乙型肝炎相关性孤立性大肝癌手术切除患者长期疗效及影响预后因素分析*

doi:10.3969/j.issn.1672-5069.2018.03.027

摘要/Abstract

摘要： 目的探讨HBV相关孤立性大肝癌患者手术切除后长期疗效,并分析影响其预后的危险因素。方法 2011年1月~2012年1月在我院行手术治疗的600例HBV相关肝癌患者,其中孤立性大肝癌130例,肿瘤直径>5 cm,小肝癌组470例,肿瘤直径≤5 cm。术后门诊随访超过5年,采用Kaplan-Meier法绘制生存曲线,采用Log-rank检验行生存分析,采用Logistic回归分析影响预后的因素。结果除孤立性大肝癌组肿瘤直径明显大于小肝癌组（P<0.05）外,其余临床特征的比较无统计学差异（P>0.05）;470例小肝癌患者生存时间为（55.0±4.8）个月,无瘤生存时间为（38.6±2.4）个月,1 a、3 a和5 a 生存率为90.1 %、71.5 %和57.1 %,无瘤生存率为71.8 %、47.0 %和36.8 %,而130例大肝癌患者生存时间为（50.0±3.6）个月（x2=12.175,P=0.001）,无瘤生存时间为（30.6±2.7）个月（x2=0.669,P=0.102）,1 a、3 a和5 a生存率为87.5 %、58.4 %和47.1 %,无瘤生存率为66.8 %、45.3 %和32.8 %;肿瘤直径5~10 cm的孤立性大肝癌患者总体生存率和无瘤生存率与小肝癌组比较无统计学差异（x2=0.489,P=0.202;x2=1.257,P=0.098）,肿瘤直径>10 cm的患者总体生存率和无瘤生存率短于小肝癌患者,差异有统计学意义（x2=15.271,P<0.001;x2=8.124,P=0.013）;多因素分析结果显示,HBV DNA载量（≥1×104 U/ml）和肿瘤直径（>10 cm）是影响患者5 a总生存率（OR=1.679,95 % CI:0.987~2.341,P=0.025;OR=2.348,95% CI: 1.024~4.357, P=0.013）和无瘤生存率（OR=2.365,95% CI:2.542~4.368,P=0.013;OR=2.674,95% CI:0.874~1.934,P=0.049）的独立危险因素。结论肿瘤直径在5~10 cm的孤立性大肝癌患者总体生存率和无瘤生存率与小肝癌患者类似,而肿瘤直径>10 cm的孤立性大肝癌患者总体生存率和无瘤生存率较小肝癌患者短。应针对影响预后的因素给予积极的处理措施,以延长患者术后生存。

关键词: 肝细胞癌, 大肝癌, 肝叶切除术, 生存率, 预后

Abstract: Objective To investigate the factors influencing long-term survival in patients with hepatocellular carcinoma （HCC） with underlying hepatitis B virus （HBV） infection after hepatectomy. Methods 600 patients with hepatitis B virus related single large HCC were recruited in our hospital between January 2011 and January 2012, all patients received hepatectomy and followed-up for 5 years. Out of them,130 cases had tumors with diamiters greater than 5 cm,and 470 had tumors with less than 5 cm. The survival curve was drawn by the Kaplan-Meier method,the survival analysis was estimated by Log-rank test, and the Logistic regression analysis was applied to analyze the prognostic factors. Results There was no significant differences as respect to the clinical features （P>0.05） except the diameter of the tumors in the two groups;in 470 patients with small liver cancer,the survival time was 55.0±4.8 months,the tumor free survival time was 38.6±2.4 months,1 a,3 a and 5 a overall survival rates were 90.1%,71.5% and 57.1%,and the 1 a,3 a and 5 a tumor free survival rate was 57.1%,71.5% and 57.1%,while in 130 patients with large liver cancer,the survival time was 50.0±3.6 months （x2=12.175,P=0.001）,the tumor free survival time was 30.6±2.7 months （x2=0.669,P=0.102）,1 a,3 a and 5 a overall survival rates were 87.5%,58.4% and 47.1%,and the tumor free survival rates were 47.1%,58.4% and 47.1%;there were no significant differences as respect to overall survival rates and disease-free survival rates between patients with large liver cancer （5~10 cm） and those with small liver cancer （x2=0.489,P=0.202;x2=1.257,P=0.098）;the overall survival rates and disease-free survival rates in patients with tumor greater than 10 cm were shorter than in with small liver cancer（x2=15.271,P<0.001;x2=8.124,P=0.013）;multivariate analysis showed that serum HBV DNA loads（≥1×104 U/ml） and tumor size（>10 cm） were the independent risk factor for 5 a overall survival rate （OR=1.679,95% confidence interval:0.987~2.341;OR=2.348,P=0.025,95% CI:1.024~4.357,P=0.013） and 5 a disease-free survival rate（OR=2.365,95% CI:2.542~4.368,P=0.013;OR=2.674,95% CI:0.874~1.934,P=0.049）. Conclusion The overall survival and disease-free survival in patients with large liver cancer（5~10 cm） are similar with those in with small liver cancer,while the overall survival and disease-free survival in patients with tumors greater than 10 cm are poor. Measures should be taken to improve the prognosis of patients with large liver cancer.

