TACE联合氩氦刀冷冻消融治疗原发性肝癌临床疗效研究

发布时间：2018-01-25 12:39

本文关键词： 氩氦刀冷冻消融肝动脉化疗栓塞原发性肝癌甲胎蛋白 T细胞亚群 1年生存率　出处：《河北医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的:原发性肝细胞癌是恶性程度高,预后不良的恶性肿瘤之一。目前原发性肝癌治疗的首选治疗手段仍然是手术治疗,然而患者在初诊时大多数已经发展为中晚期病人,已失去手术切除机会。微创介入治疗目前是失去手术切除机会的的原发性肝癌患者重要治疗手段。微创介入治疗不仅可以改善原发性肝癌患者的生存质量和生存期,甚至对早期肝癌可达到临床治愈的效果。微创介入治疗分为非血管性介入治疗和血管性介入治疗。血管性介入治疗主要是经导管通过动脉进行化疗药物灌注和应用栓塞剂堵塞肿瘤血管,也称TACE(transcatheter arterial chemoembolization)。非血管性介入治疗包括射频消融、微波消融、无水酒精瘤体注射、高强度聚焦超声、氩氦刀等。氩氦刀技术以局部肿瘤靶细胞灭活为主的治疗技术,是近年来从传统冷冻治疗发展起来新的冷冻消融技术,因安全有效,损伤小、痛苦小、恢复快,对不能手术切除或不能忍受手术的患者提供了一种新的治疗方法。氩氦刀技术可单独及联合应用治疗肿瘤,对肝癌的治疗是安全有效的。因此,我们分析了中晚期肝癌患者接受肝动脉化疗栓塞治疗、氩氦刀冷冻消融治疗及经肝动脉化疗及栓塞联合应用氩氦刀冷冻消融治疗的疗效,为失去手术机会的中晚期肝癌患者选择合适的治疗方法提供临床依据。方法:我们回顾性分析2012-05~2015-06我科共156例不能手术的中晚期原发性肝癌患者,所有患者均经B超、CT、核磁等影像学检查,并行超声引导下活检,病理证实,依照肝癌诊断标准确诊的原发性肝癌患者,且肿瘤直径≥2cm,≤15cm。原发性肝癌癌灶≤3个,肝内转移病灶≤5个;ECOG生活状况评分≤2分;肝功能Child分级A~B;心、肺、肾功能正常,凝血功能无明显障碍,无并发严重感染;生存期预计≥3个月。把肝癌患者分入TACE联合应用氩氦刀冷冻消融组(47例)、TACE(肝动脉化疗栓塞)组(51例)、氩氦刀冷冻消融组(49例)。所有病例治疗周期3~6月以内,以治疗后6个月评效,各组治疗根据患者治疗过程中病情,两种治疗手段可反复多次或交替使用。以肝脏CT增强扫描监测病灶变化,采用m RECIST标准判定疗效;采用电化学发光法进行AFP测定观察治疗前后血清AFP水平变化;采用流式细胞仪测定T细胞亚群观察机体免疫功能变化。采用SPSS15.0统计学软件进行数据统计分析,采用卡方检验进行差异显著性检验和率的比较,P0.05时差异有统计学意义;采用Log-Rank法进行生存分析;均数采用单因素方差分析。结果:1联合治疗组总有效率(72.3%)明显高于氩氦刀冷冻消融组(53.1%)和TACE组(47.1%),差异均有统计学意义(P0.05)氩氦刀冷冻消融组总有效率高于TACE组,但无统计学意义(P0.05)。2甲胎蛋白(AFP)变化情况147例患者中有104例明显升高,其中AFP400ng/m L者104例,1000ng/m L者28例,高于正常值但小于400ng/m L者40例。三组治疗后AFP水平均有明显下降,差异具有统计学意义(P0.05)。TACE组AFP异常者共50例,下降50%者35例(70.0%);氩氦刀冷冻消融组中AFP异常者47例,38例肝癌患者AFP下降50%(78.7%);联合组中AFP异常者49例,41例肝癌患者AFP下降50%(83.7%)。联合组AFP下降明显优于单纯TACE组及氩氦刀冷冻消融组,具有统计学差异(P0.05)。3治疗后T细胞亚群检测:氩氦刀冷冻消融组、TACE组、联合治疗组CD3+、CD4+细胞明显上升,以联合治疗组最为显著,差异具有统计学意义(P0.05);治疗后各组CD8+、CD16+/CD56+细胞检测无明显差异,无统计学意义(P0.05)。4对生存率的影响三组6个月生存率无明显差异(P0.05)。1年生存率TACE联合氩氦刀冷冻消融组较TACE组、氩氦刀冷冻消融组明显提高(P0.01)。而氩氦刀冷冻消融组6个月生存率和1年生存率均高TACE组,但均无统计学差异(P0.05)。5不良反应其中入组的147例患者顺利完成TACE治疗和氩氦刀冷冻消融治疗,术中死亡病例无;肝区胀痛不适、发热、转氨酶及胆红素轻度升高等为常见不良反应,偶有胸腔积液。结论:本研究结果显示,TACE联合氩氦刀冷冻消融治疗原发性肝癌较任何单一方案有效率高,能显著降低甲胎蛋白水平,增强机体免疫机能,且能明显提高患者1年生存率,不良反应轻微。
[Abstract]:Objective: primary hepatocellular carcinoma is one of the high degree of malignancy and poor prognosis of malignant tumors. The treatment of choice for the treatment of primary liver cancer is still surgery, but patients at diagnosis has been developed for the most advanced patients have lost the opportunity of surgery. Minimally invasive interventional therapy is currently lost operation opportunity the patients with primary liver cancer treatment. Not only can improve the interventional treatment of primary liver cancer with minimally invasive quality of life and survival, even for early cancer can achieve clinical cure effect. Minimally invasive interventional treatment for vascular interventional therapy and vascular interventional treatment. Vascular interventional treatment is mainly by catheter through the artery perfusion chemotherapy and Application of embolic agents blocking tumor blood vessels, also known as TACE (transcatheter arterial chemoembolization). Non vascular interventional therapy including injection Frequency ablation, microwave ablation, percutaneous ethanol injection, high intensity focused ultrasound, cryoablation. Argon helium knife technology to local tumor target cell inactivation treatment technology in recent years, from the traditional cryotherapy developed new cryoablation technology for safe and effective, little injury, little pain. Fast recovery, provides a new method for the treatment of unresectable or cannot tolerate surgery. Argon helium knife can be used alone and combined treatment of tumors is safe and effective for the treatment of liver cancer. Therefore, we analyzed the advanced liver cancer patients received chemotherapy of hepatic artery embolization, cryoablation treatment and transcatheter arterial chemotherapy and embolization with cryoablation therapy, for unresectable advanced hepatocellular carcinoma patients to choose the appropriate treatment to provide clinical basis. Methods: We retrospectively analyzed 2012-05 Advanced ~2015-06 a total of 156 patients with primary liver cancer patients, all patients were treated by ultrasound, CT examination, magnetic imaging, parallel