, 坂谷 慧, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 盛一 健太郎, 藤谷 幹浩

    日本消化器がん検診学会雑誌   62 ( 2 )   128 - 128   2024.3

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  • 免疫チェックポイント阻害薬関連胃炎の臨床像における検討

    入部 航平, 杉山 雄哉, 立花 史音, 佐藤 允洋, 小林 裕, 佐々木 貴弘, 高橋 慶太郎, 坂谷 慧, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 谷野 美智枝, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   44 - 44   2024.3

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  • 経口細径・通常径内視鏡の挿入性および認容性の比較

    立花 史音, 高橋 慶太郎, 佐藤 允洋, 杉山 雄哉, 小林 裕, 佐々木 貴弘, 坂谷 慧, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   134回・128回   50 - 50   2024.3

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  • 潰瘍性大腸炎におけるトファシチニブの長期治療成績とその位置付け

    伊藤 貴博, 前本 篤男, 横山 佳浩, 桂田 武彦, 安藤 勝祥, 藤谷 幹浩, 蘆田 知史, 那須野 正尚, 田中 浩紀, 仲瀬 裕志

    日本消化器病学会雑誌   121 ( 臨増総会 )   A318 - A318   2024.3

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  • クローン病の病態に応じた治療戦略 骨格筋筋肉量や脂肪量から考えるクローン病術後の経過と治療戦略

    安藤 勝祥, 小林 裕, 杉山 雄哉, 坂谷 慧, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩

    日本消化器病学会雑誌   121 ( 臨増総会 )   A140 - A140   2024.3

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  • Liquid Biopsy for Pancreatic Cancer by Serum Extracellular Vesicle–Encapsulated Long Noncoding RNA HEVEPA

    Kenji Takahashi, Tatsutoshi Inuzuka, Yuta Shimizu, Kazuki Sawamoto, Kenzui Taniue, Yusuke Ono, Fumi Asai, Kazuya Koyama, Hiroki Sato, Hidemasa Kawabata, Hidetaka Iwamoto, Keisuke Yamakita, Yohei Kitano, Takashi Teramoto, Mikihiro Fujiya, Satoshi Fujii, Yusuke Mizukami, Toshikatsu Okumura

    Pancreas   2024.2

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    Publishing type:Research paper (scientific journal)   Publisher:Ovid Technologies (Wolters Kluwer Health)  

    Objectives

    The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)–encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs.

    Materials and Methods

    Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR.

    Results

    Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA, in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA, which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC, which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA, HULC, or CA19-9 alone.

    Conclusions

    Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.

    DOI: 10.1097/mpa.0000000000002315

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  • The Lambda stenting technique: a new approach to address EUS-guided biliary drainage-associated adverse events. International journal

    Hiroki Sato, Hidemasa Kawabata, Mikihiro Fujiya

    VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy   9 ( 2 )   107 - 114   2024.2

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    BACKGROUND AND AIMS: EUS-guided biliary drainage (EUS-BD) has been performed increasingly worldwide, especially in patients with malignant tumors in which ERCP is difficult, patients with surgically altered GI tracts, and older patients who are at high risk for surgery. EUS-BD requires high-level skills and has limited options for managing adverse events, particularly when stent migration and cholangitis occur. Adverse events, such as persistent bile leakage from the fistula and continuous reflux from the GI tract, are believed to always have a risk of severe exacerbation that could threaten the patient's life. METHODS: We encountered 2 cases of stent migrations and 1 case with repeated cholangitis in patients with malignant tumors among the patients who underwent EUS-BD. The migrated stent was visualized under EUS in 2 patients with stent migration, and an EUS-guided FNA needle was used to puncture the mesh of the stent. The cannulation catheter was directly inserted into the mesh of the stent in 1 case with repeated retrograde cholangitis, while the stent was visualized with an endoscope. Subsequently, a guidewire was inserted through the puncture site, and a second metal stent was deployed between the meshes of the first stent, bridging the GI wall again (Lambda stenting technique). All procedures were performed with the patient under general anesthesia, and the patients safely completed the intervention. RESULTS: Patients' conditions significantly improved after the second stent insertion, allowing for chemotherapy resumption while maintaining their activities of daily living. The second stent remained in place without any migration, and the stent successfully prevented further cholangitis. CONCLUSIONS: The Lambda stenting technique is considered highly effective for managing stent migration and repeated cholangitis, which is a major EUS-BD adverse event. This procedure helps avoid more invasive surgeries when stent migration and cholangitis occur and contributes to expanding EUS-BD applicability.

    DOI: 10.1016/j.vgie.2023.10.010

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  • A case of steroid-refractory chronic diarrhea in a patient undergoing chemotherapy with immune checkpoint inhibitor for lung cancer. Reviewed

    Kashima S., Moriichi K., Kamikokura Y., Fujiya M.

    J Gastroenterol Hepatol   2024.2

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  • Cardiac sarcoidosis in a patient with ulcerative colitis: A case report and literature review. International journal

    Kentaro Moriichi, Shin Kashima, Yu Kobayashi, Yuya Sugiyama, Yuki Murakami, Takahiro Sasaki, Takehito Kunogi, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Hiroki Tanabe, Ayumi Date, Sayaka Yuzawa, Mikihiro Fujiya

    Medicine   103 ( 1 )   e36207   2024.1

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    RATIONALE: Both ulcerative colitis (UC) and sarcoidosis are chronic inflammatory diseases with unknown etiologies and are rare. However, the odds ratio in UC patients has been reported to range from 1.7 to 2.1, suggesting a potential etiology between sarcoidosis and UC. Furthermore, the underlying etiologies of UC and sarcoidosis remain unidentified. Sharing the experience of a UC patient with cardiac sarcoidosis could provide valuable insights to prevent sudden death in UC patients. PATIENT CONCERNS: A 71-year-old Japanese woman was diagnosed with UC at 58-year-old and maintained remission on mesalazine treatment. She complained of just palpitation; therefore, she consulted a cardiologist. DIAGNOSES: The patient received a diagnosis of cardiac sarcoidosis with complicating ulcerative colitis based on the results of N-terminal prohormone of the brain natriuretic peptide (NT-proBNP), imaging examinations, and histology. INTERVENTION: The patient was treated with prednisolone and methotrexate. The prednisolone was then tapered, and the methotrexate dose was adjusted based on her symptoms, imaging results, and laboratory findings. OUTCOME: She no longer had any symptoms, and the abnormal FDG uptake had disappeared after 2 years. LESSON: In UC patients, periodic or additional (in case of symptomatic) electrocardiography and NT-proBNP are recommended for the early detection of cardiac sarcoidosis, a life-threatening complication.

    DOI: 10.1097/MD.0000000000036207

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  • Endoscopic lesions of postoperative anastomotic area in patients with Crohn's disease in the biologic era: A Japanese multi-center nationwide cohort study. Reviewed

    Ueda T., Koyama F., Sugita A., Ikeuchi H., Futami K., Fukushima K., Nezu R., Iijima H., Mizushima T., Itabashi M., Watanabe K., Hata K., Shinagawa T., Matsuoka K., Takenaka K., Sasaki M., Nagayama M., Yamamoto H., Shinozaki M., Fujiya M., Kato J., Ueno Y., Tanaka S., Okita Y., Hashimoto Y., Kobayashi T., Koganei K., Uchino M., Fujii H., Suzuki Y., Hisamatsu T.

    J Crohns Colitis   2023.12

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  • 【第51回超音波ドプラ・新技術研究会 臨床報告集】FNH-like noduleの1例

    大竹 晋, 麻生 和信, 太田 雄, 岡田 充巧, 林 秀美, 中嶋 駿介, 長谷部 拓夢, 澤田 康司, 藤谷 幹浩, 奥村 利勝, 上小倉 佑機, 谷野 美智枝

    Rad Fan   21 ( 14 )   23 - 26   2023.11

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    FNH-like noduleはFNHと似た画像を呈することが知られている。今回、我々は、造影3DSMIがFNHとの鑑別に有用であったFNH-like noduleの一例を経験したので報告する。(著者抄録)

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  • 重複癌への化学放射線療法後,ESDで治癒切除しえたcT1b食道癌の一例

    立花 史音, 高橋 慶太郎, 盛一 健太郎, 藤谷 幹浩

    北海道医学雑誌   98 ( 2 )   136 - 137   2023.11

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  • The Lambda stenting technique: A new approach to address endoscopic ultrasonography-guided biliary drainage-associated adverse events. Reviewed

    Sato H., Kawabata H., Fujiya M.

    VideoGIE   2023.10

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  • Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis.

    Makoto Naganuma, Taku Kobayashi, Reiko Kunisaki, Katsuyoshi Matsuoka, Shojiro Yamamoto, Ami Kawamoto, Daisuke Saito, Kosaku Nanki, Kazuyuki Narimatsu, Hisashi Shiga, Motohiro Esaki, Shinichiro Yoshioka, Shingo Kato, Masayuki Saruta, Shinji Tanaka, Eriko Yasutomi, Kaoru Yokoyama, Kei Moriya, Yoshikazu Tsuzuki, Makoto Ooi, Mikihiro Fujiya, Atsushi Nakazawa, Takayuki Abe, Tadakazu Hisamatsu

    Journal of gastroenterology   2023.10

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    BACKGROUND: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC). METHODS: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT. RESULTS: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization. CONCLUSION: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.

    DOI: 10.1007/s00535-023-02048-w

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  • Stroke risk related to intentional discontinuation of antithrombotic therapy for invasive procedures Reviewed

    Nobuyuki Mitsui, Manabu Kinoshita, Jun Sawada, Mikihiro Fujiya, Hiroyuki Furukawa

    Neurosurgical Focus   55 ( 4 )   E7 - E7   2023.10

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    OBJECTIVE

    Antithrombotic medications pose a challenge for conducting surgical or invasive procedures, because their discontinuation is required to avoid postprocedural hemorrhagic complications but potentially increases the ischemic risk for the patient. This study aimed to estimate the increased risk of developing cerebral ischemic events during hospitalization requiring discontinuation of antithrombotic therapy.

    METHODS

    This investigation was a single-center retrospective observational study. Clinical data in patients scheduled for admission between January 1, 2021, and December 31, 2022, were collected. Patients requiring discontinuation of antithrombotic therapy were identified by referring to the admission database. Patients who developed cerebral ischemia were identified by referring to the institution’s stroke center database.

    RESULTS

    Seven hundred ninety-six patients scheduled for nonneurosurgical procedures and 39 scheduled for neurosurgical procedures underwent discontinuation of antithrombotic therapy. Anticoagulation therapy was prescribed in 40.0%, and antiplatelet therapy was prescribed in 69.1% of the patients. A total of 9.2% of the entire cohort of patients were receiving both anticoagulation and antiplatelet therapy. Bridging therapy was administered in 20.9% of nonneurosurgical patients. No ischemic event was observed in the patients undergoing neurosurgical procedures. Among the entire cohort, 3 patients encountered some kind of thrombotic event—2 of which were cerebral ischemia—accounting for an incidence of 0.24%, which was significantly higher than incidental in-hospital stroke unrelated to discontinuation of antithrombotic therapy (p = 0.04). Patients undergoing both anticoagulation and antiplatelet therapy harbored a significantly higher risk for cerebral ischemia related to discontinuation of antithrombotic therapy (p &lt; 0.0001).

    CONCLUSIONS

    Discontinuing antithrombotic therapy during hospitalization for elective invasive procedures—including neurosurgical procedures—entailed a relatively small risk of developing cerebral ischemic events, but the risk was significantly higher compared to hospitalized patients without discontinuation of antithrombotic therapy.

    DOI: 10.3171/2023.7.focus23341

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  • The effect of heat-killed Lactobacillus brevis SBL88 on improving selective hepatic insulin resistance in non-alcoholic fatty liver disease mice without altering the gut microbiota. International journal

    Hidemi Hayashi, Koji Sawada, Hiroki Tanaka, Kazuki Muro, Takumu Hasebe, Shunsuke Nakajima, Toshikatsu Okumura, Mikihiro Fujiya

    Journal of gastroenterology and hepatology   38 ( 10 )   1847 - 1854   2023.10

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    BACKGROUND AND AIM: There have been several reports that some probiotics improve non-alcoholic fatty liver disease (NAFLD); however, many studies have involved cocktail therapies. We evaluated whether heat-killed Lactobacillus brevis SBL88 (L. brevis SBL88) monotherapy improves the clinical features of NAFLD. METHODS: The NAFLD model was induced in mice fed a high-fat diet (HFD) (HFD mice) or HFD + 1% heat-killed L. brevis SBL88 (SBL mice) for 16 weeks. Histopathological liver findings were analyzed. To evaluate the gut microbiota, a modified terminal restriction fragment length polymorphism analysis of the feces was performed. RNA sequencing in the liver was performed with Ion Proton™. To investigate the direct effects of heat-killed L. brevis SBL88, an in vitro study was performed. RESULTS: Histopathological findings revealed that fat droplets in the liver were significantly reduced in SBL mice; however, terminal restriction fragment length polymorphism did not show alterations in the gut microbiota between HFD mice and SBL mice. RNA sequencing and pathway analysis revealed that the regulation of lipid and insulin metabolism was affected. The mRNA expression of insulin receptor substrate 2 (IRS-2) was significantly higher in SBL mice, whereas the expression of IRS-1 was not significantly different. Phospho-IRS-2 expression was also significantly increased in SBL mice. In addition, an in vitro study revealed significant alterations in IRS-2 and forkhead box protein O1 expression levels. CONCLUSION: SBL mice exhibited partially improved selective hepatic insulin resistance. Our data suggest that heat-killed L. brevis SBL88 could attenuate the clinical features of NAFLD that are not mediated by alterations in the gut microbiota.

    DOI: 10.1111/jgh.16337

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  • 肺病変を伴わないマイコプラズマ感染による急性肝炎の1例

    田村 ゆき穂, 澤田 康司, 大竹 晋, 林 秀美, 太田 雄, 長谷部 拓夢, 中嶋 駿介, 岡田 充巧, 麻生 和信, 藤谷 幹浩, 奥村 利勝

    肝臓   64 ( Suppl.3 )   A944 - A944   2023.10

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  • 循環EVs中miR-425による膵癌進展制御機構およびリキッドバイオプシー標的としての有用性の検討

    小山 一也, 高橋 賢治, 梶浦 麻未, 岡田 哲弘, 河端 秀賢, 岩本 英孝, 北野 陽平, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    日本消化器病学会雑誌   120 ( 臨増大会 )   A832 - A832   2023.10

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  • 肺癌患者に免疫チェックポイント阻害剤を併用した化学療法中に発生した慢性下痢の1例

    嘉島 伸, 盛一 健太郎, 藤谷 幹浩

    日本癌治療学会学術集会抄録集   61回   P9 - 7   2023.10

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  • Trajectory analyses to identify persistent low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicenter controlled study, J-COMBAT. Reviewed

    Watanabe K., Nojima M., Nakase H., Sato T., Matsuura M., Aoyama N., Kobayashi T., Sakuraba H., Nishishita M., Yokoyama K., Esaki M., Hirai F., Nagahori M., Nanjo S., Omori T., Tanida S., Yokoyama Y., Moriya K., Maemoto A., Shiotani A., Ohmiya N., Tsuchiya K., Shinzaki S., Kato S., Uraoka T., Tanaka N., Takatsu N., Nishida A., Umeno J., Nakamura M., Ishihara S., Fujiya M., Tsuchida K., Hiraoka S., Yamamoto S., Saruta M., Matsuoka K., Ando A., Hirota Y., Hisamatsu T., on behalf of, he, J-COMBAT study group

    J Gastroenterol   2023.10

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  • 重複癌への化学放射線療法後、ESDで治癒切除したcT1b食道癌の1例

    後藤 聖樹, 立花 史音, 高橋 慶太郎, 盛一 健太郎, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   133回・127回   26 - 26   2023.9

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  • ERCPでのガイドワイヤ操作が難しい症例に対する新規ガイドワイヤの使用経験

    馬場 佑介, 河端 秀賢, 小山 一也, 梶浦 麻未, 佐藤 裕基, 岡田 哲弘, 岩本 英孝, 高橋 賢治, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   133回・127回   31 - 31   2023.9

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  • EUS下胆道ドレナージにおけるステント迷入への対策

    石黒 達也, 河端 秀賢, 小山 一也, 梶浦 麻未, 佐藤 裕基, 岡田 哲弘, 岩本 英孝, 高橋 賢治, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   133回・127回   28 - 28   2023.9

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  • 当院における化学療法時のHBV再活性化対策の現状

    澤田 康司, 室 和希, 林 秀美, 中嶋 駿介, 大竹 晋, 太田 雄, 岡田 充巧, 麻生 和信, 藤谷 幹浩, 奥村 利勝

    肝臓   64 ( Suppl.2 )   A613 - A613   2023.9

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  • 大腸癌においてRNA結合タンパクhnRNP A0の腫瘍特異的リン酸化はRAB3GAP1 mRNAを安定化し細胞分裂・増殖を促進する(A tumor-specific phosphorylation of hnRNP A0 promotes mitosis in colon cancer cells via stabilization of RAB3GAP1 mRNA)

    小西 弘晃, 村上 雄紀, 安藤 勝祥, 坂谷 慧, 佐々木 貴弘, 高橋 慶太朗, 上野 伸展, 嘉島 伸, 田中 宏樹, 盛一 健太郎, 藤谷 幹浩

    日本癌学会総会記事   82回   2020 - 2020   2023.9

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  • 胃底腺型腺癌と胃底腺ポリープの鑑別診断にはwhite ring structureが新指標として有用である

    立花 史音, 高橋 慶太郎, 佐藤 允洋, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   133回・127回   51 - 51   2023.9

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  • Infliximabからinfliximab-BSへの変更により薬剤性肝障害を発症したクローン病患者の1例

    ム・チル, 嘉島 伸, 立花 史音, 佐藤 允洋, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   133回・127回   49 - 49   2023.9

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  • 短腸症候群のクローン病に対するGLP-2アナログ製剤長期投与の1例

    佐藤 允洋, 上野 伸展, 立花 史音, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 安藤 勝祥, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   133回・127回   45 - 45   2023.9

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  • 生物学的製剤の変更に伴い腸管外合併症が出現した難治性潰瘍性大腸炎の2例

    関口 竣也, 安藤 勝祥, 立花 史音, 佐藤 允洋, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   133回・127回   33 - 33   2023.9

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  • エヌトレクチニブの投与により重篤な認知障害・運動失調をきたしたNTRK1融合遺伝子陽性肝内胆管癌の1例

    小山 一也, 梶浦 麻未, 佐藤 裕基, 岡田 哲弘, 河端 秀賢, 岩本 英孝, 高橋 賢治, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   133回・127回   51 - 51   2023.9

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  • Effectiveness and Factors Associated with Response to Golimumab in Japanese Patients with Ulcerative Colitis in Real Clinical Practice: The Phoenix Study. Reviewed

    Hirayama D., Motoya S., Ashida T., Ando K., Fujiya M., Ito T., Furukawa S., Maemoto A., Katsurada T., Hinotsu S., Sato N., Mizuno N., Ikawa Y., Nakase H.

    Inflamm Intest Dis   2023.8

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  • 免疫チェックポイント阻害薬関連胃炎の臨床像に関する検討

    杉山 雄哉, 田邊 裕貴, 小林 裕, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 谷野 美智枝, 藤谷 幹浩, 奥村 利勝

    潰瘍   50   60 - 60   2023.8

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  • The safety of vedolizumab in a patient with Crohn's disease who developed anti-TNF-alpha agent associated latent tuberculosis infection reactivation: A case report. International journal

    Yuya Sugiyama, Nobuhiro Ueno, Shion Tachibana, Yu Kobayashi, Yuki Murakami, Takahiro Sasaki, Aki Sakatani, Keitaro Takahashi, Katsuyoshi Ando, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura, Mikihiro Fujiya

    Medicine   102 ( 28 )   e34331   2023.7

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    RATIONALE: Latent tuberculosis (TB) infection screening before inducing anti-tumor necrosis factor (anti-TNF) alpha agents is important to prevent TB reactivation. However, latent TB infection reactivation may still occur, and the ideal therapeutic strategy for patients with inflammatory bowel disease (IBD) who develop active TB infection has not been established. Vedolizumab (VDZ) has a good safety profile, with low incidence rates of serious infections. However, its safety in patients with latent TB infection reactivation associated with anti-TNF-alpha agents remains unknown. PATIENT CONCERNS: A 21-year-old Vietnamese male patient presented to our hospital with hemorrhagic stool. He had no personal or family history of IBD or TB. DIAGNOSES: Colonoscopy revealed multiple longitudinal ulcers and a cobblestone appearance in the terminal ileum, as well as multiple small erosions and aphtha throughout the colon. Computed tomography revealed a right lung nodular lesion. Serological interferon-gamma release assay and several culture tests were all negative. Thus, he was diagnosed with ileocolonic Crohn's disease (CD) without TB. INTERVENTIONS: The intravenous anti-TNF-alpha agent administration with an immunomodulator was initiated. OUTCOMES: Computed tomography revealed nodular lesion expansion at the right lung, and serological interferon-gamma release assay was positive. He was diagnosed with latent TB infection reactivation. Anti-TNF-alpha agent with an immunomodulator was immediately discontinued, and anti-TB therapy was initiated. His endoscopic findings were still active, and VDZ was selected for maintenance therapy because VDZ has a favorable safety profile with low incidence rates of serious infections. Consequently, mucosal healing was achieved without active TB relapse. LESSONS: This case report presented a patient in whom VDZ was continued as maintenance therapy without inducing TB relapse in a patient with CD who developed latent TB infection reactivation associated with anti-TNF-alpha agents and summarized the safety profile of VDZ for patients with IBD with active or latent TB infection. VDZ may be a safe option for induction and maintenance therapy in patients with CD, even in cases with latent TB infection reactivation.

    DOI: 10.1097/MD.0000000000034331

    PubMed

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  • 北海道道北・道東圏内における炎症性腸疾患患者の医療連携構築に向けた課題

    佐藤 允洋, 上野 伸展, 杉村 浩二郎, 岩間 琢哉, 田中 一之, 坂谷 慧, 芹川 真哉, 安藤 勝祥, 嘉島 伸, 石川 千里, 武藤 桃太郎, 稲葉 勇平, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会雑誌   120 ( 7 )   590 - 601   2023.7

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    炎症性腸疾患(IBD)患者の基幹病院と地域中核病院における医療連携の確立は,本邦において重要な課題となっている.本研究は,北海道内の多施設による後ろ向きコホート研究とアンケート調査から,その診療実態と医療連携構築の課題を明らかにすることを目的とした.その結果,IBD患者の基幹病院へ集中と診療格差が明らかとなり,地域中核病院での病院機能,メディカルスタッフのIBD診療理解度の低さが逆紹介の課題と考えられた.課題の解決には,重症度に応じた診療の棲み分け,教育活動やチーム医療の充実化が重要と考える.基幹病院と地域中核病院でIBD医療連携が進むことで,IBD診療の均てん化を実現できると考える.(著者抄録)

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01118&link_issn=&doc_id=20230721350007&doc_link_id=1390015333244307072&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390015333244307072&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_2.gif

  • 細胞外小胞EV内RNAに着目した膵癌バイオマーカー探索

    高橋 賢治, 梶浦 麻未, 小杉 英史, 佐藤 裕基, 岡田 哲弘, 河端 秀賢, 岩本 英孝, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    膵臓   38 ( 3 )   A320 - A320   2023.7

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  • IPMNの発癌機構と治療方針決定 IPMN関連膵癌におけるGNAS遺伝子の病態解明からみた治療戦略

    河端 秀賢, 高橋 賢治, 佐藤 裕基, 岡田 哲弘, 岩本 英孝, 北野 陽平, 大森 優子, 古川 徹, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    膵臓   38 ( 3 )   A213 - A213   2023.7

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  • 急性膵炎の致命率改善への集学的治療 DIC合併重症急性膵炎の臨床的アウトカムに関する検討

    岩本 英孝, 高橋 賢治, 梶浦 麻未, 小杉 英史, 佐藤 裕基, 岡田 哲弘, 河端 秀賢, 北野 陽平, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    膵臓   38 ( 3 )   A171 - A171   2023.7

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  • 細胞外小胞EV内RNAに着目した膵癌バイオマーカー探索

    高橋 賢治, 梶浦 麻未, 小杉 英史, 佐藤 裕基, 岡田 哲弘, 河端 秀賢, 岩本 英孝, 北野 陽平, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    膵臓   38 ( 3 )   A320 - A320   2023.7

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  • IPMNの発癌機構と治療方針決定 IPMN関連膵癌におけるGNAS遺伝子の病態解明からみた治療戦略

    河端 秀賢, 高橋 賢治, 佐藤 裕基, 岡田 哲弘, 岩本 英孝, 北野 陽平, 大森 優子, 古川 徹, 藤谷 幹浩, 奥村 利勝, 水上 裕輔

    膵臓   38 ( 3 )   A213 - A213   2023.7

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  • 急性膵炎の致命率改善への集学的治療 DIC合併重症急性膵炎の臨床的アウトカムに関する検討

    岩本 英孝, 高橋 賢治, 梶浦 麻未, 小杉 英史, 佐藤 裕基, 岡田 哲弘, 河端 秀賢, 北野 陽平, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    膵臓   38 ( 3 )   A171 - A171   2023.7

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  • 【第50回超音波ドプラ・新技術研究会臨床報告集 萃点からの転換】若年者に発症した巨大肝エキノコックス症の一例

    宿田 耕之介, 麻生 和信, 大竹 晋, 太田 雄, 岡田 充巧, 室 和希, 林 秀美, 中嶋 駿介, 澤田 康司, 藤谷 幹浩, 奥村 利勝, 横尾 英樹, 湯澤 明夏

    Rad Fan   21 ( 8 )   14 - 17   2023.6

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    造影3D超音波が病態把握に有用と考えられた若年発症の巨大肝エキノコックス症を経験したので文献的考察を加え報告する。(著者抄録)

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  • 全大腸内視鏡検査による適切な大腸がん検診の検討

    盛一 健太郎, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 田中 一之, 安藤 勝祥, 野村 好紀, 上野 伸展, 嘉島 伸, 田邊 裕貴, 藤谷 幹浩

    日本消化器がん検診学会雑誌   61 ( Suppl総会 )   468 - 468   2023.6

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  • 全大腸内視鏡検査による適切な大腸がん検診の検討

    盛一 健太郎, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 田中 一之, 安藤 勝祥, 野村 好紀, 上野 伸展, 嘉島 伸, 田邊 裕貴, 藤谷 幹浩

    日本消化器がん検診学会雑誌   61 ( Suppl総会 )   468 - 468   2023.6

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  • The Effectiveness of the Combination of Arterial Infusion Chemotherapy and Radiotherapy for Biliary Tract Cancer: A Prospective Pilot Study Reviewed

    Goto T., Sato H., Fujibayashi S., Okada T., Hayashi A., Kawabata H., Yuzawa S., Ishitoya S., Yamashina M., Fujiya M.

    Cancers   2023.5

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  • 肝細胞癌に対するAtezolizumab+Bevacizumab併用療法中のCOVID19感染後に発症したirAE肺障害の1例

    田村 ゆき穂, 澤田 康司, 室 和希, 大竹 晋, 林 秀美, 太田 雄, 中嶋 駿介, 岡田 充巧, 麻生 和信, 藤谷 幹浩, 奥村 利勝

    肝臓   64 ( Suppl.1 )   A326 - A326   2023.4

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  • 薬剤性消化管障害の最前線(下部) 潰瘍性大腸炎における5-ASA不耐の臨床像と内視鏡所見

    坂谷 慧, 安藤 勝祥, 藤谷 幹浩

    Gastroenterological Endoscopy   65 ( Suppl.1 )   784 - 784   2023.4

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  • 肝硬変の成因と病態の推移 道北医療圏の5基幹病院における肝硬変の成因と推移

    林 秀美, 澤田 康司, 室 和希, 中嶋 駿介, 大竹 晋, 太田 雄, 岡田 充巧, 麻生 和信, 藤谷 幹浩, 本田 宗也, 長谷部 拓夢, 助川 隆士, 横浜 吏郎, 奥村 利勝

    肝臓   64 ( Suppl.1 )   A240 - A240   2023.4

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  • 高次元モードの実質的効果を検証する:二次元vs三-四次元 肝良性腫瘍の造影3D超音波による血行動態評価

    大竹 晋, 麻生 和信, 宿田 耕之介, 太田 雄, 岡田 充巧, 林 秀美, 中嶋 駿介, 澤田 康司, 藤谷 幹浩, 奥村 利勝

    超音波医学   50 ( Suppl. )   S221 - S221   2023.4

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  • 肝臓疾患の血流診断の最前線 肝腫瘍診断における造影3D超音波の臨床応用

    麻生 和信, 岡田 充巧, 太田 雄, 大竹 晋, 宿田 耕之介, 林 秀美, 中嶋 駿介, 澤田 康司, 藤谷 幹浩, 奥村 利勝

    超音波医学   50 ( Suppl. )   S186 - S186   2023.4

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  • Treatment escalation and de-escalation decisions in Crohn’s disease: Delphi consensus recommendations from Japan, 2021 Reviewed

    Nakase H., Esaki M., Hirai F., Kobayashi T., Matsuoka K., Matsuura M., Naganuma M., Saruta M., Tsuchiya K., Uchino M., Watanabe K., Hisamatsu T on, behalf, of, he, TRADE consensus group

    J Gastroenterol   2023.4

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  • 重症アルコール性肝炎に対して顆粒球除去療法(GCAP)を施行した1例

    宿田 耕之介, 岡田 充巧, 室 和希, 大竹 晋, 林 秀美, 太田 雄, 中嶋 駿介, 澤田 康司, 麻生 和信, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   132回・126回   44 - 44   2023.3

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  • 切除不能進行膵癌に対するゲムシタビン関連レジメン使用後の二次治療 mFOLFIRINOXとnal-IRI+5-FU/LV療法の比較

    梶浦 麻未, 岩本 英孝, 小杉 英史, 岡田 哲弘, 河端 秀賢, 高橋 賢治, 北野 陽平, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   132回・126回   72 - 72   2023.3

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  • 直腸癌を併発した難治性irAE腸炎に対しトファシチニブが著効した1例

    藤井 尚三郎, 安藤 勝祥, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 武田 智宏, 湯澤 明夏, 谷野 美智枝, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   132回・126回   50 - 50   2023.3

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  • 経鼻内視鏡検査時の呼吸法に関する検討 多施設前向きランダム化比較試験

    小林 裕, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   132回・126回   41 - 41   2023.3

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  • 食道アカラシアに対する経口内視鏡的筋層切開術(Per Oral Endoscopic Myotomy POEM)の治療成績

    真口 遼香, 高橋 慶太郎, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   132回・126回   39 - 39   2023.3

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  • Nasal breathing is superior to oral breathing when performing and undergoing transnasal endoscopy: a randomized trial. International journal

    Keitaro Takahashi, Yuki Murakami, Takahiro Sasaki, Nobuhiro Ueno, Shion Tachibana, Junpei Ikeda, Kenichi Ishigaki, Masashi Horiuchi, Moe Yoshida, Kyoko Uehara, Yu Kobayashi, Yuya Sugiyama, Takehito Kunogi, Mizue Muto, Katsuyoshi Ando, Momotaro Muto, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Nobuyuki Yanagawa, Kazumichi Harada, Takashi Teramoto, Toshikatsu Okumura, Mikihiro Fujiya

    Endoscopy   55 ( 3 )   207 - 216   2023.3

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    BACKGROUND : Transnasal endoscopy presents a technical difficulty when inserting the flexible endoscope. It is unclear whether a particular breathing method is useful for transnasal endoscopy. Therefore, we conducted a prospective randomized controlled trial to compare endoscopic operability and patient tolerance between patients assigned to nasal breathing or oral breathing groups. METHODS : 198 eligible patients were randomly assigned to undergo transnasal endoscopy with nasal breathing or with oral breathing. Endoscopists and patients answered questionnaires on the endoscopic operability and patient tolerance using a 100-mm visual analog scale ranging from 0 (non-existent) to 100 (most difficult/unbearable). The visibility of the upper-middle pharynx was recorded. RESULTS : Patient characteristics did not differ significantly between the groups. Nasal breathing showed a higher rate of good visibility of the upper-middle pharynx than oral breathing (91.9 % vs. 27.6 %; P < 0.001). Nasal breathing showed lower mean [SD] scores than oral breathing in terms of overall technical difficulty (21.0 [11.4] vs. 35.4 [15.0]; P < 0.001). Regarding patient tolerance, nasal breathing showed lower scores than oral breathing for overall discomfort (22.1 [18.8] vs. 30.5 [20.9]; P = 0.004) and other symptoms, including nasal and throat pain, choking, suffocating, gagging, belching, and bloating (all P < 0.05). The pharyngeal bleeding rate was lower in the nasal breathing group than in the oral breathing group (0 % vs. 9.2 %; P = 0.002). CONCLUSIONS : Nasal breathing is superior to oral breathing for those performing and undergoing transnasal endoscopy. Nasal breathing led to good visibility of the upper-middle pharynx, improved endoscopic operability, and better patient tolerance, and was safer owing to decreased pharyngeal bleeding.

    DOI: 10.1055/a-1900-6004

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  • 直腸癌を併発した難治性irAE腸炎に対しトファシチニブが著効した1例

    藤井 尚三郎, 安藤 勝祥, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 武田 智宏, 湯澤 明夏, 谷野 美智枝, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   132回・126回   50 - 50   2023.3

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  • 経鼻内視鏡検査時の呼吸法に関する検討 多施設前向きランダム化比較試験

    小林 裕, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   132回・126回   41 - 41   2023.3

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  • 食道アカラシアに対する経口内視鏡的筋層切開術(Per Oral Endoscopic Myotomy POEM)の治療成績

    真口 遼香, 高橋 慶太郎, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   132回・126回   39 - 39   2023.3

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  • 【特殊状況下でのIBD診療を身につける!】IBD患者の血栓症マネージメントを身につける

    安藤 勝祥, 藤谷 幹浩

    IBD Research   17 ( 1 )   28 - 33   2023.3

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    炎症性腸疾患(IBD)では,健常人の約2~3倍の静脈血栓塞栓症(VTE)リスクを有し,死亡率が高いことも報告されている.わが国においても全国調査により欧米と同等のVTEリスクがあることが明らかとなった.加えて,IBDでは心血管関連イベントの合併も多いことが明らかにされている.ステロイドの血栓リスクはよく知られているが,近年JAK阻害薬に伴う血栓症合併リスクが高まる可能性が報告されており,治療薬選択においても血栓症リスクを考慮する必要がある.欧米のコンセンサスではIBD入院患者への薬物的VTE予防が推奨されており,VTE合併および死亡リスクを把握したうえで,わが国においても積極的なスクリーニングや予防法を確立する必要がある.(著者抄録)

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  • 実臨床におけるベドリズマブのクローン病患者に対する有効性と治療反応予測因子

    青山 慶哉, 桂田 武彦, 福島 新弥, 桜井 健介, 古川 滋, 前本 篤男, 藤谷 幹浩, 安藤 勝祥, 折居 史佳, 蘆田 知史, 那須野 正尚, 田中 浩紀, 本谷 聡, 平山 大輔, 仲瀬 裕志

    日本消化器病学会雑誌   120 ( 臨増総会 )   A287 - A287   2023.3

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  • 消化器疾患の遠隔医療の現状と課題 IBD診療における通院距離が臨床所見・入院や治療に及ぼす影響の解析

    嘉島 伸, 盛一 健太郎, 藤谷 幹浩

    日本消化器病学会雑誌   120 ( 臨増総会 )   A155 - A155   2023.3

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  • Cancer Research in Adenocarcinoma, Adenoma, Adenomatous Polyposis Coli, and Colitis-Associated Neoplasia: A Special Issue. International journal

    Kentaro Moriichi, Mikihiro Fujiya

    Cancers   15 ( 4 )   2023.2

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    Recent technological advancements have enabled us to analyze a variety of aspects of colorectal cancer (CRC), including both clinical and basic science [...].

