医药学论文：体外循环全身热灌注治疗恶性肿瘤的疗效及安全性评估

关键词：体外循环全身热灌注治疗

【Abstract】 Objective To assay the primary effects and clinical safety of the treatment of advanced malignant tumor with extracorporeal whole body hyperthermia(EWBH)，and to evaluate the impairment of it to the vital organs and tissues.Methods 60 patients of advanced malignant tumor were treated with EWBH and chemotherapy from June 2002 to June 2004， while the control group (n=45) with same spectrum and same stage of tumors were treated with similar chemotherapy alone. We assayed the primary effects of EWBH through comparing with controls. The stability and safety of EWBH in monitoring and controlling the body temperature were evaluated by real-time temperature measurement as well as the impairments of vital organs and tissues， such as brain， liver， kidney and lung， were by examination functional index of body peripheral blood.Results (1) The effective rate (CR+PR+SD) of EWBH and chemotherapy was 72.6% on treating advanced malignant tumor， PD was 27.4%， the descent rate of index concerning tumor (as AFP， CER， CA199， CA242， CA125 and so on) was 72.6 %， the rate of pain relieve was 70.2%， the percentage of cases， whole body weight had increased post-EWBH after four weeks， reached 50.0%， and that of those appetite advanced was 76.5%， of those sleep improved was 56.7%. The indexes of Karnofsky was increased. 66.1%.51.2% patients alive were over one year and 80.4%over half one year. All of them are better than controls (P＜0.05). (2)Although there are some impairment on function and tissues in the vital organ， the damage is venial and reversible. (3) The method of EWBH is steadily and safe on monitoring and controlling body temperature.Conclusion EWBH can make some reversible impair to the some vital organs and tissues， the whole procedure is steady and safe as one of hyper thermia therapy to the malignant tumor. EWBH can improve the patients live quality and prolong their life.
【Key words】 extracorporeal；whole body hyperthermia；chemotherapy；malignant tumor；effect；safety
体外循环全身热灌注治疗(extracorporeal whole body hyperthermia，EWBH)是肿瘤全身热疗的一种方法，近年来在国内外越来越受到重视，并在临床上取得了良好的治疗效果［1，2］。我院采用美国FCM的TEMETTM1000型体外循环全身热灌注治疗系统，对各类复发、转移性肿瘤病人进行全身热疗联合化疗，并分析其疗效和安全性。
1 资料与方法
1.1 一般资料 自2002年6月～2004年6月，笔者对60例各类复发、转移性肿瘤患者进行EWBH共62例次，其中2例病人进行EWBH 2次，余均为1次。所有病人行EWBH的同时加用相应化疗药物。男39例，女21例；平均年龄43.6±1.4岁，其中年龄最大76岁，最小26岁。其中结直肠癌11例，肝癌10例，肺癌8例，胃癌5例，胰腺癌4例，上颌窦癌4例，乳腺癌3例，肾癌3例，骨肉瘤2例，恶性神经鞘膜瘤2例，胸腔恶性间皮瘤2例，卵巢癌1例，腹腔恶性间皮瘤1例，鼻咽癌1例，舌癌1例，左颚腺样囊性癌1例，纵隔神经母细胞瘤1例。选择同期相同肿瘤类型及其化疗方案的患者45例作为对照组。
1.2 病例选择 EWBH治疗前对病人进行选择的标准如下：(1)有病理或细胞学证实的各类型恶性肿瘤，或已无手术机会、或术后复发、转移，或经过放疗、化疗无效者。(2)KPS评分≥60分。(3)能耐受全身麻醉。
1.3 治疗方法 全身麻醉下，采用美国FCM的TEMET1000型体外循环全身热灌注治疗系统。经双侧股静脉穿刺置管，连接替外循环治疗系统，通过由静脉至静脉，低流量，低压力的体外转流方式，治疗系统缓慢升高患者的血温，通过血液循环，血液灌注的作用，缓慢、均匀地升高全身体温，此为升温期，需60min左右；当患者体温达到42.5℃时，即进入治疗的高温平台期，维持60～120min；然后逐渐缓慢降温（降温期），至体温降至38℃时停机，结束治疗，进行麻醉复苏。监测食道、直肠、后鼻道温度（颅底参考温度）作为体温调控点。术中严密观测生命体征、尿量、定时检测血气分析和肝肾功能，调整酸碱电解质平衡。治疗组病人术中依据肿瘤类型加用相应的化疗药物。
1.4 临床观察指标 治疗后评估以下指标：(1)近期疗效评估：①KPS评分。②疼痛缓解情况：据主诉疼痛程度分级法（VRS），观察VRS评分提高程度。③肿瘤病灶的变化：分完全缓解（CR）-肿瘤消失并持续1个月以上；部分缓解（PR）-肿瘤两个最大的相互垂直的直径乘积缩小50%以上，并持续1个月以上；稳定（SD）-肿瘤两个最大的相互垂直的直径乘积缩小不足50%以上，增大不超过25%，并持续1个月以上；恶化（PD）-肿瘤两个最大的相互垂直的直径乘积增大超过25%。④血液肿瘤标志物。(2)EWBH过程中各时间点不同部位温度的变化情况。(3)EWBH术前术后血液成分变化，肝功能变化，肾功能变化等。(4)术后临床精神神经症状改变。
1.5 统计学处理 用t检验分析EWBH过程中病人相应数据变化，资料用均数±标准差；用卡方检验列表分析比较EWBH组和对照组的近期疗效，P＜0.05为差异有显著性。
2 结果
本组全身热疗的病人多为各类型复发、转移性肿瘤病人，预后较差且参差不齐，治疗组60例病人进行62例次的EWBH，术中无1例发生死亡。近期疗效初步评估见表1。