解剖性肝切除术治疗合并微血管侵犯肝细胞癌的临床疗效

Clinical efficacy of anatomic liver resection in the treatment of hepatocellular carcinoma with microvascular invasion

目的：探讨解剖性肝切除术治疗合并微血管侵犯（MVI）的肝细胞癌（HCC）的临床疗效。方法：采用回顾性队列研究和病例对照研究方法。收集2007年6月至2012年6月安徽医科大学附属省立医院收治的150例合并MVI的HCC手术患者的临床资料。60例患者行解剖性肝切除术，设为AR组； 90例患者行非解剖性肝切除术，设为NR组。AR组患者根据术前ICG R15试验结果确定拟切除肝段，行解剖性肝切除术。NR组患者行非解剖性肝切除术。观察指标：（1）手术情况：手术时间、术中出血情况、术中输血例数。（2）术后恢复情况：术后腹腔引流管拔除时间、术后住院时间、术后30 d内并发症Clavein分级、术后30d内肝衰竭例数、术后30d内死亡例数。（3）随访情况：患者术后中位生存时间，5年总体生存率、5年无瘤生存率。（4）影响150例合并MVI的HCC手术患者预后因素分析。采用门诊和电话方式进行随访，了解患者生存情况。随访时间截至2016年4月。正态分布的计量资料以x^-±s表示，组间比较采用独立样本t检验。计数资料比较采用χ^2检验或Fisher确切概率法。采用KaplanMeier法计算生存率，采用Logrank检验进行生存分析。采用COX模型进行单因素和多因素分析。结果：（1）手术情况：150例患者均顺利完成HCC根治术。AR组患者手术时间、术中出血情况、术中输血例数分别为（165±39）min，≥500 mL 12例、〈500 mL 48例，15例；NR组患者分别为（136±30）min，≥500 mL 34例、〈500 mL 56例，38例；两组患者上述指标比较，差异均有统计学意义（t=29.172，χ^2=5.351，4.673，P〈0.05）。（2）术后恢复情况：AR组患者术后腹腔引流管拔除时间、术后住院时间分别为（2.7±1.1）d、（5.2±1.3）d，NR组患者分别为（3.8± 1.6）d、（7.1±2.3）d；两组患者上述指标比较，差异均有统计学意义（t=4.641，5.812，P〈0.05）。AR组患者术后30 d内并发症Clavein分级、术后30 d内死亡例数分别为Ⅰ～Ⅱ级45例、Ⅲ～Ⅳ级15例，1例；NR组患者分别为Ⅰ～Ⅱ级61例、Ⅲ～Ⅳ级29例，2例；两组患者上述指标比较，差异均无统计学意义（χ^2=0.906， P〉0.05）。AR组和NR组患者术后30 d内肝衰竭例数分别为4例和17例，两组患者比较，差异有统计学意义（χ^2=4.467，P〈0.05）。（3）随访情况：150例患者均获得术后随访。随访时间为1～106个月，中位随访时间为26个月。AR组60例患者中位生存时间为46个月，5年总体生存率为33.3%，5年无瘤生存率为21.7%。NR组90例患者中位生存时间为18个月，5年总体生存率为15.6%，5无瘤生存率为2.2%。两组患者总体生存和无瘤生存情况比较，差异均有统计学意义（χ^2=23.718，63.932，P〈0.05）。（4）影响150例合并MVI的HCC手术患者预后因素分析：单因素分析结果显示：肿瘤最大直径、肿瘤包膜、肿瘤TNM分期、肿瘤Edmondson分级、手术方式是影响合并MVI的HCC手术患者总体生存和无瘤生存的相关因素，差异有统计学意义（χ^2=5.519、2.790，13.639、8.321，42.470、31.057，15.963、19.594，23.718、63.932，P〈0.05）。多因素分析结果显示：肿瘤包膜缺失、肿瘤TNM分期为Ⅲ～Ⅳ期、肿瘤Edmondson分级为Ⅲ～ Ⅳ级、手术方式为非解剖性肝切除术是合并MVI的HCC手术患者总体生存和无瘤生存不良的独立因素；肿瘤最大直径〉5 cm是合并MVI的HCC手术患者总体生存不良的独立因素，差异均有统计学意义（HR=0.527、0.683，0.333、0.522，0.576、0.514，0.523、0.268，95%可信区间：0.355～0.782、0.475～0.983，0.219～0.504、0.361～0.755，0.389～0.852、0.358～0.737，0.342～0.800、0.174～0.413；HR=0.559，95%可信区间：0.370～0.845，P〈0.05）。结论：解剖性肝切除术治疗合并MVI的HCC安全有效，近、远期疗效好，可改善患者预后。肿瘤包膜缺失、肿瘤TNM分期为Ⅲ～Ⅳ期、肿瘤Edmondson分级为Ⅲ～Ⅳ级、手术方式为非解剖性肝切除术是合并MVI的HCC手术患者总体生存和无瘤生存不良的独立因素；肿瘤最大直径〉5 cm是合并MVI的HCC手术患者总体生存不良的独立因素。

