原发性肝癌10966例外科治疗分析

目的探讨原发性肝癌外科治疗的临床经验。方法回顾性分析1986年1月至2019年12月南京医科大学第一附属医院肝胆中心手术治疗的10966例原发性肝癌患者的临床资料。采用寿命表法进行生存率和肿瘤复发率的计算,Log-rank检验比较不同组别的差异,采用Cox回归模型进行多因素分析。选取2009—2019年随访数据更详尽的2884例肝细胞癌病例纳入长期生存分析,其中接受肝切除患者2549例,男性2107例,女性442例,年龄(56.6±11.1)岁(范围:20~86岁);接受肝移植患者335例,男性292例,女性43例,年龄(51.0±9.7)岁(范围:21~73岁)。比较肝切除与肝移植的效果、解剖性肝切除与非解剖性肝切除的效果等。结果10966例原发性肝癌患者中,10331例行肝切除,635例行肝移植。根据收治时间,将10331例行肝切除的原发性肝癌患者分为3组:1986—1995年组(712例)、1996—2008年组(3988例)、2009—2019年组(5631例)。1986—1995年组肝细胞癌肝切除患者的5年生存率为32.9%。2009—2019年组原发性肝癌患者肝切除后5年总体生存率为51.7%,其中肝细胞癌、肝内胆管细胞癌和混合性肝癌的5年总体生存率分别为57.4%、26.6%和50.6%。进一步分析行首次肝切除的肝细胞癌患者(2549例),其1、3、5、10年累积总体生存率分别为88.1%、71.9%、60.0%、41.0%,围手术期病死率为1.0%;行一期肝移植的肝细胞癌患者247例,1、3、5、10年累积总体生存率分别为84.0%、64.8%、61.9%、57.6%,行补救性肝移植88例,1、3、5、10年累积总体生存率分别为86.8%、65.2%、52.5%、52.5%,两组患者总体生存率的差异无统计学意义(P>0.05)。2549例接受首次肝切除和247例接受一期肝移植患者的总体生存率和复发率相比,符合米兰标准的肝切除和肝移植患者的1、3、5、10年总体生存率分别为96.3%、87.1%、76.9%、54.7%和95.4%、79.4%、77.4%、71.7%(P=0.754),1、3、5年复发率分别为16.3%、35.9%、47.6%和8.1%、11.7%、13.9%(P<0.01);超米兰标准无大血管侵犯的肝切除和肝移植患者的1、3、5、10年总体生存率分别为87.2%、65.9%、53.0%、33.0%和87.6%、71.8%、71.8%、69.3%(P=0.003),1、3、5年复发率分别为39.2%、57.8%、69.7%和29.7%、36.7%、36.7%(P<0.01);超米兰标准有大血管侵犯的肝切除和肝移植患者的1、3、5、10年总体生存率分别为62.1%、36.1%、22.2%、15.0%和62.9%、31.8%、19.9%、0(P=0.387),1、3、5年复发率分别为61.5%、74.7%、80.8%和59.7%、82.9%、87.2%(P=0.909)。影响肝细胞癌肝切除患者生存率及无复发生存率的独立预后因素有性别、术前辅助治疗、症状、AST、术中或术后输血、肿瘤数目、肿瘤最大径、肝硬化、大血管侵犯、微血管侵犯和病理分化(P值均<0.05)。采用倾向性评分匹配法匹配解剖性肝切除和非解剖性肝切除患者资料,得到443对病例,非解剖性肝切除术后患者的生存率与解剖性肝切除的差异无统计学意义(P=0.895),但非解剖性肝切除术后患者的复发率高于解剖性肝切除(P=0.035)。结论近十年,肝癌手术治疗的生存率较之前明显升高。对于肝功能储备较好的肝细胞癌患者可以先行切除手术,复发后再行补救性肝移植,补救性肝移植的效果与一期肝移植相当。在确保阴性切缘的前提下可以选择保留更多肝脏组织的非解剖性肝切除。

