经肝动脉栓塞化疗序贯联合射频消融和细胞因子诱导的杀伤细胞治疗肝细胞癌的随机研究

Cytokine-induced killer cell fusion to lower recurrence of hepatocellular carcinoma after transcatheter arterial chemoembolization sequentially combined with radiofrequency ablation:a randomized trial

目的随机对照研究一组经肝动脉栓塞化疗(TACE)序贯联合CT导向下射频消融(RFA)与TACE序贯联合CT导向下RFA及细胞因子诱导的杀伤细胞(CIK)治疗原发性肝癌(HCC)的病例,并评价两种方法在原发性肝癌治疗中的疗效和抗病毒作用。方法2002年7月至2005年12月在广州中山大学肿瘤医院确诊为原发性肝癌有195例,经过增强CT扫描,PET-CT,数字减影血管造影(DSA)和／或病理活检结合临床检查结果综合判断排除肿瘤残留后,符合入组标准的共64例患者,64例原发性肝癌患者经TACE序贯联合RFA治疗后6-8周,经临床评价无明确残留病变,进行分组。联合CIK治疗组33例患者,首先连续完成4次CIK细胞经静脉／肝动脉回输,每次间隔时间为1-3周;再每4周1次,共行4次CIK细胞经静脉/肝动脉回输,每次回输CIK的数量为(1．1- 1.5)×1010。患者随访1年以上并每1-2个月评价肿瘤情况。TACE联合RFA治疗组31例患者出院每1-2月评价肿瘤情况,随访1年以上。结果2组病例1年生存期均达到100％。联合CIK组共33例,6个月内复发2例,为肝内复发;6月到1年之间共2例复发,1例出现肝内复发,1例出现肝门区淋巴结转移,29／33例为无瘤生存(90．19％)。TACE联合RFA治疗组31例中6月内2例复发, 6月到1年之间共有6例复发,其中5例为肝内复发,1例出现肺转移,23／31例为无瘤生存(68．01％)。随访6个月,1年无瘤生存率两组差异无统计学意义(P=0．1309)。联合CIK组,治疗前HBV DNA含量小于1．0×103者为19例,治疗后上升到29例,其中有2例乙肝表面抗原转阴。治疗前HBV DNA含量在1．0×103-1．0×106之间者为13例,治疗后为3例,治疗前HBV DNA含量在1．0×106以上者1例,治疗后为1．6×104。而TACE联合RFA治疗组仅1例血HBV DNA含量由治疗前的1．1×105下降1．0×103以下。HBV-DNA含量在治疗前后两组差异有统计学意义(P< 0．01)。结论TACE序贯联合RFA治疗和抗肿瘤效应细胞(CIK)是治疗原发性肝癌一种新的模式,它明显降低乙肝病毒体内含量或消除乙肝病毒,阻断致癌因素,但对提高原发性肝癌无瘤生存期需进一步观察。

Objective To ed evaluate the clinical effects of autologous cytokine-induced killer cell （CIK） fusion to lower recurrence of primary hepatoceillular carcinoma （HCC） and the anti-hepatitis B virus （HBV） effect after transcatheter arterial chemoembolization （TACE） sequentially combined with radiofrequency ablation （RFA）. Methods Sixty-four HCC patients underwent TACE sequentially combined with RFA without residual tumor or extrahepatie metastasis were randomly divided into 2 groups： study group （ n = 33 ）, receiving autologous CIK fusion of the dose of （ 1.1-1.5 ） × 10^10 via the peripheral vein or hepatic artery, firstly once every 3-4 weeks for 4 times, and then once every 4 weeks for 4 times; and control group （n=31）. All patients were followed up for 1 year. Results Inthe study group, 29 patients （29/33） were recurrence-free during the 1 year follow-up, 3 had recurrence in the liver 5, 6, and 7 months later respectively, and 1 patient had lymphoadenopathy in the hepatic portal 9 months later. In the control group, 23 patients （68. 01% ） were recurrence-free, 7 had recurrence in the liver within 1 year, and 1 had lung metastasis 11 months later. In the study group, the number of the patients with the HBV DNA content 〈 1× 10^3 before treatment was 19, and increased to 29 after the treatment; 2 of the 19 patients who were HBsAg positive before the treatment became HBsAg negative after the treatment, and number of the patients with the HBV DNA content of 10^3-10^4 was 3 before the treatment, and became 13 after the treatment among which 1 patient had his HBV DNA content dropping from 1.6 × 10^7 to 1.6 × 10^4. In the control group, only 1 patient showed his HBV DNA content dropping from 1.1 × 10^5 to below 10^3. Conclusion Capable of reducing recurrence, prolonging the recurrence-free span, and attacking HBV, autologous CIK fusion after TACE sequentially combined with RFA is an effective novel therapeutic strategy for HCC.