    DOI: 10.3390/cancers15041328

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  • 骨髄異形成症候群(5q-症候群)に合併した腸管型ベーチェット病の1例

    黒田 祥平, 安藤 勝祥, 杉山 雄哉, 小林 裕, 久野木 健仁, 佐々木 貴弘, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本大腸肛門病学会雑誌   76 ( 2 )   250 - 250   2023.2

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  • Epstein-Barrウイルス関連早期胃癌の内視鏡AI診断の可能性

    田邊 裕貴, 水上 裕輔, 小林 裕, 安藤 勝祥, 藤谷 幹浩, 奥村 利勝

    日本胃癌学会総会記事   95回   360 - 360   2023.2

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  • 内視鏡的切除しえた肛門上皮内腫瘍を合併した尖圭コンジローマの1例

    久野木 健仁, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本大腸肛門病学会雑誌   76 ( 2 )   254 - 254   2023.2

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  • Local recurrence after successful endoscopic submucosal dissection for rectal mucinous mucosal adenocarcinoma: A case report

    Yuki Murakami, Hiroki Tanabe, Yusuke Ono, Yuya Sugiyama, Yu Kobayashi, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Sayaka Yuzawa, Kentaro Moriichi, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    World Journal of Gastrointestinal Oncology   15 ( 1 )   186 - 194   2023.1

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    DOI: 10.4251/wjgo.v15.i1.186

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  • Concomitant pharmacologic medications influence the clinical outcomes of granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis: A multicenter retrospective cohort study. International journal

    Nobuhiro Ueno, Yuya Sugiyama, Yu Kobayashi, Yuki Murakami, Takuya Iwama, Takahiro Sasaki, Takehito Kunogi, Aki Sakatani, Keitaro Takahashi, Kazuyuki Tanaka, Shinya Serikawa, Katsuyoshi Ando, Shin Kashima, Momotaro Muto, Yuhei Inaba, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura, Mikihiro Fujiya

    Journal of clinical apheresis   38 ( 4 )   406 - 421   2023.1

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    BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn has been used as a remission induction therapy for patients with active ulcerative colitis (UC). Herein, we investigated the influence of concomitant medications in the remission induction of GMA in patients with active UC. METHODS: This multicenter retrospective cohort study included patients with UC underwent GMA in five independent institutions in Japan from January 2011 to July 2021. Factors including concomitant medications associated with clinical remission (CR) were analyzed statistically. RESULT: A total of 133 patients were included. Seventy-four patients achieved a CR after GMA. The multivariable analysis revealed that concomitant medication with 5-aminosalicylic acid, Mayo endoscopic subscore (MES), and concomitant medication with immunosuppressors (IMs) remained as predictors of CR after GMA. In the subgroup analysis in patients with MES of 2, concomitant medication with IMs was demonstrated as a significant negative factor of CR after GMA (P = .042, OR 0.354). Seventy-four patients who achieved CR after GMA were followed up for 52 weeks. In the multivariable analysis, the maintenance therapy with IMs was demonstrated as a significant positive factor of sustained CR up to 52 weeks (P = .038, OR 2.214). Furthermore, the rate of sustained CR in patients with biologics and IMs was significantly higher than that in patients with biologics only (P = .002). CONCLUSION: GMA was more effective for patients with active UC that relapsed under treatment without IMs. Furthermore, the addition of IMs should be considered in patients on maintenance therapy with biologics after GMA.

    DOI: 10.1002/jca.22040

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  • Gastro-colic Fistula-associated Hypersplenism Causes Pancytopenia in a Patient with Crohn's Disease.

    Seisuke Saito, Nobuhiro Ueno, Yuki Kamikokura, Yuya Sugiyama, Yu Kobayashi, Yuki Murakami, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Mishie Tanino, Toshikatsu Okumura, Mikihiro Fujiya

    Internal medicine (Tokyo, Japan)   62 ( 1 )   69 - 74   2023.1

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    A 24-year-old woman was admitted to our hospital due to abdominal pain and a high fever. She was diagnosed with ileocolonic Crohn's disease (CD), complicated with a gastro-colic fistula and splenomegaly. After initial treatment with an infliximab-biosimilar, all blood cell line counts markedly decreased. Three-dimensional reconstructed computed tomography revealed splenic vein narrowing. Thus, her pancytopenia was deemed to have likely been caused by hypersplenism. Surgery was performed, and clinical remission was maintained without pancytopenia. This is the first report of a CD patient with pancytopenia caused by hypersplenism that was triggered by gastro-colic fistula-associated splenic vein obstruction.

    DOI: 10.2169/internalmedicine.9590-22

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  • 大腸ESD施行困難因子の一つである腸管蠕動への対策

    佐々木 貴弘, 上野 伸展, 上原 恭子, 小林 裕, 杉山 雄哉, 村上 雄紀, 高橋 慶太郎, 安藤 勝祥, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本大腸肛門病学会雑誌   76 ( 1 )   89 - 89   2023.1

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  • 免疫チェックポイント阻害薬関連胃炎の臨床像に関する検討

    杉山 雄哉, 田邊 裕貴, 小林 裕, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 谷野 美智枝, 藤谷 幹浩, 奥村 利勝

    日本消化管学会雑誌   7 ( Suppl. )   117 - 117   2023.1

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  • Long-term effectiveness and safety of infliximab-biosimilar: A multicenter Phoenix retrospective cohort study. International journal

    Tomoe Kazama, Katsuyoshi Ando, Nobuhiro Ueno, Mikihiro Fujiya, Takahiro Ito, Atsuo Maemoto, Keisuke Ishigami, Masanori Nojima, Hiroshi Nakase

    PloS one   18 ( 9 )   e0288393   2023

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    BACKGROUND: Infliximab (IFX) effectively treats patients with inflammatory bowel disease (IBD). IFX-biosimilar (IFX-BS) has the same amino acid sequence as that of the IFX originator, and its increasing use is expected to reduce national healthcare costs. Long-term efficacy and safety of IFX-BS in patients with Crohn's disease (CD) and ulcerative colitis (UC) have not been completely investigated. METHODS: We conducted a retrospective, multicenter observational study of patients with IBD who received IFX-BS treatment at three hospitals between October 2016 and April 2022. Clinical data were collected from electronic medical records and evaluated for achieving clinical remission (CR) using Crohn's disease activity index (CDAI) and partial Mayo (pMayo) score, persistency of long-term IFX-BS administration, and clinical response rate in the bio-naïve and bio-failure groups. RESULTS: A total of 117 patients with IBD (90 CD and 27 UC) were included. The study findings indicated that both bio-naïve and bio-failure groups of patients with UC showed similar effectiveness of IFX-BS. The treatment persistence rate in patients with CD was significantly higher in the bio-naïve (P = 0.042) and switch (P = 0.010) groups than in the bio-failure group. In the former two groups, the treatment persistence rate was high at two years after administration (more than 80%). In patients with UC, the findings indicated higher treatment persistence rate in the switch group than in the bio-naïve group. Univariable and multivariable analyses for treatment persistence rate showed that the albumin level at the initial IFX-BS administration and groups (bio-naïve, bio-failure and switch) were effective factors for patients with CD. Adverse events were reported in 18 patients (15.4%). CONCLUSION: The present study demonstrates the long-term effectiveness and safety of IFX-BS. In addition to the favorable remission induction in the bio-naïve and bio-failure groups, we demonstrated remission maintenance and treatment persistence rates beyond two years. Albumin level and groups were associated with better treatment persistence in patients with CD.

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  • [The task of the medical cooperation system for patients with inflammatory bowel disease in the northern and eastern regions of Hokkaido].

    Masahiro Sato, Nobuhiro Ueno, Kojiro Sugimura, Takuya Iwama, Kazuyuki Tanaka, Aki Sakatani, Shinya Serikawa, Katsuyoshi Ando, Shin Kashima, Chisato Ishikawa, Momotaro Muto, Yuhei Inaba, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura, Mikihiro Fujiya

    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology   120 ( 7 )   590 - 601   2023

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    In Japan, establishing a medical cooperation system for patients with inflammatory bowel disease (IBD) between IBD flagship and local care hospitals is a crucial task. Thus, this retrospective multicenter cohort study aims to examine the actual state of medical treatment in patients with IBD via a questionnaire survey administered to eight dependent institutes in Hokkaido, Japan. The present results clarified the clinical disparities of IBD treatment and hospital function between IBD flagship hospitals and local care hospitals. Moreover, the understanding level of IBD treatment in medical staff was significantly lower in local care than in IBD flagship hospitals. Furthermore, an abounding experience of IBD treatment affected the understanding level of IBD treatment of both medical doctors and staff. These findings indicate that selecting patients with IBD corresponding to disease activity, educational system for the current IBD treatment, and promotion of team medicine with multimedical staff can resolve clinical discrepancies between IBD flagship and local care hospitals. The IBD treatment inequities in Japan will be eliminated with the development of an appropriate medical cooperation system between IBD flagship and local care hospitals.

    DOI: 10.11405/nisshoshi.120.590

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  • A Successful Case of Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab with Multisystem Immune-related Adverse Events.

    Hidemi Hayashi, Koji Sawada, Takumu Hasebe, Shunsuke Nakajima, Jun Sawada, Yuri Takiyama, Yumi Takiyama, Toshikatsu Okumura, Mikihiro Fujiya

    Internal medicine (Tokyo, Japan)   61 ( 23 )   3497 - 3502   2022.12

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    A 63-year-old man with hepatitis C was treated with atezolizumab plus bevacizumab for unresectable diffuse hepatocellular carcinoma (HCC). After four cycles of atezolizumab plus bevacizumab, the diffuse HCC markedly shrank; however, he complained of general fatigue, loss of appetite, and slight loss of muscle strength in the lower legs. He was diagnosed with isolated adrenocorticotropic hormone deficiency (IAD), hypothyroidism, and myopathy, suggesting multisystem immune-related adverse events (irAEs). After administration of hydrocortisone, the clinical symptoms rapidly disappeared. Patients with multisystem irAEs can have favorable outcomes; thus, to continue immune-checkpoint inhibitors therapy, a correct diagnosis and management of multisystem irAEs are important.

    DOI: 10.2169/internalmedicine.9393-22

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  • Contrast-enhanced ultrasonography for the diagnosis of spontaneous necrosis of hepatocellular carcinoma: A report of 2 cases. Reviewed

    Ota Y., Aso K., Otake S., Okada M., Shukuda K., Sawada K., Yokoo H., Tanino M., Fujiya M., Okumura T.

    Radiol Case Rep   2022.11

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  • B細胞悪性リンパ腫小腸病変診断における内視鏡の有用性および予後との関連性

    嘉島 伸, 盛一 健太郎, 藤谷 幹浩

    日本小腸学会学術集会プログラム・抄録集   60回   46 - 46   2022.11

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  • 消化器疾患領域 便中カルプロテクチンは顆粒球吸着除去療法(GMA)の臨床効果予測に有用なバイオマーカーである

    上野 伸展, 安藤 勝祥, 田中 一之, 稲場 勇平, 藤谷 幹浩

    日本アフェレシス学会雑誌   41 ( Suppl. )   87 - 87   2022.11

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  • Real-world Insurance Claims Analysis of Venous Thromboembolism in Japanese Patients with Inflammatory Bowel Disease. Reviewed

    Fujiya M., Kawaguchi T., Arai S., Isogawa N., Hiro S., Matsumoto F., Yamaguchi S., Yoshii N., Nakamura M., Matsuoka K.

    Dig Dis Sci   2022.11

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  • 【胃疾患アトラス 改訂版】陥凹を呈する病変 上皮性・非腫瘍性陥凹病変 Crohn病の胃病変

    久野木 健仁, 盛一 健太郎, 藤谷 幹浩

    消化器内視鏡   34 ( 増刊 )   206 - 207   2022.10

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  • 細胞外小胞によるmiR-45の細胞間伝達は上皮間葉形質転換を促進し膵癌進展を制御する

    小山 一也, 高橋 賢治, 藤林 周吾, 林 明宏, 河端 秀賢, 岩本 英孝, 後藤 拓磨, 北野 陽平, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    日本消化器病学会雑誌   119 ( 臨増大会 )   A815 - A815   2022.10

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  • Testis-specific hnRNP is expressed in colorectal cancer cells and accelerates cell growth mediating ZDHHC11 mRNA stabilization. International journal

    Yuki Murakami, Hiroaki Konishi, Mikihiro Fujiya, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura

    Cancer medicine   11 ( 19 )   3643 - 3656   2022.10

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    Various heterogeneous nuclear ribonucleoproteins (hnRNPs) have been reported to be associated with cancer cell growth. However, it remains unclear whether hnRNP G-T, which is specifically expressed in the testis, is expressed in tumor cells, and whether hnRNP G-T expressed in colorectal cancer (CRC) cells is associated with tumor progression. We herein report that hnRNP G-T promoted cancer cell growth and stabilized mRNA of ZDHHC11 in CRC. The cell growth was inhibited by transfection of siRNA of hnRNP G-T in cancer cells, but not in non-cancerous epithelial cells. The tumor promotive effect of hnRNP G-T was confirmed in an HCT116 transplanted mouse model. RT-PCR and western blotting indicated the augmentation of hnRNP G-T in CRC in comparison to non-cancerous cells. The downregulation of hnRNP G-T inhibited cancer cell growth and promoted apoptosis in CRC. A transcriptome analysis combined with immunoprecipitation revealed that hnRNP G-T stabilized 174 mRNAs, including ZDHHC11 mRNA. The cell growth was also suppressed by the transfection of siRNA of ZDHHC11 and the mRNA and the protein expression were decreased by the transfection of siRNA of hnRNP G-T. These results suggested that hnRNP G-T promotes the cell growth of CRC by regulating the mRNA of ZDHHC11. Therefore, hnRNP G-T will be highlighted as an effective therapeutic target with less adverse effects in CRC therapy.

    DOI: 10.1002/cam4.4738

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  • Carbazochrome sodium sulfonate is not effective for prevention of post-gastric endoscopic submucosal dissection bleeding: A retrospective study. International journal

    Keitaro Takahashi, Takahiro Sasaki, Nobuhiro Ueno, Kyoko Uehara, Yu Kobayashi, Yuya Sugiyama, Yuki Murakami, Takehito Kunogi, Katsuyoshi Ando, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura, Mikihiro Fujiya

    Surgical endoscopy   36 ( 10 )   7486 - 7493   2022.10

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    BACKGROUND: Carbazochrome sodium sulfonate (CSS) is conventionally administered to prevent post-endoscopic submucosal dissection (ESD) bleeding in many institutions, but research on its preventive efficacy is lacking. Therefore, we investigated the risk of post-ESD bleeding and the preventive efficacy of CSS administration. METHODS: We retrospectively reviewed 304 lesions in 259 patients with gastric neoplasms who underwent ESD at Asahikawa Medical University Hospital from 2014 to 2021. In the CSS group, CSS 100 mg/day was intravenously infused with maintenance fluid replacement on postoperative days 0-2. The risk factors of post-ESD bleeding, including CSS administration, were investigated. RESULTS: The overall rate of post-ESD bleeding was 4.6% (14/304). The univariate analysis showed that atrial fibrillation (Af), warfarin intake, heparin replacement, and tumor location in the lower third were significant risk factors for increasing the likelihood of postoperative bleeding. In the multivariate analysis, Af (odds ratio [OR] 3.83, 95% CI 1.02-14.30; p &lt; 0.05), heparin replacement (OR 4.60, 95% CI 1.02-20.70; p &lt; 0.05), and tumor location in the lower third of the stomach (OR 6.67, 95% CI 1.43-31.00; p &lt; 0.05) were independent factors for post-ESD bleeding. Post-ESD bleeding was observed in 5.2% (9/174) of the CSS group and 3.8% (5/130) of the non-CSS group, with no significant difference between the two groups (p = 0.783). Additionally, CSS was not shown to have preventive effects in groups with higher-risk factors, such as Af diagnosis, warfarin use, heparin replacement, and tumor location in the lower third of the stomach. CONCLUSION: CSS administration was not effective for the prevention of the post-ESD bleeding in the overall patient population as well as in higher-risk patients. This suggests that the administration of CSS for post-ESD bleeding prevention may need to be reconsidered.

    DOI: 10.1007/s00464-022-09171-4

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  • 併用する薬物療法が顆粒球吸着除去療法(GMA)の臨床効果に与える影響に関する検討

    岩間 琢哉, 上野 伸展, 田中 一之, 安藤 勝祥, 芹川 真哉, 武藤 桃太郎, 嘉島 伸一, 盛一 健太郎, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会雑誌   119 ( 臨増大会 )   A786 - A786   2022.10

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  • 炎症性腸疾患における動静脈血栓塞栓症の重症化・死亡頻度に関する全国多施設調査

    安藤 勝祥, 上野 伸展, 藤谷 幹浩

    日本消化器病学会雑誌   119 ( 臨増大会 )   A725 - A725   2022.10

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  • 死者率減少を目指した大腸がん検診 Interval cancerに配慮した適正な大腸内視鏡検診間隔の検討および血清RNA診断の有用性

    盛一 健太郎, 上野 伸展, 藤谷 幹浩

    日本消化器がん検診学会雑誌   60 ( Suppl大会 )   962 - 962   2022.10

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  • 肝硬変症例における観血的処置前ルストロンボバブ投与の効果

    中嶋 駿介, 宿田 耕之介, 室 和希, 大竹 晋, 林 秀美, 太田 雄, 澤田 康司, 岡田 充巧, 麻生 和信, 藤谷 幹浩, 奥村 利勝

    肝臓   63 ( Suppl.3 )   A786 - A786   2022.10

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  • 炎症性腸疾患患者における大腸癌の臨床的特徴 多施設共同後ろ向き研究

    久野木 健仁, 上野 伸展, 杉村 浩二郎, 高橋 慶太郎, 田中 一之, 芹川 真哉, 安藤 勝祥, 嘉島 伸, 石川 千里, 稲場 勇平, 武藤 桃太郎, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本癌治療学会学術集会抄録集   60回   P39 - 2   2022.10

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  • 免疫チェックポイント阻害剤(ICI)関連胃炎の臨床病理学的検討

    田邊 裕貴, 杉山 雄哉, 小林 裕, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本癌治療学会学術集会抄録集   60回   O23 - 2   2022.10

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  • 骨転移再発を契機に診断された肝原発MiNENの1例

    室 和希, 澤田 康司, 林 秀美, 中嶋 駿介, 長谷部 拓夢, 大竹 晋, 太田 雄, 岡田 充巧, 麻生 和信, 高橋 裕之, 今井 浩二, 横尾 英樹, 藤谷 幹浩, 奥村 利勝

    肝臓   63 ( Suppl.3 )   A806 - A806   2022.10

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  • Cytomegalovirus infection in patients with malignant lymphomas who have not received hematopoietic stem cell transplantation. International journal

    Kazuya Sato, Sho Igarashi, Nodoka Tsukada, Junki Inamura, Masayo Yamamoto, Motohiro Shindo, Kentaro Moriichi, Yusuke Mizukami, Mikihiro Fujiya, Yoshihiro Torimoto

    BMC cancer   22 ( 1 )   944 - 944   2022.9

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    BACKGROUND: Life-threatening cytomegalovirus infection (CMVI) has been reported even in patients with malignant lymphoma (ML) who have not received hematopoietic stem cell transplantation (w/o HSCT) but had been treated with chemotherapy or radiotherapy. However, the CMVI incidence and risk factors (RFs) in patients with ML w/o HSCT have not been fully elucidated. This study aimed to evaluate the clinical aspects, including incidence and RFs, of CMVI in patients with ML w/o HSCT. METHODS: We retrospectively reviewed all patients with ML who received chemotherapy or radiotherapy in our department from 2005 to 2013. The overall survival (OS), incidence and RFs of CMVI, and other characteristics of patients with CMVI were analyzed. RESULTS: Overall, 236 patients with ML w/o HSCT were evaluated. Of these, 5.5% (13/236) developed CMVI; 54% (7/13) received steroid pretreatment before primary therapy (PT) for ML; and 62% (8/13) received > 2 therapeutic regimens for ML. The OS curve of patients with CMVI was significantly worse than that of patients without CMVI (p < 0.0001, log-rank test). A univariate analysis identified B symptoms (p = 0.00321), serum albumin < 3.5 g/dL (p = 0.0007837), C-reactive protein level > the upper limit of normal (p = 0.0006962), steroid pretreatment before PT for ML (p = 0.0004262), > 2 therapeutic regimens for ML (p = 0.0000818), T cell lymphoma (p = 0.006406), and non-complete remission (p = 0.02311) as RFs for CMVI. A multivariate analysis identified steroid pretreatment before PT for ML [odds ratio (OR): 4.71 (95% confidence interval [CI]: 1.06-21.0); p = 0.0419] and > 2 therapeutic regimens for ML [OR: 9.25 (95% CI: 2.33-36.8); p = 0.00159] as independent RFs for CMVI in patients with ML w/o HSCT. CONCLUSIONS: Attention should be paid to CMVI development in patients with ML w/o HSCT pretreated with steroids or who had multiple therapeutic regimens.

    DOI: 10.1186/s12885-022-10008-5

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  • 胆摘時の腹腔内落下胆石が原因で発症した後腹膜炎症性偽腫瘍の1例

    長谷川 千紘, 安藤 勝祥, 小林 裕, 杉山 雄哉, 久野木 健仁, 佐々木 貴弘, 坂谷 慧, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 鈴木 康秋, 林 真奈美, 湯澤 明夏, 谷野 美知枝, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   131回・125回   52 - 52   2022.9

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  • 新規バスケットカテーテルとEHLプローブを用いた内視鏡的膵石治療の経験

    小杉 英史, 河端 秀賢, 久保田 寛之, 梶浦 麻未, 佐藤 裕基, 藤林 周吾, 岩本 英孝, 後藤 拓磨, 高橋 賢治, 北野 陽平, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   131回・125回   59 - 59   2022.9

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  • 経乳頭的ドレナージが困難な急性閉塞性化膿性膵管炎に対し、EUS-PDにより化学療法を継続し得た膵頭部癌の1例

    久保田 寛之, 河端 秀賢, 梶浦 麻未, 小杉 英史, 佐藤 裕基, 藤林 周吾, 岩本 英孝, 高橋 賢治, 北野 陽平, 齋藤 敦, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   131回・125回   32 - 32   2022.9

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  • Usefulness of endoscopic band ligation with gel immersion endoscopy for colonic diverticular bleeding and hemorrhoidal bleeding. International journal

    Yu Kobayashi, Katsuyoshi Ando, Takahiro Sasaki, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Mikihiro Fujiya

    Endoscopy   54 ( 7 )   E384-E385   2022.7

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    DOI: 10.1055/a-1550-1913

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  • Severe immune checkpoint inhibitor-associated gastritis: A case series and literature review. International journal

    Yuya Sugiyama, Hiroki Tanabe, Taisuke Matsuya, Yu Kobayashi, Yuki Murakami, Takahiro Sasaki, Takehito Kunogi, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Mishie Tanino, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    Endoscopy international open   10 ( 7 )   E982-E989   2022.7

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    Background and study aims  Recent advances in cancer treatment have involved the clinical application of immune checkpoint inhibitors (ICIs) for various type of cancers. The adverse events associated with ICIs are generally referred to as immune-related adverse events (irAEs). Gastrointestinal irAEs are a major disorder, but gastritis is not frequently observed. The aims of this study were to elucidate the clinical, endoscopic, and histological characteristics of irAE gastritis. Patients and methods  Information on patients treated with ICIs were collected from a single institute over 3 years. IrAE gastritis was identified based on the clinical course and endoscopic and histopathological findings. Of the 359 patients treated with ICIs, four cases of irAE gastritis were identified in clinical records from the endoscopy unit. The endoscopic and histopathological findings were analyzed, and further immunohistochemical studies with immune subtype markers and programmed cell death ligand-1 (PD-L1) antibody were conducted. Results  Among four patients with irAE gastritis, the remarkable endoscopic characteristics were network-pattern erosion, erythematous and edematous mucosa with thick purulent discharge, and fragile mucosa. Corresponding histological features were fibrinopurulent exudate, severe inflammatory cell infiltration, and epithalaxia, respectively. The PD-L1 expression rate was ≥ 1 % in the gastric tissue of all patients with gastritis. These patients were treated with prednisolone (PSL) and their symptoms improved within a few days to 2 weeks. Conclusions  IrAE gastritis were characterized by specific endoscopic findings. The appropriate endoscopic diagnosis may lead to effective treatment with PSL.

    DOI: 10.1055/a-1839-4303

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  • Artificial intelligence-assisted detection of colorectal polyps in Lynch syndrome. International journal

    Hiroki Tanabe, Kentaro Moriichi, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    Gastrointestinal endoscopy   95 ( 6 )   1276 - 1277   2022.6

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    DOI: 10.1016/j.gie.2022.02.009

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  • PET-CTによる悪性リンパ腫の消化管病変診断能の解析

    嘉島 伸, 盛一 健太郎, 藤谷 幹浩

    日本消化器がん検診学会雑誌   60 ( Suppl総会 )   602 - 602   2022.5

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  • Submarine volcanic eruption of esophageal varices induced by failed variceal ligation and identified by the gel immersion method. International journal

    Takumu Hasebe, Koji Sawada, Mikihiro Fujiya

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   34 ( 4 )   e85-e86   2022.5

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    DOI: 10.1111/den.14281

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  • Probiotic-derived heptelidic acid exerts antitumor effects on extraintestinal melanoma through glyceraldehyde-3-phosphate dehydrogenase activity control. International journal

    Shotaro Isozaki, Hiroaki Konishi, Hiroki Tanaka, Chikage Yamamura, Kentaro Moriichi, Naoki Ogawa, Mikihiro Fujiya

    BMC microbiology   22 ( 1 )   110 - 110   2022.4

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    BACKGROUND: Several microorganisms inhabit the mammalian gastrointestinal tract and are associated with the pathogenesis of various diseases, including cancer. Recent studies have indicated that several probiotics produce antitumor molecules and inhibit host tumor progression. We demonstrated that heptelidic acid (HA), a sesquiterpene lactone derived from the probiotic Aspergillus oryzae, exerts antitumor effects against pancreatic cancer in vitro and in vivo. In this study, the antitumor effects of HA against extraintestinal melanoma were assessed in vitro and in vivo. RESULTS: Sulforhodamine B (SRB) assay revealed that the growth of B16F10 cells was significantly inhibited by HA in a concentration-dependent manner. The enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) decreased in proportion with the growth inhibition effect of HA. Moreover, oral HA administration significantly suppressed the growth of transplanted B16F10 tumors without any significant changes in biochemical test values. Moreover, GAPDH activity in the transplanted tumor tissues in the HA group significantly decreased compared with that in the PBS group. CONCLUSION: This study suggests that orally administered HA was absorbed in the gastrointestinal tract, reached the cancer cells transplanted in the skin, and inhibited GAPDH activity, thereby inhibiting the growth of extraintestinal melanoma cells. Thus, this study proposes a novel system for extraintestinal tumor regulation via gut bacteria-derived bioactive mediators.

    DOI: 10.1186/s12866-022-02530-0

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  • リンチ症候群に対するAI大腸内視鏡の使用経験

    田邊 裕貴, 久野木 健仁, 佐々木 貴弘, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本大腸検査学会雑誌   38 ( 2 )   132 - 132   2022.4

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  • 慢性肝疾患患者における血清亜鉛濃度と骨格筋量の関係

    澤田 康司, 室 和希, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    肝臓   63 ( Suppl.1 )   A348 - A348   2022.4

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  • 小児内視鏡の現況と課題 小児消化管内視鏡の有効性およびその影響因子の解析

    嘉島 伸, 盛一 健太郎, 藤谷 幹浩

    Gastroenterological Endoscopy   64 ( Suppl.1 )   726 - 726   2022.4

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  • 脂質異常症合併NAFLD患者に対するPemafibrateの治療効果

    中嶋 駿介, 大竹 晋, 林 秀美, 太田 雄, 長谷部 拓夢, 澤田 康司, 岡田 充巧, 麻生 和信, 藤谷 幹浩, 奥村 利勝

    肝臓   63 ( Suppl.1 )   A406 - A406   2022.4

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  • UC診療における内視鏡の役割 寛解期潰瘍性大腸炎における通常・拡大内視鏡による再燃予測と治療適正化

    安藤 勝祥, 盛一 健太郎, 藤谷 幹浩

    Gastroenterological Endoscopy   64 ( Suppl.1 )   592 - 592   2022.4

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  • Endoscopic recanalization for the complete closure of long-gap esophageal atresia after reconstruction surgery. International journal

    Shin Kashima, Kentaro Moriichi, Yu Kobayashi, Yuya Sugiyama, Yuki Murakami, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Hiroki Tanabe, Mikihiro Fujiya

    BMC gastroenterology   22 ( 1 )   132 - 132   2022.3

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    BACKGROUND: Reconstruction surgery-associated stricture frequently occurs in patients with long-gap esophageal atresia (LGEA). While several endoscopic dilatation methods have been applied and would be desirable, endoscopic recanalization is very difficult in cases with complete esophageal closure. Surgical treatment has been performed for a severe stricture, which causes extensive damage to the infant. No reports have described successful endoscopic recanalization for complete closure due to scarring after surgery for LGEA. We herein report the case of successful endoscopic recanalization by single endoscopist in an LGEA patient with complete closure after reconstruction surgery. CASE PRESENTATION: A seven-month-old boy with LGEA who received reconstruction surgery and gastrostomy immediately after birth presented to our unit due to vomiting and malnutrition. Contrast radiography and peroral endoscopy detected complete closure of the esophagus at the anastomotic site. After confirming the length of stricture as several millimeters, we punctured the center of the lumen with a 25-G puncture needle under fluoroscopy. An endoscope was then inserted via the gastrostomy and the puncture hole was detected at the center of the lumen. After passing the guidewire, endoscopic balloon dilation was performed three times, and the hole was sufficiently dilatated. Oral ingestion was feasible, and his nutritional condition was improved. CONCLUSIONS: To our knowledge, this is the first report to propose a less invasive endoscopic approach to recanalize a site of complete esophageal closure in a LGEA patient after reconstruction surgery by single endoscopist. Our endoscopic procedure using an ultrathin endoscope and puncture needle may be a therapeutic option for the treatment of patients with complete esophageal closure in a LGEA patient after reconstruction surgery.

    DOI: 10.1186/s12876-022-02207-y

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  • Hypoxia-induced nuclear translocation of β-catenin in the healing process of frostbite. International journal

    Shotaro Isozaki, Hiroki Tanaka, Kie Horioka, Hiroaki Konishi, Shin Kashima, Shuhei Takauji, Mikihiro Fujiya, Henrik Druid

    Biochimica et biophysica acta. Molecular basis of disease   1868 ( 6 )   166385 - 166385   2022.3

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    Frostbite occurs when the skin is exposed to localized low temperatures. The main causes of frostbite are thought to be direct cell injury due to freezing of cells and tissue ischemia due to abnormal blood circulation. However, the molecular mechanism of frostbite has not been elucidated. This study aims to explain the molecular dynamics of frostbite using a mouse frostbite model and keratinocyte cell culture. Comprehensive gene expression analysis performed on mouse skin samples revealed that β-catenin signaling is activated by frostbite. Immunohistochemistry showed nuclear translocation of β-catenin in the skin of frostbite model mice that was not observed in mice subjected to a mechanical skin damage model induced by tape stripping. Tissue hypoxia, as detected by pimonidazole staining, coexisted with nuclear expression of β-catenin. In keratinocyte cell cultures, nuclear translocation of β-catenin was induced by hypoxia, but not by low temperature. Hypoxia induced epithelial-mesenchymal transition - an important biological event in the healing process of skin - and in vitro wound-healing activity, both of which were suppressed by β-catenin inhibition. Our results suggest that during frostbite, impaired blood flow causes hypoxia, which in turn activates β-catenin that promotes keratinocyte motility and tissue repair.

    DOI: 10.1016/j.bbadis.2022.166385

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  • 自然壊死を来した肝細胞癌の2症例

    太田 雄, 大竹 晋, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 澤田 康司, 岡田 充巧, 麻生 和信, 萩原 正弘, 横尾 英樹, 谷野 美智枝, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   130回・124回   70 - 70   2022.3

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  • 背景膵に多発する異型病変を伴った膵上皮内癌の1例

    川尻 はるな, 高橋 賢治, 藤林 周吾, 河端 秀賢, 林 明宏, 岩本 英孝, 後藤 拓磨, 北野 陽平, 高橋 裕之, 今井 浩二, 横尾 英樹, 谷野 美智枝, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   130回・124回   74 - 74   2022.3

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  • 総胆管結石陥頓が診断契機となった胆管内乳頭状腫瘍を伴う遠位胆管癌の1例

    小杉 英史, 河端 秀賢, 藤林 周吾, 林 明宏, 岩本 英孝, 後藤 拓磨, 高橋 賢治, 北野 陽平, 萩原 正弘, 横尾 英樹, 谷野 美智枝, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   130回・124回   61 - 61   2022.3

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  • Underwater tunneling ESDが有効であった脾彎曲部LST-NGの1例

    石垣 憲一, 高橋 慶太郎, 吉田 萌, 上原 恭子, 小林 裕, 杉山 雄哉, 村上 雄紀, 久野木 健仁, 佐々木 貴弘, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   130回・124回   44 - 44   2022.3

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  • 骨格筋と内臓脂肪が抗TNF-α抗体投与後のクローン病に与える影響

    安藤 勝祥, 小林 裕, 杉山 雄哉, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会雑誌   119 ( 臨増総会 )   A307 - A307   2022.3

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  • 【炎症性腸疾患update-診断・治療の最新知見-】炎症性腸疾患の治療 合併症の診断とマネージメント 静脈血栓塞栓症

    安藤 勝祥, 藤谷 幹浩

    日本臨床   80 ( 3 )   499 - 503   2022.3

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  • 老化と消化器がんの病態・診療 高齢肝癌治療における内臓脂肪と予後の関係

    澤田 康司, 長谷部 拓夢, 藤谷 幹浩

    日本消化器病学会雑誌   119 ( 臨増総会 )   A186 - A186   2022.3

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  • Large bowel: White-light and chromoendoscopy. Invited Reviewed

    Saitoh Y., Fujiya M.

    Digestive Endoscopy   2022.3

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  • Interim analysis of a multicenter registry study of COVID-19 patients with inflammatory bowel disease in Japan (J-COSMOS). Reviewed

    Nakase H., Hayashi Y., Hirayama D., Matsumoto T., Matsuura M., Iijima H., Matsuoka K., Ohmiya N., Ishihara S., Hirai F., Abukawa D., Hisamatsu T., J-COSMOS group

    J Gastroenterol   2022.3

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  • A novel telerehabilitation with an educational program for caregivers using telelecture is feasible for fall prevention in elderly people – A Case Series. Reviewed

    Moriichi K., Fujiya M., Ro T., Ota T., Nishimiya H., Kodama M., Yoshida N., Hattori Y., Hosokawa T., Hishiyama H., Kunimoto M., Hayashi H., Hirokawa H., Yoshida A.

    Medicine   2022.2

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  • Mutant GNAS limits tumor aggressiveness in established pancreatic cancer via antagonizing the KRAS-pathway.

    Hidemasa Kawabata, Yusuke Ono, Nobue Tamamura, Kyohei Oyama, Jun Ueda, Hiroki Sato, Kenji Takahashi, Kenzui Taniue, Tetsuhiro Okada, Syugo Fujibayashi, Akihiro Hayashi, Takuma Goto, Katsuro Enomoto, Hiroaki Konishi, Mikihiro Fujiya, Keita Miyakawa, Mishie Tanino, Yuji Nishikawa, Daisuke Koga, Tsuyoshi Watanabe, Chiho Maeda, Hidenori Karasaki, Andrew S Liss, Yusuke Mizukami, Toshikatsu Okumura

    Journal of gastroenterology   57 ( 3 )   208 - 220   2022.1

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    BACKGROUND: Mutations in GNAS drive pancreatic tumorigenesis and frequently occur in intraductal papillary mucinous neoplasm (IPMN); however, their value as a therapeutic target is yet to be determined. This study aimed at evaluating the involvement of mutant GNAS in tumor aggressiveness in established pancreatic cancer. METHODS: CRISPR/Cas9-mediated GNAS R201H silencing was performed using human primary IPMN-associated pancreatic cancer cells. The role of oncogenic GNAS in tumor maintenance was evaluated by conducting cell culture and xenograft experiments, and western blotting and transcriptome analyses were performed to uncover GNAS-driven signatures. RESULTS: Xenografts of GNAS wild-type cells were characterized by a higher Ki-67 labeling index relative to GNAS-mutant cells. Phenotypic alterations in the GNAS wild-type tumors resulted in a significant reduction in mucin production accompanied by solid with massive stromal components. Transcriptional profiling suggested an apparent conflict of mutant GNAS with KRAS signaling. A significantly higher Notch intercellular domain (NICD) was observed in the nuclear fraction of GNAS wild-type cells. Meanwhile, inhibition of protein kinase A (PKA) induced NICD in GNAS-mutant IPMN cells, suggesting that NOTCH signaling is negatively regulated by the GNAS-PKA pathway. GNAS wild-type cells were characterized by a significant invasive property relative to GNAS-mutant cells, which was mediated through the NOTCH regulatory pathway. CONCLUSIONS: Oncogenic GNAS induces mucin production, not only via MUC2 but also via MUC5AC/B, which may enlarge cystic lesions in the pancreas. The mutation may also limit tumor aggressiveness by attenuating NOTCH signaling; therefore, such tumor-suppressing effects must be considered when therapeutically inhibiting the GNAS pathway.

