title: Contrast-enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: clinical and biological significance.
abstract: Abnormal tumor vascularity is one of the typical features of hepatocellular carcinoma (HCC). In this study, the significance of contrast-enhanced intraoperative ultrasonography (CEIOUS) images of HCC vasculature was evaluated by clinicopathological and gene expression analyses. We enrolled 82 patients who underwent curative hepatic resection for HCC with CEIOUS. Clinicopathological and gene expression analyses were performed according to CEIOUS vasculature patterns. CEIOUS images of HCC vasculatures were classified as reticular HCC or thunderbolt HCC. Thunderbolt HCC was significantly correlated with higher alpha-fetoprotein levels, tumor size, histological differentiation, portal vein invasion, and tumor-node-metastasis stage, and these patients demonstrated a significantly poorer prognosis for both recurrence-free survival (P = 0.0193) and overall survival (P = 0.0362) compared with patients who had reticular HCC. Gene expression analysis revealed that a rereplication inhibitor geminin was significantly overexpressed in thunderbolt HCCs (P = 0.00326). In vitro knockdown of geminin gene reduced significantly the proliferation of human HCC cells. Immunohistochemical analysis confirmed overexpression of geminin protein in thunderbolt HCC (P < 0.0001). Multivariate analysis revealed geminin expression to be an independent factor in predicting poor survival in HCC patients (P = 0.0170).
  
  
  CONCLUSIONS
  CEIOUS vascular patterns were distinctly identifiable by gene expression profiling associated with cellular proliferation of HCC and were significantly related to HCC progression and poor prognosis. These findings might be clinically useful as a determinant factor in the postoperative treatment of HCC.
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine and Dental University, Tokyo, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Sato
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mitsunori
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Mahmut
authors.initials: M
authors.lastname: Yasen
authors.forename: Arihiro
authors.initials: A
authors.lastname: Aihara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ban
authors.forename: Takanori
authors.initials: T
authors.lastname: Ochiai
authors.forename: Takumi
authors.initials: T
authors.lastname: Irie
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kudo
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arii
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000601:surgery; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D064248:Geminin; D006498:Hepatectomy; D006801:Humans; D066298:In Vitro Techniques; D007432:Intraoperative Period; D008099:Liver / Q000098:blood supply / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging; D011379:Prognosis; D014463:Ultrasonography / Q000379:methods*
chemical_list: D018797:Cell Cycle Proteins; C577995:GMNN protein, human; D064248:Geminin