李 猛， 陆荫英， 董景辉， 皋月娟， 董 政， 陈 敏， 刘 静

1 北京大学国际医院 超声科， 北京 102206；2 解放军总医院第五医学中心 a. 超声科； b. 肝脏肿瘤诊疗中心； c. 放射科， 北京 100039

Clinicaleffectoftranscatheterarterialchemoembolizationcombinedwithmicrowaveablationintreatmentofadvancedprimarylivercancer

LIMeng1,2a,LUYinying2b,DONGJinghui2c,GAOYuejuan2a,DONGZheng2b,CHENMin2a,LIUJing2a.

(1.DepartmentofUltrasound,PekingUniversityHospital,Beijing102206,China;2.a.DepartmentofUltrasound,b.ComprehensiveLiverCancerCenter,c.DepartmentofRadiology,TheFifthMedicalCenterofChinesePLAGeneralHospital,Beijing100039,China)

Abstract:ObjectiveTo investigate the clinical effect and safety of transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA) in the treatment of advanced primary liver cancer.MethodsA total of 186 patients with advanced primary liver cancer who were treated in The Fifth Medical Center of Chinese PLA General Hospital from April 2015 to June 2019 were enrolled and divided into study group and control group using a random number table, with 93 patients in each group. Both groups of patients underwent TACE, and the patients in the study group were treated with ultrasound-guided percutaneous MWA. The two groups were compared in terms of clinical outcome and complications. Quantitative real-time PCR was used to measure the serum level of microRNA-202 (miR-202), ELISA was used to measure the serum levels of fragile histidine triad (FHIT) and P16 protein, and the changes in the above three indices at 3 months after treatment were compared. The two-independent-samplesttest was used for comparison of continuous data between two groups, and the pairedt-test was used for comparison within one group before and after treatment; The chi-square testwas used for comparison of categorical data between groups.ResultsThe study group had a significantly higher objective response rate than the control group (47.32% vs 27.96%,χ2=7.422,P=0.006), and there was no significant difference in disease control rate between the two groups(P>0.05). Both groups had significant increases in the serum levels of miR-202, FHIT, and P16 protein at 3 months after treatment (allP<0.05), and compared with the control group, the study group had significantly higher serum levels of miR-202 (0.84±0.14 vs 0.58±0.17,t=11.385,P<0.001), FHIT (1126.35±73.05 pg/ml vs 762.87±56.71 pg/ml,t=37.904,P<0.001), and P16 protein (52.86±6.51 pg/ml vs 39.06±5.37 pg/ml,t=15.770,P<0.001).ConclusionUltrasound-guided MWA in addition to TACE can improve the short-term response of patients with advanced primary liver cancer and increase the serum levels of miR-202, FHIT, and P16 protein, with relatively high safety.

Keywords：liver neoplasms； chemoembolization, therapeutic； catheter ablation

原发性肝癌是全球发病率和死亡率最高的恶性肿瘤之一，我国每年新增原发性肝癌患者约占全球总数的55%，这与我国居民中乙型肝炎或HBV携带者人数巨大有关[1]。原发性肝癌发病隐匿，部分患者确诊时往往处于中晚期，丧失了手术治疗机会，非手术治疗成为首选，其中以经肝动脉化疗栓塞术(TACE)和消融治疗应用较为广泛[2]。研究[3]表明，单独采用TACE治疗肝癌能够取得一定效果，但治疗后转移和复发率较高。本研究以中晚期原发性肝癌患者作为研究对象，探讨在TACE基础上采用超声引导下微波消融(MWA)的治疗效果，并分析血清microRNA-202(miR-202)、脆性组氨酸三联体(fragile histine traid, FHIT)和P16蛋白等3种提示原发性肝癌患者预后的生物标志物的变化情况。

1 资料与方法

1.1 研究对象 选取2015年4月-2019年6月在解放军总医院第五医学中心接受治疗的中晚期原发性肝癌患者。纳入标准：(1)符合原发性肝癌诊疗规范(2019年版)[4]诊断标准，经手术切除组织或穿刺组织病理学检查确诊，符合消融治疗指征；(2)TNM分期Ⅱb期～Ⅲb期；(3)预期生存期≥6个月；(4)治疗前未接受其他抗癌治疗。排除标准：(1)合并其他恶性肿瘤；(2)治疗前检查发现有静脉栓、胆管癌和肝外转移；(3)合并顽固性肝腹水、肝性脑病者；(4)治疗依从性较差或失访者。采用随机数字表法将所纳入患者分为试验组和对照组。

1.2 治疗方法 所有患者在治疗前常规行CT、MRI、超声等影像学检查，确定肿瘤位置、体积和数量。对……