    DOI: 10.1007/s00535-021-01846-4

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  • Balloon endoscopy and capsule endoscopy are useful in the diagnosis of small bowel lesions in Whipple's disease. International journal

    Takehito Kunogi, Katsuyoshi Ando, Mikihiro Fujiya

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   34 ( 1 )   248 - 248   2022.1

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    DOI: 10.1111/den.14180

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  • Prognostic factors to predict the survival in patients with advanced gastric cancer who receive later-line nivolumab monotherapy-The Asahikawa Gastric Cancer Cohort Study (AGCC). International journal

    Kazuyuki Tanaka, Hiroki Tanabe, Hiroki Sato, Chisato Ishikawa, Mitsuru Goto, Naoyuki Yanagida, Hiromitsu Akabane, Shiro Yokohama, Kimiharu Hasegawa, Yohei Kitano, Yuya Sugiyama, Kyoko Uehara, Yu Kobayashi, Yuki Murakami, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Keisuke Sato, Sayaka Yuzawa, Mishie Tanino, Masaki Taruiishi, Yasuo Sumi, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    Cancer medicine   11 ( 2 )   406 - 416   2022.1

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    BACKGROUND: Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later-line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens. PATIENTS AND METHODS: A regional cohort study was undertaken to determine the real-world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated. RESULTS: In total, 70 patients who received nivolumab as ≥third-line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8-10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68-0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2-positive status (27.3%) or microsatellite instability-high (27.3%) status. CONCLUSIONS: The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival.

    DOI: 10.1002/cam4.4461

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  • Genetic background of mesalamine-induced fever and diarrhea in Japanese patients with inflammatory bowel disease. Reviewed

    Suzuki K., Kakuta Y., Naito T., Takagawa T., Hanai H., Araki H., Sasaki Y., Sakuraba H., Sasaki M., Hisamatsu T., Motoya S., Matsumoto T., Onodera M., Ishiguro Y., Nakase H., Andoh A., Hiraoka S., Shinozaki M., Fujii T., Katsurada T., Kobayashi T., Fujiya M., Otsuka T., Oshima N., Suzuki Y., Sato Y., Hokari R., Noguchi M., Ohta Y., Matsuura M., Kawai Y., Tokunaga K., Nagasaki M., Kudo H., Minegishi N., Okamoto D., Shimoyama Y., Moroi R., Kuroha M., Shiga H., Li D., McGovern DPB, KinouchiY., Masamune A.

    Inflammatory Bowel Diseases   2022.1

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  • A case report of drug-induced liver injury due to the infliximab biosimilar CT-P13 on switching from original infliximab in a patient with Crohn's disease. International journal

    Shin Kashima, Koji Sawada, Kentaro Moriichi, Mikihiro Fujiya

    Therapeutic advances in drug safety   13   20420986221100118 - 20420986221100118   2022

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    UNLABELLED: Inflammatory bowel diseases (IBDs) are chronic immune disorders of unclear etiology. Tumor necrosis factor (TNF) inhibitors are effective for IBD treatment and are cost-effective because they reduce hospital admissions and are associated with fewer surgery requirements and a better quality of life in IBD patients. A large number of clinical trials of infliximab biosimilar (CT-P13) have suggested that the administration of biosimilars provides high efficacy and safety similar to that of the originators, with a lower cost, so switching from the original to a biosimilar is considered an acceptable treatment. While several abnormalities of blood examination have been observed in patients with CT-P13 administration, no cases of drug-induced liver injury (DILI) caused by CT-P13 has been reported. A 23-year-old woman had been diagnosed with Crohn's disease and was treated with original infliximab (O-IFX) for 9 years. She developed severe jaundice 1 month after switching from O-IFX to CT-P13. Serologic tests of autoimmune and hepatitis viruses were negative, and ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography revealed no abnormalities. A liver biopsy showed prominent pericentral canalicular cholestasis, without features of steatosis or sclerosing cholangitis, which was consistent with drug-induced cholestasis. The cholestasis improved 10 weeks after the discontinuation of CT-P13, and no DILI redeveloped even after re-switching from CT-P13 to O-IFX. This is the first report of DILI due to switching from O-IFX to CT-P13. While the efficacy and safety of CT-P13 are considered equal to those of O-IFX, clinicians need to be alert for certain severe DILIs when switching from O-IFX to CT-P13 with careful monitoring and appropriate treatment. PLAIN LANGUAGE SUMMARY: A case report of drug-induced liver injury due to switch from original infliximab to infliximab biosimilar Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the entire gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor (TNF) inhibitors are effective for IBD treatment and are cost-effective because they reduce hospital admissions and are associated with fewer surgery requirements and a better quality of life in IBD patients. A biological medicinal product that contains a version of the active substance of an already authorized biological medicinal product. Biosimilars of TNF inhibitors, such as CT-P13, are thought to possess equal efficacy and safety to the original with a lower cost, so switching from the original to a biosimilar considered an acceptable treatment. While several serious adverse reactions of TNF inhibitors have been reported, drug-induced liver injury (DILI) is uncommon, and liver dysfunction due to the administration of CT-P13 has not been reported in IBD patients. We herein report the first case of DILI due to CT-P13 after switching from original infliximab (O-IFX) in a patient with Crohn's disease. While the efficacy and safety of CT-P13 are considered equal to those of O-IFX, clinicians need to be alert for certain severe DILIs when switching from O-IFX to CT-P13 with careful monitoring and appropriate treatment.

    DOI: 10.1177/20420986221100118

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  • Correlation Among Body Composition Parameters and Long-Term Outcomes in Crohn's Disease After Anti-TNF Therapy. International journal

    Katsuyoshi Ando, Kyoko Uehara, Yuya Sugiyama, Yu Kobayashi, Yuki Murakami, Hiroki Sato, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura, Mikihiro Fujiya

    Frontiers in nutrition   9   765209 - 765209   2022

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    Background: The impact of the body composition on the pathophysiology and clinical course of Crohn's disease (CD) has not been fully elucidated. Aims: To reveal the correlations among body composition and long-term outcomes in CD after anti-TNF therapy. Methods: Ninety-one patients who received anti-TNF therapy as their first biologic treatment were enrolled. The skeletal muscle index (SMI), visceral and subcutaneous fat area (VFA, SFA), and the ratio of the VFA to SFA (mesenteric fat index; MFI) at the 3rd lumbar level were measured using computed tomography (CT) imaging before the induction. The correlation among the body composition and outcomes were retrospectively analyzed. Results: The 5-year cumulative secondary failure- and resection-free rates in patients with a low SMI (39.1% and 64.8%) were significantly lower than those with a high SMI (67.5% and 92.7%; p = 0.0071 and 0.0022, respectively). The 5-year cumulative secondary failure-free rate in the patients with low VF (45.0%) was significantly lower than that in those with high VF (77.6%; p = 0.016), and the 5-year cumulative resection-free rate in patients with a high MFI (68.9%) was significantly lower than that in those with a low MFI (83.0%; p = 0.031). Additionally, patients with low age and BMI had significantly lower cumulative secondary failure- and resection-free rates than those with high age and BMI (low age: 37.4% and 71.2%; high age: 70.7% and 88.9%; p = 0.0083 and 0.027, respectively) (low BMI: 27.2% and 64.8%; high BMI: 68.3% and 87.9%; p = 0.014 and 0.030, respectively), respectively. In the multivariate analyses, a low SMI was the only independent risk factor for secondary failure (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.04-4.44), while low age (HR 4.06, 95% CI 1.07-15.4), a low SMI (HR 4.19, 95% CI 1.01-17.3) and high MFI were risk factors for bowel resection (HR 4.31, 95% CI 1.36-13.7). Conclusion: The skeletal muscle mass and ratio of visceral to subcutaneous fat were suggested to reflect the long-term clinical outcome and may be helpful as prognostic markers after anti-TNF therapy in CD.

    DOI: 10.3389/fnut.2022.765209

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  • 【IBDの粘膜治癒を論じる!】粘膜治癒とは? 通常内視鏡、色素拡大内視鏡の観点から

    盛一 健太郎, 安藤 勝祥, 上野 伸展, 藤谷 幹浩

    IBD Research   15 ( 4 )   207 - 214   2021.12

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    近年、炎症性腸疾患(IBD)の治療目標として粘膜治癒が求められるようになってきており、粘膜治癒を評価するうえで内視鏡は欠くことのできないmodalityである。内視鏡による評価は依然として通常内視鏡観察によるものが多く、IBDの粘膜炎症評価や再燃予測に有用である。また、現在では多くの内視鏡に拡大観察機能があることから色素拡大観察での評価もおこない、その所見を付加することによりIBD、とくに潰瘍性大腸炎に対する評価能の向上が期待される。(著者抄録)

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  • A nationwide survey concerning the mortality and risk of progressing severity due to arterial and venous thromboembolism in inflammatory bowel disease in Japan.

    Katsuyoshi Ando, Mikihiro Fujiya, Kenji Watanabe, Sakiko Hiraoka, Hisashi Shiga, Shinji Tanaka, Hideki Iijima, Tsunekazu Mizushima, Taku Kobayashi, Masakazu Nagahori, Hiroki Ikeuchi, Shingo Kato, Takehiro Torisu, Kiyonori Kobayashi, Masaaki Higashiyama, Toshiro Fukui, Takashi Kagaya, Motohiro Esaki, Shunichi Yanai, Daiki Abukawa, Makoto Naganuma, Satoshi Motoya, Masayuki Saruta, Shigeki Bamba, Makoto Sasaki, Kazuhiko Uchiyama, Katsuyuki Fukuda, Hideo Suzuki, Hiroshi Nakase, Toshiaki Shimizu, Masahiro Iizuka, Mamoru Watanabe, Yasuo Suzuki, Tadakazu Hisamatsu

    Journal of gastroenterology   56 ( 12 )   1062 - 1079   2021.12

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    BACKGROUND: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. AIMS: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. METHODS: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. RESULTS: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. CONCLUSION: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed.

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  • Tumor-Progressive Mechanisms Mediating miRNA-Protein Interaction. International journal

    Hiroaki Konishi, Hiroki Sato, Kenji Takahashi, Mikihiro Fujiya

    International journal of molecular sciences   22 ( 22 )   2021.11

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    MicroRNAs (miRNAs) are single-stranded short-chain RNAs that are endogenously expressed in vertebrates; they are considered the fine-tuners of cellular protein expression that act by modifying mRNA translation. miRNAs control tissue development and differentiation, cell growth, and apoptosis in cancer and non-cancer cells. Aberrant regulation of miRNAs is involved in the pathogenesis of various diseases including cancer. Numerous investigations have shown that the changes in cellular miRNA expression in cancerous tissues and extracellular miRNAs enclosed in exosomes are correlated with cancer prognosis. Therefore, miRNAs can be used as cancer biomarkers and therapeutic targets for cancer in clinical applications. In the previous decade, miRNAs have been shown to regulate cellular functions by directly binding to proteins and mRNAs, thereby controlling cancer progression. This regulatory system implies that cancer-associated miRNAs can be applied as molecular-targeted therapy. This review discusses the roles of miRNA-protein systems in cancer progression and its future applications in cancer treatment.

    DOI: 10.3390/ijms222212303

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  • Endoscopic findings of hepatocellular carcinoma invading the duodenum. International journal

    Koji Sawada, Mikihiro Fujiya, Shunsuke Nakajima, Toshikatsu Okumura

    Japanese journal of clinical oncology   51 ( 11 )   1689 - 1690   2021.11

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    DOI: 10.1093/jjco/hyab125

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  • 【炎症性腸疾患の鑑別診断】炎症性腸疾患の画像所見と鑑別診断 敷石像,炎症性ポリポーシス,多発隆起

    佐々木 貴弘, 上野 伸展, 上原 恭子, 小林 裕, 杉山 雄哉, 村上 雄紀, 高橋 慶太郎, 安藤 勝祥, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩

    胃と腸   56 ( 12 )   1555 - 1561   2021.11

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    <文献概要>潰瘍性大腸炎やCrohn病は炎症性腸疾患と総称され,潰瘍形成と組織再生を慢性的に繰り返すことによって,多彩な内視鏡所見を呈し,診断に苦慮する症例も少なくない.本稿では,敷石像・炎症性ポリポーシス・多発隆起などの特徴的な所見に焦点を当て,炎症性腸疾患の鑑別診断について解説する.敷石像,炎症性ポリポーシス,多発隆起はいずれも背景粘膜の炎症や潰瘍,浮腫により形成される非腫瘍性の変化であり,隆起部分のみにとらわれることなく,背景粘膜の炎症や併存する縦走潰瘍の存在などの腸管全体像を正確に把握することが鑑別診断のポイントとなる.

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  • Atezolizumab+Bevacizumab併用療法で多臓器irAEsを発症した肝細胞癌の1著効例

    林 秀美, 澤田 康司, 室 和希, 大竹 晋, 本田 宗也, 太田 雄, 長谷部 拓夢, 中嶋 駿介, 岡田 充巧, 麻生 和信, 藤谷 幹浩, 齊藤 義徳, 奥村 利勝

    肝臓   62 ( Suppl.3 )   A808 - A808   2021.11

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  • 高トリグリセライド血症合併NAFLD症例に対するペマフィブラートの長期治療効果

    澤田 康司, 室 和希, 大竹 晋, 林 秀美, 太田 雄, 長谷部 拓夢, 中嶋 駿介, 岡田 充巧, 麻生 和信, 藤谷 幹浩, 奥村 利勝

    肝臓   62 ( Suppl.3 )   A732 - A732   2021.11

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  • Development of pulmonary sarcoidosis in Crohn's disease patient under infliximab biosimilar treatment after long-term original infliximab treatment: a case report and literature review. International journal

    Shin Kashima, Kentaro Moriichi, Katsuyoshi Ando, Nobuhiro Ueno, Hiroki Tanabe, Sayaka Yuzawa, Mikihiro Fujiya

    BMC gastroenterology   21 ( 1 )   373 - 373   2021.10

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    BACKGROUND: Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor inhibitors (TNF-I) are effective for the treatment. Recently, biosimilars of TNF-I, such as CT-P13, have been developed and are thought to possess equal efficacy and safety to the original TNF-I. Sarcoidosis is also a systemic granulomatous disease of unknown etiology. In steroid-resistant cases of sarcoidosis, TNF-I have been reported effective for achieving resolution. However, the progression of sarcoidosis due to the TNF-I also has been reported. We herein report a case of pulmonary sarcoidosis with a Crohn's disease (CD) patient developed after a long period administration (15 years) of TNF-I. CASE PRESENTATIONS: A 37-year-old woman with CD who had been diagnosed at 22 years old had been treated with the TNF-I (original infliximab; O-IFX and infliximab biosimilar; IFX-BS). Fifteen years after starting the TNF-I, she developed a fever and right chest pain. Chest computed tomography (CT) revealed clustered small nodules in both lungs and multiple enlarged hilar lymph nodes. Infectious diseases including tuberculosis were negative. Bronchoscopic examination was performed and the biopsy specimens were obtained. A pathological examination demonstrated noncaseating granulomatous lesions and no malignant findings. TNF-I were discontinued because of the possibility of TNF-I-related sarcoidosis. After having discontinued for four months, her symptoms and the lesions had disappeared completely. Fortunately, despite the discontinuation of TNF-I, she has maintained remission. CONCLUSIONS: To our knowledge, this is the first case in which sarcoidosis developed after switching from O-IFX to IFX-BS. To clarify the characteristics of the cases with development of sarcoidosis during administration of TNF-I, we searched PubMed and identified 106 cases. When developing an unexplained fever, asthenia, uveitis and skin lesions in patients with TNF-I treatment, sarcoidosis should be suspected. Once the diagnosis of sarcoidosis due to TNF-I was made, the discontinuation of TNF-I and administration of steroid therapy should be executed promptly. When re-starting TNF-I, another TNF-I should be used for disease control. Clinicians should be aware of the possibility of sarcoidosis in patients under anti-TNF therapy.

    DOI: 10.1186/s12876-021-01948-6

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  • Immune checkpoint inhibitor-related gastritis in a patient with metastatic melanoma

    Yuya Sugiyama, Hiroki Tanabe, Mikihiro Fujiya

    JGH Open   5 ( 10 )   1218 - 1219   2021.10

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    DOI: 10.1002/jgh3.12657

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  • 炎症性腸疾患のモニタリングと治療選択 潰瘍性大腸炎に対するウステキヌマブの実臨床での治療成績と短期有効性予測因子

    安藤 勝祥, 藤谷 幹浩, 仲瀬 裕志

    日本消化器病学会雑誌   118 ( 臨増大会 )   A652 - A652   2021.10

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  • 進行胃癌に対するニボルマブ単剤後方ライン治療の予後規定因子 旭川胃癌コホート研究

    田邊 裕貴, 田中 一之, 柳田 尚之, 垂石 正樹, 石川 千里, 上野 伸展, 嘉島 伸, 北野 陽平, 盛一 健太郎, 長谷川 公治, 谷野 美智枝, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本癌治療学会学術集会抄録集   59回   P18 - 2   2021.10

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  • Case Report: A Rare Case of Esophagogastric Junctional Squamous Cell Carcinoma After the Successful Treatment of Neuroendocrine Carcinoma: Clonal Tumor Evolution Revealed by Genetic Analysis

    Hiroki Sato, Takeshi Saito, Hiroshi Horii, Mami Kajiura, Noriaki Kikuchi, Nobuhisa Takada, Koichi Taguchi, Mika Yoshida, Masakazu Hasegawa, Hiroyuki Taguchi, Yukinori Yoshida, Katsuyoshi Ando, Mikihiro Fujiya, Yuko Omori, Thomas Hank, Andrew S. Liss, Manish A. Gala, Yoshio Makita, Yusuke Ono, Yusuke Mizukami, Toshikatsu Okumura

    Frontiers in Genetics   12   2021.9

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    Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for &amp;gt;3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed <italic>TP53</italic> Q192X mutation, whereas <italic>SMAD4</italic> S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in <italic>TP53</italic>. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the <italic>TP53</italic> gene might have occurred during the differentiation of the founder clone into NEC, while a <italic>SMAD4</italic> mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.

    DOI: 10.3389/fgene.2021.608324

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  • 術後吻合部完全狭窄に対して局注射による口側腸管造影と針状メスによる切開・穿通を併用し内視鏡的バルーン拡張術を施行した1例

    池田 淳平, 村上 雄紀, 小野田 翔, 上原 恭子, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   129回・123回   49 - 49   2021.9

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  • 抗TNF-α抗体製剤の長期投与中にサルコイドーシスを発症したクローン病患者の1例

    小野田 翔, 嘉島 伸, 池田 淳平, 上原 恭子, 小林 裕, 杉山 雄哉, 村上 雄紀, 佐々木 貴弘, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   129回・123回   29 - 29   2021.9

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  • Nivolumab/Ipilimumab併用療法により発症した免疫関連副作用(irAE)gastritisの1例

    菅井 博達, 杉山 雄哉, 小野田 翔, 池田 淳平, 上原 恭子, 小林 裕, 村上 雄紀, 佐々木 貴弘, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   129回・123回   28 - 28   2021.9

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  • 肝細胞癌における初回TACE後の予後と骨格筋低下に関する検討

    澤田 康司, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    肝臓   62 ( Suppl.2 )   A561 - A561   2021.9

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  • 胃ESD後出血リスク因子と予防的止血剤投与に関する検討

    高橋 慶太郎, 上原 恭子, 小林 裕, 杉山 雄哉, 村上 雄紀, 佐々木 貴弘, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 奥村 利勝, 藤谷 幹浩

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   129回・123回   34 - 34   2021.9

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  • Solid pseudopapillary neoplasmとの鑑別に苦慮した限局型自己免疫性膵炎の1例

    寺澤 賢, 河端 秀賢, 中田 裕隆, 佐藤 裕基, 藤林 周吾, 林 明宏, 岩本 英孝, 後藤 拓磨, 山北 圭佑, 高橋 賢治, 北野 陽平, 今井 浩二, 横尾 英樹, 上小倉 佑機, 青木 直子, 湯澤 明夏, 谷野 美智枝, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   129回・123回   43 - 43   2021.9

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  • 22年間の経過観察の後に膵全摘を行った膵管内乳頭粘液性腫瘍の1例

    中田 裕隆, 河端 秀賢, 寺澤 賢, 佐藤 裕基, 藤林 周吾, 林 明宏, 岩本 英孝, 後藤 拓磨, 山北 圭介, 高橋 賢治, 北野 陽平, 荻原 正弘, 横尾 英樹, 湯澤 明夏, 谷野 美智枝, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   129回・123回   28 - 28   2021.9

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  • 急性膵炎が診断契機となった膵臓癌の3例

    小杉 英史, 北野 陽平, 川尻 はるな, 岩本 英孝, 山北 圭介, 高橋 賢治, 大竹 晋, 太田 雄, 岡田 充巧, 麻生 和信, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   129回・123回   45 - 45   2021.9

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  • クローン病に対するウステキヌマブの実臨床での治療成績と有効性に関する指標

    安藤 勝祥, 藤谷 幹浩, 奥村 利勝

    潰瘍   48   71 - 71   2021.9

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  • Fecal calprotectin is a useful biomarker for predicting the clinical outcome of granulocyte and monocyte adsorptive apheresis in ulcerative colitis patients: a prospective observation study. International journal

    Nobuhiro Ueno, Yuya Sugiyama, Yu Kobayashi, Yuki Murakami, Takuya Iwama, Takahiro Sasaki, Takehito Kunogi, Keitaro Takahashi, Kazuyuki Tanaka, Katsuyoshi Ando, Shin Kashima, Yuhei Inaba, Kentaro Moriichi, Hiroki Tanabe, Masaki Taruishi, Yusuke Saitoh, Toshikatsu Okumura, Mikihiro Fujiya

    BMC gastroenterology   21 ( 1 )   316 - 316   2021.8

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    BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) is widely used as a remission induction therapy for active ulcerative colitis (UC) patients. However, there are no available biomarkers for predicting the clinical outcome of GMA. We investigated the utility of Fecal calprotectin (FC) as a biomarker for predicting the clinical outcome during GMA therapy in active UC patients. METHODS: In this multicenter prospective observation study, all patients received 10 sessions of GMA, twice a week, for 5 consecutive weeks. FC was measured at entry, one week, two weeks, and at the end of GMA. Colonoscopy was performed at entry and after GMA. The clinical activity was assessed based on the partial Mayo score when FC was measured. Clinical remission (CR) was defined as a partial Mayo score of ≤ 2 and endoscopic remission (ER) was defined as Mayo endoscopic subscore of either 0 or 1. We analyzed the relationships between the clinical outcome (CR and ER) and the change in FC concentration. RESULT: Twenty-six patients were included in this study. The overall CR and ER rates were 50.0% and 19.2%, respectively. After GMA, the median FC concentration in patients with ER was significantly lower than that in patients without ER (469 mg/kg vs. 3107 mg/kg, p = 0.03). When the cut-off value of FC concentration was set at 1150 mg/kg for assessing ER after GMA, the sensitivity and specificity were 0.8 and 0.81, respectively. The FC concentration had significantly decreased by one week. An ROC analysis demonstrated that the reduction rate of FC (ΔFC) at 1 week was the most accurate predictor of CR at the end of GMA (AUC = 0.852, P = 0.002). When the cut-off value of ΔFC was set at ≤ 40% at 1 week for predicting CR at the end of GMA, the sensitivity and specificity were 76.9% and 84.6%, respectively. CONCLUSION: We evaluated the utility of FC as a biomarker for assessing ER after GMA and predicting CR in the early phase during GMA in patients with active UC. Our findings will benefit patients with active UC by allowing them to avoid unnecessary invasive procedures and will help establish new strategies for GMA.

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  • The identification of rna-binding proteins functionally associated with tumor progression in gastrointestinal cancer

    Hiroaki Konishi, Shin Kashima, Takuma Goto, Katsuyoshi Ando, Aki Sakatani, Hiroki Tanaka, Nobuhiro Ueno, Kentaro Moriichi, Toshikatsu Okumura, Mikihiro Fujiya

    Cancers   13 ( 13 )   2021.7

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    Previous investigations have indicated that RNA-binding proteins (RBPs) are key molecules for the development of organs, differentiation, cell growth and apoptosis in cancer cells as well as normal cells. A bioinformatics analysis based on the mRNA expression and a somatic mutational database revealed the association between aberrant expression/mutations of RBPs and cancer progression. However, this method failed to detect functional alterations in RBPs without changes in the expression, thus leading to false negatives. To identify major tumor-associated RBPs, we constructed an siRNA library based on the database of RBPs and assessed the influence on the growth of colorectal, pancreatic and esophageal cancer cells. A comprehensive analysis of siRNA functional screening findings using 1198 siRNAs targeting 416 RBPs identified 41 RBPs in which 50% inhibition of cell growth was observed in cancer cells. Among these RBPs, 12 showed no change in the mRNA expression and no growth suppression in non-cancerous cells when downregulated by specific siRNAs. We herein report for the first time cancer-promotive RBPs identified by a novel functional assessment using an siRNA library of RBPs combined with expressional and mutational analyses.

    DOI: 10.3390/cancers13133165

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  • Clinicopathological characteristics of Epstein-Barr virus and microsatellite instability subtypes of early gastric neoplasms classified by the Japanese and the World Health Organization criteria

    Hiroki Tanabe, Yusuke Mizukami, Hidehiro Takei, Nobue Tamamura, Yuhi Omura, Yu Kobayashi, Yuki Murakami, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Sayaka Yuzawa, Kimiharu Hasegawa, Yasuo Sumi, Mishie Tanino, Mikihiro Fujiya, Toshikatsu Okumura

    JOURNAL OF PATHOLOGY CLINICAL RESEARCH   7 ( 4 )   397 - 409   2021.7

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    Gastric cancer is a heterogenous disease with different phenotypes, genotypes, and clinical outcomes, including sensitivity to treatments and prognoses. Recent medical advances have enabled the classification of this heterogenous disease into several groups and the consequent analysis of their clinicopathological characteristics. Gastric cancer associated with Epstein-Barr virus (EBV) and microsatellite-unstable tumors are considered to be the two major subtypes as they are clearly defined by well-established methodologies, such as in situ hybridization and polymerase chain reaction-based analyses, respectively. However, discrepancies in the histological diagnosis of gastric neoplasms remain problematic, and international harmonization should be performed to improve our understanding of gastric carcinogenesis. We re-evaluated Japanese cases of early gastric cancer according to the current World Health Organization (WHO) criteria and classified them into genomic subtypes based on microsatellite instability (MSI) and EBV positivity to determine the initial genetic events in gastric carcinogenesis. A total of 113 Japanese early gastric cancers (including low- and high-grade dysplasias) treated with endoscopic resection over 5 years were archived in our hospital. A histological re-evaluation according to the WHO criteria revealed 54 adenocarcinomas, which were divided into 6 EBV-positive (11.1%), 7 MSI-high (MSI-H, 13.0%), and 41 microsatellite stable cases (75.9%). MSI-H adenocarcinoma was confirmed by an immunohistochemistry assay of mismatch repair proteins. Programmed death-ligand 1 immunostaining with two antibodies (E1L3N and SP263) was positive in tumor cells of one MSI-H adenocarcinoma case (1/7, 14.3%). The proportion of stained cells was higher with clone SP263 than with E1L3N. Histologically, EBV-positive carcinomas were poorly differentiated (83.8%), and MSI-H cancers were frequent in well to moderately differentiated adenocarcinoma (85.7%), indicating that the EBV-positive subtype presented with high-grade morphology even when an early lesion. Our study indicates that the WHO criteria are useful for subdividing Japanese early gastric cancers, and this subdivision may be useful for comparative analysis of precursor lesions and early carcinoma.

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  • 【実臨床超音波学-実際の臨床で治療に直結する超音波技術-】肝癌の悪性度診断における造影3D超音波の有用性

    麻生 和信, 岡田 充巧, 玉木 陽穂, 太田 雄, 大竹 晋, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 澤田 康司, 藤谷 幹浩, 奥村 利勝

    Rad Fan   19 ( 7 )   49 - 51   2021.6

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    肝癌の悪性度診断における造影3D超音波のMPR画像の有用性について検討した。造影3Dを施行した5cm以下の切除肝細胞癌19症例23結節を対象とした。MPR画像にて不整欠損像を認めたものを非単純結節型(20/23)、それ以外を単純結節型(3/23)と判定し、切除標本との対比を行った。その結果、造影3Dの後血管像における肝癌肉眼型の正診率は100%(23/23)であった。輪郭不明瞭型の83%(10/12)は中分化型肝癌、残りの17%(3/12)は高分化型であり、低分化型肝癌は1例も認めなかった。それに対し、輪郭明瞭型では中分化型肝癌9%(1/11)、低分化型肝癌73%(8/11)、硬化型肝癌9%(1/11)、混合型肝癌9%(1/11)であり、高悪性度癌の占める割合が有意に高率であった。また、輪郭明瞭型は輪郭不明瞭型に比べ有意にKupffer phase ratioが低値を示した。さらに、対照群を中分化型肝癌と低分化型肝癌に分けて検討した。その結果、低分化型肝癌は中分化型肝癌に比べ有意にKupffer phase ratioが低値を示し、そのカットオフ値は0.34であった。

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  • Safety and efficacy of cold snare polypectomy for small colorectal polyps A prospective randomized control trial and one-year follow-up study

    Takahiro Ito, Keitaro Takahashi, Hiroki Tanabe, Keisuke Sato, Mitsuru Goto, Tomonobu Sato, Kazuyuki Tanaka, Tatsuya Utsumi, Akihiro Fujinaga, Toru Kawamoto, Nobuyuki Yanagawa, Kentaro Moriichi, Mikihiro Fujiya, Toshikatsu Okumura

    MEDICINE   100 ( 23 )   e26296   2021.6

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    Trial design: Elimination of small colorectal polyps with cold snare polypectomy (CSP) is reported to be as safe as hot snare polypectomy (HSP). The effectiveness of CSP has not been clearly defined, and the incidence of long-term recurrence has not been determined. We conducted a randomized control study and one-year follow-up study to assess their safety and efficacy. Methods: Patients with small colorectal polyps were randomized to receive CSP or HSP. Polypectomy was performed to determine the pathological curability, and patients completed a questionnaire about the tolerability of the procedure. Follow-up colonoscopy was performed to determine the local recurrence of adenoma. The major outcome was the non-inferiority of CSP to HSP in the rate of delayed bleeding and minor outcomes, including the incidence of immediate bleeding and perforation, procedural time, and the resection rate. Results: A total of 119 participants were recruited in this randomized study and underwent polypectomy. Among the 458 polyps, 332 eligible polyps were analyzed. The rate of adverse events was 0.6% (1/175) for CSP and 0% (0/157) for HSP, which showed the non-inferiority of CSP. While the complete resection rate of CSP was very high (100%), the R0 rate was not satisfactory (horizontal margin, 65.5%; vertical margin, 89.1%). Two local recurrences (2.5%) were observed in the follow-up of 80 adenomas treated with CSP. No recurrence was found in 79 lesions in the HSP group, which was not significant (P = .06). Conclusions: Colorectal polyps were safely resected using CSP, similar to HSP. Most would agree to say that CSP is considered safer than HSP. The main question is then related to efficacy. Our results of the present study demonstrate that recurrence after CSP should be carefully managed for curative treatment.

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  • 検診大腸内視鏡検査における悪性リンパ腫消化管病変の診断に有用な内視鏡所見の検討

    嘉島 伸, 盛一 健太郎, 藤谷 幹浩

    日本消化器がん検診学会雑誌   59 ( Suppl総会 )   350 - 350   2021.5

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  • 肛門科受診により発見された大腸癌の臨床的特徴

    盛一 健太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 村上 雅則, 小原 啓, 稲垣 光裕, 菱山 豊平, 鉢呂 芳一, 安部 達也, 國本 正雄, 藤谷 幹浩

    日本消化器がん検診学会雑誌   59 ( Suppl総会 )   350 - 350   2021.5

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  • 小SMT様隆起を呈した多発胃底腺型胃癌の1例

    村上 雄紀, 高橋 慶太郎, 藤谷 幹浩, 堀内 正史, 上原 聡人, 上原 恭子, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 久野木 健仁, 安藤 勝祥, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝, 上野 伸展

    Gastroenterological Endoscopy   63 ( Suppl.1 )   908 - 908   2021.4

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  • The Optimal Dose of Tacrolimus in Combination Therapy with an Anti-TNF alpha Antibody in a Mouse Colitis Model

    Yuki Murakami, Mikihiro Fujiya, Hiroaki Konishi, Shotaro Isozaki, Yuya Sugiyama, Yu Kobayashi, Takahiro Sasaki, Takehito Kunogi, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   44 ( 4 )   564 - 570   2021.4

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    An attempt to use combination therapy with anti-tumor necrosis factor alpha (TNF alpha) antibodies and tacrolimus (TAC) has been tried to induce remission in ulcerative colitis (UC). However, the optimal dose of TAC in combination therapy with anti-TNF alpha antibodies (TAC + anti-TNF alpha therapy) remains unclear. We examined the efficacy of various doses of TAC + anti-TNF alpha therapy in a mouse colitis model. Dextran sulfate sodium induced colitis model mice were divided into an anti-TNF alpha antibody monotherapy group and the groups that received various doses of TAC + anti-TNF alpha therapy. The nuclear factor expression of activated T-cells, cytoplasmic 1 (NFATc1) in the nuclei and the mRNA expression of inflammatory cytokines were assessed by immunohistochemistry and RT-PCR, respectively. The serum anti-TNF alpha antibody concentration was measured with an enzyme-linked immunosorbent assay. The colon length and histological severity were significantly improved in the groups that received any dose of TAC + anti-TNF alpha therapy. The nuclear expression of NFATc1 was inversely proportional to the administered doses of TAC. The expression levels of inflammatory cytokines tended to decrease in proportion to the dose of TAC. The serum concentration of anti-TNF alpha antibodies in the high-dose TAC + anti-TNF alpha therapy was significantly higher than those in the other groups. Low-dose TAC exerted its immunosuppressive effect on T-cells, and additionally, high-dose TAC maintained the serum anti-TNF alpha antibody concentration. When administered in combination with anti-TNF alpha antibodies, the dose of TAC should be adjusted according to the disease severity.

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  • Successful Treatment of Myeloid Sarcoma in an Elderly Patient with Myelodysplastic Syndrome with Reduced-Dose Azacitidine

    Kazuya Sato, Nodoka Tsukada, Junki Inamura, Shigetsuna Komatsu, Keisuke Sato, Masayo Yamamoto, Motohiro Shindo, Kentaro Moriichi, Yusuke Mizukami, Mikihiro Fujiya, Yoshihiro Torimoto, Toshikatsu Okumura

    CASE REPORTS IN HEMATOLOGY   2021   2021.4

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    Myeloid sarcoma (MS), which involves extramedullary lesions, is classified as a unique subtype of acute myeloid leukemia (AML). At present, no standard treatments for MS have been established. The patient was an 89-year-old man with myelodysplastic syndrome-excess blast-2 (MDS-EB-2) with a 2-year history of intermittent treatment with azacitidine (AZA) during a 4-year history of MDS. He developed painful cutaneous tumors 8 months after the second discontinuation of AZA. They were refractory for antibiotics and topical tacrolimus hydrate. A tumor biopsy was performed, and the histological findings of the tumor lesion showed a proliferation of tumor cells that were positive for myeloperoxidase and CD68 and negative for CD4 and CD123. The patient was diagnosed with MDS-associated MS. MDS-EB-2 quickly progressed to AML with the appearance of peripheral blood blasts and 25% bone marrow blasts. Monotherapy with reduced-dose AZA (37.5 mg/m(2) for 7 days, every 4-6 weeks) was restarted, and the MS quickly disappeared. The patient's MS was successfully treated with 16 cycles of AZA treatment over a 22-month period. There have been 10 reported cases in which MS was successfully treated with AZA. Among the 10 cases, the patient in the present case was the oldest. Treatment with reduced-dose AZA should be considered as a therapeutic option for MS in elderly patients with MDS, especially patients who are ineligible for intensive chemotherapy.

