title: Extrahepatic metastasis of hepatocellular carcinoma: incidence and risk factors.
abstract: BACKGROUND
  Extrahepatic metastasis of hepatocellular carcinoma (HCC) is of growing importance as the survival of patients has been improved owing to advances in treatments to intrahepatic lesions.
  
  
  METHODS
  To elucidate the incidence and risk factors of extrahepatic metastasis of HCC, we enrolled 1573 (1131 treatment-naïve and 442 previously treated on referral) patients with HCC without extrahepatic tumour spread treated at the authors' department between 1990 and 2003. Patients received medical treatment including percutaneous ablation and transcatheter arterial chemoembolization, and followed by dynamic computed tomography (CT) or magnetic resonance imaging (MRI) and tumour markers every 3-4 months. Extrahepatic metastasis was diagnosed by plain X-ray, CT, MRI and scintigraphy. Clinical parameters at the time of treatment to intrahepatic lesions were evaluated as a predictor of subsequent extrahepatic metastasis among the 1131 treatment-naïve patients by Cox's proportional hazard model.
  
  
  RESULTS
  During the average observation period of 3.9 years, extrahepatic metastasis was diagnosed in 123 in the treatment-naïve and 53 in the patients treated previously. The incidence rate of extrahepatic metastasis, as detected during the lifetime after medical treatment of HCC, was approximately 13% at 5 years. Multivariate analysis with Cox proportional hazard model revealed that positivity for viral markers, lager tumour diameter, multiple tumour nodules, presence of vascular tumour invasion and elevated tumour markers were associated with the development of extrahepatic metastasis.
  
  
  CONCLUSIONS
  The incidence of extrahepatic metastasis of HCC diagnosed during clinical course was not frequent. Advanced intrahepatic lesions, presence of vascular tumour invasion, elevated tumour markers and presence of viral hepatitis were risk factors for extrahepatic metastasis.
authors: Department of Gastroenterology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
authors: Miho
authors: M
authors: Kanda
authors: Ryosuke
authors: R
authors: Tateishi
authors: Haruhiko
authors: H
authors: Yoshida
authors: Takahisa
authors: T
authors: Sato
authors: Ryota
authors: R
authors: Masuzaki
authors: Takamasa
authors: T
authors: Ohki
authors: Jun
authors: J
authors: Imamura
authors: Tadashi
authors: T
authors: Goto
authors: Hideo
authors: H
authors: Yoshida
authors: Keisuke
authors: K
authors: Hamamura
authors: Shuntaro
authors: S
authors: Obi
authors: Fumihiko
authors: F
authors: Kanai
authors: Shuichiro
authors: S
authors: Shiina
authors: Masao
authors: M
authors: Omata
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000556:secondary; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000473:pathology*; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D016016:Proportional Hazards Models; D012307:Risk Factors