多源微波同步消融扩大组织消融范围的机制及临床前研究

Most large hepatocellular carcinoma patients in China are diagnosed at their advanced stage and 70% of which are not suitable for surgical resection. Although ablation has become the first choice for the small HCC, a patient with liver tumor diameter in 7cm cancer had to be ablated 26 times using 4cm-ablatiove-sphere under the theory of a mathematical model "large sphere overlapped by small spheres" in order to achieve a complete ablation. The disadvantages of this model are time-consuming, unsafe and technical challenging. In our former ex vivo bovine liver experiment, it was found that four and five applicators microwave ablation simultaneously achieved ablation zones in diameter of 7cm and 9cm, respectively. However, its mechanism of expanding the ablation zone and safety remain unknown and ought to be explored. Therefore, we propose the following scientific problems: 1. Whether multi-applicators microwave ablation simultaneously expands the ablation zone by increasing the thermal deposition dose in unit time or thermal efficiency? 2. Whether a function could be established between the ablative conditions and the volume in multi-applicators microwave ablation simultaneously and the 3D morphologic structure of ablation zone could be reconstructed? 3. What about the local and systemic safety of multi-applicators simultaneous microwave ablation in vivo porcine liver? This study aims to discuss the mechanism of expanding the tissue ablation zone and the safety of multi-applicators microwave simultaneously as well as establish function relations between parameters and ablation zone by using thermal dose calculation, FEM (finite element analysis method), phantom and in/ex vivo animal liver experiment, to provide scientific and standard protocol to ablation therapy for large hepatocellular carcinoma.

我国肝癌病人就诊晚、肿瘤大，70%以上不适合切除。尽管消融已成为小肝癌治疗首选，但以现有“小球体覆盖大球体”数学模型完成7cm肝癌消融，用4cm球灶需布针二十余次，存在治疗时间长、安全性差、缺乏操作性等问题。前期我们采用四源、五源微波同步消融离体牛肝，消融范围达7cm、 9cm。但其扩大组织消融范围的机制尚未明确，消融安全性有待研究。因此，我们提出以下科学问题：1.多源微波同步消融是否通过提高单位时间热沉积剂量及热效率，从而发挥扩大消融范围的作用？2.多源微波同步消融参数与消融灶体积存在着怎么样的函数关系？3.在动物活体肝脏上评估多源微波同步消融对全身和局部组织器官功能有何影响？本项目拟通过热定量计算、有限元分析、实验体模及动物肝脏消融实验，探讨多源微波同步消融扩大组织消融范围的机制、建立消融函数关系式、明确其安全性，为多源微波同步消融应用于大肝癌消融治疗提供科学规范的依据。

我国肝癌病人就诊晚、肿瘤大，70%以上不适合切除。尽管消融已成为小肝癌治疗首选，但以现有“小球体覆盖大球体”数学模型完成7cm肝癌消融，用4cm球灶需布针二十余次，存在治疗时间长、安全性差、缺乏操作性等问题。前期我们采用四源、五源微波同步消融离体牛肝，消融范围达7cm、 9cm。但其扩大组织消融范围的机制尚未明确，消融安全性有待研究。本项目拟通过热定量计算、有限元分析、实验体模及动物肝脏消融实验，探讨多源微波同步消融扩大组织消融范围的机制、建立消融函数关系式、明确其安全性，为多源微波同步消融应用于大肝癌消融治疗提供科学规范的依据。.本项目主要研究进展如下：1. 通过大量离体牛肝实验，完成多源微波同步消融针数、功率、时间和针距等参数与消融灶体积的量效关系实验研究，并将部分消融后的离体牛肝采用MR扫描后三维重建，计算消融灶体积；2. 在前期离体实验基础上，开展多源微波同步消融治疗大肝癌的临床治疗，并回顾分析本团队多源微波同步消融治疗大肝癌的病例，结论表明大范围消融对于大肝癌消融治疗的安全性和有效性；3. 针对大肝癌采用TACE联合微波治疗后的疗效预测问题，对比了血小板-胆红素-白蛋白评分与胆红素-白蛋白评分和传统Child-Pugh评分对于总生存的预测效能，结果提示纳入三个因素的血小板-胆红素-白蛋白模型具有最佳疗效预测价值；4. 项目组成员还建立了一种稳健的BCLC中期肝癌采用TACE-MWA治疗长期生存的基于胆红素-白蛋白评分的预测模型，可以在辅助诊疗决策制定、增强医患沟通方面提供有效的数据支撑。通过以上多项重要研究的开展，我们探索多源微波同步消融治疗大肝癌的初步有效性与安全性数据，为这项新技术的普及、应用、推广提供了重要的理论和数据支撑。