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  • 反復する回腸末端炎を契機に診断に至ったMEFV遺伝子変異陰性家族性地中海熱の一例

    関口 竣也, 安藤 勝祥, 粂井 志麻, 上原 聡人, 上原 恭子, 小林 裕, 杉山 雄哉, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   128回・122回   43 - 43   2021.3

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  • Probiotic-Derived Polyphosphate Accelerates Intestinal Epithelia Wound Healing through Inducing Platelet-Derived Mediators

    Shotaro Isozaki, Hiroaki Konishi, Mikihiro Fujiya, Hiroki Tanaka, Yuki Murakami, Shin Kashima, Katsuyoshi Ando, Nobuhiro Ueno, Kentaro Moriichi, Toshikatsu Okumura

    MEDIATORS OF INFLAMMATION   2021   2021.3

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    Inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD), is an intractable intestinal inflammation associated with the disruption of the intestinal mucosa. We previously demonstrated that Lactobacillus brevis-derived long-chain polyphosphate (poly P) improved the intestinal barrier function by the upregulation of cell adhesion and relieved intestinal inflammation, thereby exerting a curing effect on colitis in vitro, in vivo, and in an investigator-initiated clinical study of UC. However, how poly P improves mucosal defects induced by intestinal inflammation has not been elucidated. In this study, we detected the accumulation of platelets in inflamed tissues induced by poly P in a dextran sulfate sodium- (DSS-) induced colitis mouse model. A light transmission aggregometry analysis and scanning electron microscopy showed that poly P promoted the platelet aggregation. An SRB assay and ki-67 staining showed that the supernatant of poly P-treated platelet-rich plasma (PRP) increased intestinal epithelial cell growth. A wound healing assay showed that the supernatant of poly P-treated PRP, but not poly P itself, accelerated wound healing. A Western blotting analysis indicated that mitogen-activated protein kinase activation was induced by the supernatant of poly P-treated human PRP in the epithelial cells and its wound healing effect was significantly decreased by the inhibition of ERK signaling. These data suggested that platelet-derived mediators induced by poly P improved intestinal inflammation through the promotion of epithelial cell growth by the activation of the ERK signaling pathway. The mechanism is a novel host-microbe interaction through mammalian platelet-derived mediators induced by bacterial molecules.

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  • IBDのトータルマネージメント 血栓症発症例や手術例からみた炎症性腸疾患入院患者のマネジメント

    安藤 勝祥, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   118 ( 臨増総会 )   A61 - A61   2021.3

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  • 大腸ESDにおけるリドカイン粘膜下局注の蠕動抑制効果に関する前向きランダム化比較試験

    佐々木 貴弘, 小林 裕, 杉山 雄哉, 村上 雄紀, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本大腸肛門病学会雑誌   74 ( 3 )   196 - 196   2021.3

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  • 脂肪性肝疾患:新規治療法を目指した基礎研究とトランスレーショナルリサーチ Lactobacillus brevis SBC8803のNAFLD改善効果の解析

    林 秀美, 澤田 康司, 藤谷 幹浩

    日本消化器病学会雑誌   118 ( 臨増総会 )   A222 - A222   2021.3

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  • 乳酸菌由来長鎖ポリリン酸は上皮インテグリンβ1活性化を介して腸炎治療効果を発揮する

    小西 弘晃, 嘉島 伸, 磯崎 翔太郎, 山村 千景, 奥村 利勝, 藤谷 幹浩

    日本薬学会年会要旨集   141年会   27V05 - pm07   2021.3

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  • Long-term Observation of Gastric Adenocarcinoma of Fundic Gland Mucosa Type before and after Helicobacter pylori Eradication: a Case Report

    Keitaro Takahashi, Nobuhiro Ueno, Takahiro Sasaki, Yu Kobayashi, Yuya Sugiyama, Yuki Murakami, Takehito Kunogi, Katsuyoshi Ando, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Yuki Kamikokura, Sayaka Yuzawa, Mishie Tanino, Toshikatsu Okumura, Mikihiro Fujiya

    JOURNAL OF GASTRIC CANCER   21 ( 1 )   103 - 109   2021.3

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    Gastric adenocarcinoma of the fundic gland mucosa type (GA-FGM) was proposed as a new variant of gastric adenocarcinoma of the fundic gland type (GA-FG). However, at present, the influence of Helicobacter pylori and the speed of progression and degree of malignancy in GA-FGM remain unclear. Herein, we report the first case of intramucosal GA-FGM that was endoscopically observed before and after H. pylori eradication over 15 years. The lesion showed the same tumor size with no submucosal invasion and a low MIB-1 labeling index 15 years after its detection using endoscopy. The endoscopic morphology changed from 0-IIa before H. pylori eradication to 0-IIa+IIc and then 0-I after H. pylori eradication. These findings suggest that the unaltered tumor size reflects low-grade malignancy and slow growth, and that the endoscopic morphology is influenced by H. pylori eradication.

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  • Endoscopic finding of a lace pattern in a case of Epstein-Barr virus-associated early gastric carcinoma

    Yu Kobayashi, Hiroki Tanabe, Katsuyoshi Ando, Mikihiro Fujiya, Toshikatsu Okumura

    GASTROINTESTINAL ENDOSCOPY   93 ( 3 )   768 - 769   2021.3

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    DOI: 10.1016/j.gie.2020.10.008

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  • 切除不能膵癌化学療法例において骨格筋量低下は予後不良因子である

    佐藤 裕基, 水上 裕輔, 藤谷 幹浩, 岡田 哲弘, 藤林 周吾, 河端 秀賢, 林 明宏, 後藤 拓磨, 小野 裕介, 杉谷 歩, 奥村 利勝

    日本消化器病学会雑誌   118 ( 臨増総会 )   A353 - A353   2021.3

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  • 切除不能膵癌化学療法例において骨格筋量低下は予後不良因子である

    佐藤 裕基, 水上 裕輔, 藤谷 幹浩, 岡田 哲弘, 藤林 周吾, 河端 秀賢, 林 明宏, 後藤 拓磨, 小野 裕介, 杉谷 歩, 奥村 利勝

    日本消化器病学会雑誌   118 ( 臨増総会 )   A353 - A353   2021.3

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  • Gel Immersion EndoscopyがEndoscopic Band Ligation(EBL)法の視野確保に有用であった下部消化管出血の2例

    上原 聡人, 小林 裕, 堀内 正史, 上原 恭子, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   128回・122回   60 - 60   2021.3

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  • びまん性発赤の画像解析による客観的評価の検討

    野村 好紀, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 藤谷 幹浩

    日本消化器がん検診学会雑誌   59 ( 1 )   42 - 48   2021.1

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    びまん性発赤(以下、DR)は、Helicobacter pylori(以下、H.pylori)現感染を強く示唆する内視鏡所見であるが、機器の設定や内視鏡施行医の主観により判断が異なる問題点がある。そこで、画像解析ソフトによるDR数値化の有用性を検討した。上部消化管内視鏡検査及びH.pylori検査を行った115例を対象に、6名の内視鏡医(内視鏡専門医3名、非専門医3名)により後方視的に内視鏡画像でDR判定一致率(κ値)及びH.pylori判定正診率を検討したところ、前庭部と体部大彎の2画像評価では、一致率、正診率は0.31、55.8%、全画像評価の場合は、それぞれ0.43、67.7%と全画像評価で一致率が高く、H.pylori正診率も有意に高かった。非専門医と専門医で一致率、正診率を比較したところいずれも専門医が高かった。解析ソフトでDRを数値化した場合、一致率が0.93と最も高い結果であった。H.pylori正診率は64.1%と2画像評価より有意に高い結果であり、全画像評価と有意差は認めなかった。画像解析によるDRの数値化は内視鏡医間の一致率が向上することから検診での応用が期待される。(著者抄録)

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J04447&link_issn=&doc_id=20210125350004&doc_link_id=10.11404%2Fjsgcs.59.42&url=https%3A%2F%2Fdoi.org%2F10.11404%2Fjsgcs.59.42&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

  • 炎症性消化管疾患の最前線 多様化する炎症性腸疾患の治療戦略-外科手術も含めて- 炎症性腸疾患におけるインフリキシマブバイオシミラーの使用成績

    村上 雄紀, 安藤 勝祥, 齊藤 成亮, 上原 恭子, 小林 裕, 杉山 雄哉, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化管学会雑誌   5 ( Suppl. )   151 - 151   2021.1

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  • Rare case of fecal impaction caused by a fecalith originating in a large colonic diverticulum: A case report

    Hiroki Tanabe, Kazuyuki Tanaka, Mitsuru Goto, Tomonobu Sato, Keisuke Sato, Mikihiro Fujiya, Toshikatsu Okumura

    WORLD JOURNAL OF CLINICAL CASES   9 ( 2 )   416 - 421   2021.1

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    BACKGROUND Fecal impaction is defined as a large mass of compacted feces in the colon and has the potential to induce a serious medical condition in elderly individuals. Fecal impaction is generally preventable, and early recognition of the typical radiological findings is important for making an early diagnosis. The factors that lead to fecal impaction are usually similar to those causing constipation. Few cases with fecal impaction associated with a diverticulum have been reported.CASE SUMMARY We present the case of a 62-year-old woman who suffered from abdominal pain and vomiting, had a medical history of repeated acute abdomen and was diagnosed with fecal impaction in the descending colon based on X-ray and computed tomography (CT) imaging. After examination by gastrografin-enhanced colonography following colonoscopy and CT colonography, the fecalith was suspected to have been produced at the site of a large diverticulum in the transverse colon. The fecalith was surgically resected, and a histological diagnosis of pseudodiverticulum was made. There was no recurrence during 33 mo of follow-up.CONCLUSION This case highlights the importance of accurate identification and treatment of a fecal impaction. This case indicated that the endoscopic evacuation and subsequent colonography were effective for identifying a diverticulum that might have caused fecal impaction. A fecal impaction was associated with the diverticulum. Consequently, the planned diverticulectomy was performed. Appropriate emergency medical treatment and maintenance treatments should be selected in such cases to prevent recurrence.

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  • Polyphosphate, Derived from Lactobacillus brevis, Modulates the Intestinal Microbiome and Attenuates Acute Pancreatitis

    Shuhei Takauji, Hiroaki Konishi, Mikihiro Fujiya, Nobuhiro Ueno, Hiroki Tanaka, Hiroki Sato, Shotaro Isozaki, Shin Kashima, Kentaro Moriichi, Yusuke Mizukami, Toshikatsu Okumura

    DIGESTIVE DISEASES AND SCIENCES   2021.1

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    Background We previously showed that Lactobacillus brevis-derived polyphosphate (poly P) exerts a curative effect on intestinal inflammation. However, whether or not poly P improves the inflammation and injury of distant organs remains unclear. Aims We aimed to investigate the change in the intestinal microbiome and to evaluate the protective effect of poly P on injuries in a cerulein-induced acute pancreatitis (AP) mouse. Methods Poly P was orally administered to BALB/C mice every day for 24 days, and then mice were intraperitoneally injected with cerulein. Before cerulein injection, stool samples were collected and analyzed by 16S rRNA gene sequencing. Mice were sacrificed at 24 h after the last cerulein injection; subsequently, the serum, pancreas, and colon were collected. Results The microbial profile differed markedly between poly P and control group. Notably, the levels of beneficial bacteria, including Alistipes and Candidatus_Saccharimonas, were significantly increased, while those of the virulent bacteria Desulfovibrio were decreased in the poly P group. The elevations of the serum amylase and lipase levels by cerulein treatment were suppressed by the pre-administration of poly P for 24 days, but not for 7 days. The numbers of cells MPO-positive by immunohistology were decreased and the levels of MCP-1 significantly reduced in the AP + Poly P group. An immunofluorescence analysis showed that the ZO-1 and occludin in the colon was strongly augmented in the epithelial cell membrane layer in the AP + Poly P group. Conclusions Poly P attenuates AP through both modification of the intestinal microbiome and enhancement of the intestinal barrier integrity.

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  • Long Non-Coding RNAs in Epithelial-Mesenchymal Transition of Pancreatic Cancer. International journal

    Kenji Takahashi, Kenzui Taniue, Yusuke Ono, Mikihiro Fujiya, Yusuke Mizukami, Toshikatsu Okumura

    Frontiers in molecular biosciences   8   717890 - 717890   2021

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    Non-coding RNAs (ncRNAs), or RNA molecules that do not code for proteins, are generally categorized as either small or long ncRNA (lncRNA) and are involved in the pathogenesis of several diseases including many cancers. Identification of a large number of ncRNAs could help to elucidate previously unknown mechanisms in phenotype regulation. Some ncRNAs are encapsulated by extracellular vesicles (EVs) and transferred to recipient cells to regulate cellular processes, including epigenetic and post-transcriptional regulations. Recent studies have uncovered novel molecular mechanisms and functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC), one of the most intractable cancers that is highly invasive and metastatic. As the epithelial-mesenchymal transition (EMT) triggers tumor cell invasion and migration, clarification of the roles of lncRNA in EMT and tumor cell stemness would be critical for improving diagnostic and therapeutic approaches in metastatic cancers. This review provides an overview of relevant studies on lncRNA and its involvement with EMT in PDAC. Emerging knowledge offers evidence for the dysregulated expression of lncRNAs and essential insights into the potential contribution of both lncRNAs and EVs in the pathogenesis of PDAC. Future directions and new clinical applications for PDAC are also discussed.

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  • A Gastric Submucosal Polypoid Lesion With Whitish Protuberance

    Shin Kashima, Mikihiro Fujiya, Takuma Goto

    Clinical Gastroenterology and Hepatology   2021

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    DOI: 10.1016/j.cgh.2020.08.039

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  • Colorectum: White-light and chromoendoscopy

    Yusuke Saitoh, Mikihiro Fujiya

    Digestive Endoscopy   2021

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    DOI: 10.1111/den.14150

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  • Prognostic significance of skeletal muscle decrease in unresectable pancreatic cancer: Survival analysis using the Weibull exponential distribution model

    Hiroki Sato, Takuma Goto, Akihiro Hayashi, Hidemasa Kawabata, Tetsuhiro Okada, Shuhei Takauji, Junpei Sasajima, Katsuro Enomoto, Mikihiro Fujiya, Kyohei Oyama, Yusuke Ono, Ayumu Sugitani, Yusuke Mizukami, Toshikatsu Okumura

    Pancreatology   2021

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    Background/objectives: Decrease in skeletal muscle mass and function is associated with a poor prognosis following surgical resection of pancreatic ductal adenocarcinomas (PDAs). This study evaluated whether skeletal muscle mass decrease affects PDA outcomes. Methods: Data of 112 patients with advanced and unresectable PDA who underwent chemotherapy in a single institution were retrospectively analyzed. Information on age, sex, hematological investigations, including systemic inflammation-based markers and nutritional assessment biomarkers, and imaging parameters of skeletal muscle mass and visceral adipose tissue were retrieved from the patients’ medical records. The efficiency of the Cox, Weibull, and standardized exponential models were compared using hazard ratios and the Akaike Information Criterion (AIC). Results: Results from the Weibull, Cox, and standardized exponential model analyses indicated that low skeletal muscle mass, Eastern Cooperative Oncology Group performance status (PS), and the requirement of biliary drainage were associated with the highest risk of death, followed by carcinoembryonic antigen (CEA) levels and the presence of ascites. The AIC value from the four significant parameters was lowest for the Weibull-exponential distribution (222.3) than that of the Cox (653.7) and standardized exponential models (265.7). We developed a model for estimating the 1-year survival probability using the Weibull-exponential distribution. Conclusions: Low-skeletal muscle index, PS, requirement of biliary drainage, CEA levels, and presence of ascites are independent factors for predicting poor patient survival after chemotherapy. Improved survival modeling using a parametric approach may accurately predict the outcome of patients with advanced-stage PDA.

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  • Cardiac Metastasis Caused Fatal Ventricular Arrhythmia in a Patient with a Rectal Neuroendocrine Tumor

    Katsuyoshi Ando, Mikihiro Fujiya, Moe Yoshida, Yu Kobayashi, Yuya Sugiyama, Yuki Murakami, Takuya Iwama, Hiroki Sato, Takahiro Sasaki, Takehito Kunogi, Keitaro Takahashi, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura

    INTERNAL MEDICINE   60 ( 3 )   373 - 378   2021

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    A 60-year-old man had received octreotide for a metastatic neuroendocrine tumor (NET) in the rectum. Computed tomography and ultrasonography revealed a cardiac tumor, diffuse thickness of the ventricular wall and pericardial effusion, which was diagnosed as cardiac metastasis. The metastatic lesions continued to grow despite the alteration of chemotherapy, and the patient complained of repeated syncope and was admitted to our hospital at 11 months after the diagnosis of cardiac metastasis. An electrocardiogram during syncope showed sustained ventricular tachycardia, which was considered to be caused by the cardiac metastasis. We herein report a case of NET with cardiac metastasis which caused lethal arrhythmia along with a review of the pertinent literature.

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  • Genetic background of mesalamine-induced fever and diarrhea in Japanese patients with inflammatory bowel disease. Reviewed

    Suzuki K., Kakuta Y., Naito T., Takagawa T., Hanai H., Araki H., Sasaki Y., Sakuraba H., Sasaki M., Hisamatsu T., Motoya S., Matsumoto T., Onodera M., Ishiguro Y., Nakase H., Andoh A., Hiraoka S., Shinozaki M., Fujii T., Katsurada T., Kobayashi T., Fujiya M., Otsuka T., Oshima N., Suzuki Y., Sato Y., Hokari R., Noguchi M., Ohta Y., Matsuura M., Kawai Y., Tokunaga K., Nagasaki M., Kudo H., Minegishi N., Okamoto D., Shimoyama Y., Moroi R., Kuroha M., Shiga H., Li D., McGovern DPB, KinouchiY., Masamune A.

    Inflammatory Bowel Diseases   2021

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  • Digital PCR-based plasma cell-free DNA mutation analysis for early-stage pancreatic tumor diagnosis and surveillance

    Tetsuhiro Okada, Yusuke Mizukami, Yusuke Ono, Hiroki Sato, Akihiro Hayashi, Hidemasa Kawabata, Kazuya Koizumi, Sakue Masuda, Shinichi Teshima, Kuniyuki Takahashi, Akio Katanuma, Yuko Omori, Hirotoshi Iwano, Masataka Yamada, Tomoki Yokochi, Shingo Asahara, Kazumichi Kawakubo, Masaki Kuwatani, Naoya Sakamoto, Katsuro Enomoto, Takuma Goto, Junpei Sasajima, Mikihiro Fujiya, Jun Ueda, Seiji Matsumoto, Kenzui Taniue, Ayumu Sugitani, Hidenori Karasaki, Toshikatsu Okumura

    JOURNAL OF GASTROENTEROLOGY   55 ( 12 )   1183 - 1193   2020.12

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    Background Cell-free DNA (cfDNA) shed from tumors into the circulation offers a tool for cancer detection. Here, we evaluated the feasibility of cfDNA measurement and utility of digital PCR (dPCR)-based assays, which reduce subsampling error, for diagnosing pancreatic ductal adenocarcinoma (PDA) and surveillance of intraductal papillary mucinous neoplasm (IPMN). Methods We collected plasma from seven institutions for cfDNA measurements. Hot-spot mutations inKRASandGNASin the cfDNA from patients with PDA (n = 96), undergoing surveillance for IPMN (n = 112), and normal controls (n = 76) were evaluated using pre-amplification dPCR. Results Upon Qubit measurement and copy number assessment of hemoglobin-subunit (HBB) and mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in plasma cfDNA,HBBoffered the best resolution between patients with PDA relative to healthy subjects [area under the curve (AUC) 0.862], whereasMT-ND1revealed significant differences between IPMN and controls (AUC 0.851). DPCR utilizing pre-amplification cfDNA afforded accurate tumor-derived mutantKRASdetection in plasma in resectable PDA (AUC 0.861-0.876) and improved post-resection recurrence prediction [hazard ratio (HR) 3.179, 95% confidence interval (CI) 1.025-9.859] over that for the marker CA19-9 (HR 1.464; 95% CI 0.674-3.181). CapturingKRASandGNAScould also provide genetic evidence in patients with IPMN-associated PDA and undergoing pancreatic surveillance. Conclusions Plasma cfDNA quantification by distinct measurements is useful to predict tumor burden. Through appropriate methods, dPCR-mediated mutation detection in patients with localized PDA and IPMN likely to progress to invasive carcinoma is feasible and complements conventional biomarkers.

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  • High Response Rate and Prolonged Survival of Unresectable Biliary Tract Cancer Treated With a New Combination Therapy Consisting of Intraarterial Chemotherapy Plus Radiotherapy

    Takuma Goto, Hiroya Saito, Junpei Sasajima, Toru Kawamoto, Akihiro Fujinaga, Tatsuya Utsumi, Nubuyuki Yanagawa, Kazuhide Hiramatsu, Akio Takamura, Hiroki Sato, Shugo Fujibayashi, Mikihiro Fujiya

    FRONTIERS IN ONCOLOGY   10   2020.11

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    SynopsisA new combination therapy consisting of intraarterial chemotherapy plus radiotherapy was demonstrated to have the potential to improve the response rate and survival time in patients with unresectable biliary tract cancer.PurposeWe retrospectively investigated the effectiveness and safety of a new combination therapy consisting of intraarterial chemotherapy plus radiation therapy (AI+RT), which may have the potential to improve unresectable biliary tract cancer (BTC).MethodsWe retrospectively reviewed 52 BTC cases treated with AI+RT and analyzed the anti-tumor effect, survival time and adverse events. The AI+RT regimen consisted of one-shot intraarterial chemotherapy (AI) at the first angiography session, almost 6 months of reservoir AI (5-FU and cisplatin, q/week) and external radiation with a maximum dose of 50.6 Gy.ResultsThe response rate and disease control rate were high, at 40.4% and 96.2%, respectively, and the median overall and progression-free survival time were 463 and 431 days; thus, long-term survival was achieved. A univariate analysis identified 12 prognostic factors, and a performance status of 2 (hazard ratio [HR]: 4.82, p=0.02), jaundice (HR: 3.22, p<0.01), peritoneal dissemination (HR: 22.5, p<0.01), number of AI (HR: 0.35, p=0.01) and response to AI+RT (HR: 0.23, p<0.01) were extracted as significant prognostic factors in a multivariate analysis. The following: grade >= 3 adverse events occurred: leucopenia (11.5%), neutropenia (1.9%), anemia (15.4%), thrombocytopenia (11.5%), anorexia (3.8%), gastroduodenal ulcer (25.0%), and cholangitis (23.1%). There were no cases of treatment-related death.ConclusionsAI+RT was shown to contribute to a high response rate and prolonged survival in patients with unresectable BTC. A sufficient number of AI and the response to this therapy were thought to be significant prognostic factors in patients receiving AI+RT. Advances in multidisciplinary therapies, such as AI+RT, which was described in the present study, are also considered to be important for the future.

    DOI: 10.3389/fonc.2020.597813

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  • 【基礎と臨床から炎症性腸疾患を診る】炎症性腸疾患の内科治療 新規治療の作用機序を学び、臨床に生かす!

    安藤 勝祥, 上野 伸展, 藤谷 幹浩

    Pharma Medica   38 ( 11 )   37 - 42   2020.11

  • 肝細胞癌におけるサルコペニア肥満とTACEの予後に関する検討

    澤田 康司, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    肝臓   61 ( Suppl.3 )   A900 - A900   2020.11

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  • THE EFFECTS AND UNDERLING MECHANISMS OF LACTOBACILLUS BREVIS SBC8803 MONOTHERAPY ON A MOUSE MODEL OF NON-ALCOHOLIC FATTY LIVER DISEASE

    Koji Sawada, Hiroki Tanaka, Hidemi Hayashi, Takumu Hasebe, Shunsuke Nakajima, Mikihiro Fujiya, Toshikatsu Okumura

    HEPATOLOGY   72   350A - 350A   2020.11

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  • Long-term clinical effectiveness of ustekinumab in patients with Crohn’s disease: A retrospective cohort study

    Takahiro Ito, Atsuo Maemoto, Takehiko Katsurada, Hiroki Tanaka, Satoshi Motoya, Nobuhiro Ueno, Mikihiro Fujiya, Toshifumi Ashida, Daisuke Hirayama, Hiroshi Nakase

    Crohn's and Colitis 360   2 ( 4 )   1 - 9   2020.10

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    Background: This study clarifies the long-term effectiveness of ustekinumab based on real-life data from Japanese Crohn’s disease (CD) patients. Methods: A total of 137 patients were included, and 124 patients (90.5%) were exposed to anti-tumor necrosis factor-α agents. Results: The clinical remission rate at week 52 was 32.4% in moderate to severely active CD patients. The achievement of clinical remission for 8 weeks after ustekinumab therapy induction was associated with clinical remission at week 52. Ustekinumab persistence rate at week 104 was 81.4%. Conclusion: Ustekinumab is effective and persistent in CD patients with the previous treatment history of several biologics.

    DOI: 10.1093/crocol/otaa061

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  • 潰瘍性大腸炎の発症年齢層別の臨床経過からみた病態の検討

    杉山 雄哉, 上野 伸展, 齊藤 成亮, 上原 恭子, 小林 裕, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127回・121回   27 - 27   2020.10

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  • 筋肉量と脂肪量からみたクローン病に対する抗TNF-α抗体投与後の長期経過

    安藤 勝祥, 小林 裕, 杉山 雄哉, 村上 雄樹, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   117 ( 臨増大会 )   A746 - A746   2020.10

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  • 早期胃癌におけるサブタイプ解析 Microsatellite instability and Epstein-Barr virus subtype

    田邊 裕貴, 水上 裕輔, 小林 裕, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   117 ( 臨増大会 )   A737 - A737   2020.10

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  • 難治性過敏性腸症候群として紹介された家族性地中海熱の1例

    川上 ひかる, 植村 洋紀, 石王 応知, 村上 雄紀, 粂井 志麻, 安藤 勝祥, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127回・121回   36 - 36   2020.10

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  • Serrated adenomas with a BRAF mutation in a young patient with familial adenomatous polyposis Reviewed International journal

    Kentaro Moriichi, Hiroki Tanabe, Yusuke Ono, Yu Kobayashi, Yuki Murakami, Takuya Iwama, Takehito Kunogi, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Hidehiro Takei, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE   35 ( 10 )   1967 - 1972   2020.10

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    Introduction Familial adenomatous polyposis (FAP) is typically characterized by more than hundred adenomatous polyps in the colorectum, caused by germline APC mutation. A small proportion of the polyps progress to colorectal adenocarcinoma via adenoma-carcinoma sequence. Serrated lesions and polyps, characterized by a serrated architecture of the epithelium, are noted for two types of genetic pathways in colorectal carcinogenesis. BRAF and KRAS mutations are observed in the serrated pathway. Case Report We report a young FAP patient with rectal serrated adenomas that were removed by colonoscopic procedures. The histological features with villiform projections and slit-like serration indicated traditional serrated adenoma. A genetic examination with next-generation sequencing showed a somatic BRAF mutation in the serrated adenoma and APC mutations in the tubular adenomas. His germline mutation was found at APC p.Q1928fs*. Conclusion Serrated adenomas with dual genetic alterations in a FAP patient may be associated with colorectal carcinogenesis and should be considered a target lesion for treatment. The present study demonstrated the malignant potential of serrated adenoma in a FAP patient.

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  • プロバイオティクス由来フェリクロームは大腸癌細胞に対して抗腫瘍効果を発揮する

    小西 弘晃, 藤谷 幹浩, 田中 宏樹, 奥村 利勝

    日本癌学会総会記事   79回   OJ17 - 1   2020.10

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  • 小腸検査法の進歩:小腸内視鏡、カプセル内視鏡、SIBO、Leaky gut 無症候期のクローン病におけるカプセル内視鏡所見と便中カルプロテクチンの相関性と再燃予測に関する検討

    杉山 雄哉, 上野 伸展, 齊藤 成亮, 上原 恭子, 小林 裕, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 嘉島 伸, 盛一 健太郎, 田邉 裕貴, 藤谷 幹浩, 奥村 利勝

    日本小腸学会学術集会プログラム・抄録集   58回   48 - 48   2020.10

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  • サイトメガロウイルス初感染により難治化した潰瘍性大腸炎の1例

    臺 一樹, 安藤 勝祥, 齊藤 成亮, 杉山 雄哉, 小林 裕, 村上 雄紀, 久野木 健仁, 佐々木 貴弘, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127回・121回   63 - 63   2020.10

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  • 長期経過観察後にESDで一括切除した胃底腺粘膜型胃癌の1例

    齊藤 成亮, 高橋 慶太郎, 上原 恭子, 小林 裕, 杉山 雄哉, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127回・121回   50 - 50   2020.10

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  • 家族性大腸腺腫症患者に見られた大腸鋸歯状病変の1例

    入部 航平, 盛一 健太郎, 田邊 裕貴, 武井 英博, 斎藤 成亮, 杉山 雄哉, 小林 裕, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 安藤 勝祥, 上野 伸展, 嘉島 伸, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127回・121回   34 - 34   2020.10

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  • 食道アカラシアに対する経口内視鏡的筋層切開術(Per Oral Endoscopic Myotomy:POEM)導入後の短期治療成績

    高橋 慶太郎, 藤谷 幹浩, 上原 恭子, 小林 裕, 杉山 雄哉, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   127回・121回   32 - 32   2020.10

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  • 当院で経験した免疫チェックポイント阻害薬による肝障害の特徴

    林 秀美, 澤田 康司, 中嶋 駿介, 長谷部 拓夢, 藤谷 幹浩, 奥村 利勝

    肝臓   61 ( Suppl.2 )   A704 - A704   2020.9

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  • Genetic alteration of colorectal adenoma-carcinoma sequence among gastric adenocarcinoma and dysplastic lesions in a patient with attenuated familial adenomatous polyposis Reviewed

    Hiroki Tanabe, Kentaro Moriichi, Keitaro Takahashi, Yusuke Ono, Yu Kobayashi, Yuki Murakami, Takuya Iwama, Takehito Kunogi, Takahiro Sasaki, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Hidehiro Takei, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    MOLECULAR GENETICS & GENOMIC MEDICINE   8 ( 9 )   2020.9

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    Background Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and adenocarcinoma that is frequently accompanied by extracolonic neoplasm. The risk of gastric carcinoma is increasing in Western FAP patients as well as Asian patients. Methods We report the case of an FAP patient with fundic gland polyposis who developed gastric adenocarcinoma and metachronous pyloric gland adenomas. These tumors were endoscopically resected, and immunohistochemistry with gastric mucin (i.e., MUC6, MUC5AC) showed that the tumors belonged to the gastric subtype. Somatic mutation profiles were determined by target amplicon sequencing using a next-generation sequencer. Results GermlineAPCvariant c.5782delC was found by direct sequencing and somaticKRASmutations in these tumors were identified by next-generation sequencing. DifferentKRASmutation alleles (KRASp.Gly12Ala, p.Gly12Arg, and p.Gly12Asp) indicated these dysplastic lesions developed from a distinct origin in fundic gland polyposis. Sequential mutations of theAPCandKRASwere judged-based on a database search-to be characteristic of the adenoma-carcinoma sequence in colorectal carcinogenesis. Conclusion The colonic adenoma-carcinoma sequence among gastric adenocarcinoma and dysplastic lesions was indicated in FAP-associated gastric carcinogenesis.

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  • Endoscopic findings of gastric mixed adenoneuroendocrine carcinoma A case report

    Keitaro Takahashi, Mikihiro Fujiya, Takahiro Sasaki, Yuya Sugiyama, Yuki Murakami, Takuya Iwama, Takehito Kunogi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Sayaka Yuzawa, Hidehiro Takei, Toshikatsu Okumura

    MEDICINE   99 ( 38 )   2020.9

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    Rationale: Gastric mixed adenoneuroendocrine carcinoma (gMANEC) is a rare malignant tumor. Most gMANECs are diagnosed at an advanced stage and have a worse prognosis than gastric adenocarcinoma. In order to improve the prognosis, it is necessary to diagnose gMANEC at an early stage. However, the endoscopic features of early gMANECs are unclear. We, herein, report a case of early gMANEC that showed characteristic magnifying endoscopic findings. Patient concerns: A 78-year-old man was referred to our institution for endoscopic resection of a gastric lesion. He had a medical history of distal gastrectomy due to early gastric cancer with negative surgical margins 9 years previously. Diagnosis: Esophagogastroduodenoscopy showed a reddish depressed lesion on the suture line of the gastric remnant, which was classified as type 0-IIc according to the Paris classification. ME-NBI at the oral side of the lesion revealed the absence of the microsurface pattern (MSP) and scattered microvessels with dilation and caliber variation, while ME-NBI at the anal side showed an irregularly tubular MSP. An endoscopic forceps biopsy showed a well- to moderately differentiated adenocarcinoma. Interventions: We performed endoscopic submucosal dissection, anden blocresection of the tumor was successfully achieved. Outcomes: The histological findings showed two distinct components: neuroendocrine carcinoma (NEC) and well-differentiated adenocarcinoma, which comprised similar to 60% and 40% of the tumor, respectively. The NEC component corresponded to the site with the absence of an MSP and scattered microvessels on ME-NBI, while the well-differentiated adenocarcinoma component corresponded to the site with an irregularly tubular MSP. The pathological diagnosis was mixed adenoneuroendocrine carcinoma, infiltrating into the deep submucosal layer. Lessons: We propose that the absence of an MSP plus an irregular MSP is characteristics of gMANEC, which was useful for the diagnosis of gMANEC before treatment.

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  • Probiotic-derived ferrichrome inhibits the growth of refractory pancreatic cancer cells

    Akemi Kita, Mikihiro Fujiya, Hiroaki Konishi, Hiroki Tanaka, Shin Kashima, Takuya Iwama, Masami Ijiri, Yuki Murakami, Shuhei Takauji, Takuma Goto, Aki Sakatani, Katsuyoshi Ando, Nobuhiro Ueno, Naoki Ogawa, Toshikatsu Okumura

    INTERNATIONAL JOURNAL OF ONCOLOGY   57 ( 3 )   721 - 732   2020.9

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    Pancreatic cancer is associated with a poor prognosis due to challenges in early detection, severe progression of the primary tumor, metastatic lesions, and resistance to antitumor agents. However, previous studies have indicated a relationship between the microbiome and pancreatic cancer outcomes. Our previous study demonstrated that ferrichrome derived fromLactobacillus casei, a probiotic bacteria, exhibited tumor-suppressive effects in colorectal and gastric cancer, and that the suppressive effects were stronger than conventional antitumor agents, such as 5-fluorouracil (5-FU) and cisplatin, suggesting that certain probiotics exert antitumorigenic effects. However, whether or not probiotic-derived molecules, including ferrichrome, exert a tumor-suppressive effect in other gastrointestinal tumors, such as pancreatic cancer, remains unclear. In the present study, it was demonstrated that probiotic-derived ferrichrome inhibited the growth of pancreatic cancer cells, and its tumor-suppressive effects were further revealed in 5-FU-resistant pancreatic cancer cellsin vitroandin vivoin a mouse xenograft model. Ferrichrome inhibited the progression of cancer cells via dysregulation of the cell cycle by activating p53. DNA fragmentation and cleavage of poly (ADP-ribose) polymerase were induced by ferrichrome treatment, suggesting that ferrichrome induced apoptosis in pancreatic cancer cells. A transcriptome analysis revealed that the expression p53-associated mRNAs was significantly altered by ferrichrome treatment. Thus, the tumor-suppressive effects of probiotics may mediated by probiotic-derived molecules, such as ferrichrome, which may have applications as an antitumor drug, even in refractory and 5-FU-resistant pancreatic cancer.

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  • The efficacy of the submucosal injection of lidocaine during endoscopic submucosal dissection for colorectal neoplasms: a multicenter randomized controlled study

    Masami Ijiri, Takahiro Sasaki, Mikihiro Fujiya, Takuya Iwama, Yuki Murakami, Keitaro Takahashi, Kazuyuki Tanaka, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Yusuke Saito, Toshikatsu Okumura

    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES   2020.9

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    Background Endoscopic submucosal dissection (ESD) is currently a common procedure although it requires a long procedural time. We conducted a prospective study to determine the efficacy and safety of lidocaine injection for shortening the procedural time and relieving bowel peristalsis during ESD.Methods A multicenter randomized controlled study was conducted in three hospitals. Ninety-one patients who underwent colorectal ESD were enrolled. Patients were randomly divided into two groups using the envelope method: the lidocaine group and saline group. The primary endpoint was the procedural time, and the secondary endpoints were the procedural time in each part of the colon and the grade of bowel peristalsis and the incidence and amounts of antispasmodic drugs use and adverse events.Results The patients' demographics were not markedly different between the two groups. The mean procedural time in the lidocaine group was not markedly different from that in the saline group. In contrast, at the proximal site, the procedural time in the lidocaine group (57 min) was significantly shorter in the saline group (80 min). The grade of bowel peristalsis in the lidocaine group (0.67) was significantly lower than in the saline group (1.17). Antispasmodic drug use was significantly rarer in the lidocaine group than in the saline group. The incidence of adverse events was not markedly different between the two groups.Conclusions Local lidocaine injection is a feasible option for preventing bowel peristalsis, particularly in the proximal colon, leading to a reduced procedural time for ESD and decreased antispasmodic drug use.University Hospital Medical Information Network Center (UMIN number: 000022843).

