Prognostic Evaluation Of Microvascular Invasion Of Hepatocellular Carcinoma And Establishment Of A Preoperative Predictive Model

Part 1.The Effect of Anatomical Resection on Long-term Prognosis of Hepatocellular Carcinoma with Microvascular InvasionObjective: Microvascular invasion(MVI),which is the early stage of vascular invasion in hepatocellular carcinoma(HCC),is considered to be an important risk factor affecting the prognosis of HCC.The choice of operation for the HCC patients with MVI remains controversial.Therefore,the purpose of the study is to investigate the prognostic outcomes of anatomical resection(AR)and non-anatomical resection(NAR)for solitary HCC patients with and without MVI,using a propensity score matching(PSM)analysis.Methods: From January 2004 to December 2013,a total of 305 consecutive HCC patients without macroscopic vascular invasion underwent curative hepatectomy in the Department of Hepatobiliary Surgery at Nanjing Drum Tower Hospital were included in our study.PSM was performed in order to eliminate possible selection bias.The prognosis of HCC patients was analyzed by Kaplan-Meier survival analysis and Cox proportional hazards models.Results: By PSM,the patients were divided into PS-AR(n=114)and PS-NAR(n=114)groups.Kaplan-Meier survival analysis indicated that AR significantly improved the recurrence-free survival(RFS)rate in patients compared with NAR(P=0.005).But there was no difference in the overall survival(OS)rate between the two groups(P=0.053).Multivariate analysis showed that ICG-R15,BCLC staging and MVI were independent risk factors for the OS rate,while type of resection,surgical margin and MVI were independent risk factors for the RFS rate.In patients with MVI,the RFS rate of AR was significantly better than that of NAR(P=0.016).In pa-tients without MVI,there was no significant difference in the OS and RFS rates between the two groups(P=0.174 and P=0.143).Subgroup analysis indicated that the RFS rate was significantly better in AR than that in NAR with surgical margin ?1cm(P=0.022).Conclusions: AR contributed to improve the RFS rate in solitary HCC patients with MVI using PSM analysis.Part 2.Prognostic Value of A Novel Risk Classification of Microvascular Invasion In Patients With Hepatocellular Carcinoma After ResectionObjective: MVI is generally considered as a risk factor for the OS and RFS rates of postoperative HCC patients.However,there is no definite risk classification of MVI based on histopathological characteristics.The present research aimed to evaluate the prognostic value of a novel risk classification of MVI in HCC after resection.Methods: From January 2004 to December 2013,a total of 295 consecutive HCC patients without macroscopic vascular invasion underwent curative hepatectomy were included in our study.We evaluated the degree of MVI according to the following three features: the number of invaded microvessels(?5 vs >5),the number of invading carcinoma cells(?50 vs >50),the distance of invasion from tumor edge(?1 cm vs >1 cm).Results: In survival analysis,the three histopathological features were associated with the OS and RFS rates of HCC patients.Thus all patients were divided into threegroups according to the three risk factors of MVI: non-MVI group(n=180),low-MVI group(patients with no and one risk factor,n=58)and high-MVI group(patients with two and three risk factors,n=57).The OS and RFS rates of high-MVI group were significantly poorer than those of low-MVI and non-MVI groups(P<0.001 and P=0.001;P<0.001 and P=0.003).Multivariate analysis showed high-MVI,type of resection,ICG-R15 and tumor size were risk factors for OS after hepatectomy,while high-MVI,type of resection and tumor size were risk factors for RFS.The median time to recurrence and early recurrence rates of high-MVI group were significantly poorer than those of low-MVI and non-MVI groups(P=0.003 and P<0.001;P=0.003 and P=0.024).Compared with non-MVI group,the marginal recurrence rate of high-MVI group was obviously poorer(P=0.001).Conclusions: The novel risk classification of MVI based on histopathological features is valuable for predicting prognosis of HCC patients without macroscopic vascular invasion after hepatectomy.Part 3.Development of A Novel Predictive Scoring Model for Microvascular Invasion in Patients With Hepatocellular CarcinomaObjective: The present of MVI is important to guide the preoperative treatment of HCC patients.However,MVI is only confirmed after operation by histopathological diagnosis,which greatly limits the application of MVI.This study aimed to establish a predictive scoring model of MVI in solitary HCC patients without macroscopic vascular invasion.Methods: From January 2007 to March 2016,a total of 309 consecutive HCC patients who underwent curative hepatectomy were divided into the derivation(n=206)and validation cohort(n=103).A predictive scoring model of MVI was established according to the valuable predictors in the derivation cohort based on multivariate logistic regression analysis.The performance of the predictive model was evaluated in the derivation and validation cohorts.Results: Preoperative imaging features on CT,such as intratumoral arteries,non-nodular type of HCC and absence of peritumoral hyperdense hole were independent predictors for MVI.The predictive scoring model was established according to the ? coefficients of the 3 predictors.Area under receiver operating characteristic of the predictive scoring model was 0.872(95% CI,0.817-0.928)and 0.856(95% CI,0.771-0.940)in the derivation and validation cohorts.The positive and negative predictive values were 76.5% and 88.0% in the derivation cohort and 74.4% and 88.3% in the validation cohort.The performance of the model was similar between the patients with tumor size ? 5 cm and > 5 cm in AUROC(P=0.910).The OS and RFS rates of high-risk group(score ? 3)were significantly poorer than those of low-risk group(score < 3)(P=0.003 and P<0.001).Anatomical resection significantly improved the OS and RFS rates of high-risk group compared with non-anatomical resection(P=0.005 and P=0.041).However,there were no significant difference in low-risk group(P=0.257 and P =0.312).Conclusions: The predictive scoring model based on intratumoral arteries,non-nodular type of HCC,and absence of peritumoral hyperdense hole on preoperative CT is of great value in the prediction of MVI.Anatomical resection significantly improved the prognosis of HCC patients in high-risk group(score ? 3).