title: Liver transplantation for advanced hepatocellular carcinoma using poor tumor differentiation on biopsy as an exclusion criterion.
abstract: BACKGROUND
  Liberal acceptance criteria are used when offering liver transplantation (LTx) for treatment of hepatocellular carcinoma (HCC) at our center. This provides a unique opportunity to assess outcomes in a large North American series of patients with advanced tumors.
  
  
  OBJECTIVE
  We hypothesized that acceptable survival rates can be achieved with LTx for any size or number of HCC provided that (a) imaging studies ruled out vascular invasion; (b) the HCC was confined to the liver; and (c) the HCC was not poorly differentiated on biopsy.
  
  
  METHODS
  Survival, based on pretransplant imaging staging, was compared between 189 Milan Criteria (M) and 105 beyond Milan Criteria (M+) HCC patients who received an LTx between 1996 and 2008.
  
  
  RESULTS
  Imaging understaged 30% of the M group and over staged 23% of the M+ group. There was no difference in the 5-year overall survival in the M (72%) and M+ (70%) groups or 5-year disease-free survival in the M (70%) and M+ (66%) groups. The introduction of a protocol for a biopsy to exclude patients with poorly differentiated tumors and use of aggressive bridging therapy improved overall survival in the M+ group (P = 0.034). Serum alpha-fetoprotein more than 400 at LTx was associated with poorer disease-free survival (hazard ratio: 2.3; P = 0.031).
  
  
  CONCLUSIONS
  Cross-sectional imaging did not reliably stage patients with HCC for LTx. A protocol using a biopsy to exclude poorly differentiated tumors and aggressive bridging therapy achieved excellent survival rates with LTx for otherwise incurable advanced HCC, irrespective of tumor size and number.
authors.affiliation: Liver Transplant Unit, Multiorgan Transplant Program, University of Toronto and Toronto General Hospital, University Health Network, Toronto, Ontario, M5M 1G2, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: DuBay
authors.forename: Charbel
authors.initials: C
authors.lastname: Sandroussi
authors.forename: Lakhbir
authors.initials: L
authors.lastname: Sandhu
authors.forename: Sean
authors.initials: S
authors.lastname: Cleary
authors.forename: Markus
authors.initials: M
authors.lastname: Guba
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cattral
authors.forename: Ian
authors.initials: I
authors.lastname: McGilvray
authors.forename: Anand
authors.initials: A
authors.lastname: Ghanekar
authors.forename: Markus
authors.initials: M
authors.lastname: Selzner
authors.forename: Paul D
authors.initials: PD
authors.lastname: Greig
authors.forename: David R
authors.initials: DR
authors.lastname: Grant
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult