根治性切除术后辅助性肝动脉化疗栓塞改善伴有高危因素肝细胞癌患者预后的作用分析

发布时间：2018-07-03 13:19

本文选题：肝细胞癌(HCC) + 总生存率(OS)　；参考：《山东大学》2017年硕士论文

【摘要】：目的:肝细胞癌(HCC)在全球范围内是严重危害人类健康的疾病,肝癌在我国尤为高发,目前手术切除仍然是肝癌最重要的治疗手段。然而,即便是接受根治性切除术后的患者其高复发率及死亡率仍然是制约肝癌手术治疗效果的主要因素,70%接受肝癌根治切除术的患者最终会在5年内复发,因此研究者便希望通过根治性手术后的辅助治疗来改善预后。本研究通过对肝细胞癌根治性切除术后不同次数肝动脉化疗栓塞治疗(TACEE)产生的生存和预后差异分析,评估其在伴有不同危险因素的肝细胞癌患者根治性切除术后的作用,并确定合适的介入次数,筛选出从这项辅助治疗中获益的人群。资料和方法:回顾性分析了山东大学齐鲁医院在2010年1月至2014年1月间320例行根治性切除术的肝细胞癌患者的临床病例资料,包括性别,年龄,血清总胆红素、谷丙转氨酶、谷草转氨酶、谷氨酰转肽酶、碱性磷酸酶、血清白蛋白水平,乙肝表面抗原,肝硬化,Chi ld-pugh分级,血清甲胎蛋白水平,肿瘤大小,肿瘤数目,肿瘤细胞分化程度,是否合并微血管侵犯,以及术后辅助性TACE的次数,并根据肝癌根治术后所行辅助性TACE次数(0-3次)将其分为4组,为了进一步明确辅助性TACE在具有不同复发及死亡风险人群中的作用并筛选出最终的获益人群,又采用了多因素分析,筛选出包括肝细胞癌根治性切除术后辅助性TACE次数,肿瘤大小,Edmondson分级在内的复发及生存的影响因素,并将患者进一步分层为具有低或高危因素复发或死亡的亚组(肿瘤直径≤5厘米或5厘米)。复发或死亡的低危因素被定义为无微血管侵犯(MiVI)的EdmondsonⅠ/Ⅱ级,而高危因素被定义为EdmondsonⅢ/Ⅳ级或微血管侵犯。使用Kaplan-Meier方法比较生存和复发率,Cox回归进行单因素和多因素分析。结果:四个组的患者在性别,年龄,血清总胆红素、谷丙转氨酶、谷草转氨酶、谷氨酰转肽酶、碱性磷酸酶、血清白蛋白水平,乙肝表面抗原,肝硬化,Child-pugh分级,血清甲胎蛋白水平,肿瘤大小,肿瘤数目,肿瘤细胞分化程度,是否合并微血管侵犯等方面具有可比性(P0.05),在没有接受根治术后辅助性TACE的患者相比,接受了2次(log-rank,χ 2= 9.054,P=0.003)或3次(log-rank,χ2=4.228,P=0.04)TACE的患者显示复发延迟,且接受2次或3次TACE患者与其他患者相比,总生存率(OS)增加。随后的亚组分析中,采用多因素分析显示,肝细胞癌根治性切除术后辅助性TACE次数(HR = 0.797,95%CI:0.707-0.897,P0.001),肿瘤大小(HR = 0.649,95%,CI:0.484-0.871,P = 0.004),Edmondson分级(Edmondson分级:HR = 0.563,95%,CI:0.423-0.750,P0.001)和MiVI(HR = 0.240,95%,CI:0.155-0.373,P0.001)是复发的影响因素。同时,这些因素也是生存的影响因素(辅助性TACE次数:HR = 0.523,95%CI:0.411-0.666,P0.001;肿瘤大小:HR = 0.434,95%,CI:0.261-0.719,P =0.001;Edmondson等级:HR = 0.317,95%,CI:0.193-0.521,P0.001;MiVI:HR = 0.137,95%,CI:0.072-0.259,P0.001)。然后我们根据肿瘤直径进行分层分析,以确定对复发或死亡的影响。复发或死亡的低危因素被定义为没有微血管侵犯(MiVI)的Edmondson Ⅰ/Ⅱ级,而高危因素被定义为Edmondson Ⅲ/Ⅳ级或微血管侵犯。低危亚组肿瘤直径≤5cm的患者人数分别为66,24,24,29例。而高危亚组肿瘤直径≤5cm的患者,分别为32,12,11,10。在肿瘤直径5cm的低危亚组中,人数分别为26,14,7,11,肿瘤直径5cm高危亚组,人数分别为22,10,9,13。在低危亚组,所有组无病生存率(DFS)和总生存率(OS)之间无统计学差异。在肿瘤直径≤5的高危亚组患者中,与不接受根治性术后辅助TACE的患者相比,TACE组显示复发延迟,且2次或3次TACE可改善OS。对于肿瘤直径5的高危亚组,2次或3次TACE可延缓复发并改善OS。结论:根治性切除术后2-3次辅助性TACE对肿瘤分化差和伴有微血管侵犯的肝细胞癌患者有利,特别是对于肿瘤直径5 cm的患者。
[Abstract]:Objective: hepatocellular carcinoma (HCC) is a worldwide disease which seriously endangers human health. Liver cancer is especially high in our country. Surgical resection is still the most important treatment for liver cancer. However, even after radical resection, the high recurrence rate and death rate are still the main factors restricting the effect of liver cancer. 70% patients who undergo radical resection of liver cancer will eventually have a recurrence within 5 years, so the researchers hope to improve the prognosis by adjuvant therapy after radical resection. This study evaluated the differences in survival and prognosis by different times of hepatic arterial chemoembolization (TACEE) after radical resection of hepatocellular carcinoma. The effect of radical excision of hepatocarcinoma patients with risk factors, and the appropriate number of interventions, and screening out people who benefit from this adjuvant therapy. Data and methods: a retrospective analysis of the clinical cases of 320 cases of hepatocarcinoma in the Qilu Hospital from January 2010 to January 2014 in Shandong University. Data, including sex, age, serum total bilirubin, alanine aminotransferase, cereal aminotransferase, glutamyl transpeptidase, alkaline phosphatase, serum albumin level, hepatitis B surface antigen, liver cirrhosis, Chi ld-pugh grading, serum alpha fetoprotein level, tumor size, tumor number, tumor cell differentiation, microvascular invasion, and postoperative The number of auxiliary TACE was divided into 4 groups according to the number of auxiliary TACE times (0-3 times) after radical resection of liver cancer. In order to further clarify the role of auxiliary TACE in people with different recurrence and death risk and to screen out the final benefiting crowd, the multifactor analysis was used to screen out the radical resection of hepatocellular carcinoma after radical resection. Adjuvant TACE times, tumor size, Edmondson classification, recurrence and survival factors, and further stratifying patients into subgroups with low or high risk factors for relapse or death (tumor diameter less than 5 cm or 5 cm). Low risk factors for recurrence or death are defined as Edmondson I / II of MiVI without microvascular invasion, and high risk The factors were defined as Edmondson III / IV or microvascular invasion. Kaplan-Meier method was used to compare survival and recurrence rates and Cox regression for single factor and multifactor analysis. Results: four groups of patients were in sex, age, serum total bilirubin, alanine transaminase, glutamine transaminase, glutamyl transpeptidase, alkaline phosphatase, serum albumin level, Hepatitis B surface antigen, liver cirrhosis, Child-pugh grading, serum alpha fetoprotein level, tumor size, tumor number, tumor cell differentiation, and microvascular invasion were comparable (P0.05), and received 2 times (log-rank, X 2= 9.054, P=0.003) or 3 times (log-rank, chi square) in patients who had not received radical resection (log-rank, 2=, P=0.003). 2=4.228, P=0.04) TACE patients showed delayed recurrence, and the total survival rate (OS) increased in 2 or 3 TACE patients compared with other patients. In subsequent subgroup analysis, multivariate analysis showed that the number of auxiliary TACE times after radical resection of hepatocellular carcinoma (HR = 0.797,95%CI:0.707-0.897, P0.001), tumor size (HR = 0.649,95%, CI:0.4) 84-0.871, P = 0.004), Edmondson classification (Edmondson grading: HR = 0.563,95%, CI:0.423-0.750, P0.001) and MiVI (HR = 0.240,95%, CI:0.155-0.373,) are the factors affecting the recurrence. 0.719, P =0.001; Edmondson grade: HR = 0.317,95%, CI:0.193-0.521, P0.001; MiVI:HR = 0.137,95%, CI:0.072-0.259, P0.001). Then we make a stratified analysis based on the diameter of the tumor to determine the effect on recurrence or death. The low risk factors for recurrence or death are defined as grade I / II without microvascular invasion (MiVI), and high risk The factors were defined as Edmondson III / IV or microvascular invasion. The number of patients with a diameter of less than 5cm in the low risk subgroup was 66,24,24,29, respectively. The patients in the high risk subgroup, with a diameter of less than 5cm, were 32,12,11,10. in the low risk subgroup of the tumor diameter 5cm, respectively, the number was 26,14,7,11, and the tumor diameter 5cm high risk subgroup, the number was 22, respectively. 10,9,13. in the low risk subgroup, there was no statistical difference between all groups of disease free survival (DFS) and total survival (OS). In the high risk subgroups with a tumor diameter less than 5, the TACE group showed a delayed recurrence compared with those who did not receive radical postoperative adjuvant TACE, and the 2 or 3 times TACE could improve the high risk subgroup of the tumor diameter 5, 2 or 3 times TAC. E can delay recurrence and improve the OS. conclusion: 2-3 adjuvant TACE after radical resection are favorable for poor differentiation of tumors and patients with hepatocellular carcinoma with microvascular invasion, especially for patients with a diameter of 5 cm.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.7

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