The Effect Of Surgical Margin On Postoperative Recurrence And Prognosis In Patients With Non-anatomical Resection Of Hepatocellular Carcinoma

Background: The effect of surgical margin on the postoperative recurrence and prognosis of hepatocellular carcinoma(HCC)is quite controversial.Most Chinese liver cancer patients have cirrhosis,so non-anatomical resection(NAR)is often used for surgical treatment,but there are few studies on the impact of the margin of NAR on postoperative recurrence and prognosis.Objective: To study the effect of surgical margin on postoperative recurrence and prognosis,and to investigate the risk factors and recurrence patterns in NAR patients.Methods:Clinical data of 230 patients with NAR for HCC were reviewed retrospectively from January 2012 to December 2017,The cases were divided into narrow margin group(<5mm,n=134)、medium margin group(≥5mm,<10mm,n=50)and wide margin group(≥10mm,n=46)based on the size of resection margin.Survival curves were drawn using the Kaplan-Meier method,and recurrence-free survival(RFS)、overall survival(OS)and recurrence patterns were compared between the three groups;Proproportional hazards models such as Cox were used to analyze risk factors affecting recurrence and overall survival in HCC patients with NAR.Results:The median follow-up time was 58 months,post-operative recurrence occurred in 144(62.6%)patients,and 107(46.5%)patients died during the follow-up time.The relapse-free and overall survival rates among the narrow margin group at 1,3 and 5 years were 50.7%、30.6%、19.4% and 93.3%、67.2%、41.0%,the middle margin group were 72.0%、52.0%、30.0% and 94.0%、84.0%、52.0%,the middle margin group were 82.6%、58.7%、45.7% and 97.8%、84.8%、65.2%respectively.Comparison of RFS and OS among the three groups was statistically significant(P < 0.001).In pairwise comparisons,RFS(P=0.008)and OS(P=0.002)in the middle margin group were better than those in the narrow margin group,RFS(P< 0.001)and OS(P < 0.001)in the wide margin group were better than those in the narrow margin group,but there was no significant difference in RFS(P=0.117)and OS(P=0.316)between the middle margin and wide margin group.Multivariate Cox regression analysis showed that the resection margin distance<5mm(HR 2.092,P=0.006)and tumor diameter ≥5cm(HR 1.663,P=0.009),microvascular invasion(MVI)were high-risk group(M2)(HR 1.938,P=0.027),tumor without capsule(HR 2.218,P<0.001)and Alpha-fetoprotein(AFP)>400μg/L(HR 1.541,P=0.022)were independent risk factors for RFS.Cutting edge <5mm(HR 2.324,P=0.015),M2(HR 2.029,P=0.036),Edmondson-Steiner grade III-IV(HR 2.018,P=0.001),tumor without capsule(HR1.802,P=0.08)is an independent risk factor for OS.In terms of recurrence mode,early recurrence was dominant in the three groups(50%),multiple recurrence was dominant in the number of recurrences(40.3%),intrahepatic recurrence was the most common in the whole group at the site of recurrence(46.5%),and the most common recurrences were in the whole liver at the relative location of intrahepatic recurrence(16.5%).In peripheral recurrence,Periph-eral recurrence was more likely to occur with narrow margin group(15.7%)than with wide margin group(2.2%)(P=0.016).Conclusions: When NAR was performed on HCC patients with diameter ≥5cm,5m-10 mm margin distance was sufficient to obtain better RFS and OS,while extending margin distance(≥10mm)did not significantly reduce postoperative recurrence or improve prognosis of HCC patients.Resection margin distance < 5mm,tumor diameter ≥5cm,microvascular invasion of M2,no tumor envelope,AFP >400μg/L were independent risk factors for RFS.Margin distance < 5mm,microvascular invasion of M2,tumor without capsule,edmondson-Steiner grade III-IV were independent risk factors for OS.Most of NAR recurrences occurred within 2 years after surgery,and the number of recurrences was mainly multiple,Most of the recurrence sites were intrahepatic,and most of the recurrence sites were whole liver.Peripheral recurrence was more likely to occur when the margin distance < 5mm than when the margin distance ≥10mm.