射频消融联合盐酸灌注治疗不可切除大肝癌的基础和临床研究

Radiofrequency ablation (RFA) can completely ablate small heaptocellur carcinoma (HCC) with a diameter shorter than 3 cm, and its efficacy is similar to that of surgery. However, the present RFA techniques can not completely ablate large HCC with a diameter longer than 5 cm due to limited ablation areas. In our preliminary study, we found that hydrochloric acid (HCl) significantly enhanced the effect of radiofrequency. Hydrochloric acid (HCl) perfusion increased the ablation area of single-electrode RFA from 3.7 cm × 2.7 cm to 6.5 cm × 5.5 cm. However, the mechanism and safety of enhancing the effect of RFA by HCl perfusion as well as the efficacy of RFA with HCl perfusion on unresectable large HCC are unknown. In the present study program, we plan to apply the simulation gel phantom, ANSYS12.1 sofrware, and comprehensive detection techniques to determine the electrothemics mechanism of HCl perfusion in enhancing the effect of RFA. We will then use finite element model to establish the mathematic equation between the parameters of RFA with HCl perfusion and the volume of ablation area. In addition, we will carry out animal experiment to verify the safety of this technique and develop preliminary clinical research on applying RFA with HCl perfusion to treat large HCC. This project will provide the rationale basis for translating this new technology into clinical care of unresectable large HCC.

射频消融（radiofrequency ablation, RFA）可灭活3cm以下肝癌，疗效与手术相似。但是，现有技术消融范围小，对5cm以上大肝癌不能完全灭活，疗效差。我们前期研究发现盐酸有强大的射频增强作用，盐酸灌注使单电极射频消融范围从2.7×3.5cm增大到6.5×7.5cm。那么，盐酸射频消融的"增强"机制是什么？盐酸灌注射频消融安全、可控吗？盐酸灌注射频消融对不可手术切除大肝癌的疗效如何？本课题拟：1.运用仿真体模、ANSYS软件、综合探测系统等手段阐明盐酸灌注射频消融的"增强" 电热力学机制；2. 运用有限元模型建立盐酸灌注射频消融与消融体积之间的"量效关系"方程式；3.进行盐酸灌注射频消融的动物安全性研究。4.初步开展大肝癌盐酸灌注射频消融的临床研究。本项目的完成有望为盐酸灌注射频消融这一新技术的临床医学转化提供科学依据，为不可手术切除大肝癌的治疗提供新的有效治疗技术。

射频消融（radiofrequency ablation, RFA）可灭活3cm以下肝癌，疗效与手术相似。但单纯射频消融范围小，对5cm以上大肝癌不能完全灭活，疗效差。课题组前期研究发现盐酸有强大的射频增强作用，盐酸灌注使单电极射频消融范围从2.7×3.5cm增大到6.5×7.5cm。本项目在国家自然科学基金的资助下完成了以下几项研究：1. 采用单针灌注型射频消融电极，在离体猪肝上进行不同浓度的稀盐酸在相同的功率和时间条件下消融时，对消融灶大小影响的研究，探讨产生最大消融范围的盐酸浓度，研究结果显示10%的稀盐酸作为灌注液获得最大的消融范围; 2.设计不同消融时间对于单针消融离体牛肝消融灶大小的影响实验以及预灌注盐酸联合射频消融离体牛肝时功率、温度及消融灶体积变化的实验研究，进一步验证射频消融联合盐酸灌注扩大消融范围的机制，探讨相关参数条件与消融范围的量-效关系方程式；3. 在实验基础上，运用电脑模拟分析软件建立有限元模型，探讨射频消融联合盐酸灌注扩大消融范围的电热学机制; 4.进行盐酸灌注射频消融活体兔肝的安全性试验；5. 临床研究方面，进行50多例中大肝脏肿瘤的盐酸灌注射频消融治疗，疗效比较满意。对一些特殊案例，如尾状叶大肝癌使用盐酸灌注射频消融，治疗4例均取得了突破性的疗效。在此基础上，课题组获得了中山大学临床医学研究5010计划项目资助，开展“TAE同步联合热消融治疗大肝癌的前瞻性、多中心随机对照研究”的临床试验研究，对满足适应症的大肝癌患者，使用盐酸灌注射频消融。本项目为盐酸灌注射频消融这一新技术的临床医学转化提供科学依据，为不可手术切除大肝癌的治疗提供了新的有效治疗技术。