ultrasound guided biopsy, pathology, in accordance with the standard confirmed diagnosis of hepatocellular carcinoma in patients with primary liver cancer, and the tumor diameter is larger than 2cm, less than 15cm. in primary hepatocellular carcinoma the cancer is less than 3, intrahepatic metastasis lesions less than 5 ECOG; the living conditions were below 2 points; Child classification of liver function A~B; heart, lung, kidney function, blood coagulation function has no obvious obstacles, no severe infection; survival period is expected to exceed 3 months. The patients were divided into TACE hepatocellular carcinoma combined with argon cryoablation group (47 cases), TACE (TACE) group (51 cases), cryoablation group (49 cases). All patients within 3~6 months period, in 6 months after the treatment group were treated according to the assessment results, the treatment process of patients, two treatment methods repeated or alternate to To use. Hepatic CT enhancement scanning and monitoring changes to determine the efficacy of using the m RECIST standard; luminescence method to observe the changes of serum AFP levels before and after treatment were measured by using electrochemical AFP; Determination of T cell subsets on immune function was measured by flow cytometry. Using SPSS15.0 statistical data analysis software, using chi square test comparison a significant difference test and rate, the difference was statistically significant P0.05; survival analysis was performed using Log-Rank method; mean by single factor variance analysis. Results: 1 the total effective rate of combined treatment group (72.3%) was significantly higher than that of cryoablation group (53.1%) and TACE group (47.1%), the differences were statistically meaning (P0.05) cryoablation group total efficiency is higher than that of TACE group, but no statistical significance (P0.05.2) and alpha fetoprotein (AFP) changes in 147 cases, 104 cases markedly increased, AFP400ng/m L In 104 cases, 28 cases of 1000ng/m L were higher than normal in 40 cases, but less than 400ng/m L. The three groups after treatment AFP levels were significantly decreased, the difference was statistically significant (P0.05) group.TACE AFP abnormalities were 50 cases, 35 cases decreased 50% (70%); 47 cases of cryoablation group AFP abnormal, 38 cases of AFP patients with liver cancer decreased by 50% (78.7%); 49 cases with abnormal AFP group, 41 cases of AFP patients with liver cancer decreased by 50% (83.7%). Group AFP were lower than that of the pure TACE group and cryoablation group, with statistical difference (P0.05) after the treatment of.3 T cell subsets: Cryoablation group, TACE group, CD3+ treatment group, CD4+ cells increased significantly, with the combined treatment group was the most significant, the difference was statistically significant (P0.05); CD8+ after treatment, no significant difference was detected in CD16+/CD56+ cell (P0.05), there was no significant effect of.4 on survival rate the three group of 6 month survival No significant differences in the rates of (P0.05).1 year survival rate of TACE combined with argon helium cryoablation group than TACE group, cryoablation group was significantly increased (P0.01). While cryoablation group, the survival rate of 6 months and 1 year survival rates were higher in TACE group, but there were no significant differences (P0.05.5) adverse reactions including 147 cases of patients were treated with TACE successfully and cryoablation treatment, intraoperative death cases; liver area pain and discomfort, fever, transaminase and bilirubin increased slightly as the common adverse reactions, with pleural effusion. Conclusion: the results of this study show that TACE combined with argon helium cryoablation for the treatment of primary hepatocellular carcinoma is more effective than any single solution rate, can significantly reduce the level of alpha fetoprotein, enhance immune function, and can significantly improve the 1 year survival rate of patients, mild adverse reactions.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.7

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