Prognostic Value and Prediction of Extratumoral Microvascular Invasion for Hepatocellular Carcinoma.

Background: There are few reports on microvascular invasion (MVI) located intra- or extratumorally and prognosis of hepatocellular carcinoma (HCC).

Objective: The aim of this study was to evaluate patient outcome according to the location of MVI, and to build a nomogram predicting extratumoral MVI.

Methods: We included 681 consecutive patients who underwent hepatic resection (HR) or liver transplantation (LT) for HCC from January 1994 to June 2012, and evaluated patient outcome according to the degree of vascular invasion (VI). A nomogram for predicting extratumoral MVI was created using 637 patients, excluding 44 patients with macrovascular invasion, and was validated using an internal (n = 273) and external patient cohort (n = 256).

Results: The 681 patients were classified into four groups based on pathological examination (148 no VI, 33 intratumoral MVI, 84 extratumoral MVI, and 29 macrovascular invasion in patients who underwent HR; 238 no VI, 50 intratumoral MVI, 84 extratumoral MVI, and 15 macrovascular invasion in patients who underwent LT). Multivariate analysis revealed that extratumoral MVI was an independent risk factor for overall survival in patients who underwent HR (hazard ratio 2.62, p < 0.0001) or LT (hazard ratio 1.99, p = 0.0005). Multivariate logistic regression analysis identified six independent risk factors for extratumoral MVI: α-fetoprotein, tumor size, non-boundary type, alkaline phosphatase, neutrophil-to-lymphocyte ratio, and aspartate aminotransferase. The nomogram for predicting extratumoral MVI using these factors showed good concordance indices of 0.774 and 0.744 in the internal and external validation cohorts, respectively.

Conclusions: The prognostic value of MVI differs according to its invasiveness. The nomogram allows reliable prediction of extratumoral MVI in patients undergoing HR or LT.