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Clarification of pathogenesis and development of therapeutic strategy for small-for size syndrome after major hepatectomy in biliary tract cancer

Research Project

Project/Area Number 17390361
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionChiba University

Principal Investigator

MIYAZAKI Masaru  Chiba University, General Surgery, Professor, 大学院医学研究院, 教授 (70166156)

Co-Investigator(Kenkyū-buntansha) KIMURA Fumio  Chiba University, General Surgery, Associate Professor, 大学院医学研究院, 助教授 (70334208)
SHIMIZU Hiroki  Chiba University, General Surgery, Assistant Professor, 大学院医学研究院, 講師 (80272318)
YOSHIDOME Hiroyuki  Chiba University, General Surgery, Assistant Professor, 大学院医学研究院, 講師 (10312935)
KATO Atsushi  Chiba University, General Surgery, Research Associate, 医学部附属病院, 助手 (70344984)
YOSHITOMI Hideyuki  Chiba University, General Surgery, Research Associate, 医学部附属病院, 助手 (60375631)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2006: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2005: ¥11,600,000 (Direct Cost: ¥11,600,000)
Keywordsbiliary tract cancer / hepatectomy / obstructive jaundice / surgical resection / liver failure / 管切除
Research Abstract

(1)Clinical Study
Postoperative hepatic insufficiency is a critical complication after extended hepatic resection in patients with biliary tract malignancies, the majority of whom suffer from obstructive jaundice. The aim of this study was to assess clinical parameters linked to this type of liver dysfunction.
Methods : A total of 111 patients were retrospectively reviewed. Patient background, pre- and intra-operative parameters, and a ratio of remnant liver volume/entire liver volume (RLV/ELV) as a volumetric parameter, were compared between patients with and without postoperative hyperbilirubinemia and subsequent fatal outcome.
Results : Logistic regression indicated that only RLV/ELV ratio was an independent factor influencing postoperative hyperbilirubinemia, and RLV/ELV ratio and indocyanine green retention rate at 15 minutes (ICG-R15) were factors affecting survival. Patients with RLV/ELV<40% had 7.6 times the risk of postoperative hyperbilirubinemia, while no patients having RLV/EL … More V>40% and ICG-R15<25% died of liver failure.
Conclusions : The RLV/ELV ratio was the factor with the greatest impact on liver dysfunction after extended hepatic resection in patients with biliary tract malignancies. To prevent these morbidities, volumetric analysis should be performed in a prospective fashion, and, when necessary, preoperative portal vein embolization, or, if possible, limited hepatic resection should be applied.
(2)Experimental Study
The effects of obstructive jaundice on liver regeneration after partial hepatectomy are not yet fully understood.
Methods : Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-f31 (TGF-β1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and α-smooth muscle actin (α-SMA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal biliary drainage in BO rats or sham-operated rats.
Results : Hepatic TGF-β1 mRNA levels increased significantly 14 days after BO, and further increased with length of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-β1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed increased number of HSCs (desmin-positive cells) and activated HSCs (α-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-β1 mRNA was significantly up-regulated up to 48h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats.
Conclusion : BO induces HSCs proliferation and activation, leading to up-regulation of TGF-β1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005

All Journal Article (21 results)

  • [Journal Article] Renal function is well maintained after use of left renal vein graft for vascular reconstruction in hepatobiliary-pancreatic surgery2006

    • Author(s)
      鈴木 大, 他
    • Journal Title

      Journal of the American College of Sugeons 202

      Pages: 87-87

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy2006

    • Author(s)
      牧野 裕庸, 他
    • Journal Title

      World Journal of Gastroenterology 12・13

      Pages: 2053-2053

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Relationship between pancreatic secretory trypsin inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection2006

    • Author(s)
      登内 昭彦, 他
    • Journal Title

      American Journal of Gastroenterology 101・7

      Pages: 1601-1601

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Renal function is well maintained after use of left renal vein graft for vascular reconstruction inhepatobiliary-pancreatic surgery2006