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  • Lactobacillus brevis SBC8803はNAFLDにおける選択的インスリン抵抗性を部分的に改善させる

    澤田 康司, 田中 宏樹, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    肝臓   61 ( Suppl.2 )   A701 - A701   2020.9

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  • 寛解期潰瘍性大腸炎における通常・拡大内視鏡を用いた活動性評価と再燃予測

    安藤 勝祥, 藤谷 幹浩, 奥村 利勝

    潰瘍   47   109 - 109   2020.7

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  • 北海道におけるインフリキシマブ-BSの有効性と安全性に関するリアルワールドデータ 多施設研究 フェニックスコホート後ろ向き研究(Real world data on the clinical efficacy and safety profile of infliximab-BS in Hokkaido: A Multicenter study: Phoenix retrospective cohort)

    風間 友江, 横山 佳浩, 平山 大輔, 我妻 康平, 安藤 勝祥, 上野 伸展, 藤谷 幹浩, 伊藤 貴博, 前本 篤男, 仲瀬 裕志

    日本消化器病学会雑誌   117 ( 臨増総会 )   A284 - A284   2020.7

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  • IBD診療における通院距離と臨床所見・入院期間との関連性の検討

    嘉島 伸, 寺澤 賢, 杉山 雄哉, 村上 雄紀, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 田中 一之, 安藤 勝祥, 上野 伸展, 稲場 勇平, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   117 ( 臨増総会 )   A283 - A283   2020.7

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  • Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1

    Keitaro Takahashi, Mikihiro Fujiya, Hiroaki Konishi, Yuki Murakami, Takuya Iwama, Takahiro Sasaki, Takehito Kunogi, Aki Sakatani, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Toshikatsu Okumura

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   21 ( 12 )   2020.6

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    The oncogenic properties of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) have been reported, although the tumor-promoting mechanism remains unclear. We herein report the mechanism underlying colorectal cancer cell progression mediated by hnRNP H1. The growth of colorectal cancer cells was suppressed by hnRNP H1 downregulation. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay revealed the anti-apoptotic effect of hnRNP H1 in colorectal cancer cells. An RNA immunoprecipitation assay revealed that hnRNP H1 bound to sphingosine-1-phosphate lyase 1 (SGPL1). Reverse transcription-polymerase chain reaction revealed the high expression of hnRNP H1 mRNA in colorectal cancer cells and Spearman's rank correlation coefficient showed a strong positive correlation between hnRNP H1 mRNA and SGPL1 mRNA. An siRNA of hnRNP H1 decreased SGPL1 mRNA expression in colorectal cancer cells, but not in non-tumorous cells. These findings suggested that hnRNP H1 increased SGPL1 mRNA expression specifically in cancer cells through direct binding. Targeted knockdown of hnRNP H1 or SGPL1 with siRNAs upregulated p53 phosphorylation and p53-associated molecules, resulting in cell growth inhibition, while hnRNP H1 upregulated the mRNA of SGPL1 and inhibited p53 activation, thereby promoting tumor cell growth. This is a novel mechanism underlying colorectal cancer cell progression mediated by hnRNP H1-SGPL1 mRNA stabilization.

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  • Resection for pancreatic cancer metastases contributes to survival A case report with sequential tumor genotype profiling during the long-term postoperative course Reviewed

    Hiroki Sato, Junpei Sasajima, Tetsuhiro Okada, Akihiro Hayashi, Hidemasa Kawabata, Takuma Goto, Kazuya Koizumi, Nobue Tamamura, Hiroki Tanabe, Mikihiro Fujiya, Shin-ichi Chiba, Mishie Tanino, Yusuke Ono, Yusuke Mizukami, Toshikatsu Okumura

    MEDICINE   99 ( 25 )   e20564 - e20564   2020.6

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    Introduction: Surgical management is not a standard treatment option for metastatic recurrence of pancreatic adenocarcinoma. However, the surgical management of a solitary metastasis is useful in selected cases. Patient concerns: A 42-year-old woman was referred to our hospital on account of epigastric pain associated with a mass in the pancreatic body. The patient had a family history of branch duct-type intraductal papillary mucinous neoplasm of the pancreas. Diagnosis: The patient was diagnosed with pancreatic ductal adenocarcinoma (PDA) complicated with pancreatitis due to pancreatic duct involvement. Interventions: The patient underwent distal pancreatectomy, and pathological examination revealed a tubular adenocarcinoma. Solitary liver and lung metastatic tumors were found 6 and 43 months after the initial presentation, respectively, and sequential metastasectomies were performed. Outcomes: The patient survived until 8 years after her initial presentation. The genetic profiles of the resected specimens, primary PDA, and recurrent tumors in the liver and lung possessed identical KRAS mutations at codon 12, whereas there were no mutations in the main tumor suppressor genes, such as TP53, CDKN2A, and SMAD4. Multiplex polymerase chain reaction-based microsatellite instability assay demonstrated microsatellite stability. Conclusion: In our case, the patient with pancreatic adenocarcinoma survived for over 8 years following the resection of the primary tumor and resections of metachronous metastatic tumors. The outcome of PDA may be associated with the genetic profile that regulates its biological behavior. Operative management of solitary metastatic tumors may be a therapeutic options for selected patients with pancreatic cancer.

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  • Non-alcoholic fatty liver disease is a potential risk factor for liver injury caused by immune checkpoint inhibitor

    Koji Sawada, Hidemi Hayashi, Shunsuke Nakajima, Takumu Hasebe, Mikihiro Fujiya, Toshikatsu Okumura

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   35 ( 6 )   1042 - 1048   2020.6

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    Background and Aim Because of their survival benefits, immune checkpoint inhibitors (ICIs) are widely administered to patients with various advanced-stage malignancies. During ICI treatment, drug-induced liver injury (DILI) occasionally occurs. In particular, hepatic immune-related adverse events (irAEs) are rare but serious and fatal. In patients with hepatic irAEs, immediate steroid treatment is generally recommended; however, the risk factors for ICI-associated DILI remain unknown. In the present study, we identified a risk factor for ICI-associated DILI. Methods We retrospectively analyzed 135 patients treated with anti-programmed cell death-1 (PD-1) antibodies, such as nivolumab and pembrolizumab, at Asahikawa Medical University Hospital. We investigated grade >= 2 hepatotoxic AEs during anti-PD-1 therapy, and PD-1 inhibitor-associated DILI was then diagnosed according to the Digestive Disease Week Japan (DDW-J) 2004 scale. The risk factors for PD-1 inhibitor-associated DILI were identified by Cox hazard analysis. Results Thirty-six patients developed grade >= 2 hepatic AEs during anti-PD-1 therapy. Among them, eight patients were diagnosed with PD-1 inhibitor-associated DILI based on the DDW-J 2004 scale. Cox hazard analysis revealed that non-alcoholic fatty liver disease (NAFLD) was a risk factor for PD-1 inhibitor-associated DILI. In addition, we revealed that the outcomes of patients with the DDW-J 2004 score = 3 were improved without steroid treatment. Conclusions NAFLD is a potential risk factor for PD-1 inhibitor-associated DILI based on the DDW-J 2004 scale. The DDW-J 2004 scale might be useful for determining whether steroid treatment is required in patients with PD-1 inhibitor-associated DILI.

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  • Significance of Conducting 2 Types of Fecal Tests in Patients With Ulcerative Colitis

    Makoto Naganuma, Taku Kobayashi, Masanao Nasuno, Satoshi Motoya, Shingo Kato, Katsuyoshi Matsuoka, Ryota Hokari, Chikako Watanabe, Hirotsugu Sakamoto, Hironori Yamamoto, Makoto Sasaki, Kenji Watanabe, Hideki Iijima, Yutaka Endo, Hitoshi Ichikawa, Keiji Ozeki, Satoshi Tanida, Nobuhiro Ueno, Mikihiro Fujiya, Minako Sako, Ken Takeuchi, Shinya Sugimoto, Takayuki Abe, Toshifumi Hibi, Yasuo Suzuki, Takanori Kanai

    CLINICAL GASTROENTEROLOGY AND HEPATOLOGY   18 ( 5 )   1102 - +   2020.5

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    BACKGROUND & AIMS: We compared the diagnostic accuracy of the fecal calprotectin (FCP) test vs the fecal immunochemical blood test (FIT) in determining the endoscopic severity and predicting outcomes of patients with ulcerative colitis (UC).METHODS: We performed a nationwide study of 879 patients with UC, enrolled at medical centers across Japan, from March 2015 to March 2017. We collected data on fecal biomarkers, endoscopic severities, and other clinical indices from Cohort 1 (n = 427) and assessed the diagnostic accuracy of FCP measurement and FIT results in determining clinical severity, based on Mayo score, and endoscopic remission, based on Mayo endoscopic sub-score (MES) or UC endoscopic index of severity. We also followed 452 patients in clinical remission from UC (Cohort 2) for 12 months and evaluated the associations of FCP levels and FIT results with clinical recurrence.RESULTS: The levels of FCP and FIT each correlated with the MES and UC endoscopic index of severity. There were no significant differences in the areas under the curve of FCP vs FIT in distinguishing patients with MES <= 1 from those with MES >= 2 (P = .394) or in distinguishing patients with MES = 0 from those with MES >= 1 (P = .178). Among 405 patients in clinical remission at baseline, 38 (9.4%) had UC recurrences within 3 months and 90 (22.2%) had recurrences within 12 months. FCP >= 146 mg/kg (hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.80-8.33) and FIT >= 77 ng/mL (HR, 2.92; 95% CI, 1.76-4.83) were independently associated with clinical recurrence within 12 months. UC recurred within 12 months in 69% of patients with levels of FCP >= 146 mg/kg and FIT >= 77 ng/mL; this value was significantly higher than the rate of recurrence in patients with levels of FCP146 mg/kg and FIT <77 ng/mL (31.5%, P < .001) or patients with levels of FCP<146 mg/kg and FIT >= 77 ng/mL (30.0%, P < .001).CONCLUSION: In a nationwide study of patients with UC in Japan, we found that the level of FCP and FIT could each identify patients with endoscopic markers of disease severity (MES >= 2). The combination of FCP and FIT results can identify patients in remission who are at risk for disease recurrence.

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  • 肝細胞癌に対する初回治療TACEにおけるサルコペニア肥満合併の意義

    澤田 康司, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    肝臓   61 ( Suppl.1 )   A516 - A516   2020.4

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  • 食道アカラシアに対する経口内視鏡的筋層切開術(Per Oral Endoscopic Myotomy:POEM)導入後の治療成績

    高橋 慶太郎, 藤谷 幹浩, 小林 裕, 杉山 雄哉, 村上 雄紀, 久野木 健仁, 佐々木 貴弘, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   126回・120回   48 - 48   2020.3

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  • 精神遅滞を有し免疫不全を伴わない患者に発症したWhipple病の一例

    久野木 健仁, 小林 裕, 杉山 雄哉, 村上 雄紀, 佐藤 裕基, 佐々木 貴弘, 高橋 慶太郎, 安藤 勝祥, 河端 秀賢, 林 明宏, 上野 伸展, 嘉島 伸, 後藤 拓磨, 盛一 健太郎, 田邊 裕貴, 水上 裕輔, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会プログラム・抄録集   126回   70 - 70   2020.3

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  • 【すべてがわかるIBDの内視鏡】IBDの上部消化管病変

    嘉島 伸, 藤谷 幹浩, 杉山 雄哉, 村上 雄紀, 岩間 琢哉, 安藤 勝祥, 上野 伸展, 盛一 健太郎, 田邊 裕貴, 奥村 利勝

    消化器内視鏡   32 ( 2 )   290 - 296   2020.2

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    炎症性腸疾患(IBD)にはCrohn病(CD)と潰瘍性大腸炎(UC)が存在し、いずれの疾患も下部消化管が病変の主座の慢性炎症性疾患である。しかし上部消化管にも特徴的所見を伴うことがあり、診断確定に寄与する症例が少なくない。そのためIBD上部消化管病変の特徴を把握し診療にあたる必要がある。CDでは、胃体部~穹窿部の竹の節状外観や縦走配列の幽門部びらん、十二指腸病変としてはnotch様外観や数珠状隆起などの所見が高い特異性を示し、確定診断の一助となる。またUCの上部消化管病変は、大腸病変に類似したびまん性の脆弱な細顆粒状の粘膜であり、出血を伴う場合はUCに準じた治療が必要となる。以上から、IBD診断においては下部に加え、上部消化管内視鏡検査を行うべきである。(著者抄録)

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J02312&link_issn=&doc_id=20200225170019&doc_link_id=%2Faq9syokd%2F2020%2F003202%2F020%2F0290-0296%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9syokd%2F2020%2F003202%2F020%2F0290-0296%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 早期胃癌におけるマイクロサテライト不安定性の検討

    田邊 裕貴, 水上 裕輔, 小林 裕, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 藤谷 幹浩, 奥村 利勝

    日本内科学会雑誌   109 ( Suppl. )   228 - 228   2020.2

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  • Correction to: High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype (Journal of Gastroenterology, (2020), 55, 1, (67-77), 10.1007/s00535-019-01638-x)

    Yoichi Kakuta, Yasuhiro Izumiyama, Daisuke Okamoto, Takeru Nakano, Ryo Ichikawa, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Hisaaki Kudo, Naoko Minegishi, Yosuke Kawai, Katsushi Tokunaga, Masao Nagasaki, Yoshitaka Kinouchi, Yasuo Suzuki, Atsushi Masamune, Tetsuya Takagawa, Shiro Nakamura, Kentaro Ikeya, Hiroyuki Hanai, Hirotake Sakuraba, Atsushi Nishida, Akira Andoh, Shoko Nakagawa, Makoto Sasaki, Miki Miura, Tadakazu Hisamatsu, Takahiko Toyonaga, Taku Kobayashi, Kei Onodera, Hiroshi Nakase, Masaru Shinozaki, Yoh Ishiguro, Shinta Mizuno, Makoto Naganuma, Masahiro Takahara, Sakiko Hiraoka, Shunichi Yanai, Takayuki Matsumoto, Ryota Hokari, Tomoo Nakagawa, Hiroshi Araki, Satoshi Motoya, Shunji Ishihara, Naoki Oshima, Takehiko Katsurada, Yu Sasaki, Takafumi Otsuka, Mikihiro Fujiya, Motoyuki Onodera, Masakazu Nagahori, Katsuyoshi Matsuoka, Katsuhiro Arai, Yuichiro Sato, Mitsunori Noguchi, Minoru Matsuura, Tomoaki Ishikawa, Hiroki Nakajima, Hiroshi Terasaki, Yukiko Abe, Mai Kato

    Journal of Gastroenterology   55 ( 1 )   132   2020.1

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    The correct name of the last author should be ‘‘Atsushi Masamune’’, and not ‘‘Atsushi Masasmune’’ as given in the original publication of the article.

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  • Acute Colchicine Poisoning Causes Endotoxemia via the Destruction of Intestinal Barrier Function: The Curative Effect of Endotoxin Prevention in a Murine Model

    Kie Horioka, Hiroki Tanaka, Shotaro Isozaki, Hiroaki Konishi, Mikihiro Fujiya, Katsuhiro Okuda, Masaru Asari, Hiroshi Shiono, Katsuhiro Ogawa, Keiko Shimizu

    DIGESTIVE DISEASES AND SCIENCES   65 ( 1 )   132 - 140   2020.1

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    Background Colchicine binds to intracellular tubulin and prevents mitosis. Colchicine is also used as an anti-inflammatory drug. Meanwhile, excess administration of medication or accidental ingestion of colchicine-containing plants can cause acute colchicine poisoning, which initially results in gastrointestinal effects that may be followed by multiorgan dysfunction. However, the mechanism of colchicine poisoning remains unclear, and there are no standard therapeutic strategies. Aims We focused on intestinal barrier function and attempted to reveal the underlying mechanism of colchicine poisoning using an animal model. Methods Colchicine was orally administered to C57Bl/6 mice. Then, we performed histopathological analysis, serum endotoxin assays, and intestinal permeability testing. Additionally, the LPS-TLR4 signaling inhibitor TAK-242 was intraperitoneally injected after colchicine administration to analyze the therapeutic effect. Results We observed villus height reduction and increased numbers of apoptotic cells in the gastrointestinal epithelium of colchicine-treated mice. Both intestinal permeability and serum endotoxin levels were higher in colchicine-treated mice than in control mice. Although colchicine-poisoned mice died within 25 h, those that also received TAK-242 treatment survived for more than 48 h. Conclusion Colchicine disrupted intestinal barrier function and caused endotoxin shock. Therapeutic inhibition of LPS-TLR4 signaling might be beneficial for treating acute colchicine poisoning.

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  • High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype

    Yoichi Kakuta, Yasuhiro Izumiyama, Daisuke Okamoto, Takeru Nakano, Ryo Ichikawa, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Hisaaki Kudo, Naoko Minegishi, Yosuke Kawai, Katsushi Tokunaga, Masao Nagasaki, Yoshitaka Kinouchi, Yasuo Suzuki, Atsushi Masasmune, Tetsuya Takagawa, Shiro Nakamura, Kentaro Ikeya, Hiroyuki Hanai, Hirotake Sakuraba, Atsushi Nishida, Akira Andoh, Shoko Nakagawa, Makoto Sasaki, Miki Miura, Tadakazu Hisamatsu, Takahiko Toyonaga, Taku Kobayashi, Kei Onodera, Hiroshi Nakase, Masaru Shinozaki, Yoh Ishiguro, Shinta Mizuno, Makoto Naganuma, Masahiro Takahara, Sakiko Hiraoka, Shunichi Yanai, Takayuki Matsumoto, Ryota Hokari, Tomoo Nakagawa, Hiroshi Araki, Satoshi Motoya, Shunji Ishihara, Naoki Oshima, Takehiko Katsurada, Yu Sasaki, Takafumi Otsuka, Mikihiro Fujiya, Motoyuki Onodera, Masakazu Nagahori, Katsuyoshi Matsuoka, Katsuhiro Arai, Yuichiro Sato, Mitsunori Noguchi, Minoru Matsuura, Tomoaki Ishikawa, Hiroki Nakajima, Hiroshi Terasaki, Yukiko Abe, Mai Kato

    JOURNAL OF GASTROENTEROLOGY   55 ( 1 )   67 - 77   2020.1

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    Background The genetic variants of NUDT15 have been verified to induce adverse events (AEs) of thiopurines. Codon 139 variants are frequently observed in Asians, while multiple variants are seen in codon 18 which also cause AEs including the European ancestry. The purpose of this study is to establish a technique capable of the simple genotyping of NUDT15 codon 18 and to evaluate its efficacy. Methods A high-resolution melt (HRM) technique is performed to simply determine genotypes. The accuracy of HRM analysis was evaluated with DNAs from 1245 Japanese patients with inflammatory bowel diseases. Subsequently, another group of 572 patients was analyzed to verify the method. The diplotypes and the frequency of their AEs were estimated on the basis of codon 18 and 139 genotypes. Results The HRM analysis enabled the correct identification of the three main genotypes, ref/ref, ref/ins, and ref/V18I, in 1236 of 1241 cases. All rare genotypes including ref/del were identified as the impossible-to-determine group, the proper diagnosis rate was 99.6%. In the verification test using other samples, the diagnosis rate was 99.7%. By estimating diplotypes using both codon 18 and 139 genotypes, 2.74% and 2.13% of Japanese patients with Arg/Arg and Arg/Cys of codon 139 have a lower enzymatic activity of NUDT15 and a higher risk for adverse responses than those estimated by codon 139 genotypes alone. Conclusions Our study showed that HRM method enables simple genotyping of complicated codon 18 variants essential to haplotype estimation of the NUDT15.

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  • Lymph Node Metastasis From Gastroesophageal Cancer Successfully Treated by Nivolumab: A Case Report of a Young Patient Reviewed International journal

    Shin Kashima, Hiroki Tanabe, Mishie Tanino, Yu Kobayashi, Yuki Murakami, Takuya Iwama, Takahiro Sasaki, Takehito Kunogi, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Kentaro Moriichi, Masahide Fukudo, Yoshikazu Tasaki, Masao Hosokawa, Yusuke Mizukami, Mikihiro Fujiya, Toshikatsu Okumura

    FRONTIERS IN ONCOLOGY   9   1375 - 1375   2019.12

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    Background: Immuno-oncology is a novel target of cancer therapy. Nivolumab is a monoclonal anti-programed death-1 antibody recently used to treat patients with chemotherapy-resistant gastric and gastroesophageal cancer. Although the disease control rate is reported to be very high, few cases demonstrate a complete response. Case Presentation: A 25-year-old man diagnosed with gastroesophageal cancer was treated with chemotherapy followed by surgical resection. Pathological diagnosis was poorly differentiated adenocarcinoma with distant lymph node metastasis. Residual lymph node metastasis was treated with nivolumab monotherapy, resulting in complete disappearance. No recurrence has been observed for 2 years since discontinuation of nivolumab. This rare case was additionally subjected to pathological and genetic analysis, suggesting that a high tumor mutation burden (10.7 mutations/Mb) might be associated with sensitivity to nivolumab. Summary: We reported a case of advanced gastroesophageal junction cancer with distal lymph node metastasis that was successfully treated with chemotherapy, surgical resection, and nivolumab therapy. An aggressive search for biomarkers implying benefit effects of nivolumab should be performed.

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  • Genetic analysis of postoperative recurrence of pancreatic cancer potentially owing to needle tract seeding during EUS-FNB Reviewed

    Hidemasa Kawabata, Yuki Miyazawa, Hiroki Sato, Tetsuhiro Okada, Akihiro Hayashi, Takuya Iwama, Shugo Fujibayashi, Takuma Goto, Junpei Sasajima, Shuhei Takauji, Mikihiro Fujiya, Yoshihiro Torimoto, Mishie Tanino, Yuko Omori, Yusuke Ono, Hidenori Karasaki, Yusuke Mizukami, Toshikatsu Okumura

    ENDOSCOPY INTERNATIONAL OPEN   7 ( 12 )   E1768 - E1772   2019.12

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    Background and study aims Needle tract seeding during endoscopic ultrasound fine-needle biopsy (EUS-FNB) remains a concern. We investigated whether such seeding occurred in a patient with pancreatic ductal adenocarcinoma (PDA). Patient and methods Surgically resected and EUS-FNB-derived specimens were genotyped to determine if a gastric wall tumor that emerged 3 years after curative resection of an early-stage PDA was clonally related to the original tumor. Results The gastric tumor histologically resembled the primary PDA; the lesions also shared KRAS , SMAD4 , and RNF43 mutations. Genotyping of the preoperative EUS-FNB specimen, in which cancer was not detected, nevertheless revealed mutations that were identical to those in the resected primary and recurrent tumors. While the primary PDA had a low frequency of mutant SMAD4 , such mutations were highly prevalent in both the EUS-FNB and recurrent tumor specimens. Conclusions The genetic lineages of sampled tissues from our patient revealed that needle tract seeding may have incidentally occurred when a subset of neoplastic cells within a heterogeneous tumor ( i. e. , an aggressive clone) was targeted during EUS-FNB.

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  • 多彩な組織像を呈したニボルマブ関連胆管炎の1例

    林 秀美, 澤田 康司, 長谷部 拓夢, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    肝臓   60 ( Suppl.3 )   A1016 - A1016   2019.11

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  • The Incidence and Risk Factors of Venous Thromboembolism in Patients with Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study Reviewed

    Katsuyoshi Ando, Mikihiro Fujiya, Yoshiki Nomura, Yuhei Inaba, Yuya Sugiyama, Yu Kobayashi, Takuya Iwama, Masami Ijiri, Keitaro Takahashi, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hiroki Tanabe, Yusuke Mizukami, Kazumi Akasaka, Satoshi Fujii, Satoshi Yamada, Hiroshi Nakase, Toshikatsu Okumura

    DIGESTION   100 ( 4 )   229 - 237   2019.11

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    Background: Venous thromboembolism (VTE) has been shown to be more frequent in inflammatory bowel disease (IBD) than in the general population in Western studies. However, the actual state of VTE in Asian IBD remains poorly understood. Aims: To reveal the incidence of VTE in IBD patients in Japan. Methods: Eighty-five patients admitted to 3 gastroenterology centers were registered from 2013 to 2018. The incidence of VTE in patients with IBD (n = 42) was prospectively compared to that among patients with other digestive diseases (n = 43). The presence of VTE was surveyed using contrast-enhanced computed tomography and/or ultrasonography at admission and at 1-2 weeks after admission. The patient characteristics and laboratory data of IBD patients with or without VTE were compared to determine the risk factors for VTE. Results: The incidence of VTE with IBD was 16.7%, which was significantly more frequent than with other digestive diseases (2.3%; p = 0.0296). In IBD patients, VTE was detected in 6 of 22 patients with ulcerative colitis (27.2%) but in only 1 of 20 patients with Crohn's disease (5.0%). VTE was diagnosed at admission in 4 IBD patients and 2 weeks after admission in 3 IBD patients. The risk factors of VTE in IBD were the presence of an indwelling central venous catheter, a low level of total protein, a low activated partial thromboplastin time, and a high level of fibrinogen degradation products. Conclusion: VTE was frequently detected in Japanese IBD patients both at and after admission. Adequate screening and prophylaxis for VTE is deemed necessary in IBD. (C) 2018 S. Karger AG, Basel

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  • The Temporal Order of KRAS and GNAS Mutations in Intraductal Papillary Mucinous Neoplasms of the Pancreas and Evolution to Invasive Carcinoma

    Y. Mizukami, H. Karasaki, Y. Ono, Y. Omori, A. Hayashi, S. Tachibana, Y. Sugiyama, H. Sato, H. Kawabata, T. Goto, M. Fujiya, K. Takahashi, A. Katanuma, H. Maguchi, T. Furukawa, T. Okumura

    PANCREAS   48 ( 10 )   1493 - 1493   2019.11

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  • 炎症性腸疾患入院患者における静脈血栓塞栓症の発症頻度 多施設前向き研究

    岩間 琢哉, 安藤 勝祥, 稲葉 勇平, 杉山 雄哉, 村上 雄紀, 久野木 健仁, 佐々木 貴弘, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 山田 聡, 仲瀬 裕志, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   116 ( 臨増大会 )   A772 - A772   2019.11

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  • 精神遅滞を有し免疫不全を伴わない患者に発症したWhipple病の一例

    久野木 健仁, 杉山 雄哉, 村上 雄紀, 岩間 琢哉, 佐々木 貴弘, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本小腸学会学術集会プログラム・抄録集   57回   66 - 66   2019.11

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  • 大腸ESDにおけるリドカイン粘膜下局注の有効性に関する前向きランダム化比較試験

    佐々木 貴弘, 岩間 琢哉, 村上 雄紀, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    Gastroenterological Endoscopy   61 ( Suppl.2 )   2201 - 2201   2019.10

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  • Gastric submucosa-invasive carcinoma associated with Epstein-Barr virus and endoscopic submucosal dissection: A case report

    Yu Kobayashi, Takehito Kunogi, Hiroki Tanabe, Yuki Murakami, Takuya Iwama, Takahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Hidehiro Takei, Mikihiro Fujiya, Toshikatsu Okumura

    WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY   11 ( 10 )   925 - 932   2019.10

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    BACKGROUNDEpstein-Barr virus (EBV)-associated carcinoma is a gastric cancer subtype with a morphology characterized by gastric carcinoma with lymphoid stroma (GCLS). Clinicopathological studies have indicated a better prognosis for GCLS than for common gastric carcinomas. Some previous cases of early gastric cancer associated with EBV had been diagnosed by endoscopic resection.CASE SUMMARYWe present two GCLS cases subjected to endoscopic submucosal dissection (ESD) for a definitive diagnosis. A protruded gastric lesion was identified by routine endoscopic examination, but forceps biopsy showed no atypical cells before ESD. The resected specimen showed a poorly differentiated adenocarcinoma with lymphoid cells involving the mucosa and submucosa. The final diagnosis was submucosa-invasive poorly differentiated gastric adenocarcinoma. Accordingly, additional gastrectomy was recommended to obtain a complete cure. One patient underwent additional distal gastrectomy with lymph node dissection, but the other was refused because of cardiovascular complications. Both patients remained in remission for more than half a year. EBV positivity was determined by EBV-encoded RNA in situ hybridization. We also conducted a literature review of cases of early gastric cancer associated with EBV that had been diagnosed by ESD.CONCLUSIONSubmucosa-invasive GCLS could be dissected using ESD, and EBV positivity should be subsequently assessed to determine whether or not any additional curative surgery is required. Further prospective investigations on the prevalence of lymph node metastasis in EBV-associated carcinoma should be performed to expand the indications for endoscopic resection.

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  • NBI併用拡大内視鏡観察にて特徴的所見を認めた胃mixed adenoneuroendocrine carcinoma(MANEC)の1例

    宮澤 佑貴, 高橋 慶太郎, 吉田 萌, 杉山 雄哉, 村上 雄紀, 岩間 琢哉, 佐々木 貴弘, 久野木 健仁, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   125回・119回   28 - 28   2019.9

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  • A Case of Alpha-Fetoprotein-Producing Adenocarcinoma of the Esophagogastric Junction in which Long-Term Survival Was Achieved by Means of Individualized Multidisciplinary Therapy Reviewed

    Kazuyuki Tanaka, Mikihiro Fujiya, Masami Ijiri, Keitaro Takahashi, Katsuyoshi Ando, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Takuma Goto, Junpei Sasajima, Takahiro Ito, Kentaro Moriichi, Yusuke Mizukami, Hiroki Tanabe, Toshikatsu Okumura

    JOURNAL OF GASTROINTESTINAL CANCER   50 ( 3 )   617 - 620   2019.9

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  • A case of gastric carcinoma with lymphoid stroma diagnosed by an endoscopic ultrasound-guided fine-needle biopsy

    Hiroki Tanabe, Katsuyoshi Ando, Daisuke Sutoh, Katsuhisa Ohta, Hironori Ohdaira, Yutaka Suzuki, Mikihiro Fujiya, Toshikatsu Okumura

    JOURNAL OF CLINICAL ULTRASOUND   47 ( 7 )   419 - 422   2019.9

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    Endoscopic ultrasound-guided sampling is indicated to achieve an accurate diagnosis of subepithelial lesions of the stomach when a standard biopsy fails. Gastric carcinoma with lymphoid stroma (GCLS) is located under the epithelial layer with dense lymphocytic infiltration, making a pathological diagnosis by a biopsy difficult. We herein report a case of the pathological diagnosis of GCLS using an endoscopic ultrasound-guided fine-needle biopsy. The patient underwent distal gastrectomy and was diagnosed with Epstein-Barr virus-negative cancer.

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  • Long-term growth of intrahepatic papillary neoplasms: A case report

    Takumu Hasebe, Koji Sawada, Hidemi Hayashi, Shunsuke Nakajima, Hiroyuki Takahashi, Masahiro Hagiwara, Koji Imai, Sayaka Yuzawa, Mikihiro Fujiya, Hiroyuki Furukawa, Toshikatsu Okumura

    WORLD JOURNAL OF GASTROENTEROLOGY   25 ( 36 )   5569 - 5577   2019.9

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    BACKGROUNDIntraductal papillary neoplasm of the bile duct (IPNB) is a type of tumor that presents in the intra- or extrahepatic bile ducts. Cystic-type intrahepatic IPNB often mimics simple liver cysts, making the diagnosis difficult. Because the growth of IPNB is slow, careful follow-up and timely therapeutic intervention is recommended. There are few reports with a follow-up period longer than a decade; thus, we report the case of a patient with an IPNB that grew for over 13 years.CASE SUMMARYA 65-year-old man was diagnosed, 13 years prior with a cystic hepatic tumor with abnormal imaging findings. The targeted tumor biopsy results showed no malignancy. Biannual follow-up examinations were performed because of the potential for malignancy. The cystic lesions showed gradual enlargement over 11 years and a 4 mm papillary proliferation appeared on the cyst wall, which is compatible with IPNB. The tumor was observed for another 2 years because of the patient's wishes. The imaging findings showed enlargement to 8 mm and a new 9 mm papillary proliferation of the cystic tumor. Contrast-enhanced ultrasonography showed hyperenhancement during the arterial phase in both cyst wails, indicating intraductal tumor progression in both tumors. Thus, liver segment 8 subsegmentectomy was performed. The pathological findings indicated that the tumors contained mucin, and high-grade atypia was observed in the papillary lesions, showing IPNB.CONCLUSIONThe development of IPNB should be monitored in patients with cystic lesions and ultrasonography are useful tool for the evaluation.

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  • Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

    Tadakazu Hisamatsu, Takayuki Matsumoto, Kenji Watanabe, Hiroshi Nakase, Satoshi Motoya, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi, Akira Andoh, Toshifumi Ashida, Katsuya Endo, Yutaka Endo, Motohiro Esaki, Hiroshi Fujita, Mikihiro Fujiya, Ken Haruma, Toshifumi Hibi, Sakiko Hiraoka, Ichiro Hirata, Tadakazu Hisamatsu, Yutaka Honda, Hideki Iijima, Bunei Iizuka, Kentaro Ikeya, Takuya Inoue, Syuji Inoue, Tetsuya Ishida, Yo Ishiguro, Shunji Ishihara, Hiroaki Ito, Ryuichi Iwakiri, Takashi Kagaya, Takanori Kanai, Hiroshi Kashida, Shingo Kato, Jun Kato, Takehiko Katsurada, Fukunori Kinjyo, Kiyonori Kobayashi, Mayumi Kodama, Reiko Kunisaki, Koichi Kurahara, Takafumi Kurokami, Lee Kyouwon, Koichiro Matsuda, Kazuhiro Matsueda, Toshiyuki Matsui, Takayuki Matsumoto, Keiichi Mitsuyama, Yuji Mizokami, Satoshi Motoya, Yuji Naito, Tomoo Nakagawa, Shiro Nakamura, Hiroshi Nakase, Masanori Nojima, Masafumi Nomura, Atsuhiro Ogawa, Kazuichi Okazaki, Kazuaki Otsuka, Hirotake Sakuraba, Masayuki Saruta, Makoto Sasaki, Takayuki Shirai, Tomoaki Suga, Kazuhito Sugimura, Toshiro Sugiyama, Yasuo Suzuki, Fuminao Takeshima, Hiroyuki Tamaki, Shinji Tanaka, Satoshi Tanida, Keiichi Tominaga, Taku Tomizawa, Kenji Watanabe, Mamoru Watanabe, Kenji Watanabe, Syojiro Yamamoto, Masaki Yamashita, Atsushi Yoshida, Naoki Yoshimura

    JOURNAL OF CROHNS & COLITIS   13 ( 9 )   1097 - 1104   2019.9

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    Background: Combining a thiopurine with the human anti-tumour necrosis factor-a monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab.Methods: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group.Results: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group.Conclusions: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

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  • 腎機能障害・血小板増多症を伴い、不明熱が診断契機となったMEFV遺伝子変異合併クローン病の一例

    吉田 萌, 安藤 勝祥, 杉山 雄哉, 村上 雄紀, 岩間 琢哉, 久野木 健仁, 佐々木 貴弘, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 粂井 志麻, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   125回・119回   31 - 31   2019.9

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  • Middle-term prognosis in patients with ulcerative colitis who achieved clinical and endoscopic remission by budesonide rectal foam

    Makoto Naganuma, Fumihito Hirai, Kiyonori Kobayashi, Kenji Watanabe, Ken Takeuchi, Nobuo Aoyama, Hiroshi Nozawa, Satoshi Motoye, Toshihide Ohmori, Akio Harada, Yushi Nagai, Takayuki Abe, Yoji Yamada, Katsutoshi Inagaki, Naoki Shimizu, Takanori Kanai, Mamoru Watanabe, Shinji Tanaka, Takehiro Arai, Masahiro Kishi, Chiyuki Watanabe, Yasuhisa Sakata, Toshifumi Ashida, Atsuo Maemoto, Souken Sai, Atsuo Kitano, Yukinori Sameshima, Kaoru Yokoyama, Taku Kobayashi, Takehisa Suekane, Koichiro Matsuda, Hirozumi Obata, Mikihiro Fujiya, Takayuki Shirai, Keiichi Tominaga, Hidetoshi Takedatsu, Ryouichi Suzuki

    PLOS ONE   14 ( 8 )   2019.8

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    BackgroundBudesonide foam is effective in inducing clinical remission in ulcerative colitis (UC) patients with active proctosigmoiditis. The aim of this study was to evaluate the duration of remission and predictors of relapse in UC patients who achieved clinical remission and mucosal healing by 6-week treatment with topical budesonide.MethodsThis is a retrospective, observational, multicenter study with a 2-year follow-up period. UC patients who were treated with budesonide foam in phase 2 or phase 3 clinical trials and achieved both clinical remission and mucosal healing were enrolled.ResultsAmong 84 patients who met the eligibility criteria, 60 participated in the study. Eighteen of the 60 patients (30.0%; 95% confidence interval [CI]: 18.9-43.2) experienced no relapse (i.e., maintenance of remission) during the 2-year follow-up period. The median relapse-free survival time was 0.82 years (95% CI: 0.51-1.52). Of 37 patients with a Mayo endoscopic subscore of 0 after inducing remission with budesonide foam, 25 (67.6%) relapsed within 2 years. Patients with a disease duration of <1 year experienced a worse clinical outcome than patients with a disease duration of >5 years, and the hazard ratio was 2.38 (95% CI: 1.04-5.45).ConclusionThis is the first study to evaluate the short- to middle-term prognosis in UC patients who achieved mucosal healing with topical preparations. After inducing remission by budesonide foam, treatment for maintaining remissions and strict follow-up may be needed for patients with shorter disease duration.

