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《中华消化外科杂志》2018年5月第17卷第5期论著

微血管侵犯对肝癌肝切除术后预后的影响

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引用本文:
张小晶,刘静,刘坤,等.微血管侵犯对肝癌肝切除术后预后的影响[J].中华消化外科杂志,2018,17(5):483-487.DOI:10.3760/cma.j.issn.1673-9752.2018.05.012.
【摘要】

目的:探讨微血管侵犯(MVI)对肝癌患者肝切除术后肿瘤复发的影响;术后经导管动脉内化疗栓塞术(TACE)对MVI阳性患者的疗效以及综合治疗对肿瘤复发患者预后的影响。
方法:采用回顾性横断面研究方法。收集2015年2月至2016年12月空军军医大学第一附属医院收治的136例行肝切除术肝癌患者的临床病理资料。患者行肝切除术后选择TACE、射频消融、分子靶向药物治疗,肿瘤复发患者选择上述3种方法中1种或2种为综合治疗。患者行肝切除术后每3个月门诊复查,了解患者肿瘤复发和生存情况。随访开始时间为手术当日,随访终点为患者死亡或随访时间截至2017年12月。观察指标:(1)肝癌患者肝切除术后治疗情况。(2)MVI对肝癌患者肝切除术后肿瘤复发的影响:MVI阳性和阴性患者的临床病理特征和肿瘤复发率。(3)TACE对MVI阳性患者的疗效:是否行TACE治疗MVI阳性患者的临床病理特征和肿瘤复发率。(4)综合治疗对肿瘤复发患者预后的影响。正态分布的计量资料以±s表示,采用独立样本t检验,计数资料比较采用x2检验或Fisher确切概率法,采用Kaplan-Meier法计算肿瘤复发率和生存率,Log-rank检验进行生存分析。
结果:(1)肝癌患者肝切除术后治疗情况:136例肝癌患者中117例单纯行肝切除术,19例肝癌切除术后序贯联合TACE治疗;59例肿瘤复发患者中22例行综合治疗。(2)MVI对肝癌患者肝切除术后肿瘤复发的影响:①临床病理特征。117例单纯行肝切除术患者中MVI阳性49例,男44例,女5例;年龄(52±10)岁;肝功能Child-Pugh分级均为A级,合并肝硬化36例,无肝硬化13例;甲胎蛋白(AFP)阳性34例,AFP阴性15例。MVI阴性患者68例,男54例,女14例;年龄(55±11)岁;肝功能Child-Pugh分级A级65例,B级3例;合并肝硬化52例,无肝硬化16例;AFP阳性39例,AFP阴性29例。两者性别、年龄、肝功能Child-Pugh分级、肝硬化、AFP比较,差异均无统计学意义(x2=2.258,t=-1.626,x2=0.804,0.138,1.758,P>0.05)。②肿瘤复发率。117例单纯行肝切除术患者6个月和1年肿瘤复发率分别为30.77%、30.61%。其中49例MVI阳性患者6个月和1年肿瘤复发率分别为42.86%、51.02%;68例MVI阴性患者6个月和1年肿瘤复发率分别为22.06%、27.94%。两者6个月和1年肿瘤复发率比较,差异均有统计学意义(x2=5.738,6.465,P<0.05)。(3)TACE对MVI阳性患者的疗效:①临床病理特征。56例MVI阳性患者,其中术后序贯联合TACE治疗7例,男7例;年龄(50±4)岁;肝功能Child-Pugh分级均为A级,合并肝硬化5例,无肝硬化2例;AFP阳性2例,AFP阴性5例。未序贯联合TACE治疗患者49例,男44例,女5例;年龄(52±10)岁;肝功能Child-Pugh分级均为A级,合并肝硬化36例,无肝硬化13例;AFP阳性34例,AFP阴性15例。两者性别、年龄、肝功能Child-Pugh分级、肝硬化、AFP比较,差异均无统计学意义(x2=0.784,t=-0.512, x2=0.013,2.844,P>0.05)。②肿瘤复发率。7例肝切除术后序贯联合TACE治疗的MVI阳性患者6个月和1年肿瘤复发率分别为0、28.57%;49例肝切除术后未序贯联合TACE治疗的MVI阳性患者6个月和1年肿瘤复发率分别为42.86%、51.02%。两者6个月肿瘤复发率比较,差异有统计学意义(x2=4.800,P<0.05),1年肿瘤复发率比较,差异无统计学意义(x2=1.236,P>0.05)。(4)综合治疗对肿瘤复发患者预后的影响:59例肿瘤复发患者,37例未行综合治疗患者中34例1年内死亡,其中30例为术后6个月死亡,1年生存率为8.10%。22例行综合治疗的患者中4例1年内死亡,1年生存率为81.80%。两者1年生存率比较,差异有统计学意义(x2=32.698,P<0.05)。
结论:MVI是肝癌患者肝切除术后肿瘤复发的重要危险因素之一;MVI阳性患者行肝切除术后序贯联合TACE治疗可降低肿瘤复发率;肝切除术后肿瘤复发积极行综合治疗可明显提高患者的生存率。