    • Author(s)
      Suzuki, Takeshi
    • Journal Title

      Journal of the American College of Sugeons 202

      Pages: 87-87

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy2006

    • Author(s)
      Makino, Hironobu
    • Journal Title

      World Journal of Gastroenterology 12・13

      Pages: 2053-2053

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Relationship between pancreatic secretory trypsin inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection2006

    • Author(s)
      Tonouchi, Akihito
    • Journal Title

      American Journal of Gastroenterology 101・7

      Pages: 1601-1601

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Renal function is well maintained after use of left renal vein graft for vascular reconstruction in hepatobiliary-pancreatic surgery2006

    • Author(s)
      鈴木大, 他
    • Journal Title

      Journal of the American College of Sugeons 202

      Pages: 87-87

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy2006

    • Author(s)
      牧野裕庸, 他
    • Journal Title

      World Journal of Gastroenterology 12・13

      Pages: 2053-2053

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Relationship between pancreatic secretory tryps in inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection.2006

    • Author(s)
      登内昭彦, 他
    • Journal Title

      American Journal of Gastroenterology 101・7

      Pages: 1601-1601

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Decreased cell-mediated Immune status in colorectal cancer patients with hepatic metastasis2005

    • Author(s)
      清水 宏明, 他
    • Journal Title

      Hepato-Gastroenterology 52

      Pages: 1106-1106

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Extended cold preservation of the graft liver enhances neutrophil-mediated pulmonary injury after liver transplation2005

    • Author(s)
      清水 宏明, 他
    • Journal Title

      Hepato-Gastroenterology 52

      Pages: 1172-1172

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Should the inferior vena cava be reconstructed after resection for malignant tumors?2005

    • Author(s)
      吉留 博之, 他
    • Journal Title

      The American Journal of Surgery 189

      Pages: 419-419

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Vascular endothelial growth factor angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats2005

    • Author(s)
      清水 宏明, 他
    • Journal Title

      World Journal of Gastroenterology 11・46

      Pages: 7254-7254

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Extended cold preservation of the graft liver enhances neutrophil-mediated pulmonary injury after liver transplation2005

    • Author(s)
      Shimizu, Hiroaki
    • Journal Title

      Hepato-Gastroenterology 52

      Pages: 1172-1172

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Decreased cell-mediated Immune status in colorectal cancer patients with hepatic metastasis2005

    • Author(s)
      Shimizu, Hiroaki
    • Journal Title

      Hepato-Gastroenterology 52

      Pages: 1106-1106

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Should the inferior vena cava be reconstructed after resection for malignant tumors?2005

    • Author(s)
      Yoshidome, Hiroyuki
    • Journal Title

      The American Journal of Surgery 189

      Pages: 419-419

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Vascular endothelial growth factor angiopoietins regulate sinusoidal regeneration and remodeling after partial hepatectomy in rats2005

    • Author(s)
      Shimizu, Hiroaki
    • Journal Title

      World Journal of Gastroenterology 11・46

      Pages: 7254-7254

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Should the inferior vena cava be reconstructed after resection for malignant tumors?2005

    • Author(s)
      Yoshidome H, Miyazaki M, et al.
    • Journal Title

      Am J Surg 189

      Pages: 419-424

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Extended cold preservation of the graft liver enhances neutrophil-mediated pulmonary injury after liver transplantation2005

    • Author(s)
      Shimizu H, Miyazaki M, et al.
    • Journal Title

      Hepatogastroenterol 52

      Pages: 1172-1175

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 胆嚢癌手術における拡大肝切除とその適応2005

    • Author(s)
      宮崎 勝, 他
    • Journal Title

      消化器外科 28

      Pages: 1507-1513

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 胆嚢癌における血管合併切除の問題点とその意義2005

    • Author(s)
      宮崎 勝, 他
    • Journal Title

      胆と膵 26

      Pages: 625-629

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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