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  • Skeletal muscle mass is associated with toxicity, treatment tolerability, and additional or subsequent therapies in patients with hepatocellular carcinoma receiving sorafenib treatment

    Koji Sawada, Yoshinori Saitho, Hidemi Hayashi, Takumu Hasebe, Shunsuke Nakajima, Katsuya Ikuta, Mikihiro Fujiya, Toshikatsu Okumura

    JGH OPEN   3 ( 4 )   329 - 337   2019.8

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    Background and Aim: Several reports have demonstrated that skeletal muscle mass influences mortality in patients with hepatocellular carcinoma (HCC) receiving sorafenib treatment; however, there is still controversy with regard to whether skeletal muscle and adipose tissue are associated with the prognosis in HCC patients. We examined the relationship between body composition and prognosis in HCC patients.Methods: We retrospectively analyzed 82 patients with unresectable HCC receiving sorafenib treatment. The skeletal muscle area and adipose tissue area were measured by computed tomography. Patients with low skeletal muscle index (male <= 36.2 cm(2)/m(2), female <= 2.9.6 cm(2)/m(2)) and high visceral to subcutaneous adipose tissue area ratio (VSR) (male >= 1.33, female >= 0.93) were diagnosed as low skeletal muscle mass (LSMM) and high VSR, respectively.Results: A total of 16 and 34 patients were classified as LSMM and high VSR, respectively. LSMM patients frequently experienced serious adverse events (SAEs) and thus had a shorter duration of sorafenib treatment than non-LSMM patients. High VSR was a significant factor for progression-free survival. LSMM patients less frequently received additional/subsequent therapies combined with sorafenib than non-LSMM patients. Multivariate Cox hazard analysis demonstrated that LSMM was a significant factor for the duration of sorafenib treatment. The treatment duration and receiving of additional/subsequent therapies were significantly associated with overall survival (OS) but not with LSMM or high VSR.Conclusion: LSMM was associated with the frequency of SAEs, treatment tolerability, and treatment duration. LSMM patients were less likely to receive additional/subsequent therapies than non-LSMM patients. Thus, LSMM could identify a subgroup of patients with poor OS.

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  • White coat status is a predictive marker for post-esophageal endoscopic submucosal dissection stricture: a retrospective study

    Keitaro Takahashi, Mikihiro Fujiya, Nobuhiro Ueno, Takeshi Saito, Yuya Sugiyama, Yuki Murakami, Takuya Iwama, Takahiro Sasaki, Masami ijiri, Kazuyuki Tanaka, Aki Sakatani, Katsuyoshi Ando, Yoshiki Nomura, Shin Kashima, Mitsuru Goto, Kentaro Moriichi, Toshikatsu Okumura

    ESOPHAGUS   16 ( 3 )   258 - 263   2019.7

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    BackgroundSteroid therapy is primarily used to prevent esophageal stricture after endoscopic submucosal dissection (ESD). However, esophageal stricture can still occur after preventive therapy, and the effect of preventive steroid therapy cannot be predicted before stricture formation. This study aimed to clarify the risk factors for esophageal stricture after preventive steroid therapy.MethodsThis was a retrospective study conducted at three institutions. From January 2011 to February 2018, 28 large-sized SENs in 26 patients who had a mucosal defect that involved more than three-quarters of the esophageal circumference were enrolled. We classified white coats on artificial ulcers after esophageal ESD into three groups (thin, moderately thick, thick) based on endoscopic images obtained on postoperative day 7.ResultsThe white coat status on the artificial ulcer after ESD was a significant risk factor for post-ESD stricture (p<0.05). The stricture rates in patients with thin, moderately thick and thick white coats were 10.0, 36.4 and 85.7%, respectively. When thin and moderately thick white coats were combined, the stricture rate was 23.8%. The rate of stricture in lesions with thick white coats was significantly higher than that in patients with thin white coats or thin to moderately thick white coats (p<0.05). The multivariate analysis revealed that the white coat status was an independent factor related to esophageal stricture (odds ratio 13.70, 95% confidence interval 1.22-154.0; p=0.034).ConclusionsThe thickness of the white coat is a useful marker for predicting the risk of post-ESD stricture and the effectiveness of preventive steroid therapy.

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  • 小腸障害モデルマウスにおけるRNA結合蛋白hnRNP A1の粘膜修復作用

    安藤 勝祥, 藤谷 幹浩, 奥村 利勝

    潰瘍   46   74 - 74   2019.6

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  • PREDICTION OF RELAPSE IN PATIENTS WITH ULCERATIVE COLITIS USING CONVENTIONAL ENDOSCOPY AND AUTOFLUORESCENCE IMAGING

    Kentaro Moriichi, Mikihiro Fujiya, Yu Kobayashi, Masami Ijiri, Yuuki Murakami, Takuya Iwama, Takehito Kunogi, Talahiro Sasaki, Keitaro Takahashi, Katsuyoshi Ando, Nobuhiro Ueno, Shin Kashima, Hiroki Tanabe, Toshikatsu Okumura

    GASTROINTESTINAL ENDOSCOPY   89 ( 6 )   AB634 - AB634   2019.6

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  • ABNORMAL ACTIVATION OF HNRNPA0 INHIBITS CANCER CELL APOPTOSIS AND PROMOTES EXCESSIVE MITOSIS IN CANCER CELLS

    Hiroaki Konishi, Mikihiro Fujiya, Akemi Kita, Hiroki Tanaka, Shin Kashima, Aki Sakatani, Tatsuya Dokoshi, Katsuyoshi Ando, Nobuhiro Ueno, Kentaro Moriichi, Takuya Iwama, Keitaro Takahashi, Yuuki Murakami, Katsuya Ikuta, Yusuke Mizukami, Takuma Goto, Toshikatsu Okumura

    GASTROENTEROLOGY   156 ( 6 )   S484 - S484   2019.5

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  • びまん性発赤の画像解析による客観的評価の検討

    野村 好紀, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    日本消化器がん検診学会雑誌   57 ( 3 )   521 - 521   2019.5

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  • full ESDと比較したrescue EMRの治療成績とリスク因子の検討

    高橋 慶太郎, 藤谷 幹浩, 奥村 利勝, 岩間 琢哉, 佐々木 貴弘, 久野木 健仁, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 村上 雄紀

    Gastroenterological Endoscopy   61 ( Suppl.1 )   945 - 945   2019.5

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  • 潰瘍性大腸炎における通常観察と拡大内視鏡観察による粘膜治癒の評価と再燃予測

    安藤 勝祥, 藤谷 幹浩, 奥村 利勝

    Gastroenterological Endoscopy   61 ( Suppl.1 )   690 - 690   2019.5

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  • 免疫チェックポイント阻害薬による肝障害のリスク因子の検討

    澤田 康司, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    肝臓   60 ( Suppl.1 )   A330 - A330   2019.4

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  • 【知っておきたい小腸疾患】小腸の腫瘍性・腫瘍様疾患 小腸リンパ増殖性疾患(悪性リンパ腫)

    嘉島 伸, 藤谷 幹浩, 村上 雄紀, 岩間 琢哉, 佐々木 貴弘, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 盛一 健太郎, 田邊 裕貴, 奥村 利勝

    胃と腸   54 ( 4 )   461 - 472   2019.4

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    <文献概要>消化管は悪性リンパ腫の好発部位であり,肉眼型は多彩である.悪性リンパ腫の確定診断には,生検または外科的切除標本における病理組織学的診断が必要である.消化管の中でも,小腸は診断が最も困難な部位であり,CTやPET-CTなどのモダリティーでは小腸悪性リンパ腫の検出は困難な場合が多く,カプセル内視鏡やダブルバルーン内視鏡を用いた小腸精査を積極的に行うべきである.また腸管悪性リンパ腫と良性リンパ濾胞過形成の鑑別には積極的にNBI拡大観察を併用し,血管網減少や不整血管出現などの特徴的所見を拾い上げることが,リンパ腫の小病変の診断に有用である.

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  • IBD治療のピットフォール(第21回) IBD患者における血栓症の予防、スクリーニング、対処法

    安藤 勝祥, 藤谷 幹浩

    IBD Research   13 ( 1 )   49 - 54   2019.3

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    炎症性腸疾患(IBD)に合併する静脈血栓塞栓症(VTE)は、IBD患者の主要な死因であり、QOLや生命予後を左右する重要な合併症として認識されている。欧米では健常者に比べ2~3倍の静脈血栓症発症リスクを有することが明らかにされており、近年わが国を含むアジア地域においてもVTEの頻度が高いことやその危険因子が明らかにされつつある。血栓症に対するスクリーニング・診断法としては、D-ダイマーや超音波・造影CTが推奨されており、欧米においては入院患者・ハイリスクの外来患者に対して、抗凝固療法による予防の推奨についてガイドラインに記載されている。わが国においては明確なスクリーニング法・予防介入に関しては明らかにされておらず、今後、適切なスクリーニングや予防の確立に向けたエビデンスを集積する必要がある。(著者抄録)

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  • Autofluorescence Imaging Reflects the Nuclear Enlargement of Tumor Cells as well as the Cell Proliferation Ability and Aberrant Status of the p53, Ki-67, and p16 Genes in Colon Neoplasms Reviewed

    Kentaro Moriichi, Mikihiro Fujiya, Yu Kobayashi, Yuki Murakami, Takuya Iwama, Takehito Kunogi, Takahiro Sasaki, Masami Ijiri, Keitaro Takahashi, Kazuyuki Tanaka, Aki Sakatani, Katsuyoshi Ando, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Katsuya Ikuta, Hiroki Tanabe, Yusuke Mizukami, Yusuke Saitoh, Toshikatsu Okumura

    MOLECULES   24 ( 6 )   2019.3

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    Background: Autofluorescence imaging (AFI) is useful for diagnosing colon neoplasms, but what affects the AFI intensity remains unclear. This study investigated the association between AFI and the histological characteristics, aberrant methylation status, and aberrant expression in colon neoplasms. Methods: Fifty-three patients with colorectal neoplasms who underwent AFI were enrolled. The AFI intensity (F index) was compared with the pathological findings and gene alterations. The F index was calculated using an image analysis software program. The pathological findings were assessed by the tumor crypt density, cell densities, and N/C ratio. The aberrant methylation of p16, E-cadherin, Apc, Runx3, and hMLH1 genes was determined by a methylation-specific polymerase chain reaction. The aberrant expression of p53 and Ki-67 was evaluated by immunohistochemical staining. Results: An increased N/C ratio, the aberrant expression of p53, Ki-67, and the altered methylation of p16 went together with a lower F index. The other pathological findings and the methylation status showed no association with the F index. Conclusions: AFI reflects the nuclear enlargement of tumor cells, the cell proliferation ability, and the altered status of cell proliferation-related genes, indicating that AFI is a useful and practical method for predicting the dysplastic grade of tumor cells and cell proliferation.

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  • The utility as a biomarker of faecal calprotectin for predicting the clinical outcome of granulocyte and monocyte adsorptive apheresis treatment in patients with ulcerative colitis

    N. Ueno, Y. Murakami, T. Iwama, T. Sasaki, T. Kunogi, K. Takahashi, K. Tanaka, K. Ando, S. Kashima, Y. Inaba, K. Moriichi, H. Tanabe, M. Taruishi, M. Fujiya, T. Okumura

    JOURNAL OF CROHNS & COLITIS   13   S423 - S424   2019.3

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  • 早期発見が可能であったクローン病を背景としたColitic cancerの1例

    佐藤 允洋, 上野 伸展, 藤谷 幹浩, 奥村 利勝, 久野木 健仁, 佐々木 貴弘, 岩間 琢哉, 高橋 慶太郎, 村上 雄紀, 嘉島 伸, 盛一 健太郎, 安藤 勝祥, 田邊 裕貴, 水上 裕輔

    日本消化器病学会北海道支部例会プログラム・抄録集   124回   78 - 78   2019.3

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  • 消化器疾患におけるサルコペニア クローン病に対する生物学的製剤投与時における骨格筋筋肉量・内臓脂肪量と臨床経過

    安藤 勝祥, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   116 ( 臨増総会 )   A40 - A40   2019.3

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  • 腸重積を契機に診断された小腸形質細胞腫の一例

    石垣 憲一, 佐藤 允洋, 齋藤 豪志, 村上 雄紀, 岩間 拓哉, 久野木 健仁, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 生田 克哉, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集   124回・118回   54 - 54   2019.3

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  • インフリキシマブ療法中の潰瘍性大腸炎患者における血中トラフ値と治療効果の検討

    田邉 裕貴, 田中 一之, 後藤 充, 佐藤 智信, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    日本内科学会雑誌   108 ( Suppl. )   217 - 217   2019.2

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  • Endoscopic Fine-Needle Aspiration Is Useful for the Treatment of Pneumatosis Cystoides Intestinalis With Intussusception

    Keitaro Takahashi, Mikihiro Fujiya, Nobuhiro Ueno, Katsuyoshi Ando, Shin Kashima, Kentaro Moriichi, Toshikatsu Okumura

    AMERICAN JOURNAL OF GASTROENTEROLOGY   114 ( 1 )   13 - 13   2019.1

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    DOI: 10.14309/ajg.0000000000000069

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  • Technical tips for performing endoscopic ultrasonography for invasion depth diagnosis of T1 colon carcinomas

    Yuhei Inaba, Yusuke Saitoh, Yu Kobayashi, Ryuji Sugiyama, Ryuji Sukegawa, Kenichiro Ozawa, Masaki Taruishi, Mikihiro Fujiya, Toshikatsu Okumura

    Gastroenterological Endoscopy   61 ( 5 )   1145 - 1157   2019

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    This paper describes technical tips for performing endoscopic ultrasonography (EUS) for invasion depth diagnosis of colorectal T1 carcinomas. EUS is a unique diagnostic modality different from colonoscopy that enables observation of images of cancer invasion to the submucosal layer by obtaining cross-sectional images of the lesion. It is recommended that novice endoscopists perform EUS by using a high-frequency ultrasound probe (HFUP), which is inserted through a standard colonoscope. EUS has some disadvantages including not being able to obtain EUS images in about 10% of lesions and occasionally obtaining unsatisfactory images of lesions located in flexures of the colon or on the colonic haustra. The accuracy of invasion depth diagnosis can be improved with intensive scanning of the suspicious invasive portion of the lesion by colonoscopy and scanning while looking at only the EUS monitor and not the endoscopic monitor. In case of polypoid lesions with a height of 6mm or more, it is difficult to obtain good HFUP images of the deepest part of the lesion by deep attenuation. In such cases, additional use of low-frequency probes (12 or 7.5MHz) is helpful for obtaining satisfactory images. We performed a retrospective review of cases in which EUS was performed for invasion depth diagnosis of colonic lesions in our department between 2007 and 2017. The overall accuracy of invasion depth diagnosis for determining the choice of therapy (i.e., endoscopic resection or surgery) was not very high at 77.0% (211/274). The accuracy of invasion depth diagnosis was significantly higher in T1b carcinomas than in Tis・T1a carcinomas [87.3% (125/151) vs. 69.2% (86/123) respectively; p<0.01]. Moreover, the accuracy rate was significantly higher in flat and depressed-type T1b carcinomas than in polypoid-type T1b carcinomas [91.4% (53/58) vs. 83.3% (50/60), respectively; p<0.05]. We think that HFUP will be useful for invasion depth diagnosis of especially flat and depressed-type T1b carcinomas. Because the submucosal invasion distance measured by EUS images has a good correlation with that measured in histological specimens, EUS will become an essential diagnostic modality in oder to expand the indications for endoscopic resection of T1b carcinomas as total excisional biopsy. Therefore, it is strongly recommended that all endoscopists become familiar with EUS procedures.

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  • Successful Treatment of Nivolumab-related Cholangitis with Prednisolone: A Case Report and Review of the Literature

    Koji Sawada, Tatsuya Shonaka, Yuji Nishikawa, Kimiharu Hasegawa, Hidemi Hayashi, Takumu Hasebe, Shunsuke Nakajima, Katsuya Ikuta, Mikihiro Fujiya, Hiroyuki Furukawa, Toshikatsu Okumura

    INTERNAL MEDICINE   58 ( 12 )   1747 - 1752   2019

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    The patient was a 76-year-old man who was treated with nivolumab due to recurrent gastric cancer. A blood examination revealed grade 3 alkaline phosphatase (ALP) elevation. A histopathological examination revealed marked portal infiltration, including eosinophils and CD4+ and CD8+ T lymphocytes, suggesting nivolumab-related cholangitis accompanied by the features of both an immune-related adverse event (irAE) and drug-induced liver injury (DILI) with allergic reaction. The patient's ALP level immediately decreased after the administration of prednisolone. Although nivolumab-related cholangitis, a rare irAE, has been reported to be refractory to steroid therapy, patients with features of irAE and allergic DILI might immediately respond to prednisolone.

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  • Successful medical treatment for a Crohn's disease patient with a perforation by a second-generation patency capsule. International journal

    Hiroki Tanabe, Katsuyoshi Ando, Hironori Ohdaira, Yutaka Suzuki, Ichiro Konuma, Nobuhiro Ueno, Mikihiro Fujiya, Toshikatsu Okumura

    Endoscopy international open   6 ( 12 )   E1436-E1438   2018.12

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    Background and study aims  Symptomatic capsule retention is a very rare adverse event following patency capsule, and the vast majority of cases are resolved without either surgical or endoscopic intervention. We herein describe a rare case of small bowel perforation after swallowing a patency capsule in a 37-year-old man suspected of having Crohn's disease.

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  • NAFLDにおけるLactobacillus brevis SBL8803の有用性に関する検討

    澤田 康司, 田中 宏樹, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 生田 克哉, 藤谷 幹浩, 奥村 利勝

    肝臓   59 ( Suppl.3 )   A959 - A959   2018.11

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  • Hyaluronidase inhibits reactive adipogenesis and inflammation of colon and skin

    Tatsuya Dokoshi, Ling-juan Zhang, Teruaki Nakatsuji, Christopher A. Adase, James A. Sanford, Rudolph D. Paladini, Hiroki Tanaka, Mikihiro Fujiya, Richard L. Gallo

    JCI INSIGHT   3 ( 21 )   2018.11

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    In this study we evaluated the role of hyaluronan (HA) in reactive adipogenesis, a local expansion of preadipocytes that provides host defense by release of antimicrobial peptides. We observed that HA accumulated during maturation of adipocytes in vitro and was associated with increased expression of preadipocyte factor 1, zinc finger protein 423, and early B cell factor 1. Although HA is normally abundant in the extracellular matrix, a further increase in HA staining occurred in mice at sites of reactive adipogenesis following injury of colon by dextran sodium sulfate or injury of skin from infection with Staphylococcus aureus. HA also abundantly accumulated around adipocytes seen in the colons of patients with inflammatory bowel disease. This HA was necessary for adipocyte maturation because digestion of HA by administration of soluble hyaluronidase or transgenic expression of hyaluronidase 1 inhibited adipogenesis in vitro and in vivo. Furthermore, hyaluronidase also suppressed inflammation of both skin and colon and decreased antimicrobial peptide expression by developing preadipocytes. This resulted in increased bacterial transit across the epithelial barrier despite decreased tissue injury from inflammation. These observations suggest HA plays an important role in reactive adipogenesis and host defense after injury.

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  • 内臓脂肪と腸腰筋筋肉量の変化からみたクローン病術後長期経過の検討

    安藤 勝祥, 小林 裕, 村上 雄紀, 佐藤 裕基, 岩間 琢哉, 久野木 健仁, 高橋 慶太郎, 河端 秀賢, 林 明宏, 上野 伸展, 後藤 拓磨, 嘉島 伸, 笹島 順平, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 水上 裕輔, 奥村 利勝

    日本消化器病学会雑誌   115 ( 臨増大会 )   A720 - A720   2018.10

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  • 多発性骨髄腫に合併し腸重積をきたした小腸形質細胞腫の一例

    久野木 健仁, 小林 裕, 村上 雄紀, 岩間 琢哉, 佐々木 貴弘, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 嘉島 伸, 盛一 健太郎, 田邊 裕貴, 藤谷 幹浩, 奥村 利勝

    日本小腸学会学術集会プログラム・抄録集   56回   50 - 50   2018.10

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  • 通常内視鏡およびAFIによる潰瘍性大腸炎の再燃予測

    小林 裕, 井尻 学見, 盛一 健太郎, 齊藤 成亮, 岩間 琢哉, 高橋 慶太郎, 安藤 勝祥, 野村 好紀, 上野 伸展, 嘉島 伸, 藤谷 幹浩, 奥村 利勝

    Gastroenterological Endoscopy   60 ( Suppl.2 )   2147 - 2147   2018.10

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  • 炎症性腸疾患における内視鏡的重症度分類とその意義 通常・拡大観察、AFIによる潰瘍性大腸炎の重症度評価

    藤谷 幹浩, 盛一 健太郎, 奥村 利勝

    日本消化器病学会雑誌   115 ( 臨増大会 )   A506 - A506   2018.10

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  • 炎症性腸疾患における内視鏡的重症度分類とその意義 通常・拡大観察、AFIによる潰瘍性大腸炎の重症度評価

    藤谷 幹浩, 盛一 健太郎, 奥村 利勝

    Gastroenterological Endoscopy   60 ( Suppl.2 )   1926 - 1926   2018.10

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  • IBD診療における通院距離と入院頻度・期間および手術頻度との関連性

    嘉島 伸, 齊藤 成亮, 小林 裕, 岩間 拓哉, 高橋 慶太郎, 安藤 勝祥, 上野 伸展, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   115 ( 臨増大会 )   A722 - A722   2018.10

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  • 炎症性腸疾患治療の最前線 Invited Reviewed

    藤谷幹浩

    日本病院薬剤師会雑誌   2018.10

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  • The incidence and risk factors of venous thromboembolism in Japanese inpatients with inflammatory bowel disease: a retrospective cohort study Reviewed

    Katsuyoshi Ando, Mikihiro Fujiya, Yoshiki Nomura, Yuhei Inaba, Yuuya Sugiyama, Takuya Iwama, Masami Ijiri, Keitaro Takahashi, Kazuyuki Tanaka, Aki Sakatani, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Yusuke Mizukami, Toshikatsu Okumura

    INTESTINAL RESEARCH   16 ( 3 )   416 - 425   2018.7

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    Background/Aims: Venous thromboembolism (VTE) is a major extraintestinal manifestation in inflammatory bowel disease (IBD), regarded as an independent risk factor for VTE according to reports from Western countries. However, the incidence and risk factors of VTE in Asian IBD patients are not fully understood. We aimed to reveal the incidence and risk factors of VTE in Japanese IBD inpatients. Methods: The incidence of VTE in inpatients with IBD (n=340), gastrointestinal cancers (n=557), and other gastrointestinal diseases (n=569) treated at our hospital from 2009 to 2013 was retrospectively investigated. The characteristics and laboratory data of IBD inpatients with and without VTE were compared in univariate and multivariate analyses. Clinical courses of VTE in IBD were surveyed. Results: VTE was detected in 7.1% of IBD inpatients, significantly higher than in gastrointestinal cancer inpatients (2.5%) and inpatients with other gastrointestinal diseases (0.88%). The incidence of VTE in ulcerative colitis (UC) patients (16.7%) was much higher than that in those with Crohn's disease (3.6%). In the univariate analysis, the risk factors were an older age, central venous catheter, prednisolone, surgery, low serum albumin, high serum C-reactive protein and D-dimer. According to a multivariate analysis, >50 years of age and surgery were the only risk factors. The in-hospital mortality rate of IBD inpatients with VTE was 4.2%. Conclusions: The incidence of VTE with IBD, especially UC, was found to be high compared with other digestive disease, which was almost equivalent to that of Western countries. The efficacy of prophylaxis needs to be investigated in Asian IBD patients.

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  • Sorafenib治療におけるsarcopenia合併の意義

    澤田 康司, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    The Liver Cancer Journal   ( Suppl.1 )   88 - 89   2018.6

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  • Takayasu's arteritis associated with eosinophilic gastroenteritis, possibly via the overactivation of Th17 Reviewed

    Mikihiro Fujiya, Shin Kashima, Yuya Sugiyama, Takuya Iwama, Masami Ijiri, Kazuyuki Tanaka, Keitaro Takahashi, Katuyoshi Ando, Yoshiki Nomura, Nobuhiro Ueno, Takuma Goto, Kentaro Moriichi, Yusuke Mizukami, Toshikatsu Okumura, Junpei Sasajima, Daisuke Fujishiro, Kensaku Okamoto, Yuichi Makino

    GUT PATHOGENS   10 ( 1 )   22   2018.6

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    Background: Takayasu's arteritis (TA) is a large-vessel vasculitis pathologically characterized by granulomatous necrotizing vasculitis with giant cells. Although the cause of TA is still unclear, genetic factors as well as immunological abnormalities, particularly the overactivation of Th1 and Th-17, are considered to play important roles in the pathogenesis of this disease. Eosinophilic gastroenteritis (EGE) is a type of refractory inflammation in which numerous eosinophils infiltrate the inflammatory area. It is known that the overactivation of Th2 is associated with the pathogenesis of EGE, although the cause of EGE is still unclear. The immunological abnormalities in TA are therefore thought to be different from those in EGE. To date, no cases of complication of TA and EGE have been reported.Case presentations: An 18 year-old female was diagnosed with EGE and treated with prednisolone. At 6 months after completion of the treatment, the patient experienced chest pain, and was diagnosed with TA. TH1 and TH17 immunity are thought to be involved with TA, while TH2 are considered to be involved with EGE. In this case, the expression of IL-17 mRNA in the colon mucosa greatly decreased after prednisolone treatment for EGE.Conclusions: This is the first report of TA complicated with EGE, and the overactivation of TH17 is considered to be associated with the pathogenesis of these two diseases.

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  • Vonoprazan-based triple therapy is non-inferior to susceptibility-guided proton pump inhibitor-based triple therapy for Helicobacter pylori eradication Reviewed

    Hiroki Tanabe, Keiichi Yoshino, Katsuyoshi Ando, Yoshiki Nomura, Katsuhisa Ohta, Kiichi Satoh, Eiichiro Ichiishi, Akiei Ishizuka, Takaaki Otake, Yutaka Kohgo, Mikihiro Fujiya, Toshikatsu Okumura

    ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS   17 ( 1 )   29   2018.6

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    Background: All Helicobacter pylori-infected patients are recommended for eradication with an appropriate regimen in each geographic area. The choice of the therapy is somewhat dependent on the antimicrobial susceptibility. The rate of clarithromycin resistance has been increasing and is associated with failure; thus, susceptibility testing is recommended before triple therapy with clarithromycin. However, antimicrobial susceptibility testing is not yet clinically available and an alternative newly developed acid inhibitor vonoprazan is used for triple therapy in Japan. The aim of this study was to determine whether vonoprazan-based triple therapy is plausible treatment in H. pylori eradication.Methods: A retrospective observational study of H. pylori eradication was conducted in a single institute. The patients who requested antimicrobial susceptibility testing were treated with susceptibility-guided proton pump inhibitor-based triple therapy in International University of Health and Welfare Hospital from 2013 to 2016. Other patients were treated with empirical treatment with a proton pump inhibitor. From 2015 to 2016, vonoprazan-based triple treatment (vonoprazan, 20 mg; amoxicillin, 750 mg; and clarithromycin, 200 or 400 mg, b.i.d.) was conducted, and its effectiveness was compared with susceptibility-guided proton pump inhibitor-based triple therapy. We also investigated the improvement in eradication rate when antimicrobial susceptibility testing was performed, and compared the outcomes of vonoprazan-based and proton pump inhibitor-based empirical therapy.Results: A total of 1355 patients who received first-line eradication treatment were enrolled in the present study. The eradication rates of the empirical proton pump inhibitor-based therapy and the vonoprazan-based therapy group in a per-protocol analysis were 86.3% (95% CI 83.8-88.8) and 97.4% (95% CI 95.7-99.1), respectively. In 212 patients who received antimicrobial susceptibility testing, the rate of clarithromycin resistant was 23.5% and the eradication rate in susceptibility-guided treatment was 95.7% (95% CI 92.9-98.4). The difference between susceptibility-guided and vonoprazan-based therapy was - 1.7% (95% CI - 4.9 to 1.5%), and the non-inferiority of vonoprazan-based triple therapy was confirmed.Conclusions: Vonoprazan-based triple therapy was effective as susceptibility-guided triple therapy for H. pylori eradication. An empirical triple therapy with vonoprazan is preferable even in area with high rates of clarithromycin-resistance.

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  • NEUROENDOCRINE CARCINOMA OF THE GALLBLADDER: PROGNOSTIC FACTORS AND OPTIMAL TREATMENT OPTIONS

    Hiroki Sato, Junpei Sasajima, Takuma Goto, Yusuke Mizukami, Takuya Iwama, Tetsuhiro Okada, Masami Ijiri, Keitaro Takahashi, Shugo Fujibayashi, Akihiro Hayashi, Hidemasa Kawabata, Katsuyoshi Ando, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Shuhei Takauji, Kentaro Moriichi, Mikihiro Fujiya, Toshikatsu Okumura

    GASTROENTEROLOGY   154 ( 6 )   S954 - S954   2018.5

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  • Echinococcosis infection diagnosed based on the histological findings of a lymph node involvement obtained by EUS-FNA Reviewed

    Kentaro Moriichi, Mikihiro Fujiya, Takuma Goto, Toshikatsu Okumura

    ENDOSCOPIC ULTRASOUND   7 ( 3 )   210 - 211   2018.5

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  • Detection and characterization of colitis-associated cancer/dysplasia: Based on reports from the JDDW 2017 and meta-analyses of prospective studies concerning endoscopic procedure Reviewed

    Mikihiro Fujiya

    DIGESTIVE ENDOSCOPY   30 ( 3 )   332 - 337   2018.5

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    DOI: 10.1111/den.13024

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  • MULTIPLE ASCENDING DOSE, OPEN-LABEL, PHASE 1/2 STUDY OF E6011, AN ANTI-FRACTALKINE MONOCLONAL ANTIBODY, TO INVESTIGATE THE SAFETY AND CLINICAL RESPONSE IN PATIENTS WITH CROHN'S DISEASE

    Satoshi Tanida, Katsuyoshi Matsuoka, Makoto Naganuma, Kazuya Kitamura, Toshiyuki Matsui, Makoto Arai, Mikihiro Fujiya, Noriyuki Horiki, Hiroko Nebiki, Fukunori Kinjo, Takako Miyazaki, Takayuki Matsumoto, Motohiro Esaki, Keiichi Mitsuyama, Masayuki Saruta, Akio Ido, Seiichiro Hojo, Osamu Takenaka, Kiyoshi Oketani, Toshio Imai, Hirohito Tsubouchi, Toshifumi Hibi, Takanori Kanai

    GASTROENTEROLOGY   154 ( 6 )   S830 - S830   2018.5

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  • Echinococcosis infection diagnosed based on the histological findings of a lymph node involvement obtained by endoscopic ultrasound-guided fine-needle aspiration. Reviewed

    Moriichi K., Fujiya M., Goto T., Okumura T.

    Endoscopic ultrasound   2018.5

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  • X 炎症性腸疾患の患者指導、QOL 病診連携の推進 Invited Reviewed

    藤谷幹浩

    日本臨床   2018.4

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  • 【NASH/NAFLDの新知見】成因・病態 NASH/NAFLDと鉄代謝

    長谷部 拓夢, 林 秀美, 中嶋 駿介, 澤田 康司, 生田 克哉, 藤谷 幹浩, 奥村 利勝

    肝胆膵   76 ( 4 )   531 - 536   2018.4

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  • Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn's Disease

    Kenji Watanabe, Takayuki Matsumoto, Tadakazu Hisamatsu, Hiroshi Nakase, Satoshi Motoya, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi, Akira Andoh, Toshifumi Ashida, Katsuya Endo, Yutaka Endo, Hiroshi Fujita, Mikihiro Fujiya, Ken Haruma, Sakiko Hiraoka, Ichiro Hirata, Yutaka Honda, Hideki Iijima, Bunei Iizuka, Kentaro Ikeya, Takuya Inoue, Syuji Inoue, Yo Ishiguro, Shyunji Ishihara, Hiroaki Ito, Ryuichi Iwakiri, Takashi Kagaya, Hiroshi Kashida, Jun Kato, Takehiko Katsurada, Fukunori Kinjyo, Kiyonori Kobayashi, Mayumi Kodama, Reiko Kunisaki, Koichi Kurahara, Takafumi Kurokami, Lee Kyouwon, Koichiro Matsuda, Kazuhiro Matsueda, Keiichi Mitsuyama, Yuji Mizokami, Shiro Nakamura, Masafumi Nomura, Atsuhiro Ogawa, Kazuichi Okazaki, Kazuaki Otsuka, Hirotake Sakuraba, Masayuki Saruta, Makoto Sasaki, Takayuki Shirai, Tomoaki Suga, Kazuhito Sugimura, Toshiro Sugiyama, Fuminao Takeshima, Hiroyuki Tamaki, Shinji Tanaka, Satoshi Tanida, Keiichi Tominaga, Taku Tomizawa, Kenji Watababe, Syojiro Yamamoto, Masaki Yamashita, Atsushi Yoshida

    Clinical Gastroenterology and Hepatology   16 ( 4 )   542 - 549.e1   2018.4

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    Background & Aims: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. Methods: We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. Results: The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14–1.58; P for trend =.001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P <.001). Conclusions: In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.

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  • Sorafenib内服肝細胞癌症例のsarcopeniaに関する検討

    澤田 康司, 斎藤 義徳, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   115 ( 臨増総会 )   A318 - A318   2018.3

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  • Detection and characterization of colitis-associated cancer/dysplasia: Based on reports from the JDDW2017 and meta-analyses of prospective studies concerning endoscopic procedure. Reviewed

    Fujiya M

    Digestive Endoscopy   33 ( 2 )   332 - 337   2018.3

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  • 【IBDの内視鏡的粘膜治癒-評価法と臨床的意義】潰瘍性大腸炎の内視鏡的重症度評価 画像強調内視鏡(AFI,拡大内視鏡)所見からみた重症度

    井尻 学見, 藤谷 幹浩, 杉山 雄哉, 岩間 琢哉, 田中 一之, 高橋 慶太郎, 安藤 勝祥, 野村 好紀, 上野 伸展, 嘉島 伸, 盛一 健太郎, 奥村 利勝

    胃と腸   53 ( 2 )   169 - 176   2018.2

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    潰瘍性大腸炎の内視鏡検査では白色光観察のほか,画像強調内視鏡(IEE)を組み合わせることで疾患の診断や,より詳細な重症度・治療効果の評価が行われてきている.IEEには消化管組織から出る微弱な自家蛍光を画像化し病理組織学的な炎症強度を数値として評価する客観性の高い自家蛍光内視鏡(AFI)や,粘膜表層の微細構造変化から炎症を評価する拡大内視鏡などがある.これらのIEEによる炎症の評価は病理組織学的活動性と相関するため,重症度や粘膜治癒の評価,再燃の予測が可能となり,最適な治療選択と長期の寛解維持へとつながることが期待される.(著者抄録)

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  • Efficacy of Quantitated Autofluorescence Imaging Endoscopy in Patients With Ulcerative Colitis: A Multicenter Study

    Moriichi Kentaro, Fujiya Mikihiro, Sugiyama Yuya, Iwama Takuya, Ijiri Masami, Tanaka Kazuyuki, Takahashi Keitaro, Sakatani Aki, Ando Katsuyoshi, Nomura Yoshiki, Ueno Nobuhiro, Kashima Shin, Inaba Yuhei, Ito Takahiro, Okumura Toshikatsu

    AMERICAN JOURNAL OF GASTROENTEROLOGY   113   S25 - S25   2018.2

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    DOI: 10.14309/00000434-201802001-00107

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  • Efficacy and safety of anti-fractalkine monoclonal antibody, E6011, in patients with Crohn's disease who had lost response to anti-TNF alpha agents: A multicentre, open-label, Phase 1/2 study

    K. Matsuoka, M. Naganuma, S. Tanida, K. Kitamura, T. Matsui, M. Arai, M. Fujiya, N. Horiki, H. Nebiki, F. Kinjo, T. Miyazaki, T. Matsumoto, M. Esaki, K. Mitsuyama, M. Saruta, A. Ido, S. Hojo, O. Takenaka, K. Oketani, T. Imai, H. Tsubouchi, T. Hibi, T. Kanai

    JOURNAL OF CROHNS & COLITIS   12   S70 - S70   2018.2

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  • 3.潰瘍性大腸炎の内視鏡的重症度評価 2)画像強調内視鏡所見からみた重症度 Invited Reviewed

    井尻学見, 藤谷幹浩, 杉山雄哉, 岩間琢哉, 田中一之, 高橋慶太朗, 安藤勝祥, 野村好紀, 上野伸展, 嘉島伸, 盛一健太郎, 奥村利勝

    胃と腸   2018.2

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  • An elevated expression of serum exosomal microRNA-191,-21,-451a of pancreatic neoplasm is considered to be efficient diagnostic marker Reviewed

    Takuma Goto, Mikihiro Fujiya, Hiroaki Konishi, Junpei Sasajima, Shugo Fujibayashi, Akihiro Hayashi, Tatsuya Utsumi, Hiroki Sato, Takuya Iwama, Masami Ijiri, Aki Sakatani, Kazuyuki Tanaka, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Yusuke Mizukami, Yutaka Kohgo, Toshikatsu Okumura

    BMC CANCER   18 ( 1 )   116 - 116   2018.1

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    Background: Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers.Methods: The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC (TM). The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction.Results: The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p < 0.05). A receiver operating characteristic curve analysis showed that the area under the curve and the diagnostic accuracy of ExmiRs were 5-20% superior to those of three serum bulky circulating miRs (e.g.; ExmiR-21: AUC 0.826, accuracy 80.8%. Circulating miR-21: AUC 0.653, accuracy 62.3%). In addition, high ExmiR-451a was associated with mural nodules in IPMN (p = 0.010), and high ExmiR-21 was identified as a candidate prognostic factor for the overall survival (p = 0.011, HR 4.071, median OS of high-ExmiR-21: 344 days, median OS of low-ExmiR-21: 846 days) and chemo-resistant markers (p = 0.022).Conclusions: The level of three ExmiRs can thus serve as early diagnostic and progression markers of pancreatic cancer and IPMN, and considered more useful markers than the circulating miRs (limited to these three miRs).

