The significance of tumor associated macrophage in recurrent hepatocellular carcinoma after liver transplantation

• Project/Area Number: 24592004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: IKEGAMI TORU 九州大学, 大学病院, 助教 (80432938)
• Co-Investigator(Kenkyū-buntansha): 調 憲 九州大学, 医学研究科, 准教授 (70264025) ; 吉住 朋晴 九州大学, 大学病院, 講師 (80363373)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肝移植 / 肝癌 / 腫瘍関連マクロファージ / IL17 / 肝細胞癌 / 好中球リンパ球比 / 移植・再生医療

Outline of Final Research Achievements

Neutrophil lymphocyte ratio >4 had siniginicant impact on recurrent hepatocellular carcinoma after liver transplantation. Multivariate analyses showed that NLR >4, tumor size >5cm, the interval between last treatment and liver transplantation <3 months, were significantly associated with recurrence. In cases with NLR >4, peritumor and serum IL17 was significantly elevated, indicating that IL17 had significant impact on tumor progression. Moreover, the number of peritumor CD163 positive cells, indicating macrophage, was increased compared with those with NLR <4. Therefore, high NLR indicates that tumor progression, recurrenct heaptocellualr carcinoma after liver transplantation in this study, was positively influenced by peritumor environment especially tumor associated macrophage and IL17.

