循环胸腔热灌注治疗肺癌胸水及其机制探讨

目的 评价循环胸腔热灌注治疗肺癌胸水的综合疗效，并探讨其治疗机制。方法 采用循环胸腔43℃温生理盐水灌注60min，治疗45例肺癌胸水患者，随访观察胸水的疗效、肺原发病灶变化、副作用、生活质量以及生存期,评价其临床综合疗效。同时利用流式细胞术、光镜、电镜、末端脱氧核苷酸转移酶原位标记（TUNEL）等技术，比较了热疗前后胸液细胞学、生化学的变化以及胸膜表面癌细胞的形态学和生化学改变。结果 全组均经一次热疗后，胸水控制有效率达100％（CR93．3％＋PR6．7％），仅1例于热疗后1年胸水复发，其余均无胸水复发，平均胸水消失时间达16．5个月，最长达40个月。13例热疗后1个月复但CT，发现肺部原发灶缩小者5例，基本不变者5例。无手术死亡及并发症。42例热疗后生活质量明显提高，全组中位存活期达16．8个月，1年生存率达87％，其中1例超过3年，4例达2年以上，分别存活29、30、31个月（仍存活）、40个月。热疗后胸水癌胚抗原（CEA）下降至正常、胸水中未找到瘤细胞、流式细胞术DNA倍体分析肿瘤异倍体峰消失。光镜、电镜见热疗后胸膜表面癌细胞核固缩、碎裂和凋亡小体，TUNEL见带亮黄色 荧光的凋亡阳性细胞。结论 （1）循环胸腔热灌注为一种安全、有效的治疗肺癌胸水的新方法；（2）凋亡介导的癌细胞热杀伤作用、热疗后机体免疫功能的增强和灌注液的物理冲刷作用是循环胸腔热灌注治疗癌性胸水的重要机制。

Treatment of pleural effusion caused by hmg carcinoma with circular intrapleural hyperthermic perfusion

Objective To assess the comprehensive effectiveness of intrapleural hyperthermic perfusion in treatment of malignant pleural effusion (MPE) caused by lung carcinoma and to explore its nechanism. Methods 45 patients with MPE caused by lung carcinoma underwent circular intrapleural hyperthermic perfusion with 43 warmed normal saline for 60 minutes. Response of pleural effusion and the original lung tumor, sife effects, life qualty and survival time of the patients were followed up. Flow cytometry, optical microscopy, electron microscopy, and TUNEL method were used to compare the cytology and biochemistry of pleural effusion and cancer cells planted to the surface of pleura before and after the therapy. Results The control rate of pleural effusion was 100% (CR 93.3%, PR 6.7%). No recurrence of pleural effusion was observed in 44 cases. Pleural effusion reoccured 12 months after the thermotherapy in one case. The time without pleural effusion lasted 16.5 months on average with the longest time of 40 months. CT performed one month after the thermotherapy in 13 cases showed that the primary focus in lung dwindled in 13 case, and remained unchanged in 5 cases. Neither operative death nor post operative complication was found. The life quality was improved in all the cases. The medium survival time was 16.8 months. One year survival rate was 87%. One case survived more than 3 years, 4 cases survives more than 2 years (29, 30, 31, and 40 months respectively). Carcinoembryonic antigen decreased to normal and no carcinoma cell was found in pleural effusion. Flow cytometry showed that the tumor heteroploid peak diasappeared. Pyknosis and disintegration of nuclei, and apoptotic bodies of tumor cells planted on the surface of pleura were found by optical and electron microscopy. TUNEL showed apoptotic cells with brilliant yellow fluorescence. Conclusion (1) Circular intrapleural hyperthermic perfusion is a new, safe, and effective treatment for MPE. (2) Apoptosis mediated cytocidal function, improvement of body immunity after hyperthermic perfusion and continuous wash of the perfusion fluid are important mechanisms of intrapleural hyperthermic perfusion in treatment of MPE caused by lung carcinoma.