ABSTRACT
Objective To compare the clinical efficacy of anatomical hepatectomy (AR) and parenchymal-sparing hepatectomy (PSH) for Barcelona clinic liver cancer (BCLC) stage A hepatocellular carcinoma(HCC),and investigate its prognostic factors.Methods The propensity score matching and retrospective cohort study was conducted.The clinicopathological data of 269 patients with BCLC stage A HCC who were admitted to the First Affiliated Hospital of Nanjing Medical University from January 2009 to December 2017 were collected.There were 226 males and 43 females,aged from 23 to 84 years,with a median age of 56 years.All the 269 patients underwent radical resection and were confirmed as HCC using postoperative pathological examination.Of the 226 patients,146 undergoing AR and 123 undergoing PSH were allocated into the AR group and PSH group,respectively.Observation indicators:(1) the propensity score matching conditions and comparison of general data between groups after the propensity score matching;(2) intraoperative and postoperative situations;(3) follow-up and survival situations;(4) prognostic factors analysis.Patients were followed up by outpatient examination and telephone interview to detect survival once every 3 months within 1 year postoperatively,once every 6 months within 2-5 years postoperatively and once a year after 5 years postoperatively up to October 2018.The overall survival time was from surgery data to death or end of follow-up.The tumor-free survival time was from surgery date to time of tumor recurrence detected or end of follow-up without tumor recurrence.The propensity score matching was used to perform 1∶1 matching by nearest neighbor method.Count data were represented as absolute number,comparison between groups was analyzed using the chi-square test and McNemar test after propensity score matching.Measurement data with skewed distribution were represented as M (range),and comparison between groups was done using the Mann-Whitney U test and Wilcoxon signed rank sum test after propensity score matching.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method,and Log-rank test was used for survival analysis.The COX proportional risk model was used for univariate and multivariate analysis.Results (1) The propensity score matching conditions and comparison of general data between groups after the propensity score matching:180 of 269 patients had successful matching,including 90 in each group.The maximum tumor diameter,cases with vascular embolism,cases of stage Ⅰ and Ⅱ (TNM staging) before matching were 5.0 cm (range,0.8-17.0 cm),42,97,99 in the AR group and 3.0 cm (range,1.0-17.0 cm),16,49,24 in the PSH group,respectively,with statistically significant differences between the two groups (Z =-4.277,x2 =9.803,6.664,P＜ 0.05).The above indices after matching were 4.0 cm (range,0.8-16.0 cm),15,70,68 in the AR group and 3.5 cm (range,1.0-17.0 cm),16,20,22 in the PSH group,with no statistically significant difference between the two groups (Z =-0.241,x2=0.039,0.124,P＞0.05).The confounding bias of maximum tumor diameter,vascular embolism and TNM staging were eliminated.(2) Intraoperative and postoperative situations:the operation time,volume of intraoperative blood loss,cases with intraoperative blood transfusion,cases with surgical margin ＜ 1 cm and ≥ 1 cm,cases with postoperative severe complications,duration of hospital stay,cases with postoperative tumor recurrence,cases with tumor recurrence within 2 years postoperatively,cases undergoing surgical treatment due to postoperative tumor recurrence,cases undergoing transcatheter arterial chemoemblization due to postoperative tumor recurrence after matching were 180 minutes (range,60-448 minutes),130 mL (range,30-6 000 mL),9,2,88,8,18 days (range,8-77 days),41,32,15,23 in the AR group,and 150 minutes (range,55-400 minutes),100 mL (range,50-3 000 mL),6,2,88,6,18 days (range,9-37 days),37,29,10,24 in the PSH group,respectively,showing no statistically significant difference between the two groups (Z =-1.987,-0.439,x2 =0.655,0.000,0.310,Z=-0.805,x2=0.362,0.223,0.816,0.624,P＞0.05).