Surgical Contribution to Recurrence-Free Survival in Patients with Macrovascular-Invasion-Negative Hepatocellular Carcinoma

BACKGROUND: Macroscopic vascular invasion (MVI) is a well-known indicator of recurrence of hepatocellular carcinoma (HCC) even after curative hepatectomy, but the clinicopathologic and molecular features of the recurrence remain unclear in MVI-negative HCC. STUDY DESIGN: Two hundred seven consecutive patients with confirmed primary MVI-negative HCC were retrospectively assessed after curative resection, with special emphasis on the importance of anatomically systematized hepatectomy. HCC tissues were also analyzed for genome-wide gene expression profile of each tumor using a microarray technique. RESULTS: Univariant analysis of HCC recurrence revealed multiple tumors (p < 0.001), moderate to poor differentiation (p = 0.044), Child-Pugh B/C (p = 0.047), alpha-feroprotein elevation (p = 0.007), and nonanatomic hepatectomy (p = 0.010) as risk factors. According to Cox hazard multivariant analysis, multiple tumors (p = 0.002), alpha-fetoprotein elevation (p < 0.001), and nonanatomic hepatectomy (p = 0.002) were identified as independent factors of the recurrence. In the recurrent cases after anatomic hepatectomy for HCC, local recurrence was significantly infrequent compared with those after nonanatomic hepatectomy (p < 0.001). Network expression analysis using cDNA microarray revealed distinct signaling pathways of epithelial-mesenchymal transitions are associated with recurrence after anatomically systematized hepatectomy. CONCLUSIONS: Anatomically systematized hepatectomy might contribute to recurrence-free survival of HCC patients of HCC without MVI. Local recurrence could be mostly averted by anatomic hepatectomy, although specific epithelial-mesenchymal transitions signaling might regulate the biologic aggressiveness of HCC. (J Am Coll Surg 2009;208:368-374. (C) 2009 by the American College of Surgeons)