title: Surgical contribution to recurrence-free survival in patients with macrovascular-invasion-negative hepatocellular carcinoma.
abstract: 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.
  
  
  METHODS
  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-fetoprotein 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.
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan. shinji.msrg@tmd.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Mahmut
authors.initials: M
authors.lastname: Yasen
authors.forename: Norio
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authors.lastname: Noguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kudo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Noriaki
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authors.lastname: Nakamura
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arii