含胸苷激酶自杀基因的重组腺病毒预防肝细胞癌术后复发的疗效分析

Clinical effect of recombinant adenovirus containing thymidine kinase suicide gene in preventing postoperative recurrence of hepatocellular carcinoma

目的观察外科手术联合基因治疗对预防肝细胞癌(HCC)术后复发的疗效。方法选取2006年7月-2013年2月首都医科大学附属北京佑安医院收治的102例单发HCC患者(肿瘤分期TNM1~2期,肿瘤直径<10 cm),对其中60例患者在手术前后联合含胸苷激酶自杀基因的重组腺病毒(ADV-TK)基因治疗(基因组),42例患者采用单纯手术切除(手术组),对患者术后复发情况进行定期随访。2组患者的临床资料比较采用t检验(计数资料)和χ2检验(计量资料);采用log-rank检验分析2组患者的累积复发率,采用单因素和多因素Cox回归分析对患者复发率有显著影响的因素。结果基因组1、3、5年的肿瘤复发率为13.8%、33.7%和47.7%,手术组为18.5%、53.2%和69.2%,2组累积复发率比较,差异有统计学意义(χ2=2.643,P=0.041)。除术后基因组发热患者显著多于手术组外,2组并发症发生率以及住院时间无明显差别。多因素分析显示,基因治疗是肿瘤累积复发率的独立影响因素(比值比=2.752,95%可信区间:1.164~4.251,P=0.038)。结论在手术切除的基础上联合基因治疗,可以有效减少术后肿瘤复发,值得临床推广。

Objective To investigate the clinical effect of surgical operation combined with gene therapy in preventing postoperative recurrence of hepatocellular carcinoma（ HCC）. Methods A total of 102 patients with single HCC（ TNM stage 1-2,tumor diameter 10 cm） who were admitted to Beijing You An Hospital,Capital Medical University,from July 2006 to February 2013 were enrolled,and among these patients,60 underwent the gene therapy with recombinant adenovirus containing thymidine kinase suicide gene（ ADV-TK） before and after surgery（ gene group） and 42 underwent surgical resection alone（ surgery group）. The patients were followed up regularly after surgery to observe postoperative recurrence. The t-test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups. The log-rank test was used for the analysis of cumulative recurrence rate,and univariate and multivariate Cox regression analyses were used to identify influencing factors for recurrence rate. Results The 1-,3-,and 5-year recurrence rates of tumor were 13. 8%,33. 7%,and 47. 7% in the gene group and 18. 5%,53. 2%,and 69. 2% in the surgery group,and there was a significant difference between the two groups（ χ2= 2. 643,P = 0. 041）. The gene group had a significantly higher proportion of patients with pyrexia after surgery than the surgery group,and there were no significant differences in the incidence rates of other complications and length of hospital stay between the two groups. The multivariate analysis showed that gene therapy was an independent influencing factor for cumulative rumulative recurrence rate（ odds ratio = 2. 752,95 confidence interval： 1. 164-4. 251,P = 0. 038）. Conclusion Gene therapy combined with surgical resection can effectively reduce postoperative recurrence of tumor,and therefore,it holds promise for clinical application.