Development of a new multi-modality therapy for far advanced hepatocellular carcinoma : a combined therapy of a new percutaneous local tumor ablation and a chemotherapy using subcutaneously embedded port for arterial infusion or gene therapy

本研究的目的是为晚期肝癌开发一种新的多模式治疗方法，由于肿瘤的广泛传播，晚期肝癌只能通过经导管动脉栓塞或支持治疗来治疗。我们想开发一种新的经皮局部肿瘤消融和化疗的联合疗法，使用皮下埋置端口进行动脉输注或基因治疗。关于一种新的经皮肿瘤消融术的发展，我们自1999年2月引进射频消融术以来，共对400例患者进行了射频消融术（RFA）。在射频消融中，我们可以通过12分钟的消融获得直径3cm的坏死区域。在大多数情况下，一到两次治疗足以使病变在安全范围内完全坏死，从而缩短住院时间。我们认为在不久的将来，95%以上经皮肿瘤消融治疗的病例将采用RFA治疗。因此，我们希望获得更多的技术来执行RFA。在优化化疗方案方面，我们采用了“低剂量FP”化疗，采用皮下埋置端口进行动脉输注，并一直在分析数据，评价影响化疗效果的因素。最终目标是在治疗前预测治疗效果。为了做到这一点，我们将在未来使用DNA提示。我们还使用了5-FU和干扰素的新化疗方案。我们将在更多病例中使用该方案，并评估其疗效。我们已经用裸鼠来检验基因疗法的有效性和安全性，以便将其引入临床试验。然而，我们还没有取得令人满意的结果。

The aim of this study was to develop a new multi-modality therapy for far advanced hepatocellular carcinoma, which had been treated non-curatively only by transcatheter arterial embolization or supportive therapy because of wide spread of the cancer. We wanted to develop a combined therapy of a new percutaneous local tumor ablation and a chemotherapy using subcutaneously embedded port for arterial infusion or gene therapy.With regard to development of a new percutaneous tumor ablation, we have performed radio-frequency ablation(RFA)on a total of 400 cases since we introduced it in February 1999. In RFA, we can surely obtain a necrotic area of 3 cm in diameter by a 12-minute ablation. In most cases, one or two treatment sessions are enough to achieve a complete necrosis of the lesion with a safety margin, which results in a shorter hospitalization. We think more than 95% of cases treated by percutaneous tumor ablation will be treated by RFA in the near future. Thus we would like to gain more know-how to perform RFA.With regard to optimization of chemotherapy, we performed "low dose FP" chemotherapy using subcutaneously embedded port for arterial infusion and have been analyzing data to evaluate factors which contributed the chemotherapeutic efficacy. The final goal is to predict therapeutic efficacy before the treatment. To do this, we would use DNA tips in the future. We have also used a new chemotherapeutic regimen of 5-FU and interferon. We will use the regimen on more cases and evaluate its efficacy.We have used nude mice to examine usefulness and safety of a gene therapy in order to introduce it to a clinical trial. However, we have not achieved satisfactory results yet.