乙型病毒性肝炎相关小肝癌术后预防性肝动脉栓塞化疗对术后复发的影响

Effects of preventive transcatheter arterial chemoembolization on the recurrence of hepatitis B-related small hepatocellular carcinoma after radical resection

    摘要
  • 摘要: 目的:探讨预防性TACE对乙型病毒性肝炎相关小肝癌术后肿瘤复发的影响及复发影响因素。
    方法:采用倾向评分配比及回顾性病例对照研究方法。收集2008年1月至2010年 12月第二军医大学附属东方肝胆外科医院收治的795例乙型病毒性肝炎相关小肝癌患者的临床病理资料。行预防性TACE的患者337例，未行TACE治疗的患者458例。采用倾向评分配比对患者进行配对，将配比后行预防性TACE患者设为干预组，未行预防性TACE患者设为对照组，两组各337例。采用门诊和电话方式进行随访，了解患者术后复发情况，随访时间截至2015年8月30日。观察指标包括：(1)随访及肿瘤复发情况［早期复发率(2年内复发)、晚期复发率(2年后复发)］。(2)影响肿瘤复发的单因素和多因素分析指标：性别、年龄、术前HBVDNA水平、术前ALT、术前TBil、术前Alb、HBeAg、术前AFP、肿瘤直径、肿瘤数目、镜下包膜、镜下子灶、镜下微血管癌栓、肝纤维化或肝硬化、肿瘤分化程度、手术时间、肝门阻断时间、术中出血量、输血情况、肿瘤切缘距离、抗病毒治疗、术后预防性TACE。计数资料比较采用χ2检验，计量资料比较采用Student t检验，等级资料比较采用秩和检验。采用KaplanMeier法绘制肿瘤复发曲线并计算复发率，Logrank检验比较复发率。采用COX回归模型进行肿瘤复发单因素和多因素分析。
    结果:(1)随访及肿瘤复发情况：配比后674例患者均获得随访，随访时间为6～92个月。干预组患者1、3、5年复发率分别为13.6%、38.3%、51.0%，对照组患者分别为10.4%、30.6%、42.4%，两组患者整体复发情况比较，差异无统计学意义(χ2=3.418，P>0.05)。干预组和对照组患者肿瘤早期复发率分别为28.5%和21.7%，两组比较，差异有统计学意义 (χ2=4.178，P<0.05)；肿瘤晚期复发率分别为25.8%和26.1%，两组比较，差异无统计学意义(χ2=0.008，P>0.05)。(2)影响肿瘤复发的单因素和多因素分析：对配比后的674例患者进行术后肿瘤复发单因素分析结果显示：性别、术前HBVDNA水平、术前ALT、HBeAg、术前AFP、肿瘤数目、镜下子灶、镜下微血管癌栓、肝纤维化或肝硬化、抗病毒治疗是影响乙型病毒性肝炎相关小肝癌患者术后肿瘤复发的相关因素(HR=0.593，1.454，0.660，1.400，1.311，1.789，1.303，1.358，1.307，0.743，95%可信区间：0.423～0.830，1.159～1.823，0.534～0.816，1.132～1.733，1.005～1.709，1.027～3.115，1.040～1.631，1.048～1.759，1.102～1.549，0.595～0.926，P<0.05)。多因素分析结果显示：男性、术前HBVDNA水平≥200 U/mL、术前ALT≥40 U/L、HBeAg阳性、镜下血管癌栓、肝纤维化或肝硬化、术后未接受抗病毒治疗为影响肿瘤复发的独立危险因素(HR=0.645，1.285，0.758，1.419，1.497，1.291，0.629，95%可信区间：0.455～0.916，1.001～1.649，0.604～0.951，1.128～1.784，1.134～1.976，1.084～1.538，0.500～0.792，P<0.05)。
    结论: 预防性TACE治疗不能降低乙型病毒性肝炎相关小肝癌术后复发率，因此不建议采用预防性TACE治疗。患者性别为男性，术前HBVDNA水平≥200 U/mL、术前ALT≥40 U/L、HBeAg阳性、镜下血管癌栓、肝纤维化或肝硬化、术后未接受抗病毒治疗为影响乙型病毒性肝炎相关小肝癌术后复发的独立危险因素。