(3) Follow-up and survival situations:180 patients were followed up for 4-114 months,with a median time of 43 months.Forty of 180 patients died (21 in the AR group and 19 in the PSH group) and 78 had tumor recurrence (41 in the AR group and 37 in the PSH group).The 1-,3-,5-year overall survival rates and tumor-free survival rates were 92.0％,76.3％,71.8％ and 70.8％,53.0％,47.4％ in the AR group,92.3％,80.6％,62.0％ and 72.3％,56.4％,46.1％ in the PSH group,respectively,showing no statistically significant difference between the two groups (x2 =0.034,0.000,P＞0.05).Stratified analysis:of the AR group,the 1-,3-,5-year overall survival rates and median tumor-free survival rate were 95.3％,82.0％,82.0％ and 54.6％ in the patients with grade Ⅰ of preoperative albumin-bilirubin,100.0％,86.8％,86.8％ and 61.5％ in the patients with maximum tumor diameter ≤≤5 cm,91.3％,75.0％,69.7％ and 43.1％ in the patients with liver cirrhosis,89.9％,73.2％,66.6％ and 54.6％ in the patients with moderate-low differentiated tumor.Of the PSH group,the 1-,3-,5-year overall survival rates and median tumor-free survival rate were 90.9％,74.9％,63.0％ and 43.4％ in the patients with grade Ⅰ of preoperative albumin-bilirubin,98.2％,85.8％,61.7％ and 46.0％ in the patients with maximum tumor diameter ≤≤ 5 cm,98.0％,88.7％,70.0％ and 43.4％ in the patients with liver cirrhosis,90.7％,79.2％,59.0％ and 43.4％ in the patients with moderate-low differentiated tumor.There were no statistically significant difference in the 1-,3-,5-year overall survival rates between the two groups (x2 =1.892,1.320,0.732,0.002,P＞0.05) and a statistically significant difference in the tumor-free survival rate between the two groups (x2 =0.337,0.051,0.551,0.061,P ＞ 0.05).(4) Prognostic factors analysis.Results of univariate analysis showed that preoperative albumin-bilirubin grade,preoperative alpha fetoprotein (AFP),maximum tumor diameter,number of tumors,satellite lesion,vascular embolism,TNM staging,volume of intraoperative blood loss,postoperative severe complications were related factors affecting overall survival after radical resection for HCC (hazard ratio=1.762,1.001,1.139,1.955,2.561,2.495,2.766,1.000,2.599,95％ confidence interval:1.048-2.962,1.000-1.001,1.080-1.201,1.063-3.596,1.254-5.227,1.446-4.304,1.655-4.624,1.000-1.001,1.317-5.128,P＜0.05).Preoperative AST,positive HBsAg,preoperative AFP,maximum tumor diameter,vascular embolism,TNM staging,postoperative severe complications were related factors affecting tumor-free survival after radical resection for HCC (hazard ratio=1.004,1.594,1.000,1.065,2.203,2.132,1.775,95％ confidence interval:1.001-1.007,1.020-2.490,1.000-1.001,1.019-1.113,1.474-3.293,1.462-3.109,1.034-3.047,P＜0.05).Results of multivariate analysis showed that preoperative AFP,maximum tumor diameter,satellite lesion,postoperative severe complications were independent factors affecting overall survival after radical resection for HCC (hazard ratio =1.001,1.114,2.241,2.251,95％ confidence interval:1.000-1.001,1.033-1.202,1.003-5.008,1.100-4.607,P＜0.05).Positive HBsAg was an independent factor affecting tumor-free survival after radical resection for HCC (hazard =1.576,95％ confidence interval:0.987-2.516,P＜ 0.05).Conclusions There was no significant difference in long-term efficacy between AR and PSH in patients with BCLC stage A HCC.Preoperative AFP,maximum tumor diameter,number of tumors,satellite lesion,postoperative severe complications are independent factors affecting long-term survival of BCLC stage A patients after HCC radical resection.