Objective：To explore the clinical efficacy of anatomic liver resection in treatment of hepatocellular carcinoma （HCC） with microvascular invasion （MVI）. Methods：The retrospective cohort and casecontrol study was conducted. The clinical data of 150 HCC patients with MVI who were admitted to the Anhui Medical University Affiliated Provincial Hospital from June 2007 to June 2012 were collected. Sixty patients undergoing anatomic liver resection were allocated into the AR group and 90 undergoing nonanatomic liver resection in the NR group. Patients in the AR group underwent anatomic liver resection according to results of preoperative ICG R15 test, and patients in the NR group underwent nonanatomic liver resection. Observation indicators： （1） operation situations： operation time, volume of intraoperative blood loss, number of patients with blood transfusion; （2） postoperative recovery situations： time of drainagetube removal, duration of hospital stay, Clavein grade of complication within 30 days postoperatively, number of patients with hepatic failure within 30 days postoperatively and number of death within 30 days postoperatively; （3） followup： postoperative median survival time, 5year overall survival rate and 5year tumorfree survival rate; （4） prognostic factors analysis of 150 HCC patients with MVI. Measurement data with normal distribution were represented as x^-±s and comparison between groups was analyzed using the independentsample t test. Count data were represented as the chisquare test or Fisher exact probability. The survival rate was calculated using the KaplanMeier method and survival analysis was done using Logrank test. The univariate analysis and multivariate analysis were done using the COX regression model. Results：（1） Operation situations： all the 150 patients received successful radical resection of HCC. Operation time, numbers of patients with volume of intraoperative blood loss ≥500 mL and with volume of intraoperative blood loss 〈 500 mL and number of patients with blood transfusion were （165±39）minutes, 12, 48, 15 in the AR group and （136±30）minutes, 34, 56, 38 in the NR group, respectively, with statistically significant differences between the 2 groups （t=29.172, χ^2=5.351, 4.673, P〈0.05）. （2） Postoperative recovery situations： time of drainagetube removal and duration of hospital stay were （2.7±1.1）days and （5.2±1.3）days in the AR group, （3.8±1.6）days and （7.1±2.3）days in the NR group, respectively, with statistically significant differences between the 2 groups （t=4.641, 5.812, P〈0.05）. Numbers of patients with grade Ⅰ-Ⅱof Clavein grade and with grade Ⅲ-Ⅳ and number of death within 30 days postoperatively were 45, 15, 1 in the AR group and 61, 29, 2 in the NR group, respectively, with no statistically significant difference between the 2 groups （x2=0.906, P〉0.05）. Number of patients with hepatic failure within 30 days postoperatively in the AR and NR group were respectively 4 and 17, with a statistically significant difference （χ^2=4.467, P〈0.05）. （3） Followup： all the 150 patients were followed up for 1-106 months, with a median time of 26 months. The postoperative median survival time, 5year overall survival rate and 5year tumorfree survival rate were 46 months, 33.3%, 21.7% in the AR group and 18 months, 15.6%, 2.2% in the NR group, respectively, with statistically significant differences in overall survival and tumorfree survival between the 2 groups （χ^2=23.718, 63.932, P〈0.05）. （4） Prognostic factors analysis of 150 HCC patients with MVI： result of univariate analysis showed that maximum diameter of tumor, tumor capsule, TNM stage, Edmondson grade and surgical procedures were relative factors affecting overall survival and tumorfree survival of HCC patients with MVI, with statistically significant differences （χ^2=5.519, 2.790, 13.639, 8.321, 42.470, 31.057, 15.963, 19.594, 23.718, 63.932, P〈0.05）. Result of multivariate analysis showed that missing tumor capsule, stage Ⅲ-Ⅳ of TNM stage, grade Ⅲ-Ⅳof Edmondson grade and nonanatomic liver resection were independent factors affecting poor overall survival and tumorfree survival of HCC patients with MVI, and maximum diameter of tumor 〉5 cm was an independent factor affecting poor overall survival of HCC patients with MVI, with a statistically significant difference [HR=0.527, 0.683, 0.333, 0.522, 0.576, 0.514, 0.523, 0.268, 95% confidence interval （CI）： 0.355-0.782, 0.475-0.983, 0.219-0.504, 0.361-0.755, 0.389-0.852, 0.358-0.737, 0.342-0.800, 0.174-0.413; HR=0.559, 95%CI： 0.370-0.845, P〈0.05]. Conclusions：Anatomic liver resection in the treatment of HCC patients with MVI is safe and effective, with good shortterm and longterm outcomes, and it can also improve prognosis of patients. Missing tumor capsule, stage Ⅲ-Ⅳ of TNM stage, grade Ⅲ-Ⅳof Edmondson grade and nonanatomic liver resection are independent factors affecting poor overall survival and tumorfree survival of HCC patients with MVI, and maximum diameter of tumor 〉5 cm is an independent factor affecting poor overall survival of HCC patients with MVI.