Analysis of multicentric carcinogenesis of HCC patients from immunological view points

肝细胞癌（HCC）在根治性切除后经常复发。残肝复发源于原发性切除肿瘤的肝内转移（IM）和/或多中心（MC）发生。为了使肝癌患者在肝内复发后获得更好的生存率，我们根据复发模式对患者进行手术治疗。MC组再次手术后的生存率显著优于IM组（P 0.0016）。此外，MC组患者再次手术后的生存率与对照组患者初次肝切除术后的生存率无显著差异。这些结果表明，可切除或消融性复发MC HCC患者在重复手术后的生存获益与初次根治性切除HCC患者几乎相同。大多数肝细胞癌（HCC）发生在慢性肝病中。在这种情况下，经常观察到细胞免疫应答受损，但这种缺陷的机制尚不清楚。CD 3 z（T细胞受体信号转导因子中的关键分子）的下调导致T细胞功能的降低。流式细胞术检测12例HCV感染者和36例肝癌患者外周血T淋巴细胞CD 3 z表达，结果显示：HCV感染者和肝癌患者外周血T淋巴细胞CD 3 z表达均明显低于正常对照组。与11例肝癌患者的肿瘤浸润性T淋巴细胞（TIL）、肝内T淋巴细胞（IHL）和外周血T淋巴细胞（PBL）相比，TIL上CD 3 z的表达水平明显低于PBL，而IHL上CD 3 z的表达水平与TIL上CD 3 z的表达水平基本相当。提示HCV感染者T淋巴细胞CD 3 z的下调可能是HCC多中心发生和肝内转移的原因之一。

Hepatocellular carcinomas (HCC) often recur after curative resection. Recurrence in the remnant liver originates from intrahepatic metastasis (IM) from the primary resected tumor, and/or from multicentric (MC) occurrence. In order to achieve better survival after intrahepatic recurrence in HCC patients, we have surgically treated patients according to the recurrence pattern. Survival after the repeat operation was significantly better in the MC group than in the IM group (P 0.0016). Moreover, there was no significant difference between survival in the MC group after a repeat operation and survival in control patients after an initial hepatectomy. These results indicated that patients with resectable or ablative recurrent MC HCC have almost the same survival benefit after repeat operations as patients who undergo initial curative resection of HCC. Most hepatocellular carcinomas (HCC) occur in chronic liver disease. Under such conditions, an impaired cellular immune response is often observed, but the mechanisms of this deficiency are unclear. The down-modulation of CD3 z (a key molecule in signal-transducing factor of T cell receptor) leads to a reduction in the function of T cells. Flowcytometrical analysis of CD3 z on peripheral T lymphocytes from 12 HCV infected hosts and 36 HCC bearing patients showed a significantly lower CD3 z expression than normal controls. Compared with tumor infiltrating T lymphocytes (TIL), intrahepatic T lymphocytes (IHL) and peripheral T lymphocytes (PBL) from 11 HCC bearing patients, the expression of CD3 z on TIL was significantly lower than PBL, and the expression level of CD3 z on IHL was almost equal to that on TIL. These results suggest that the down-modulation of CD3 z of T lymphocytes in HCV infected hosts may be one of the reasons why multicentric occurrence and intrahepatic metastasis occur more frequently in HCC patients than another malignancies.