Key words: Hepatoma, Large liver cancer, Hepatectomy, Survival, Prognosis

许建, 张浩, 俞小炯. 乙型肝炎相关性孤立性大肝癌手术切除患者长期疗效及影响预后因素分析*[J]. 实用肝脏病杂志, 2018, 21(3): 426-430.

Xu Jian, Zhang Hao, Yu Xiaojiong. Factors influencing long-term survival in patients with hepatocellular carcinoma with underlying hepatitis B virus infection after hepatectomy[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(3): 426-430.

参考文献

[1] Ghouri YA,Mian I,Rowe JH.Review of hepatocellular carcinoma:Epidemiology,etiology,and carcinogenesis. J Carcinog,2017,16(1):1-7.
[2] Poon RT,Fan ST.Hepatectomy for hepatocellular carcinoma:patient selection and postoperative outcome. Liver Transpl,2004,10(2):39-45.
[3] 钟南保,吕光明,陈忠华,等. 原发性巨大肝癌与小肝癌立体定向放射治疗计划比较. 实用肝脏病杂志,2011,14(4):283-285.
[4] Yang LY,Fang F,Ou DP,et al.Solitary large hepatocellular carcinoma:a specific subtype of hepatocellular carcinoma with good outcome after hepatic resection. Ann Surg,2009,249(1):118-123.
[5] Liver EAFTSOT.EASL-EORTC clinical practice guidelines:management of hepatocellular carcinoma. J Hepatol,2012,56(4):908-943.
[6] Li N,Feng S,Xue J,et al.Hepatocellular carcinoma with main portal vein tumor thrombus:a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy. HPB (Oxford),2016,18(6):549-556.
[7] Zhou L,Rui JA,Zhou WX,et al.Edmondson-Steiner grade:A crucial predictor of recurrence and survival in hepatocellular carcinoma without microvascular invasio. Pathol Res Pract,2017,213(7):824-830.
[8] 张杰,段伯焕,朱功兵. HCC患者外科手术根治术后生存分析. 实用肝脏病杂志,2017,20(1):93-96.
[9] Shen JY,Li C,Wen TF,et al.A simple prognostic score system predicts the prognosis of solitary large hepatocellular carcinoma following hepatectomy. Medicine,2016,95(31):e4296.
[10] Jin YJ,Lee JW.Therapeutic priorities for solitary large:hepatocellular carcinoma in a hepatitis B virus endemic area:an analysis of a nationwide cancer registry database. J Surg Oncol,2017,115(4):407-416.
[11] Zhu SL,Ke Y,Peng YC,et al.Comparison of long-term survival of patients with solitary large hepatocellular carcinoma of BCLC stage A after liver resection or transarterial chemoembolization:a propensity score analysis. Plos One,2014,9(12):e115834.
[12] Chen WN,Chen JY,Jiao BY,et al.Interaction of the hepatitis B spliced protein with cathepsin B promotes hepatoma cell migration and invasion. J Virol,2012,86(24):13533-13541.
[13] Yang P,Lin QJ,Feng Y,et al.TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell,2012,22(3):291-303.
[14] 白石磊,项红军,夏勇,等. 乙型肝炎病毒相关孤立性大肝癌手术切除的远期疗效及预后因素分析. 中华消化外科杂志,2017,16(2):151-158.
[15] Kim JM,Hwang IH,Jang IS,et al.Houttuynia cordata thunb promotes activation of HIF-1A-FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular carcinoma cells. Integr Cancer Ther,2017,16(3):360-372.
[16] Yuan G,Zeng CL,Zhu DD,et al.Influences of RFA combined with TACE on the HIF-1α and EGR level of patients with primary hepatic carcinoma. Eur Rev Med Pharmacol Sci,201721(8):1738-1745.
[17] Liao CG,Kong LM,Zhou P,et al.miR-10b is overexpressed in hepatocellular carcinoma and promotes cell proliferation,migration and invasion through RhoC,uPAR and MMPs. J Transl Med,2015,12(1):234.
[18] Grigorie R,Alexandrescu S,Smira G,et al.Curative intent treatment of hepatocellular carcinoma-844 cases treated in a general surgery and liver transplantation center. Chirurgia,2017,112(3):289-300.
[19] Ramalho M,Matos AP,Alobaidy M,et al.Magnetic resonance imaging of the cirrhotic liver:diagnosis of hepatocellular carcinoma and evaluation of response to treatment-Part2. Radiol Bras,2017,50(1):38-47.
[20] Kudo M,Hatano E,Ohkawa S,et al.Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma:Japanese subgroup analysis of the REACH trial. J Gastroenterol,2017,52(4):1-10.