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  • Polymorphism of receptor-type tyrosine-protein phosphatase delta gene in the development of non-alcoholic fatty liver disease Reviewed

    Shunsuke Nakajima, Hiroki Tanaka, Koji Sawada, Hidemi Hayashi, Takumu Hasebe, Masami Abe, Chitomi Hasebe, Mikihiro Fujiya, Toshikatsu Okumura

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   33 ( 1 )   283 - 290   2018.1

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    Background and AimSome single-nucleotide polymorphisms (SNPs) are associated with the development of non-alcoholic fatty liver disease (NAFLD). As one of the genetic factors, PNPLA3 rs738409 (I148M) is important to associate with pathogenesis of NAFLD. Because other SNPs remain unclear in Japan, we performed a high-throughput sequencing that targeted more than 1000 genes to identify a novel genetic variant in Japanese patients with NAFLD.MethodsThe present study in 36 NAFLD patients and 27 healthy volunteers was performed. A high-throughput sequencer was used to detect the gene variations. Candidate genes were validated by TaqMan SNP genotyping assay in 53 NAFLD patients and 41 healthy volunteers. To investigate the function of candidate gene, we performed biochemical analyses in cultured hepatocytes and liver tissues.ResultsEXO1 rs1047840, PTPRD rs35929428, IFNAR2 rs2229207, CPOX rs1131857, IL23R rs1884444, IL10RA rs2228055, and FAM3B rs111988437 were identified as candidate genetic variants, and PTPRD rs35929428 was only extracted as a SNP predicting to cause protein dysfunction. In validation analysis, PTPRD rs35929428 associated with the development of NAFLD (P=0.015, odds ratio=5.00, 95% confidence interval: 1.33-18.70). In addition, PTPRD rs35929428 was associated with Fib-4 index and with hepatic fat droplets. Biochemical analyses indicated that PTPRD rs35929428 promoted dephosphorylation of tyrosine 705 signal transducer and activator of transcription 3 (Tyr 705) in hepatocytes.ConclusionPTPRD rs35929428 was a novel SNP in patients with NAFLD. Through exacerbation of the dephosphorylation of signal transducer and activator of transcription 3 (Tyr 705) in hepatocytes, PTPRD rs35929428 might play a role in hepatic lipid accumulation and fibrosis, followed by the development of NAFLD.

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  • Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial

    H. Nakase, S. Motoya, T. Matsumoto, K. Watanabe, Tadakazu Hisamatsu, N. Yoshimura, T. Ishida, S. Kato, T. Nakagawa, M. Esaki, M. Nagahori, T. Matsui, Y. Naito, T. Kanai, Y. Suzuki, M. Nojima, M. Watanabe, T. Hibi, Akira Andoh, Toshifumi Ashida, Katsuya Endo, Yutaka Endo, Motohiro Esaki, Hiroshi Fujita, Mikihiro Fujiya, Ken Haruma, Sakiko Hiraoka, Ichiro Hirata, Yutaka Honda, Hideki Iijima, Bunei Iizuka, Kentaro Ikeya, Takuya Inoue, Shuji Inoue, Yo Ishiguro, Shunji Ishihara, Hiroaki Ito, Ryuichi Iwakiri, Takashi Kagaya, Hiroshi Kashida, Shingo Kato, Jun Kato, Takehiko Katsurada, Fukunori Kinjyo, Kiyonori Kobayashi, Mayumi Kodama, Reiko Kunisaki, Koichi Kurahara, Takafumi Kurokami, Lee Kyouwon, Koichiro Matsuda, Kazuhiro Matsueda, Toshiyuki Matsui, Takayuki Matsumoto, Keiichi Mitsuyama, Yuji Mizokami, S. Motoya, Yuji Naito, Tomoo Nakagawa, Shiro Nakamura, Masafumi Nomura, Atsuhiro Ogawa, Kazuichi Okazaki, Kazuaki Otsuka, Hirotake Sakuraba, Masayuki Saruta, Makoto Sasaki, Takayuki Shirai, Tomoaki Suga, Kazuhito Sugimura, Toshiro Sugiyama, Fuminao Takeshima, Hiroyuki Tamaki, Shinji Tanaka, Satoshi Tanida, Keiichi Tominaga, Taku Tomizawa, Shojiro Yamamoto, Masaki Yamashita, Atsushi Yoshida

    Alimentary Pharmacology and Therapeutics   46 ( 9 )   873 - 882   2017.11

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    Background: Significance of monitoring adalimumab trough levels and anti-adalimumab antibodies (AAA) for disease outcome in Crohn's disease (CD) patients remained unclear. Aim: To evaluate the association of adalimumab trough levels and AAA at week 26 with clinical remission at week 52, the effect of azathiopurine on AAA and factors influencing trough levels in CD patients in the DIAMOND trial. Methods: We performed this study using adalimumab trough levels, AAA at week 26 and 6-thioguanine nucleotide (TGN) in red blood cells at week 12. A multiple regression model and receiver operating analysis was performed to identify factors influencing adalimumab trough levels and AAA, and adalimumab thresholds for predicting disease activity. Results: There was a significant difference of adalimumab trough level at week 26 between patients with disease remission and without at week 52 (7.7 ± 3.3 μg/mL vs 5.4 ± 4.3 μg/mL: P <.001). Adalimumab trough level of 5.0 μg/mL yielded optimal sensitivity and specificity for remission prediction (80.2% and 55.6%, respectively). AAA development at week 26 significantly affected remission at week 52 (P =.021), which was strongly associated with adalimumab trough levels. Female gender and increasing body weight were independently associated with low adalimumab trough levels, and female gender was associated with AAA development. A cut-off 6TGN level of >222.5 p mol/8 ×108 RBCs yielded sensitivity (100%) and specificity (60.6%) for AAA negativity. Conclusion: Adalimumab trough levels and AAA occurrence were significantly associated with clinical remission. Higher 6TGN affected AAA negativity. The combination therapy is beneficial in some relevant aspects for CD patients. (UMIN Registration No. 000005146).

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  • 当院における新規肝炎ウイルス検査陽性者への受診勧奨体制とHBV再活性化対策の状況

    澤田 康司, 林 秀美, 長谷部 拓夢, 中嶋 駿介, 生田 克哉, 藤谷 幹浩, 奥村 利勝

    肝臓   58 ( Suppl.3 )   A883 - A883   2017.11

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  • Efficacy of Vonoprazan-Based Triple Therapy for Helicobacter pylori Eradication: A Multicenter Study and a Review of the Literature Reviewed

    Hiroki Tanabe, Katsuyoshi Ando, Kiichi Sato, Takahiro Ito, Mitsuru Goto, Tomonobu Sato, Akihiro Fujinaga, Toru Kawamoto, Tatsuya Utsumi, Nobuyuki Yanagawa, Eiichiro Ichiishi, Takaaki Otake, Yutaka Kohgo, Yoshiki Nomura, Nobuhiro Ueno, Hiroko Sugano, Shin Kashima, Kentaro Moriichi, Mikihiro Fujiya, Toshikatsu Okumura

    DIGESTIVE DISEASES AND SCIENCES   62 ( 11 )   3069 - 3076   2017.11

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    Background Eradication therapies for Helicobacter pylori infection are advancing as new acid inhibitory reagents approved. The aim of this study was to assess the efficacy and safety of vonoprazan-based triple treatment.Materials and Methods Triple therapy with vonoprazan and two antibiotics (amoxicillin and clarithromycin or metronidazole) received focus in this analysis. We performed a multicenter retrospective study of patients who received vonoprazan-based eradication therapy between February 2015 and February 2016 and conducted a review of the literature.Results The eradication rate among the 799 patients in our multicenter study was 94.4% (95% confidence interval [CI] 92.6-96.2%) in the per-protocol analysis for first-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg, twice a day for 7 days) and 97.1% (95% CI 93.0-101.1%) for second-line treatment (with vonoprazan 20 mg, amoxicillin 750 mg, and metronidazole 250 mg, twice a day for 7 days). The overall incidence of adverse events was 4.4% in an intention-to-treat analysis with no patients hospitalized. In a literature review, six reports, in which 1380 patients received vonoprazan-based first-line eradication therapy, were included and were all reported by Japanese researchers. The eradication success rates in per-protocol analysis were between 85 and 93%, which was roughly the same among the studies.Conclusions Vonoprazan-based triple therapy was effective and safe for Helicobacter pylori eradication in real-world experience, confirmed by a multicenter study and a review of the pertinent literature.

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  • 画像強調内視鏡診断の最新の知見 自家蛍光内視鏡検査(AFI)の潰瘍性大腸炎における有用性の検討

    盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   114 ( 臨増大会 )   A498 - A498   2017.9

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  • 潰瘍性大腸炎の炎症評価に有用なCT重症度score(CTS)の検討

    杉山 雄哉, 嘉島 伸, 岩間 琢哉, 井尻 学見, 田中 一之, 高橋 慶太郎, 安藤 勝祥, 野村 好紀, 上野 伸展, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    Gastroenterological Endoscopy   59 ( Suppl.2 )   2179 - 2179   2017.9

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  • 食道ESD後狭窄を予測する食道狭窄リスク分類の検討

    高橋 慶太郎, 杉山 雄哉, 岩間 琢哉, 井尻 学見, 田中 一之, 安藤 勝祥, 野村 好紀, 上野 伸展, 嘉島 伸, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    Gastroenterological Endoscopy   59 ( Suppl.2 )   2125 - 2125   2017.9

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  • 炎症性腸疾患入院患者における静脈血栓塞栓症の発症頻度とリスク層別化についての検討

    安藤 勝祥, 野村 好紀, 杉山 雄哉, 岩間 琢哉, 井尻 学見, 田中 一之, 高橋 慶太郎, 上野 伸展, 嘉島 伸, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   114 ( 臨増大会 )   A797 - A797   2017.9

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  • 便中カルプロテクチンを用いた顆粒球除去療法の効果予測に関する検討

    上野 伸展, 岩間 琢哉, 井尻 学見, 田中 一之, 高橋 慶太郎, 安藤 勝祥, 野村 好紀, 嘉島 伸, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   114 ( 臨増大会 )   A796 - A796   2017.9

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  • 画像強調内視鏡診断の最新の知見 自家蛍光内視鏡検査(AFI)の潰瘍性大腸炎における有用性の検討

    盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    Gastroenterological Endoscopy   59 ( Suppl.2 )   1972 - 1972   2017.9

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  • 画像強調内視鏡診断の最新の知見 自家蛍光内視鏡検査(AFI)の潰瘍性大腸炎における有用性の検討

    盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    日本消化器がん検診学会雑誌   55 ( Suppl. )   944 - 944   2017.9

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  • Tegafur-uracil-induced rapid development of advanced hepatic fibrosis Reviewed

    Shuya Honda, Koji Sawada, Takumu Hasebe, Shunsuke Nakajima, Mikihiro Fujiya, Toshikatsu Okumura

    WORLD JOURNAL OF GASTROENTEROLOGY   23 ( 31 )   5823 - 5828   2017.8

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    Tegafur-uracil has been reported to have only minor adverse effects and is associated with liver injury in 1.79% of Japanese patients. The development of tegafur-uracil-induced hepatic fibrosis with portal hypertension is rare. Here, we report a case of a 74-year-old woman with rapidly developing tegafur-uracil-induced hepatic fibrosis. The patient had no history of liver disease and had been treated with tegafur-uracil for 8 mo after breast cancer surgery. The patient was admitted to our hospital for abdominal distension and leg edema associated with liver dysfunction. computed tomography imaging revealed massive ascites and splenomegaly, and a non-invasive assessment of liver fibrosis indicated advanced fibrosis. The histopathological findings revealed periportal fibrosis and bridging fibrosis with septation. The massive ascites resolved after discontinuing tegafur-uracil. These findings suggest that advanced hepatic fibrosis can develop from a relatively short-term administration of tegafur-uracil and that non-invasive assessment is useful for predicting hepatic fibrosis.

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  • AFIによる大腸上皮性腫瘍の組織学的および分子生物学的特徴の予測

    藤谷 幹浩, 盛一 健太郎, 奥村 利勝

    日本大腸肛門病学会雑誌   70 ( 8 )   554 - 554   2017.8

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  • The endoscopic findings of the upper gastrointestinal tract in patients with Crohn's disease Reviewed

    Yoshiki Nomura, Kentaro Moriichi, Mikihiro Fujiya, Toshikatsu Okumura

    CLINICAL JOURNAL OF GASTROENTEROLOGY   10 ( 4 )   289 - 296   2017.8

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    Crohn's disease (CD) is a type of chronic inflammatory bowel disease (IBD) associated with ulceration, and the main foci of the inflammation in CD patients are typically the terminal ileum and colon. However, in the upper gastrointestinal tract (GIT), including the esophagus, stomach and duodenum, inflammatory lesions are also detected as well, with a relatively high frequency (30-75%). Recent advances in imaging modalities, including endoscopy, have aided in the diagnosis of CD. Various lesions, including aphtha, erosion, ulcers, bamboo-joint-like appearance and notch-like appearance, are detected in the upper GI of CD patients. Of these lesions, the bamboo-joint-like appearance in the gastric cardiac region and notch-like appearance in the second portion of the duodenum are highly specific for CD, regardless of the disease activity at other sites. These two findings, particularly a bamboo-joint-like appearance, have therefore been considered as potential biomarkers for CD. Although proton pump inhibitors (PPIs) are administered as an initial treatment for upper GIT lesions of CD, the efficacy of this treatment remains controversial. The administration of mesalazine, steroids, immunosuppressant and biologic agents is expected to be effective for treating such lesions.

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  • Second-line therapy for Helicobacter pylori eradication causing antibiotic-associated hemorrhagic colitis Reviewed

    Kazuyuki Tanaka, Mikihiro Fujiya, Aki Sakatani, Shugo Fujibayashi, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Takuma Goto, Junpei Sasajima, Kentaro Moriichi, Toshikatsu Okumura

    ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS   16 ( 1 )   54 - 54   2017.8

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    Objective: Helicobacter pylori (H. pylori) eradication rarely develops into antibiotic-associated hemorrhagic colitis (AAHC), in which the etiology of colitis remains unclear. We herein report a rare case of AAHC caused by second-line therapy for H. pylori eradication.Results: A 65-year-old female was administered second-line therapy for H. pylori composed of 1500 mg of amoxicillin, 500 mg of metronidazole and 40 mg of vonoprazan for 7 days because of first-line therapy failure. A day after completing second-line therapy, she complained of abdominal pain and hematochezia. Colonoscopy revealed a hemorrhage and edematous mucosa with no transparent vascular pattern in the transverse colon. A bacterial culture detected Klebsiella oxytoca (K. oxytoca), but no other pathogenic bacteria. A drug-induced lymphocyte stimulation test (DLST) showed positive reactions for both amoxicillin and metronidazole. According to these findings, the patient was diagnosed with AAHC. Bowel rest for 6 days relieved her abdominal pain and hematochezia.Conclusions: The present case developed AAHC caused by second-line therapy for H. pylori eradication. The pathogenesis is considered to be associated with microbial substitution as well as a delayed-type allergy to antibiotics, suggesting that AAHC is a potential adverse event of second-line therapy for H. pylori eradication.

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  • Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency Reviewed

    Yasumichi Toki, Katsuya Ikuta, Yoshie Kawahara, Noriyasu Niizeki, Masayuki Kon, Motoki Enomoto, Yuko Tada, Mayumi Hatayama, Masayo Yamamoto, Satoshi Ito, Motohiro Shindo, Yoko Kikuchi, Mitsutaka Inoue, Kazuya Sato, Mikihiro Fujiya, Toshikatsu Okumura

    INTERNATIONAL JOURNAL OF HEMATOLOGY   106 ( 1 )   116 - 125   2017.7

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    Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. If RET-He is, indeed, capable of evaluating iron deficiency (ID), it would be useful for immediate diagnosis of IDA. In the present study, we examined the usefulness of RET-He for diagnosis of ID. Blood samples were obtained from 211 patients. Anemia was defined as hemoglobin (Hb) level of < 12 g/dL. Iron deficiency was defined as serum ferritin level of < 12 ng/mL. Patients were classified into four groups: IDA, ID, control, and non-ID with anemia. Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.902, indicating that RET-He facilitates the diagnosis of ID with high accuracy. RET-He changed in parallel with changes in Hb during iron administration for 21 IDA patients. Our results indicate that RET-He may be a clinically useful marker for determining ID in the general population.

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  • Ferrichrome identified from Lactobacillus casei ATCC334 induces apoptosis through its iron-binding site in gastric cancer cells Reviewed

    Masami Ijiri, Mikihiro Fujiya, Hiroaki Konishi, Hiroki Tanaka, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Junpei Sasajima, Katsuya Ikuta, Toshikatsu Okumura

    TUMOR BIOLOGY   39 ( 6 )   1010428317711311   2017.6

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    Ferrichrome is known to be a siderophore, but it was recently identified as a tumor-suppressive molecule derived from Lactobacillus casei ATCC334 (L. casei). In the present study, we investigated the effects of ferrichrome in gastric cancer cells. Cell lines and xenograft models treated with ferrichrome demonstrated growth suppression. The expression levels of cleaved poly (adenosine diphosphate-ribose) polymerase, and cleaved caspase-9 were increased by ferrichrome treatment. Although the tumor-suppressive effects of ferrichrome were almost completely diminished by the iron chelation, the reduction in the intracellular iron by ferrichrome did not correlate with its tumor-suppressive effects. An exhaustive docking simulation indicated that iron-free ferrichrome can make stable conformations with various mammalian molecules, including transporters and receptors. In conclusion, probiotic-derived ferrichrome induced apoptosis in gastric cancer cells. The iron binding site of ferrichrome is the structure responsible for its tumor suppressive function.

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  • Inverted gastric adenocarcinoma of fundic gland mucosa type colliding with well differentiated adenocarcinoma: A case report Reviewed

    Keitaro Takahashi, Mikihiro Fujiya, Shin Ichihara, Kentaro Moriichi, Toshikatsu Okumura

    MEDICINE   96 ( 23 )   e7080   2017.6

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    Rationale:Gastric adenocarcinoma of fundic gland mucosa type (GA-FGM) is a rare tumor composed of atypical cells with differentiation toward the fundic gland as well as the foveolar epithelium. Including our case, only 9 cases of GA-FGMs were reported from 2010 to 2016.Concerns of the patient:An 87-year-old man was referred to our institution for endoscopic resection of a gastric lesion. The tumor was classified as type 0-I+IIa according to the Paris classification. Magnifying endoscopy with narrow band imaging (ME-NBI) revealed different structures of crypts and vessels among the components, illustrating the collision of 2 types of gastric cancer.Interventions:We performed endoscopic submucosal dissection and successfully removed the tumor en bloc.Outcomes:The histological findings differed markedly between the 0-I lesion and the 0-IIa lesion. The superficial part of the 0-I lesion consisted of a papillary structure, and the deeper part consisted of a tubular structure that showed inverted downward growth to the submucosal layer with the lamina muscularis mucosae. Immunohistochemically, the superficial part of the 0-I lesion was positive for MUC5AC, which had differentiated to foveolar epithelium. The deeper part was positive for pepsinogen-I and MUC6, which had differentiated to fundic gland. The 0-I lesion was diagnosed as gastric phenotype of adenocarcinoma differentiated to fundic gland mucosa with upward growth in the superficial part and downward growth in the deeper part. The 0-IIa lesion was composed of a tubular structure positive for MUC2, and it was diagnosed as an intestinal phenotype of well differentiated adenocarcinoma. The boundary was clear, and no transitional tissue was observed between the 0-I and 0-IIa lesions, suggesting that the 0-I+IIa lesion was a gastric collision tumor of GA-FGM and well differentiated adenocarcinoma.Lessons:We herein report the first case of inverted GA-FGM colliding with well differentiated adenocarcinoma. ME-NBI can be used to diagnose GA-FGM even if the lesion collides with other types of adenocarcinoma.

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  • 文献紹介IBD注目のKey論文 IL−23とIL−17の腸管免疫における役割の相違 Invited Reviewed

    小西弘晃, 藤谷幹浩

    IBD Research   2017.6

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  • 肝細胞癌治療における腸腰筋筋肉量の変化 ソラフェニブとBCAA投与の検討

    澤田 康司, 斎藤 義徳, 長谷部 拓夢, 中嶋 駿介, 生田 克哉, 藤谷 幹浩, 奥村 利勝

    肝臓   58 ( Suppl.1 )   A342 - A342   2017.4

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  • NAFLDにおける肝発癌にEXO1遺伝子多型が関与する

    長谷部 拓夢, 澤田 康司, 田中 宏樹, 中嶋 駿介, 藤谷 幹浩, 奥村 利勝

    肝臓   58 ( Suppl.1 )   A392 - A392   2017.4

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  • 消化管悪性リンパ腫の診断と治療効果判定におけるNarrow Band Imaging(NBI)の有用性

    嘉島 伸, 藤谷 幹浩, 岩間 琢哉, 井尻 学見, 高橋 慶太郎, 田中 一之, 坂谷 慧, 安藤 勝祥, 野村 好紀, 上野 伸展, 盛一 健太郎, 奥村 利勝

    Gastroenterological Endoscopy   59 ( Suppl.1 )   980 - 980   2017.4

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  • Bone morphogenetic protein-binding endothelial regulator of liver sinusoidal endothelial cells induces iron overload in a fatty liver mouse model Reviewed

    Takumu Hasebe, Hiroki Tanaka, Koji Sawada, Shunsuke Nakajima, Takaaki Ohtake, Mikihiro Fujiya, Yutaka Kohgo

    JOURNAL OF GASTROENTEROLOGY   52 ( 3 )   341 - 351   2017.3

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    Non-alcoholic fatty liver disease (NAFLD) is frequently accompanied by iron overload. However, because of the complex hepcidin-regulating molecules, the molecular mechanism underlying iron overload remains unknown. To identify the key molecule involved in NAFLD-associated iron dysregulation, we performed whole-RNA sequencing on the livers of obese mice.Male C57BL/6 mice were fed a regular or high-fat diet for 16 or 48 weeks. Internal iron was evaluated by plasma iron, ferritin or hepatic iron content. Whole-RNA sequencing was performed by transcriptome analysis using semiconductor high-throughput sequencer. Mouse liver tissues or isolated hepatocytes and sinusoidal endothelial cells were used to assess the expression of iron-regulating molecules.Mice fed a high-fat diet for 16 weeks showed excess iron accumulation. Longer exposure to a high-fat diet increased hepatic fibrosis and intrahepatic iron accumulation. A pathway analysis of the sequencing data showed that several inflammatory pathways, including bone morphogenetic protein (BMP)-SMAD signaling, were significantly affected. Sequencing analysis showed 2314 altered genes, including decreased mRNA expression of the hepcidin-coding gene Hamp. Hepcidin protein expression and SMAD phosphorylation, which induces Hamp, were found to be reduced. The expression of BMP-binding endothelial regulator (BMPER), which inhibits BMP-SMAD signaling by binding BMP extracellularly, was up-regulated in fatty livers. In addition, immunohistochemical and cell isolation analyses showed that BMPER was primarily expressed in the liver sinusoidal endothelial cells (LSECs) rather than hepatocytes.BMPER secretion by LSECs inhibits BMP-SMAD signaling in hepatocytes and further reduces hepcidin protein expression. These intrahepatic molecular interactions suggest a novel molecular basis of iron overload in NAFLD.

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  • 診断講座 症例から学ぶIBD鑑別診断のコツ(第33回) IBDに合併する血栓症の現状と対策

    安藤 勝祥, 藤谷 幹浩

    IBD Research   11 ( 1 )   48 - 53   2017.3

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    静脈血栓塞栓症(VTE)は炎症性腸疾患(IBD)の1~7.7%に合併するとされる腸管外合併症であり、欧米でのコホート研究では健常人の約2~3倍のリスクがあり、再燃・入院時の合併率はさらに高率となる。IBDに合併するVTEには下肢深部静脈血栓症(DVT)・肺血栓塞栓症(PE)だけでなく、脳静脈洞血栓症や門脈血栓症、カテーテル関連血栓症があり、IBD患者の生命予後を左右する重篤な合併症である。診断と治療については、非IBD患者と対応は変わらない。現在欧米のIBDガイドラインにおいてVTEの薬物的予防が推奨されており、わが国・アジア地域においても、IBDに合併するVTEの疫学・予防に関するエビデンスの集積が必要とされる。(著者抄録)

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  • IV.炎症性腸疾患と合併症との関わり 静脈血栓塞栓症 Invited Reviewed

    藤谷幹浩

    日本臨床   2017.3

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  • Daikenchuto (TU-100) Suppresses Tumor Development in the Azoxymethane and APC(min/+) Mouse Models of Experimental Colon Cancer Reviewed

    Takumu Hasebe, Jun Matsukawa, Daina Ringus, Jun Miyoshi, John Hart, Atsushi Kaneko, Masahiro Yamamoto, Toru Kono, Mikihiro Fujiya, Yutaka Kohgo, Chong-Zi Wang, Chun-Su Yuan, Marc Bissonnette, Mark W. Musch, Eugene B. Chang

    PHYTOTHERAPY RESEARCH   31 ( 1 )   90 - 99   2017.1

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    Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APC(min/+) mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APC(min/+) mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC(min/+) mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and beta-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright (C) 2016 John Wiley & Sons, Ltd.

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  • Genetic polymorphism of PTPRD (rs35929428) and risk of non-alcoholic fatty liver disease in Japanese

    S. Nakajima, H. Tanaka, K. Sawada, T. Hasebe, H. Hayashi, M. Abe, C. Hasebe, M. Fujiya, T. Okumura

    JOURNAL OF HEPATOLOGY   66 ( 1 )   S607 - S608   2017

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  • Pilot study of endoscopic retrograde 3-dimensional - computed tomography enteroclysis for the assessment of Crohn's disease Reviewed

    Hiroki Tanabe, Takahiro Ito, Yuhei Inaba, Katsuyoshi Ando, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Mikihiro Fujiya, Toshikatsu Okumura

    EUROPEAN JOURNAL OF RADIOLOGY OPEN   4   58 - 62   2017

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    Purpose: Endoscopic retrograde ileography (ERIG) is developed in our institute and applied clinically for the diagnosis and assessment of the Crohn's disease activity. We have further improved the technique using 3-dimensional - computed tomography enteroclysis (3D-CTE) and conducted a retrospective study to determine the feasibility and the diagnostic value of endoscopic retrograde 3D-CTE (ER 3D-CTE) in Crohn's disease patients in a state of remission.Methods: Thirteen Crohn's patients were included in this pilot study. CTE was performed after the infusion of air or CO2 through the balloon tube following conventional colonoscopy. The primary endpoint of this study was to assess the safety of this method. Secondarily, the specific findings of Crohn's disease and length of the visualized small intestine were assessed.Results: The procedures were completed without any adverse events. Gas passed through the small intestine and enterographic images were obtained in 10 out of 13 cases, but, in the remaining patients, insertion of the balloon tubes into the terminal ileum failed. Various features specific to Crohn's disease were visualized using ER 3D-CTE. A cobble stone appearance or hammock-like malformation was specific and effective for diagnosing Crohn's disease and the features of anastomosis after the surgical operations were also well described. Therefore, this technique may be useful after surgery.Conclusion: In this study, ER 3D-CTE was performed safely in Crohn's disease patients and may be used for the diagnosis and follow-up of this disease.

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  • Endoscopic Submucosal Dissection for Depressed-type Early Adenocarcinoma of the Terminal Ileum Reviewed

    Keitaro Takahashi, Takahiro Ito, Tomonobu Sato, Mitsuru Goto, Toru Kawamoto, Akihiro Fujinaga, Nobuyuki Yanagawa, Yoshinori Saito, Keisuke Sato, Mikihiro Fujiya

    INTERNAL MEDICINE   56 ( 10 )   1153 - 1156   2017

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    We herein report a rare case of ileal adenocarcinoma that was completely removed by endoscopic submucosal dissection (ESD) without any complications. An 80-year-old man was referred to our hospital to undergo treatment for an ileal tumor. Conventional colonoscopy showed a reddish depressed lesion that was classified as type 0-IIc according to the Paris classification. The ileal tumor was successfully removed en bloc by ESD with a negative surgical margin. The histological findings showed a well-differentiated adenocarcinoma with no submucosal or lymphovascular invasion. Colonoscopy and CT performed one year after ESD showed no local recurrence, stenosis, or lymph node metastasis.

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  • Adalimumab monotherapy and a combination with azathioprine for Crohn's disease: A prospective, randomized trial

    Takayuki Matsumoto, Satoshi Motoya, Kenji Watanabe, Tadakazu Hisamatsu, Hiroshi Nakase, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi, Akira Andoh, Toshifumi Ashida, Katsuya Endo, Yutaka Endo, Hiroshi Fujita, Mikihiro Fujiya, Ken Haruma, Sakiko Hiraoka, Ichiro Hirata, Yutaka Honda, Hideki Iijima, Bunei Iizuka, Kentaro Ikeya, Takuya Inoue, Shuji Inoue, Yo Ishiguro, Shunji Ishihara, Hiroaki Ito, Ryuichi Iwakiri, Takashi Kagaya, Hiroshi Kashida, Jun Kato, Takehiko Katsurada, Fukunori Kinjyo, Kiyonori Kobayashi, Mayumi Kodama, Reiko Kunisaki, Koichi Kurahara, Takafumi Kurokami, Lee Kyouwon, Koichiro Matsuda, Kazuhiro Matsueda, Keiichi Mitsuyama, Yuji Mizokami, Shiro Nakamura, Masafumi Nomura, Atsuhiro Ogawa, Kazuichi Okazaki, Kazuaki Otsuka, Hirotake Sakuraba, Masayuki Saruta, Makoto Sasaki, Takayuki Shirai, Tomoaki Suga, Kazuhito Sugimura, Toshiro Sugiyama, Fuminao Takeshima, Hiroyuki Tamaki, Shinji Tanaka, Satoshi Tanida, Keiichi Tominaga, Taku Tomizawa, Shojiro Yamamoto, Masaki Yamashita, Atsushi Yoshida

    Journal of Crohn's and Colitis   10 ( 11 )   1259 - 1266   2016.11

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    Background and Aims: The efficacy of azathioprine for Crohn's disease under adalimumab treatment remains obscure. Methods: In an open-labelled prospective study, we evaluated the efficacy of adalimumab with and without azathioprine in patients with active Crohn's disease, who were naïve to biologics and thiopurines. The patients were randomly assigned to subcutaneous administration of adalimumab [monotherapy group] or to exactly the same schedule of adalimumab with azathioprine [25- 100 mg daily] [combination group] for 52 Weeks. The primary endpoint was clinical remission at WWeek 26. We also evaluated the score for simple endoscopic severity of Crohn's disease before the therapy and at WWeeks 26 and 52. Results: A total of 176 patients were randomized to either the monotherapy group [n = 85] or to the combination group [n = 91]. Eighteen patients [21.2%] from the monotherapy group and 7 patients [7.7%] from the combination group withdrew owing to active disease, and 15 patients [16.5%] from the combination group and 1 patient [1.2%] from the monotherapy group withdrew due to side effects of the medications. Non-responder imputation analysis revealed that the remission rate at WWeek 26 did not differ between the monotherapy group and the combination group [71.8% vs 68.1%; OR 0.84, p = 0.63]. The rate of endoscopic improvement at WWeek 26 was significantly higher in the combination group [84.2%, n = 57] than in the monotherapy group [63.8%, n = 58] [p = 0.019]. Conclusion: The clinical efficacy of a combination of adalimumab and azathioprine at WWeek 26 did not differ from that of adalimumab monotherapy in patients with Crohn's disease naïve to both medications.

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  • 乳酸菌由来長鎖ポリリン酸の大腸癌に対する抗腫瘍効果

    坂谷 慧, 藤谷 幹浩, 笹島 順平, 生田 克哉, 奥村 利勝

    日本癌学会総会記事   75回   P - 1275   2016.10

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  • Soluble bioactive microbial mediators regulate proteasomal degradation and autophagy to protect against inflammation-induced stress Reviewed

    Yuhei Inaba, Nobuhiro Ueno, Masatsugu Numata, Xiaorong Zhu, Jeannette S. Messer, David L. Boone, Mikihiro Fujiya, Yutaka Kohgo, Mark W. Musch, Eugene B. Chang

    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY   311 ( 4 )   G634 - G647   2016.10

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    Bifidobacterium breve and other Gram-positive gut commensal microbes protect the gastrointestinal epithelium against inflammation-induced stress. However, the mechanisms whereby these bacteria accomplish this protection are poorly understood. In this study, we examined soluble factors derived from Bifidobacterium breve and their impact on the two major protein degradation systems within intestinal epithelial cells, proteasomes and autophagy. Conditioned media from gastrointestinal Gram-positive, but not Gram-negative, bacteria activated autophagy and increased expression of the autophagy proteins Atg5 and Atg7 along with the stress response protein heat shock protein 27. Specific examination of media conditioned by the Gram-positive bacterium Bifidobacterium breve (Bb-CM) showed that this microbe produces small molecules (<3 kDa) that increase expression of the autophagy proteins Atg5 and Atg7, activate autophagy, and inhibit proteasomal enzyme activity. Upregulation of autophagy by Bb-CM was mediated through MAP kinase signaling. In vitro studies using C2BBe1 cells silenced for Atg7 and in vivo studies using mice conditionally deficient in intestinal epithelial cell Atg7 showed that Bb-CM-induced cytoprotection is dependent on autophagy. Therefore, this work demonstrates that Gram-positive bacteria modify protein degradation programs within intestinal epithelial cells to promote their survival during stress. It also reveals the therapeutic potential of soluble molecules produced by these microbes for prevention and treatment of gastrointestinal disease.

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  • Iron-induced epigenetic abnormalities of mouse bone marrow through aberrant activation of aconitase and isocitrate dehydrogenase Reviewed

    Masayo Yamamoto, Hiroki Tanaka, Yasumichi Toki, Mayumi Hatayama, Satoshi Ito, Lynda Addo, Motohiro Shindo, Katsunori Sasaki, Katsuya Ikuta, Takaaki Ohtake, Mikihiro Fujiya, Yoshihiro Torimoto, Yutaka Kohgo

    INTERNATIONAL JOURNAL OF HEMATOLOGY   104 ( 4 )   491 - 501   2016.10

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    Iron overload remains a concern in myelodysplastic syndrome (MDS) patients. Iron chelation therapy (ICT) thus plays an integral role in the management of these patients. Moreover, ICT has been shown to prolong leukemia-free survival in MDS patients; however, the mechanisms responsible for this effect are unclear. Iron is a key molecule for regulating cytosolic aconitase 1 (ACO1). Additionally, the mutation of isocitrate dehydrogenase (IDH), the enzyme downstream of ACO1 in the TCA cycle, is associated with epigenetic abnormalities secondary to 2-hydroxyglutarate (2-HG) and DNA methylation. However, epigenetic abnormalities observed in many MDS patients occur without IDH mutation. We hypothesized that iron itself activates the ACO1-IDH pathway, which may increase 2-HG and DNA methylation, and eventually contribute to leukemogenesis without IDH mutation. Using whole RNA sequencing of bone marrow cells in iron-overloaded mice, we observed that the enzymes, phosphoglucomutase 1, glycogen debranching enzyme, and isocitrate dehydrogenase 1 (Idh1), which are involved in glycogen and glucose metabolism, were increased. Digital PCR further showed that Idh1 and Aco1, enzymes involved in the TCA cycle, were also elevated. Additionally, enzymatic activities of TCA cycle and methylated DNA were increased. Iron chelation reversed these phenomena. In conclusion, iron activation of glucose metabolism causes an increase of 2-HG and DNA methylation.