【Abstract】

Objective:To investigate the effect of microvascular invasion (MVI) on tumor recurrence of hepatocellular carcinoma (HCC) patients after hepatectomy, the efficacy of sequential transcatheter arterial chemoembolization (TACE) on positive MVI patients after hepatectomy, and the effect of comprehensive treatment on the prognosis of patients with tumor recurrence.
Methods:The retrospective cross-sectional study was conducted. The clinicopathological data of 136 HCC patients who underwent hepatectomy in the First Affiliated Hospital of Air Force Medical University from February 2015 to December 2016 were collected. Patients were treated with TACE, radiofrequency ablation (RFA) and molecular-targeted drugs after hepatectomy, and patients with tumor recurrence selected 1 or 2 above treatments. The patient received postoperatively outpatient reexaminations every 3 months to detect tumor recurrence and survival. Follow-up was from the day of the surgery to death or December 2017. Observation indicators: (1) treatment after hepatectomy; (2) effect of MVI on tumor recurrence of HCC patients after hepatectomy: clinicopathological features and tumor recurrence rate between positive and negative MVI patients; (3) efficacy of TACE on positive MVI patients: clinicopathological features and tumor recurrence rate in positive MVI patients with or without TACE; (4) effect of comprehensive treatment on the prognosis of patients with tumor recurrence. Measurement data with normal distribution were represented as ±s and analyzed using the independent-samples t test. Comparisons of count data were analyzed using chi-square test or Fisher exact probalility. The tumor recurrence rate and survival rate were calculated by the Kaplan-Meier method, and Log-rank test was used for survival analysis.
Results:(1) Treatment after hepatectomy: of 136 patients undergoing hepatectomy, 117 underwent single hepatectomy and 19 combined sequential TACE; 59 had HCC recurrence, including 22 receiving comprehensive treatment. (2) Effect of MVI on tumor recurrence of HCC patients after hepatectomy: ① Clinicopathological features: of 117 patients undergoing single hepatectomy, positive MVI was detected in 49 patients, including 44 males and 5 females, with an age of (52±10)years old; 49 patients were in Child-Pugh grade A, including 36 combined with liver cirrhosis and 13 without liver cirrhosis; positive and negative alpha-fetoproteins (AFPs) were respectively detected in 34 and 15 patients. Negative MVI was detected in 68 patients, including 54 males and 14 females, with an age of (55±11)years old; 65 and 3 patients were respectively in Child-Pugh grade A and B, including 52 combined with liver cirrhosis and 16 without liver cirrhosis; positive and negative AFPs were respectively detected in 39 and 29 patients. There was no statistically significant difference in gender, age, Child-Pugh score of liver function, liver cirrhosis and comparison of AFP between positive and negative MVI patients (x2=2.258, t=-1.626, x2=0.804, 0.138, 1.758, P>0.05). ② Tumor recurrence rate: The 6-month and 1-year tumor recurrence rates after hepatectomy were respectively 30.77%, 30.61% in 117 patients undergoing single hepatectomy and 42.86%, 51.02% in 49 of 117 patients with positive MVI and 22.06%, 27.94% in 68 of 117 patients with negative MVI, showing statistically significant differences in 6-month and 1-year tumor recurrence rates between positive and negative MVI patients (x2=5.738, 6.465, P<0.05). (3) Efficacy of TACE on positive MVI patients: ① Clinicopathological features of 56 patients with positive MVI, 7 received postoperatively sequential TACE, including 7 males, with an age of (50±4)years old; 56 patients were in Child-Pugh grade A, including 5 combined with liver cirrhosis and 2 without liver cirrhosis; positive and negative AFPs were respectively detected in 2 and 5 patients. Forty-nine patients didn′t combine sequential TACE, including 44 males and 5 females, with an age of (52±10)years old; 49 patients were in Child-Pugh grade A, including 36 combined with liver cirrhosis and 13 without liver cirrhosis; positive and negative AFPs were respectively detected in 34 and 15 patients. There was no statistically significant difference in gender, age, Child-Pugh score of liver function, liver cirrhosis and comparison of AFP between patients with and without sequential TACE (x2=0.784, t=-0.512, x2=0.013, 2.844, P>0.05). ② Tumor recurrence: the 6-month and 1-year tumor recurrence rates after hepatectomy were respectively 0, 28.57% in 7 positive MVI patients with sequential TACE and 42.86%, 51.02% in 49 positive MVI patients without sequential TACE, showing a statistically significant difference in 6-month tumor recurrence rate (x2=4.800, P<0.05) and no statistically significant difference in 1-year tumor recurrence rate (x2=1.236, P>0.05). (4) Effect of comprehensive treatment on the prognosis of patients with tumor recurrence: of 59 patients with tumor recurrence, 37 didn′t receive comprehensive treatment, 34 of 37 died within 1-year postoperatively, including 30 deaths within 6-month postoperatively, and 1-year survival rate was 8.10%; 22 received comprehensive treatment, including 4 deaths within 1-year postoperatively, and 1-year survival rate was 81.80%, showing a statistically significant difference in 1-year survival rate (x2=32.698, P<0.05).
Conclusions:MVI is one of the important risk factors affecting HCC recurrence and metastasis after hepatectomy. The combined TACE after hepatectomy can reduce the HCC recurrence rate of MVI positive patients, and active comprehensive treatment after HCC recurrence can significantly prolong the survival time of patients.

DOI:10.3760/cma.j.issn.1673-9752.2018.05.012
基金项目:国家重点研发计划项目(2016YFA0102100);国家自然科学基金面上项目(81770560)
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