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Role of splenomegaly in liver fibrosis and hepatocarcinogeneis

Research Project

Project/Area Number 17K10507
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionUniversity of Yamanashi

Principal Investigator

IIMURO Yuji  山梨大学, 大学院総合研究部, 医学研究員 (30252018)

Co-Investigator(Kenkyū-buntansha) 河野 寛  山梨大学, 大学院総合研究部, 准教授 (40322127)
鈴村 和大  兵庫医科大学, 医学部, 講師 (50434949)
藤元 治朗  兵庫医科大学, 医学部, 特別招聘教授 (90199373)
川井田 博充  山梨大学, 大学院総合研究部, 講師 (00345711)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords門脈圧亢進症 / 脾腫 / 脾線維化 / 肝線維化 / サイトグロビン / 酸化ストレス / 脾摘 / 細胞・組織 / 外科
Outline of Final Research Achievements

Effective antivirus treatment has shown that even advanced hepatic fibrosis can be ameliorated by relieving causative stress. However, whether advanced portal hypertension and its complications could be reversible is still controversial. We speculated advanced functional change in the spleen possibly contribute to this phenomenon.
In the current study, we found that splenic fibrosis appears within the splenic cords in patients with advanced splenomegaly and thrombocytopenia in conjunction with congestion of the splenic sinus and that cytoglobin-expressing cells, which have been reported to affect fibrogenesis in several organs, are possibly responsible for the fibrosis in the splenic cord.
In addition, we also found that splenectomy of the fibrotic spleen often led to amelioration of liver fibrosis in these patients, indicating significant roles of splenomegaly with fibrosis in the irreversibility of advanced portal hypertension.

Academic Significance and Societal Importance of the Research Achievements

肝炎治療の進歩により肝硬変の改善などの恩恵を受けることができるが、進行した肝硬変に合併する門脈圧亢進症は遷延することが多い。今回の研究では、進行した肝硬変においては脾臓においても高度の線維化を伴うこと、またこれを摘出することにより肝線維化が改善することを見出した。
つまり、線維化に伴い機能不全に陥った脾臓が肝硬変の病態に悪影響を与えていることが示され、今後、脾摘術以外に脾臓の線維化を改善する治療法を開発することにより、肝硬変に伴う合併症の抑制、肝発癌リスクの軽減を図ることができる可能性が示されたとものと考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2020 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (15 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Cytoglobin-expressing cells in the splenic cords contribute to splenic fibrosis in cirrhotic patients2020

    • Author(s)
      Iimuro Y, Yada A, Okada T, Nakamura I, Suzumura K, Xu J, Sudo M, Nishiguchi S, Kawada N, Hatano E, Fujimoto J
    • Journal Title

      Histology and Histopathology

      Volume: ―

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of cholangiocellular carcinoma preoperatively diagnosed with typical imaging findings2018

    • Author(s)
      Mochizuki Y, Iimuro Y, et al.
    • Journal Title

      Int Surg

      Volume: 103 Issue: 1-2 Pages: 72-79

    • DOI

      10.9738/intsurg-d-18-00002.1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired Value of 99m Tc-GSA Scintigraphy as an Independent Risk Factor for Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma2018

    • Author(s)
      Nakamura Ikuo、Iimuro Yuji、Hai Seikan、Kondo Yuichi?、Hatano Etsuro、Fujimoto Jiro
    • Journal Title

      European Surgical Research

      Volume: 59 Issue: 1-2 Pages: 12-22

    • DOI

      10.1159/000484044

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] ICG Clearance Test and 99mTc-GSA SPECT/CT Fusion Images2017

    • Author(s)
      Iimuro Yuji
    • Journal Title

      Visceral Medicine

      Volume: 33 Issue: 6 Pages: 449-454

    • DOI

      10.1159/000479046

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 門亢症の脾機能異常における脾臓線維化の関与と脾摘よる肝組織改善効果2019

    • Author(s)
      飯室勇二、岡田敏弘、藤元治朗
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝組織変化からみた高度門脈圧亢進症における脾摘術(腹腔鏡下)の意義2019

    • Author(s)
      飯室勇二、岡田敏弘、鷹野敦史
    • Organizer
      第32回日本内視鏡外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 血小板減少を伴う門脈圧亢進症に対する脾摘の意義2019

    • Author(s)
      飯室勇二
    • Organizer
      第26回日本門脈圧亢進症学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Laparoscopic splenectomy in cirrhotic patients ameliorates liver fibrosis and stimulate proliferation of progenitor-like cells2019

    • Author(s)
      Yuji Iimuro, Toshihiro Okada, Jiro Fujimoto
    • Organizer
      27th International Congress of the European Association for Endoscopic Surgery
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 門脈圧亢進症患者における脾臓線維化機構の検討2018

    • Author(s)
      飯室勇二、岡田敏弘、藤元治朗
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 門亢症に伴う脾腫の組織学的検討と脾線維化メカニズムの考察2018

    • Author(s)
      飯室勇二、岡田敏弘、藤元治朗
    • Organizer
      第104回日本消化器病学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Splenic fibrosis in porta hypertension and the effect of laparoscopic splenectomy on liver fibrosis2018

    • Author(s)
      Yuji Iimuro, Toshihiro Okada, Jiro Fujimoto
    • Organizer
      26th International Congress of the European Association for Endoscopic Surgery (EAES)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 門亢症における脾臓線維化と脾摘に伴う肝線維化改善2018

    • Author(s)
      飯室勇二、岡田敏弘、藤元治朗
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 門亢症における脾線維化機構と脾摘に伴う肝組織変化2018

    • Author(s)
      飯室勇二、岡田敏弘、藤元治朗
    • Organizer
      第7回脾臓研究会(第25回門脈圧亢進症学会)
    • Related Report
      2018 Research-status Report
  • [Presentation] 門脈圧亢進症に伴う脾臓線維化の解析-脾原性悪循環の可能性-2018

    • Author(s)
      飯室勇二、岡田敏弘、藤元治朗
    • Organizer
      JDDW2018
    • Related Report
      2018 Research-status Report
  • [Presentation] Progression in splenic fibrosis in patients with portal hypertension2017

    • Author(s)
      Yuji Iimuro, Akito Yada, Toshihiro Okada, Jiro Fujimoto
    • Organizer
      The 52nd Congress of the European Society for Surgical Research
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 門脈圧亢進症における脾臓の線維化と脾摘の意義2017

    • Author(s)
      飯室勇二、矢田章人、望月理玄、鈴木修、岡田敏弘、藤元治朗
    • Organizer
      第72 回日本消化器外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Splenic fibrosis in patients with portal hypertension and splenectomy as a modality of therapy2017

    • Author(s)
      Yuji Iimuro, Akito Yada, Toshihiro Okada, Jiro Fujimoto
    • Organizer
      6th A-PHPBA and 29th JSHBPS
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 門亢症患者の脾臓組織変化からみた脾摘の意義2017

    • Author(s)
      飯室勇二、岡田敏弘、藤元治朗
    • Organizer
      第24回日本門脈圧亢進症学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脾臓の線維化からみた門脈圧亢進症における脾摘術の再考察2017

    • Author(s)
      飯室勇二、岡田敏弘、藤元治朗
    • Organizer
      JDDW 2017
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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