Research Products

• [Journal Article] Impact of epidermal growth factor single-nucleotide polymorphism on recurrence of hepatocellular carcinoma after hepatectomy in patients with chronic hepatitis C virus infection. (2014)
  • Author(s): Yoshiya S, Fujimoto Y, Bekki Y, Konishi H, Yamashita Y, Ikegami T, Yoshizumi T, Shirabe K, Oda Y, Maehara Y.
  • Journal Title: Cancer Sci. Volume: 105 Pages: 646-50
  • DOI: 10.1111/cas.12415
  • Peer Reviewed
• [Journal Article] Clinical outcomes of living donor liver transplantation for patients 65 years old or older with preserved performance status. (2014)
  • Author(s): Ikegami T, Bekki Y, Imai D, Yoshizumi T, Ninomiya M, Hayashi H, Yamashita Y, Uchiyama H, Shirabe K, Maehara Y.
  • Journal Title: Liver Transpl. Volume: 20 Pages: 408-15
  • DOI: 10.1002/lt.23825
  • Peer Reviewed
• [Journal Article] New scoring system for prediction of microvascular invasion in patients with hepatocellular carcinoma. (2014)
  • Author(s): Shirabe K, Toshima T, Kimura K, Yamashita Y, Ikeda T, Ikegami T, Yoshizumi T, Abe K, Aishima S, Maehara Y.
  • Journal Title: Liver Int. Volume: 34 Pages: 937-41
  • DOI: 10.1111/liv.12459
  • Peer Reviewed
• [Journal Article] Autophagy enhances hepatocellular carcinoma progression by activation of mitochondrialβ-oxidation (2014)
  • Author(s): Toshima T, Shirabe K, Matsumoto Y, Yoshiya S, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y.
  • Journal Title: Journal of Gastroenterology Volume: 49(5) Pages: 907-16
  • DOI: 10.1007/s00535-013-0835-9
  • Peer Reviewed / Open Access
• [Journal Article] Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma. (2013)
  • Author(s): Yoshizumi T, Ikegami T, Toshima T, Harimoto N, Uchiyama H, Soejima Y, Yamashita Y, Shirabe K, Maehara Y.
  • Journal Title: Transplant Proc. Volume: 45 Pages: 3310-3
  • DOI: 10.1016/j.transproceed.2013.05.001
  • Peer Reviewed
• [Journal Article] Prognostic factors affecting survival at recurrence of hepatocellular carcinoma after living-donor liver transplantation: with special reference to neutrophil/lymphocyte ratio. (2013)
  • Author(s): Harimoto N, Shirabe K, Nakagawara H, Toshima T, Yamashita Y, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y.
  • Journal Title: Transplantation. Volume: 96(11) Pages: 1008-12
  • DOI: 10.1097/tp.0b013e3182a53f2b
  • Peer Reviewed
• [Journal Article] Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. (2013)
  • Author(s): Mano Y, Shirabe K, Yamashita Y, Harimoto N, Tsujita E, Takeishi K, Aishima S, Ikegami T, Yoshizumi T, Yamanaka T, Maehara Y.
  • Journal Title: Ann Surg. Volume: 258（2） Pages: 301-5
  • DOI: 10.1097/sla.0b013e318297ad6b
  • Peer Reviewed
• [Journal Article] Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma. (2013)
  • Author(s): Yoshizumi T, Ikegami T, Yoshiya S, Motomura T, Mano Y, Muto J, Ikeda T, Soejima Y, Shirabe K, Maehara Y.
  • Journal Title: Hepatol Res. Volume: 43 Pages: 709-16
  • DOI: 10.1111/hepr.12016
  • Peer Reviewed
• [Journal Article] Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. (2013)
  • Author(s): Motomura T, Yoshizumi T, et al
  • Journal Title: J Hepatol. Volume: 58 Pages: 58-64
  • DOI: 10.1016/j.jhep.2012.08.017
  • Peer Reviewed
• [Journal Article] Transplantation: 3D printing of the liver in living donor liver transplantation. (2013)
  • Author(s): Ikegami T, Maehara Y.
  • Journal Title: Nat Rev Gastroenterol Hepatol, Volume: 10（12） Pages: 697-8
  • DOI: 10.1038/nrgastro.2013.195
  • Peer Reviewed
• [Journal Article] Strategies for successful left-lobe living donor liver transplantation in the 250 consecutive adult cases in a single center. (2013)
  • Author(s): Ikegami T, Shirabe K, Soejima Y, Yoshizumi T, Uchiyama H, Yamashita Y, Harimoto N, Toshima T, Maehara Y.
  • Journal Title: J Am Coll Surg, Volume: 216 Pages: 353-62
  • DOI: 10.1016/j.jamcollsurg.2012.11.011
  • Peer Reviewed
• [Journal Article] Obstructing spontaneous major shunt vessels is mandatory to keep adequate portal inflow in living donor liver transplantation. (2013)
  • Author(s): Ikegami T, Shirabe K, Nakagawara H, Yoshizumi T, Toshima T, Soejima Y, Uchiyama H, Yamashita Y, Harimoto N, Maehara Y.
  • Journal Title: Transplantation Volume: 95 Pages: 1270-7
  • DOI: 10.1097/tp.0b013e318288cadc
  • Peer Reviewed
• [Journal Article] Pathological analysis of opened round ligaments as venous patch grafts in living donor liver transplantation. (2013)
  • Author(s): Ikegami T, Wang H, Imai D, Bekki Y, Yoshizumi T, Yamashita Y, Toshima T, Shirabe K, Maehara Y.
  • Journal Title: Liver Transpl, Volume: 19 Pages: 1245-51
  • DOI: 10.1002/lt.23716
  • Peer Reviewed
• [Journal Article] Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia. (2012)
  • Author(s): Ikegami T, Shirabe K, Yoshizumi T, Aishima S, Taketomi YA, Soejima Y, Uchiyama H, Kayashima H, Toshima T, Maehara Y.
  • Journal Title: Am J Transplant. Volume: 12 Pages: 1886-97
  • DOI: 10.1111/j.1600-6143.2012.04052.x
  • Peer Reviewed
• [Journal Article] Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway (2012)
  • Author(s): Takeishi, K.
  • Journal Title: J Hepatol. Volume: 57 Pages: 77-83
  • DOI: 10.1016/j.jhep.2012.02.026
  • Peer Reviewed
• [Presentation] 生体肝移植後肝細胞癌再発に於ける外科的切除の有効性 (2014)
  • Author(s): 池上 徹、調 憲、播本憲史、吉住朋晴、山下洋市、前原喜彦
  • Organizer: 日本肝癌研究会
  • Place of Presentation: 京都
  • Year and Date: 2014-06-05 – 2014-06-06
• [Presentation] Strategies and techniques in successful left lobe living donor liver transplantation in adults (2014)
  • Author(s): Toru Ikegami, Tomoharu Yoshizumi, Mizuki Ninomiya, Yuji Soejima, Tomohiro Iguchi, Yo-ichi Yamashita, Hideaki Uchiyama, Tetsuo Ikeda, Ken Shirabe, Yoshihiko Maehara.
  • Organizer: 日本外科学会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-03 – 2014-04-05
• [Presentation] 肝細胞癌外科的治療における術前末梢血好中球リンパ球比(Neutrophil/lymphocyte ratioNLR)の意義 肝切除、生体肝移植後の新しい予後因子 (2013)
  • Author(s): 間野 洋平, 本村 貴志, 調 憲, 梶山 潔, 播本 憲史, 山下 洋市, 辻田 英司, 武石 一樹, 池上 徹, 内山 秀昭, 吉住 朋晴, 副島 雄二, 前原 喜彦
  • Organizer: 第113回日本外科学会
  • Place of Presentation: 福岡
• [Presentation] 肝移植後の短期予後改善を目指した我々の治療戦略 (2013)
  • Author(s): 吉住 朋晴, 調 憲, 池上 徹, 播本 憲史, 戸島 剛男, 吉屋 匠平, 木村 光一, 松本 佳大, 中川原 英和, 山下 洋市, 副島 雄二, 前原 喜彦
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] C型肝炎の治療最先端 肝移植後C型肝炎再発に対する三剤併用療法を含む治療戦略 (2013)
  • Author(s): 池上 徹, 調 憲, 前原 喜彦
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] 生体肝移植術後の肝細胞癌再発における好中球リンパ球比の意義 (2012)
  • Author(s): 本村 貴志, 池上 徹
  • Organizer: 第112回日本外科学会学術集会
  • Place of Presentation: 千葉
  • Invited
• [Presentation] 生体肝移植後肝細胞癌再発に於ける外科的切除の有効性 (2012)
  • Author(s): 池上 徹, 調 憲
  • Organizer: 第50回日本癌治療学会学術集会
  • Place of Presentation: 横浜
  • Invited