Surgical treatment of primary liver cancer:a report of 10966 cases

Objective To summarize the experience of surgical treatment of primary liver cancer.Methods The clinical data of 10966 surgically managed cases with primary liver cancer,from January 1986 to December 2019 at Hepatobiliary Center,the First Affiliated Hospital of Nanjing Medical University,were retrospectively analyzed.The life table method was used to calculate the survival rate and postoperative recurrence rate.Log‐rank test was used to compare the survival process of different groups,and the Cox regression model was used for multivariate analysis.In addition,2884 cases of hepatocellular carcinoma(HCC)with more detailed follow‐up data from 2009 to 2019 were selected for survival analysis.Among 2549 patients treated with hepatectomy,there were 2107 males and 442 females,with an age of(56.6±11.1)years(range:20 to 86 years).Among 335 patients treated with liver transplantation,there were 292 males and 43 females,with an age of(51.0±9.7)years(range:21 to 73 years).The outcomes of hepatectomy versus liver transplantation,anatomic versus non-anatomic hepatectomy were compared,respectively.Results Of the 10966 patients with primary liver cancer,10331 patients underwent hepatectomy and 635 patients underwent liver transplantation.Patients with liver resection were categorized into three groups:1986-1995(712 cases),1996-2008(3988 cases),2009?2019(5631 cases).The 5‐year overall survival rate was 32.9%in the first group(1986-1995).The 5‐year overall survival rate of resected primary liver cancer was 51.7%in the third group(2009‐2019),among which the 5‐year overal survival rates of hepatocellular carcinoma,intrahepatic cholangiocarcinoma and mixed liver cancer were 57.4%,26.6%and 50.6%,respectively.Further analysis was performed on 2549 HCC patients with primary hepatectomy.The 1‐,3‐,5‐,and 10‐year overall survival rates were 88.1%,71.9%,60.0%,and 41.0%,respectively,and the perioperative mortality rate was 1.0%.Two hundred and forty‐seven HCC patients underwent primary liver transplantation,with 1‐,3‐,5‐,and 10‐year overall survival rates of 84.0%,64.8%,61.9%,and 57.6%,respectively.Eighty‐eight HCC patients underwent salvage liver transplantation,with the 1‐,3‐,5‐,and 10‐year overall survival rates of 86.8%,65.2%,52.5%,and 52.5%,respectively.There was no significant difference in survival rates between the two groups with liver transplantation(P>0.05).Comparing the overall survival rates and recurrence rates of primary hepatectomy(2549 cases)with primary liver transplantation(247 cases),the 1‐,3‐,5‐,and 10‐year overall survival rates in patients within Milan criteria treated with hepatectomy and transplantation were 96.3%,87.1%,76.9%,54.7%,and 95.4%,79.4%,77.4%,71.7%,respectively(P=0.754).The 1‐,3‐,5‐year recurrence rates were 16.3%,35.9%,47.6%and 8.1%,11.7%,13.9%,respectively(P<0.01).The 1‐,3‐,5‐,10‐year overall survival rates in patients with no large vessels invasion beyond the Milan criteria treated with liver resection and transplantation were 87.2%,65.9%,53.0%,33.0%and 87.6%,71.8%,71.8%,69.3%,respectively(P=0.003);the 1‐,3‐,5‐year recurrence rate were 39.2%,57.8%,69.7%and 29.7%,36.7%,36.7%,respectively(P<0.01).The 1‐,3‐,5‐,and 10‐year overall survival rates in patients with large vessels invasion treated with liver resection and transplantation were 62.1%,36.1%,22.2%,15.0%and 62.9%,31.8%,19.9%,0,respectively(P=0.387);the 1‐,3‐,5‐year recurrence rates were 61.5%,74.7%,80.8%and 59.7%,82.9%,87.2%,respectively(P=0.909).Independent prognostic factors for both overall survival and recurrence‐free survival rates of HCC patients treated with liver resection included gender,neoadjuvant therapy,symptoms,AST,intraoperative or postoperative blood transfusion,tumor number,tumor size,cirrhosis,macrovascular invasion,microvascular invasion,and pathological differentiation.Propensity score matching analysis of 443 pairs further showed that there was no significant difference in overall survival rate between anatomical liver resection and non‐anatomical liver resection(P=0.895),but the recurrence rate of non‐anatomical liver resection was higher than that of anatomical liver resection(P=0.035).Conclusions In the past decade,the overall survival rate of HCC undergoing surgical treatment is significantly higher than before.For HCC patients with good liver function reservation,surgical resection can be performed first,and salvage liver transplantation can be performed after recurrence.The effect of salvage liver transplantation is comparable to that of primary liver transplantation.As for the choice of liver resection approaches,non‐anatomical resection can reserve more liver tissue and can be selected as long as the negative margin is guaranteed.