     

    Abstract: Objective:To investigate the effects of preventive transcatheter arterial chemoembolization(TACE) on the recurrence of hepatitis Brelated small hepatocellular carcinoma(HCC) after radical resection.
    Methods: The retrospective casecontrol study was adopted by using propensity score matching (PSM) analysis. The clinicopathological data of 795 patients with small HCC who were admitted to the Eastern Hepatobiliary Surgery Hospital between January 2008 and December 2010 were collected, including 337 receiving preventive TACE treatment and 458 not receiving preventive TACE treatment. All the patients were allocated into the intervention group and control group after PSM, with 337 patients in each group.The followup was performed to detect tumor recurrence of patients by outpatient examination and telephone interview till August 30, 2015. Observation indicators included (1) the situation of followup and tumor recurrence, including early recurrence rate and late recurrence rate, which were divided by 2 years. (2) Indicators of univariate and multivariate analyses affecting tumor recurrence included: gender, age, preoperative serum HBVDNA load, alanine aminotransferase (ALT), total bilirubin (TBil), serum albumin(Alb), HBeAg, Alpha Fetal Protein (AFP), tumor diameter, number of tumors, microscopic capsule, microscopic satellite nodules, presence of microvascular invasion, liver fibrosis or cirrhosis, degree of tumor differentiation, operation time, time of hepatic portal occlusion, volume of intraoperative blood loss, blood transfusion, length of surgical margin, antiviral treatment and postoperative preventive TACE. Comparison of count data was analyzed using the chisquare test. Measurement data were compared using the Student t test and ranked data were compared by RankSum test. The recurrence curve and recurrence rate were drawn and calculated by KaplanMeier method, respectively. Comparison of the recurrence rate was done by the Logrank test. Univariate and multivariate analyses were performed by the COX regression model.
    ResultsThe situation of followup and tumor recurrence: the matched 674 patients were followed up for 6-92 months. The 1, 3 and 5year recurrence rates after radical resection were 13.6%, 38.3% and 51.0% in the intervention group and 10.4%, 30.6% and 42.4% in the control group, respectively, with no statically significant difference (χ2=3.418, P>0.05). The early tumor recurrence rate was 28.5% and 21.7% in the intervention group and control group, respectively, with a significant difference (χ2=4.178, P<0.05). The late tumor recurrence rate was 25.8% and 26.1% in the intervention group and control group, respectively, with no significant difference (χ2=0.008, P>0.05). (2)Univariate and multivariate analyses affecting tumor recurrence: the results of univariate analysis showed that gender, preoperative serum HBVDNA load , ALT, HBeAg, AFP, number of tumors, presence of satellite nodules, presence of microvascular invasion, liver fibrosis or cirrhosis and antiviral treatment were related factors affecting the recurrence ［HR=0.593, 1.454, 0.660, 1.400, 1.311, 1.789, 1.303, 1.358, 1.307, 0.743, 95% confidence interval(CI): 0.423-0.830, 1.159-1.823, 0.534-0.816, 1.132-1.733, 1.005-1.709, 1.027-3.115, 1.040-1.631, 1.048-1.759, 1.102-1.549, 0.595-0.926, P<0.05］. The results of multivariate analysis showed that gender as male, preoperative serum HBVDNA load≥200 U/mL, preoperative ALT≥40 U/L, positive HBeAg, presence of microvascular invasion, liver fibrosis or cirrhosis and no antiviral treatment were the independent risk factors affecting the recurrence (HR=0.645, 1.285, 0.758, 1.419, 1.497, 1.291, 0.629, 95% CI: 0.455-0.916, 1.001-1.649, 0.604-0.951, 1.128-1.784, 1.134-1.976, 1.084-1.538, 0.500-0.792, P<0.05).
    Conclusions: As the recurrence rate of HCC after radical resection can not be reduced by preventive TACE treatment, TACE should not be recommended. Gender as male, preoperative serum HBVDNA load≥200 U/mL, preoperative ALT≥40 U/L, positive HBeAg, presence of microvascular invasion, liver fibrosis or cirrhosis and no antiviral treatment are the independent risk factors affecting the recurrence of hepatitis Brelated small HCC after radical resection.

     

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