【作者】 高飞；

【导师】 庞志刚；

【作者基本信息】 郑州大学 ， 外科学（专业学位）， 2016， 硕士

【摘要】 背景及目的原发性肝癌是消化系统常见的恶性肿瘤,具有发病率高、死亡率高、早期诊断率低等流行病学特征,多数患者发现时病程已属中晚期,已经失去手术机会。目前,TACE作为治疗中晚期肝癌患者的首选治疗方案已得到广泛的应用。但对于中晚期肝癌,特别是大肝癌患者,任一单一治疗方案都各有局限性。近年来,局部微创热消融技术的快速发展使经皮射频消融术(RFA)成为治疗不可手术切除的中、晚期肝癌患者的新的有效疗法。结合两者治疗的特点我们发现,TACE联合RFA治疗可能会取得良好的治疗效果。本研究主要探讨肝动脉化疗栓塞(TACE)联合射频消融术(RFA)对比单一TACE治疗大肝癌患者的临床疗效及生存分析。方法回顾性分析2011年07月至2014年07月在郑州大学第二附属医院普外科接受治疗的原发性大肝癌患者67例,按治疗方式的不同分为对照组(仅行TACE治疗)32例和研究组(TACE联合RFA治疗)35例,两组均先行TACE治疗,化疗药物选用5-FU(500 mg/m2),奥沙利铂(130 mg/m2)。栓塞剂采用超液态碘化油,根据肿瘤病灶大小选择合适剂量的碘化油与吡柔比星混悬液,酌情应用明胶海绵颗粒栓塞血管。两组均每间隔28-40天再次行TACE治疗,最多3次。对照组单纯行TACE治疗,研究组行TACE术后30天内再行RFA治疗。在B超或者CT引导下定位,根据肿瘤位置、大小以及形态,采用多次叠加、多针重叠的消融方法,消融范围为完全覆盖肿瘤并超过肿瘤病灶区域0.5-1.0 cm。采用修订的实体瘤治疗疗效评价标准(m RECIST标准)判定两组治疗后1、3个月的的近期疗效;对所有患者密切随访,统计分析两组患者的1、2、3年的生存率并进行生存分析,评价两组患者的远期疗效。结果1、近期疗效方面,术后1个月对患者治疗的近期疗效情况进行评估,研究组CR为68.5%(24/35),PR为22.8%(8/35),SD为8.6%(3/35),对比对照组CR为40.6%(13/32),PR为46.8%(15/32),SD为6.3%(2/32),PD为6.3%(2/32),两组患者CR及PR间具有统计学差异(P=0.022,P=0.039),但两组的客观有效率(ORR)以及疾病控制率(DCR)差异无统计学意义(P=0.602,P=0.136);术后3个月对患者治疗的近期疗效情况进行评估,CR为45.2%(14/31),PR为35.5%(11/31),SD为12.9%(4/31),PD为6.5%(2/31),对比对照组CR为22.2%(6/27),PR为29.6%(8/27),SD为22.2%(6/27),PD为25.9%(7/27),两组患者PD具有统计学差异(P=0.046),ORR以及DCR间差异有统计学意义(P=0.020,P=0.046)。2、两组患者术后血清AFP水平变化,治疗后研究组患者AFP水平转阴率较对照组明显,且差异具有统计学意义(P=0.011)。3、研究组1、2、3年生存率分别为74.3%、44.1%、20.5%,中位生存时间为22个月,对照组术后生存率分别为52.8%、23.1%、7.9%,中位生存时间为13个月。两组对比分析生存率差异有统计学意义(P=0.035)。结论1、TACE联合RFA治疗大肝癌患者,在近期疗效方面,术后3个月具有较高客观有效率(ORR)及疾病控制率(DCR),且差异有统计学意义。联合治疗可以更有效降低血清AFP水平。2、TACE联合RFA治疗具有较长的中位生存时间,能有效延长大肝癌患者的生存期,两者优势互补,对于提高大肝癌患者的远期预后水平具有一定的临床意义。3、TACE联合RFA及单一TACE治疗,两组的毒副反应发生率并无太大差别,联合治疗具有良好的耐受性及安全性。更多还原

【Abstract】 Background and ObjectivePrimary liver cancer is a common malignant tumor of digestive system with high incidence rate, high mortality rate, low early diagnosis rate of the epidemiological characteristics, most patients has lost the chance of operation when they were found tumor. At present, TACE has been widely used in the treatment of patients with advanced hepatocellular carcinoma. But for patients with advanced hepatocellular carcinoma, especially the patients with large HCC, any single treatment plan has limitations. In recent years, RFA has become a new effective therapy for the treatment of patients with advanced hepatocellular carcinoma. Analyze the characteristics of the two treatments, we found the treatment of TACE combined with RFA may achieve good therapeutic effect. This study aims to investigate the therapeutic efficacy and survival rate of transarterial chemoembolization(TACE) combined with radiofrequency ablation(RFA) in large hepatocellular carcinoma. MethodsThe clinical data of 67 patients with large hepatocellular carcinoma, who were admitted to the second affiliated hospital of Zhengzhou University to receive treatment during the period from July 2011 to July 2014, were retrospectively analyzed. According to the treatment plan, the patients were divided into the control group(receiving only TACE, n=32) and the study group(receiving TACE together with RFA, n=35). The two groups were treated with TACE chemotherapy firstly, using 5-FU(500 mg/m2) and oxaliplatin(130 mg/m2). The embolization is lipiodol, the dose of iodized oil is calculated according to the tumor size. The two groups were treated with TACE once every times, up to 3 times. The control group was treated with TACE alone, the study group was treated with RFA after 30 days. Located under the guidance of B ultrasound or CT, multiple overlapping and multiple needle ablation were used according to the location, the size and shape of the tumor. The ablation range was completely covered by the tumor and more than 0.5-1.0 cm. Referring to mRECIST evaluation, the efficacy were determined in all the patients and compared beteween the two groups respectively in 1 and 3 months, and the postoperative cumulative recurrent rates were also analyzed respectively. Results1. One month after the treatment, the CR of the patients in the research group was 68.5% and the PR was 22.8% which were higher than those of the patients in the control group(40.6% and 46.8%) with statistically significant differences(P=0.022, P=0.039), but there are no statistically significant differences in ORR and DCR(P=0.602, P=0.136). Three months after the treatment, the PD of the patients in the research group was 25.9% which was higher than that of the patients in the control group(6.5%) with statistically significant differences(P=0.046), and there are statistically significant differences in ORR and DCR(P=0.020, P=0.046).2. It’s worthy to reduce the AFP level of the serum, and there are statistically significant differences(P=0.011).3. The 1, 2, 3-year of survival rates in the research group were 74.3%, 44.1% and 20.5% respectively, while as were 52.8%, 23.1%, and 7.9% respectively in the research group with statistically significant differences(P=0.035). Conclusion1. In 3 months, the combined treatment has a higher level of objective effective rate and disease control rate with statistically significant differences. And it’s worthy to reduce the AFP level of the serum.2. Combination use of TACE and RFA can effectively prolong the survival time of patients with large HCC and has important clinical significance.3. Both the combined treatment and the TACE are safety and tolerability, and there are no statistically significant differences on the incidence rate of adverse reaction between the two groups.更多还原