The new strategy of treatment for unresectable hepatocellular carcinoma in living related donor liver transplantation

活体肝移植治疗不可切除性肝癌的新策略

• 批准号: 13557099
• 负责人: SATO Yoshinobu
• 金额: $ 8.9万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557099/
• 关键词: Unresectable HCC; Living liver transplantation; Milan criteria; h-TERT mRNA; AFPmRNA; Immunosuppressant; macrochimerism; intraportal DST; 肝細胞癌; AFPmRNA; h-TERT; キメリズム; NKT細胞; IFN-β; Living related donor liver transplantation; Hepatocellular

Major problem of liver transplantation for hepatocellular carcinoma (HCC) is tumor recurrence. Most of reason for tumor relaps are dissemination of cancer cells from the native liver to systemic circulation and immunosuppressants. Detection of circulating cancer cells has been performed by polymerase chain reaction of h-TERT mRNA, however, its clinical significance is still unclear. Therefore we investigated about the relations tumor recurrence and h-TERT mRNA expression in peripheral blood in the patients underwent living related donor liver transplantation (LRDLT) with preoperative immunochemotherapy We investigated the neoadjuvant immunochemotherapy (5FU+adriamycin+Interferon β(IFNβ)) and adjuvant chemotherapy with systemic administration of 10mg of adriamycin once a week and intraportal treatment with 250mg of 5FU for three consecutive days, which we called "Sandwich chemotherapy", was started as a single course on day 7 after LRDLT. FK506 and prednisolone were used as immunosuppre … More ssants following LRDLT. Transfer of donor blood via the portal vein was started immediately after the reconstruction of hepatic artery. Transfusion of 50 ml or 100 ml of donor blood via the portal vein was performed almost once a week starting on day 1.Eight times of inoculation of donor specific transfusion (DST) via portal vain were performed after LRDLT. this regimen might reduce the preoperative circulating cancer cells and prevent the postperative micrometastasis to the graft graft liver. Moreover, intra-and postoperative administration of DST via the portal vein brought rapid reduction of immunosupressants in the present clinical case. These results may be glad tidings in terms of expanding the indications for unresectable advanced HCC and may introduce an additional solution to transplantation immunology. Prognosis of liver transplantation for HCC patients deviated from Milan Criteria might be poor in spite of adjuvant immunochemotherapy. however, if circulating cancer cells are eliminated by adjuvant immunochemotheray, liver transplantation may be effective even for unresectable HCC deviated from Milan Criteria. Less

肝细胞癌（HCC）肝移植的主要问题是肿瘤复发，肿瘤复发的大部分原因是癌细胞从天然肝脏扩散到体循环，并且通过h的聚合酶链反应检测循环癌细胞。然而，h-TERT mRNA的临床意义尚不清楚，因此我们探讨了活体相关供体肝移植（LRDLT）患者术前肿瘤复发与外周血h-TERT mRNA表达的关系。免疫化疗我们研究了新辅助免疫化疗（5FU+阿霉素+干扰素β（IFNβ））和辅助化疗，每周一次全身给予阿霉素10mg，连续三天门静脉注射5FU 250mg，我们称之为“三明治化疗”。 FK506 和泼尼松龙用作免疫抑制剂后第 7 天开始作为单一疗程。 LRDLT 后立即开始通过门静脉输血，从第 1 天开始几乎每周一次通过门静脉输血 50 ml 或 100 ml。 LRDLT 后通过门静脉进行供体特异性输血 (DST) 接种，该方案可能会减少术前循环癌细胞并预防移植物的术后微转移。此外，在目前的临床病例中，通过门静脉进行术中和术后给予免疫抑制剂的量迅速减少，这些结果对于扩大不可切除的晚期 HCC 的适应症来说可能是个好消息，并可能为移植带来另一种解决方案。尽管有辅助免疫化疗，但偏离米兰标准的肝移植患者的预后可能很差，但是，如果通过辅助免疫化疗消除循环癌细胞，则肝移植。即使对于偏离米兰标准的不可切除的 HCC 也可能有效。

项目成果

市田 隆文: "肝移植のup to date [3]肝移植の適応 4)肝細胞癌"肝・胆・膵フロンティア. 12. 23-27 (2001)

Takafumi Ichida：“肝移植的最新进展 [3] 肝移植的适应症 4) 肝细胞癌” 肝脏/胆道/胰腺前沿 (Liver/Biliary/Pancreatic Frontier)。

Sato Y: "Living related donor liver transplantation forpreoperative a-feto protein (AFP) mRNA-positive patients of hepatocellular carcinoma"Transplantation Proceeding. 35. 352-353 (2003)

Sato Y：“术前甲胎蛋白（AFP）mRNA阳性肝细胞癌患者的活体相关供体肝移植”移植论文集。

Sato Y: "Real time measurement of anti-HBs levels and donor specific transfusion via portal vein may reduce amount of HBIG after living related liver transplantation."American Journal of Gastroenterology. 97. 488-489 (2002)

Sato Y：“实时测量抗 HBs 水平和通过门静脉进行供者特异性输血可能会减少活体肝移植后 HBIG 的量。”美国胃肠病学杂志。

Sato Y: "Repeating intraportal donor specific transfusion may induce tolerance following adult living related donor liver transplantation."Hepato-Gastroenterology. 51. 601-606 (2003)

Sato Y：“重复门静脉内供体特异性输血可能会在成人活体相关供体肝移植后诱导耐受性。”肝胃肠病学。

Sato Y: "Macrochimerism of donor type CD56+CD3+ T cells in donor specific transfusion via portal vein following living related donor liver transplantation"Hepato-Gastroenterology. 50. 2161-2165 (2003)

Sato Y：“活体相关供体肝移植后通过门静脉供体特异性输血中供体型 CD56 CD3 T 细胞的大嵌合”肝胃肠病学。