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  • 消化管悪性リンパ腫の診断におけるAutofluorescence Imaging(AFI)の有用性

    田中 一之, 嘉島 伸, 岩間 琢哉, 佐藤 裕基, 井尻 学見, 坂谷 慧, 高橋 慶太郎, 藤林 周吾, 野村 好紀, 上野 伸展, 後藤 拓磨, 笹島 順平, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    Gastroenterological Endoscopy   58 ( Suppl.2 )   1964 - 1964   2016.10

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  • 炎症性腸疾患患者における麻疹、風疹抗体保有率に関する検討

    上野 伸展, 岩間 琢哉, 佐藤 裕基, 内海 辰哉, 井尻 学見, 坂谷 慧, 田中 一之, 藤林 周吾, 野村 好紀, 嘉島 伸, 後藤 拓磨, 笹島 順平, 盛一 健太郎, 藤谷 幹浩, 奥村 利勝

    日本消化器病学会雑誌   113 ( 臨増大会 )   A763 - A763   2016.9

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  • In vivo behavior of NTBI revealed by automated quantification system Reviewed

    Satoshi Ito, Katsuya Ikuta, Daisuke Kato, Addo Lynda, Kotoe Shibusa, Noriyasu Niizeki, Yasumichi Toki, Mayumi Hatayama, Masayo Yamamoto, Motohiro Shindo, Naomi Iizuka, Yutaka Kohgo, Mikihiro Fujiya

    INTERNATIONAL JOURNAL OF HEMATOLOGY   104 ( 2 )   175 - 181   2016.8

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    Non-Tf-bound iron (NTBI), which appears in serum in iron overload, is thought to contribute to organ damage; the monitoring of serum NTBI levels may therefore be clinically useful in iron-overloaded patients. However, NTBI quantification methods remain complex, limiting their use in clinical practice. To overcome the technical difficulties often encountered, we recently developed a novel automated NTBI quantification system capable of measuring large numbers of samples. In the present study, we investigated the in vivo behavior of NTBI in human and animal serum using this newly established automated system. Average NTBI in healthy volunteers was 0.44 +/- 0.076 mu M (median 0.45 mu M, range 0.28-0.66 mu M), with no significant difference between sexes. Additionally, serum NTBI rapidly increased after iron loading, followed by a sudden disappearance. NTBI levels also decreased in inflammation. The results indicate that NTBI is a unique marker of iron metabolism, unlike other markers of iron metabolism, such as serum ferritin. Our new automated NTBI quantification method may help to reveal the clinical significance of NTBI and contribute to our understanding of iron overload.

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  • Perspectives of Japanese oncologists on the health economics of innovative cancer treatments Reviewed

    Tomoyuki Takura, Mikihiro Fujiya, Yasuhiro Shimada, Yutaka Kohgo

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   21 ( 4 )   633 - 641   2016.8

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    Few reports have thus far discussed the influence of economic factors on treatment decision-making by patients. The objective of the present study was to clarify the awareness among oncologists of health economics in cancer treatment.The present study was based on the questionnaire regarding health economics in cancer treatment carried out by the Japan Society of Clinical Oncology (JSCO) in July 2013. The subjects were trustees registered with JSCO. The survey investigated the influence of medical expenses on patient access to and selection of medical treatment in order to clarify the primary attributes of the respondents and their awareness of economics. The study also investigated the maximum allowable public medical expenses to prolong the life expectancy of a cancer patient by 1 year and the factors that can influence treatment selection.The 172 respondents had completed a mean of 30.3 +/- 6.2 postgraduate years, and the mean number of patients they treated annually was 1323 +/- 1963. The degree of treatment accessibility among patients was perceived positively by 112 (71.3 %) and negatively by 49 (28.7 %) of the respondents, irrespective of medical expenses. Of the 172 respondents, 66 (41.0 %) believed that the maximum allowable medical expenses for cancer treatment should be a parts per thousand currency sign4 million yen/LY, with 62 (39.8 %) reporting a value of 4.01-8 million yen/LY.The findings of this study suggest that a certain range of medical expenses has come to be regarded as the standard range of medical expenses for cancer treatment among oncologists, with answers based on the premise that patients should have access to effective medical treatment.

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  • Pancreatic metastasis of angiosarcoma (Stewart-Treves syndrome) diagnosed using endoscopic ultrasound-guided fine needle aspiration: A case report Reviewed

    Junpei Sasajima, Jiro Uehara, Takuma Goto, Shugo Fujibayashi, Kazuya Koizumi, Yusuke Mizukami, Akemi Ishida-Yamamoto, Mikihiro Fujiya, Toshikatsu Okumura

    MEDICINE   95 ( 33 )   e4316   2016.8

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    Background: Pancreatic involvement of angiosarcoma is extremely rare.Methods: We herein report a rare case of angiosarcoma associated with chronic lymphedema (Stewart-Treves syndrome) with pancreatic metastasis that was diagnosed using endoscopic ultrasound (EUS)/fine needle aspiration (FNA).Results: A 43-year-old woman with a history of radical hysterectomy with bilateral inguinal lymphadenectomy and chemoradiotherapy for cervical cancer 15 years prior noticed the presence of erythematous indurative plaques on her right femoral region, where chronic lymphedema had developed. Contrast-enhanced computed tomography (CT) revealed not only multiple nodules in the subcutaneous tissue of the right femoral region but also a 25mm x 20mm solid mass in the region of the pancreatic tail. A histological analysis of the specimens obtained using EUS/FNA revealed angiosarcoma that was immunohistochemically positive for platelet/endothelial cell adhesion molecule-1 but negative for cytokeratin. The patient was diagnosed as Stewart-Treves syndrome that had metastasized to the pancreas. Chemotherapy was performed, but the patient died 14 months after her diagnosis.Conclusion: Unfortunately, this patient was not followed up, even though she had chronic lymphedema of the right femoral region due to the repeated occurrence of phlegmon. To improve the survival rate of this fatal secondary malignant complication of radical lymphadenectomy, an early diagnosis with consecutive and long-term clinical follow-up and close monitoring for Stewart-Treves syndrome is therefore important.

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  • The efficacy of autofluorescence imaging in the diagnosis of colorectal diseases Reviewed

    Kentaro Moriichi, Mikihiro Fujiya, Toshikatsu Okumura

    CLINICAL JOURNAL OF GASTROENTEROLOGY   9 ( 4 )   175 - 183   2016.8

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    Image-enhanced endoscopy (IEE) has been developed and is applied in the clinical setting throughout the world. Most reports regarding IEE have evaluated the efficacy of narrow-band imaging (NBI) in the diagnosis of gastrointestinal disorders. Although autofluorescence imaging (AFI) is a form of IEE, its usefulness remains unclear. The present review focused on the efficacy of AFI in the diagnosis of colorectal disease, particularly neoplasia and ulcerative colitis (UC). AFI-based diagnoses are made via the subjective judgment of the color on the monitor. The efficacy of AFI in detection and differentiation in patients with colorectal neoplastic lesions remains controversial, which may be dependent on the study design and the diagnostic procedures. Although the number of the reports related to UC is very small, most suggest that AFI is effective in UC patients. AFI is distinct from other modalities in that it can quantitatively assess the lesion based on the fluorescence intensity without any morphological assessments. AFI could be useful for patients with colorectal disease.

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  • A selective splicing variant of hepcidin mRNA in hepatocellular carcinoma cell lines Reviewed

    Yasumichi Toki, Katsunori Sasaki, Hiroki Tanaka, Masayo Yamamoto, Mayumi Hatayama, Satoshi Ito, Katsuya Ikuta, Motohiro Shindo, Takumu Hasebe, Shunsuke Nakajima, Koji Sawada, Mikihiro Fujiya, Yoshihiro Torimoto, Takaaki Ohtake, Yutaka Kohgo

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   476 ( 4 )   501 - 507   2016.8

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    Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. By RT-PCR/agarose gel electrophoresis of hepcidin mRNA in a hepatocellular carcinoma cell line HLF, a smaller mRNA band was shown in addition to the wild-type hepcidin mRNA. From sequencing analysis, this additional band was a selective splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene, producing the transcript that encodes truncated peptide lacking 20 amino acids at the middle of preprohepcidin. In the present study, we used the digital PCR, because such a small amount of variant mRNA was difficult to quantitate by the conventional RT-PCR amplification. Among seven hepatoma-derived cell lines, six cell lines have significant copy numbers of this variant mRNA, but not in one cell line. In the transient transfection analysis of variant-type hepcidin cDNA, truncated preprohepcidin has a different character comparing with native preprohepcidin: its product is insensitive to digestion, and secreted into the medium as a whole preprohepcidin form without maturation. Loss or reduction of function of HAMP gene by aberrantly splicing may be a suitable phenomenon to obtain the proliferating advantage of hepatoma cells. (C) 2016 The Authors. Published by Elsevier Inc.

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  • Japanese Oncologists Perspectives for Health Economics on Innovative Cancer Treatments.

    Takura T., Fujiya M., Shimada Y., Kohgo Y.

    Int J Clin Oncol   2016.8

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  • A high-throughput sequence analysis of Japanese patients revealed 11 candidate genes associated with type 1 autoimmune pancreatitis susceptibility

    Shugo Fujibayashi, Junpei Sasajima, Takuma Goto, Hiroki Tanaka, Hidemasa Kawabata, Tsuneshi Fujii, Kazumasa Nakamura, Atsushi Chiba, Nobuyuki Yanagawa, Kentaro Moriichi, Mikihiro Fujiya, Yutaka Kohgo

    Biochemistry and Biophysics Reports   6   76 - 81   2016.7

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    The pathogenesis of autoimmune pancreatitis is unknown. In the present study we used high-throughput sequencing with next generation sequencing to identify the candidate genes associated with AIP. A total of 27 type 1 AIP patients and 30 healthy blood donors were recruited, and DNA samples were isolated from their mononuclear cells. A high-throughput sequencer with an original custom panel of 1031 genes was used to detect the genetic variants in each sample. Polymorphisms of CACNA1S (c.4642C>T), rs41554316, rs2231119, rs1042131, rs2838171, P2RX3 (c.195delG), rs75639061, SMAD7 (c.624delC) and TOP1 (c.2007delG), were identified as candidate genetic variants in patients with type 1 AIP. P2RX3 and TOP1 were significantly associated with AIP, even after adjusting bay means of Bonferroni's correction. In addition, we also identified eight candidate genetic variants that were associated with the relapse of type 1 AIP, namely: rs1143146, rs1050716, HLA-C (c.759_763delCCCCCinsTCCCG), rs1050451, rs4154112, rs1049069, CACNA1C (c.5996delC) and CXCR3 (c.630_631delGC). Finally polymorphisms of rs1050716 and rs111493987 were identified as candidate genetic variants associated with extra-pancreatic lesions in patients with type 1 AIP. These candidates might be used as markers of AIP susceptibility and could contribute to the pathogenesis of type 1 AIP.

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  • 上部消化管内視鏡を用いたクローン病診断における「竹の節状外観」の臨床的意義

    田邊 裕貴, 横田 欽一, 野村 好紀, 安藤 勝祥, 坂谷 慧, 田中 一之, 堂腰 達矢, 嘉島 伸, 上野 伸展, 稲場 勇平, 伊藤 貴博, 須藤 大輔, 太田 勝久, 一石 英一郎, 佐藤 貴一, 大竹 孝明, 高後 裕, 盛一 健太郎, 藤谷 幹浩

    日本消化器病学会雑誌   113 ( 7 )   1208 - 1215   2016.7

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    全消化管に病変が出現するクローン病では、上部消化管病変が高頻度に見られる。竹の節状外観は、胃噴門部から胃体部の小彎にかけて襞を横切る亀裂状の陥凹とされている。クローン病診断における竹の節状外観の有用性を検討するために、上部消化管内視鏡画像を用いて3名の観察者に臨床情報をブラインドにして研究を行った。観察者それぞれのクローン病診断における竹の節状外観の感度は30.5%、56.9%、51.4%で、特異度は99.6%、98.5%、99.3%であった。したがって竹の節状外観はクローン病患者の拾い上げには十分に貢献しないが、本所見を認めたときはクローン病の可能性を考えて検査を進める必要がある。(著者抄録)

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    Other Link: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01118&link_issn=&doc_id=20160726150006&doc_link_id=1390001206403545472&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001206403545472&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

  • Retrospective Analysis of Growth Speed of 54 Lesions of Colitis-associated Colorectal Neoplasia Reviewed

    Kazutomo Yamasaki, Toshiyuki Matsui, Takashi Hisabe, Yutaka Yano, Fumihito Hirai, Tsuyoshi Morokuma, Yasushi Iwao, Takayuki Matsumoto, Hidehisa Ohi, Akira Andoh, Motohiro Esaki, Kunihiko Aoyagi, Akira Sugita, Hiroshi Nakase, Mikihiro Fujiya, Daijiro Higashi, Kitaro Futami

    ANTICANCER RESEARCH   36 ( 7 )   3731 - 3740   2016.7

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    Aim: This study used a multicenter questionnaire survey to evaluate the morphology and progression of the initial lesion in cases of colitis-associated colorectal neoplasia (CRN). Patients and Methods: Endoscopic images of lesions that had been definitively diagnosed as CRN by pathological examination were retrospectively reviewed. Results: This resulted in the identification of 54 initial lesions in 49 patients. The 54 initial lesions fell into the following categories: 22 endoscopically visible localized lesions consisting of 18 elevated lesions and 4 depressed lesions, as well as 32 lesions that were not endoscopically visible as localized and consisted of 20 active-phase mucosal lesions and 12 remission-phase mucosal lesions. Nineteen of the lesions eventually became advanced cancers, while 35 lesions eventually became early-stage cancers. The final lesions were 40 elevated lesions, 5 flat or depressed lesions and 9 stenotic lesions. The form of growth of the advanced cancers was progressive stenosis or increased elevation. For approximately 69% of the early-stage cancers, the growth form was increasing elevation or development of elevation. For 73.6% of the advanced cancers, the initial lesion underwent rapid growth and became advanced cancer within 3 years; they accounted for 25.9% of the total cancers. Approximately 40% of the initial lesions of CRN were endoscopically visible as localized lesions, while approximately 60% were judged to be inflammatory mucosal lesions. Conclusion: It will be necessary to proactively take biopsy inflammatory mucosal lesions in order to discover tumors early and periodic surveillance should be performed with the knowledge that tumors may grow very quickly.

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  • The clinical importance of "bamboo joint-like appearance" on upper gastrointestinal endoscopy for the diagnosis of Crohn's disease Reviewed

    Hiroki Tanabe, Kinichi Yokota, Yoshiki Nomura, Katsuyoshi Ando, Kei Sakatani, Kazuyuki Tanaka, Tatsuya Dokoshi, Shin Kashima, Nobuhiro Ueno, Yuhei Inaba, Takahiro Ito, Daisuke Sutoh, Katsuhisa Ohta, Eiichiro Ichiishi, Kiichi Sato, Takaaki Otake, Yutaka Kohgo, Kentaro Moriichi, Mikihiro Fujiya

    Journal of Japanese Society of Gastroenterology   113 ( 7 )   1208 - 1215   2016.7

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    Upper gastrointestinal (GI) lesions are frequently reported in Crohn's disease, in which the entire GI tract is affected. In these cases, erosive fissures regularly transversing folds that are longitudinally aligned along the lesser curvature of the gastric body and cardia are described as having a "bamboo joint-like appearance". We designed a blinded experiment in which upper GI imaging without a final diagnosis was checked by three observers to determine the usefulness of the bamboo joint-like appearance in the diagnosis of Crohn's disease. For the three observers, sensitivities of appearance were 30.5%, 56.9%, and 51.4%, while specificities were 99.6%, 98.5%. and 99.3%. Thus, the bamboo joint-like appearance was not useful for the identification of Crohn's disease patients. Nevertheless, patients exhibiting the bamboo joint-like appearance in upper GI imaging should undergo further examination due to the high probability of Crohn's disease.

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  • Efficacy and adverse events of cold vs hot polypectomy: A meta-analysis Reviewed

    Mikihiro Fujiya, Hiroki Sato, Nobuhiro Ueno, Aki Sakatani, Kazuyuki Tanaka, Tatsuya Dokoshi, Shugo Fujibayashi, Yoshiki Nomura, Shin Kashima, Takuma Gotoh, Junpei Sasajima, Kentaro Moriichi, Jiro Watari, Yutaka Kohgo

    WORLD JOURNAL OF GASTROENTEROLOGY   22 ( 23 )   5436 - 5444   2016.6

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    AIM: To compare previously reported randomized controlled studies (RCTs) of cold and hot polypectomy, we systematically reviewed and clarify the utility of cold polypectomy over hot with respect to efficacy and adverse events.METHODS: A meta-analysis was conducted to evaluate the predominance of cold and hot polypectomy for removing colon polyps. Published articles and abstracts from worldwide conferences were searched using the keywords "cold polypectomy". RCTs that compared either or both the effects or adverse events of cold polypectomy with those of hot polypectomy were collected. The patients' demographics, endoscopic procedures, No. of examined lesions, lesion size, macroscopic and histologic findings, rates of incomplete resection, bleeding amount, perforation, and length of procedure were extracted from each study. A forest plot analysis was used to verify the relative strength of the effects and adverse events of each procedure. A funnel plot was generated to assess the possibility of publication bias.RESULTS: Ultimately, six RCTs were selected. No significant differences were noted in the average lesion size (less than 10 mm) between the cold and hot polypectomy groups in each study. Further, the rates of complete resection and adverse events, including delayed bleeding, did not differ markedly between cold and hot polypectomy. The average procedural time in the cold polypectomy group was significantly shorter than in the hot polypectomy group.CONCLUSION: Cold polypectomy is a time-saving procedure for removing small polyps with markedly similar curability and safety to hot polypectomy.

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  • NASH病態における鉄代謝研究の新たな展開

    大竹 孝明, 長谷部 拓夢, 中嶋 駿介, 澤田 康司, 藤谷 幹浩, 高後 裕, 田中 宏樹, 佐々木 勝則

    アルコールと医学生物学   34   96 - 97   2016.6

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  • Infection with fully mature Corynosoma cf. validum causes ulcers in the human small intestine Reviewed

    Keitaro Takahashi, Takahiro Ito, Tomonobu Sato, Mitsuru Goto, Toru Kawamoto, Akihiro Fujinaga, Nobuyuki Yanagawa, Yoshinori Saito, Minoru Nakao, Hideo Hasegawa, Mikihiro Fujiya

    CLINICAL JOURNAL OF GASTROENTEROLOGY   9 ( 3 )   114 - 117   2016.6

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    Corynosoma is a parasite that can normally be found in the intestinal tract of fish-eating mammals, particularly in seals and birds. The present case proposed that Corynosoma could attain full maturity in the human intestine. A 70-year-old female complained of abdominal pain. A computed tomography (CT) scan revealed a swelling of the intraperitoneal lymph nodes with no responsible lesion. Video capsule endoscopy and double-balloon endoscopy detected several ulcerations and one parasite in the ileum, which was tightly attached at the bottom of the ulcerations. The parasite was cylindrical and measured approximately 10 mm (long) x 3 mm (wide). Pathologically, the worm had a four-layered body wall and contained embryonated eggs. The sequences of the parasite-derived nuclear ribosomal DNA fragment and mitochondrial DNA fragment of cox1 were almost identical to those of Corynosoma validum. The patient's abdominal pain immediately improved after the administration of pyrantel pamoate (1,500 mg). Corynosoma was possibly the responsible disease in a patient who complained of abdominal pain and in whom no responsible lesion was detected by CT, gastroduodenoscopy or colonoscopy. Examinations of the small intestines should be aggressively performed in such cases.

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  • 【消化管拡大内視鏡診断2016】大腸 炎症性腸疾患の拡大内視鏡診断 炎症

    野村 好紀, 藤谷 幹浩, 岩間 琢哉, 佐藤 裕基, 本田 宗也, 内海 辰哉, 井尻 学見, 田中 一之, 坂谷 慧, 藤林 周吾, 上野 伸展, 嘉島 伸, 後藤 拓麿, 笹島 順平, 盛一 健太郎

    胃と腸   51 ( 5 )   683 - 689   2016.5

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    炎症性腸疾患における内視鏡検査は疾患の診断や鑑別のみならず,治療効果や経過の評価,治療方針の変更や継続,中止などの判断に重要な検査である.また,粘膜表層の微細構造を観察することのできる拡大内視鏡検査は,粘膜および粘膜下層を主体とした潰瘍性大腸炎の炎症の評価において,特に有用な手技であり,組織学的活動性,治癒過程の推移,再燃の予測が可能となる.潰瘍性大腸炎の拡大内視鏡所見を理解することで,粘膜治癒の評価を適切に行うことができ,症例ごとに最適な治療選択が可能となり,長期の寛解維持へとつながることが期待される.(著者抄録)

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  • 大腸炎の内視鏡診断と治療のコツ 白色光、拡大観察、AFIによる潰瘍性大腸炎の活動性評価

    野村 好紀, 盛一 健太郎, 藤谷 幹浩

    Gastroenterological Endoscopy   58 ( Suppl.1 )   508 - 508   2016.4

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  • 小腸悪性リンパ腫の診断における内視鏡検査の有用性

    田中 一之, 岩間 琢哉, 佐藤 裕基, 内海 辰哉, 井尻 学見, 坂谷 慧, 藤林 周吾, 野村 好紀, 上野 伸展, 嘉島 伸, 後藤 拓磨, 笹島 順平, 盛一 健太郎, 藤谷 幹浩

    Gastroenterological Endoscopy   58 ( Suppl.1 )   704 - 704   2016.4

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  • 潰瘍性大腸炎に対する内視鏡的活動性評価能の検討

    井尻 学見, 盛一 健太郎, 岩間 琢哉, 佐藤 裕基, 内海 辰哉, 坂谷 慧, 田中 一之, 藤林 周吾, 野村 好紀, 上野 伸展, 嘉島 伸, 後藤 拓磨, 笹島 順平, 藤谷 幹浩

    Gastroenterological Endoscopy   58 ( Suppl.1 )   618 - 618   2016.4

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  • Management of colorectal T1 carcinoma treated by endoscopic resection Reviewed

    Yusuke Saitoh, Yuhei Inaba, Takahiro Sasaki, Ryuji Sugiyama, Ryuji Sukegawa, Mikihiro Fujiya

    DIGESTIVE ENDOSCOPY   28 ( 3 )   324 - 329   2016.4

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    As a result of recent advances in endoscopic therapeutic technology, the number of endoscopic resections carried out in the treatment of early colorectal carcinomas with little risk of lymph node metastasis has increased. There are no reports of lymph node metastasis in intramucosal (Tis) carcinomas, whereas lymph node metastasis occurs in 6.8-17.8% of submucosal (T1) carcinomas. Three clinical guidelines have been published in Japan and the management strategy for early colorectal tumors has been demonstrated. According to the 2014 Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines for the Treatment of Colorectal Cancer, additional surgery should be done in cases of endoscopically resected T1 carcinoma with a histologically diagnosed positive vertical margin. Additional surgery may also be considered when one of the following histological findings is detected: (i) SM invasion depth 1000 mu m; (ii) histological type por., sig., or muc.; (iii) grade 2-3 tumor budding; and (iv) positive vascular permeation. A resected lesion that is histologically diagnosed as a T1 carcinoma without any of the above-mentioned findings can be followed up without additional surgery. As for the prognosis of endoscopically resected T1 carcinomas, the relapse ratio of approximately 3.4% (44/1312) is relatively low. However, relapse is associated with a poor prognosis, with 72 cancer-related deaths reported out of 134 relapsed cases (54%). A more detailed stratification of the lymph node metastasis risk after endoscopic resection for T1 carcinomas and the prognosis of relapsed cases will be elucidated through prospective studies. Thereafter, the appropriate indications and safe and secure endoscopic resection for T1 carcinomas will be established.

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  • Kono-S Anastomosis for Surgical Prophylaxis of Anastomotic Recurrence in Crohn's Disease: an International Multicenter Study Reviewed

    Toru Kono, Alessandro Fichera, Koutarou Maeda, Yoshiharu Sakai, Hiroki Ohge, Mukta Krane, Hidetoshi Katsuno, Mikihiro Fujiya

    JOURNAL OF GASTROINTESTINAL SURGERY   20 ( 4 )   783 - 790   2016.4

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    The Kono-S (antimesenteric functional end-to-end handsewn) anastomosis has been used for Crohn's disease in Japan and the USA since 2003 and 2010, respectively. This technique was designed to reduce the risk of anastomotic surgical recurrence. This study reviews the outcomes a decade after the introduction of the Kono-S anastomosis to clinical practice.This study was conducted at five hospitals (four in Japan and one in the USA). A total of 187 patients in Japan (144 patients, group J) and the USA (43 patients, group US) who underwent Kono-S anastomosis for Crohn's disease between September 2003 and September 2011 were included.With a median follow-up of 65 months, two surgical anastomotic recurrences have occurred in group J. Kaplan-Meier analysis showed that 5 and 10 years surgical recurrence-free survival rate was 98.6 % in group J. No surgical anastomotic recurrences have been detected in group US with a median follow-up of 32 months. The Kono-S anastomosis was technically feasible and performed in all patients.The Kono-S anastomosis appears to be safe and effective in reducing the risk of surgical recurrence in Crohn's disease.

    DOI: 10.1007/s11605-015-3061-3

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  • Translational medicineへの展開を目指した腸疾患研究 菌由来の活性物質であるポリリン酸を用いた新規炎症性腸疾患治療薬の開発

    上野 伸展, 嘉島 伸, 藤谷 幹浩

    日本消化器病学会雑誌   113 ( 臨増総会 )   A70 - A70   2016.3

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  • クローン病の腸管短縮に影響する臨床的因子の検討

    坂谷 慧, 藤谷 幹浩, 岩間 琢哉, 佐藤 裕基, 内海 辰哉, 井尻 学見, 田中 一之, 藤林 周吾, 野村 好紀, 上野 伸展, 嘉島 伸, 後藤 拓磨, 笹島 順平, 盛一 健太郎

    日本消化器病学会雑誌   113 ( 臨増総会 )   A265 - A265   2016.3

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  • 小児クローン病患者におけるMR-Enterography検査の安全性と描出能の検討

    上野 伸展, 岩間 琢哉, 佐藤 裕基, 内海 辰也, 井尻 学見, 坂谷 慧, 田中 一之, 藤林 周吾, 野村 好紀, 嘉島 伸, 後藤 拓磨, 笹島 順平, 盛一 健太郎, 藤谷 幹浩

    日本消化器病学会雑誌   113 ( 臨増総会 )   A264 - A264   2016.3

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  • ソラフェニブを用いた進行肝細胞癌に対するsequential TAI/TACEの有用性

    澤田 康司, 斎藤 義徳, 藤谷 幹浩, 長谷部 拓夢, 中嶋 駿介

    日本消化器病学会雑誌   113 ( 臨増総会 )   A352 - A352   2016.3

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  • Increased dosage of infliximab is a potential cause of Pneumocystis carinii pneumonia Reviewed

    Takuya Iwama, Aki Sakatani, Mikihiro Fujiya, Kazuyuki Tanaka, Shugo Fujibayashi, Yoshiki Nomura, Nobuhiro Ueno, Shin Kashima, Takuma Gotoh, Junpei Sasajima, Kentaro Moriichi, Katsuya Ikuta

    GUT PATHOGENS   8 ( 1 )   2   2016.2

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    Methods: Pneumocystis carinii pneumonia occasionally appears in immunodeficient patients. While several reports have shown that Pneumocystis carinii pneumonia occurred in the early phase of starting infliximab treatment in patients with Crohn's disease (CD), the present case suggests for the first time that an increased dosage of infliximab may also lead to pneumonia.Results: A 51-year-old male had been taking 5 mg of infliximab for the treatment of CD for 10 years with no adverse events. Beginning in September 2013, the dose of infliximab had to be increased to 10 mg/kg because his status worsened. Thereafter, he complained of a fever and cough, and a CT scan revealed ground-glass opacities in the lower lobes of the bilateral lung with a crazy-paving pattern. Bronchoscopy detected swelling of the tracheal mucosa with obvious dilations of the vessels. A polymerase chain reaction using a bronchoalveolar lavage fluid sample detected specific sequences for Pneumocystis jirovecii; thus he was diagnosed with Pneumocystis carinii (jirovecii) pneumonia. After discontinuing infliximab and starting antibiotic treatment, his symptoms and CT findings were dramatically improved.Conclusions: The administration of an increased dosage of infliximab can cause Pneumocystis carinii pneumonia in CD patients.

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  • Daikenchuto (TU-100) shapes gut microbiota architecture and increases the production of ginsenoside metabolite compound K Reviewed

    Takumu Hasebe, Nobuhiro Ueno, Mark W. Musch, Anuradha Nadimpalli, Atsushi Kaneko, Noriko Kaifuchi, Junko Watanabe, Masahiro Yamamoto, Toru Kono, Yuhei Inaba, Mikihiro Fujiya, Yutaka Kohgo, Eugene B. Chang

    PHARMACOLOGY RESEARCH & PERSPECTIVES   4 ( 1 )   1 - 10   2016.2

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    Many pharmaceutical agents not only require microbial metabolism for increased bioavailability and bioactivity, but also have direct effects on gut microbial assemblage and function. We examined the possibility that these actions are not mutually exclusive and may be mutually reinforcing in ways that enhance long-term of these agents. Daikenchuto, TU-100, is a traditional Japanese medicine containing ginseng. Conversion of the ginsenoside Rb1 (Rb1) to bioactive compound K (CK) requires bacterial metabolism. Dietincorporated TU-100 was administered to mice over a period of several weeks. T-RFLP and 454 pyrosequencing were performed to analyze the time-dependent effects on fecal microbial membership. Fecal microbial capacity to metabolize Rb1 to CK was measured by adding TU-100 or ginseng to stool samples to assess the generation of bioactive metabolites. Levels of metabolized TU-100 components in plasma and in stool samples were measured by LC-MS/MS. Cecal and stool short-chain fatty acids were measured by GC-MS. Dietary administration of TU-100 for 28 days altered the gut microbiota, increasing several bacteria genera including members of Clostridia and Lactococcus lactis. Progressive capacity of microbiota to convert Rb1 to CK was observed over the 28 days administration of dietary TU-100. Concomitantly with these changes, increases in all SCFA were observed in cecal contents and in acetate and butyrate content of the stool. Chronic consumption of dietary TU-100 promotes changes in gut microbiota enhancing metabolic capacity of TU-100 and increased bioavailability. We believe these findings have broad implications in optimizing the efficacy of natural compounds that depend on microbial bioconversion in general.

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  • Polyphosphate Derived from Lactobacillus brevis Inhibits Colon Cancer Progression Through Induction of Cell Apoptosis Reviewed

    Aki Sakatani, Mikihiro Fujiya, Nobuhiro Ueno, Shin Kashima, Junpei Sasajima, Kentaro Moriichi, Katsuya Ikuta, Hiroki Tanabe, Yutaka Kohgo

    ANTICANCER RESEARCH   36 ( 2 )   591 - 598   2016.2

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    Although probiotics are known to have antitumor activity, few bacteria-derived antitumor molecules have been identified. The present study explored an antitumor molecule derived from Lactobacillus brevis SBL8803 (L. brevis 8803) and the mechanisms that underlie its effects. Cell viability and apoptosis were assessed by a sulforhodamine B assay and terminal deoxynucleotidyl transferase dUTP staining, respectively. Phosphorylated extracellular signal-regulated kinase (ERK) and cleaved poly ADP-ribose polymerase (PARP) expression were detected by western blotting. The conditioned medium of L. brevis 8803 inhibited SW620 cells viability and the effect was reduced by the degradation of polyphosphate (poly P) in the conditioned medium. A xenograft model showed that poly P inhibited the growth of SW620 cells. Poly P induced the apoptosis of SW620 cells through activation of the ERK pathway. In contrast, in primary cultured cells derived from normal mouse, poly P did not affect cell viability. Probiotic-derived poly P is expected to be an antitumor drug with fewer adverse effects than conventional drugs.

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  • Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

    Daniel J. Klionsky, Kotb Abdelmohsen, Akihisa Abe, Md Joynal Abedin, Hagai Abeliovich, Abraham Acevedo Arozena, Hiroaki Adachi, Christopher M. Adams, Peter D. Adams, Khosrow Adeli, Peter J. Adhihetty, Sharon G. Adler, Galila Agam, Rajesh Agarwal, Manish K. Aghi, Maria Agnello, Patrizia Agostinis, Patricia V. Aguilar, Julio Aguirre-Ghiso, Edoardo M. Airoldi, Slimane Ait-Si-Ali, Takahiko Akematsu, Emmanuel T. Akporiaye, Mohamed Al-Rubeai, Guillermo M. Albaiceta, Chris Albanese, Diego Albani, Matthew L. Albert, Jesus Aldudo, Hana Algül, Mehrdad Alirezaei, Iraide Alloza, Alexandru Almasan, Maylin Almonte-Beceril, Emad S. Alnemri, Covadonga Alonso, Nihal Altan-Bonnet, Dario C. Altieri, Silvia Alvarez, Lydia Alvarez-Erviti, Sandro Alves, Giuseppina Amadoro, Atsuo Amano, Consuelo Amantini, Santiago Ambrosio, Ivano Amelio, Amal O. Amer, Mohamed Amessou, Angelika Amon, Zhenyi An, Frank A. Anania, Stig U. Andersen, Usha P. Andley, Catherine K. Andreadi, Nathalie Andrieu-Abadie, Alberto Anel, David K. Ann, Shailendra Anoopkumar-Dukie, Manuela Antonioli, Hiroshi Aoki, Nadezda Apostolova, Saveria Aquila, Katia Aquilano, Koichi Araki, Eli Arama, Agustin Aranda, Jun Araya, Alexandre Arcaro, Esperanza Arias, Hirokazu Arimoto, Aileen R. Ariosa, Jane L. Armstrong, Thierry Arnould, Ivica Arsov, Katsuhiko Asanuma, Valerie Askanas, Eric Asselin, Ryuichiro Atarashi, Sally S. Atherton, Julie D. Atkin, Laura D. Attardi, Patrick Auberger, Georg Auburger, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Maria Laura Avantaggiati, Limor Avrahami, Neelam Azad, Suresh Awale, Tiziana Bachetti, Jonathan M. Backer, Dong Hun Bae, Jae Sung Bae, Ok Nam Bae, Soo Han Bae, Eric H. Baehrecke, Seung Hoon Baek, Stephen Baghdiguian, Agnieszka Bagniewska-Zadworna

    Autophagy   12 ( 2 )   443   2016.1

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    DOI: 10.1080/15548627.2016.1147886

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  • The three isoforms of hepcidin in human serum and their processing determined by liquid chromatography-tandem mass spectrometry (LC-tandem MS) Reviewed

    Lynda Addo, Katsuya Ikuta, Hiroki Tanaka, Yasumichi Toki, Mayumi Hatayama, Masayo Yamamoto, Satoshi Ito, Motohiro Shindo, Yusuke Sasaki, Yasushi Shimonaka, Mikihiro Fujiya, Yutaka Kohgo

    INTERNATIONAL JOURNAL OF HEMATOLOGY   103 ( 1 )   34 - 43   2016.1

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    Hepcidin, the iron regulatory hormone, has three isoforms; -20, -22 and -25. While hepcidin-25 has been studied extensively, the physiological significance of other isoforms remains poorly understood. Using a quantitative method based on liquid chromatography-tandem mass spectrometry (LC-tandem MS) developed by our group, we quantified hepcidin isoforms in human serum to elucidate their characteristics, and investigated the role of hepatocytes in isoform processing. Hepcidin isoforms in serum obtained from 40 healthy volunteers were quantified. Synthetic hepcidin peptides were added to healthy serum, and to HepG2 culture media, and hepcidin isoform concentrations determined. All three hepcidin isoforms were detected in human serum; however, hepcidin-25 concentrations were highest. The three hepcidin isoforms showed a strong positive correlation with each other and with serum ferritin. Additionally, while hepcidin-20 was strongly correlated with serum creatinine, the other isoforms were not. Hepcidin-20 and -25 levels were also increased in chronic ki