title: The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study.
abstract: The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer-related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5-year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long-term follow-up (10-years) using an intention-to-treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow-up from listing was 59.7 (26.8-103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10-year actuarial survival from transplant between groups. On an intention-to-treat basis, the dropout rate was higher in the M+ group and the 5-year and 10-year survival rates from listing were decreased in the M+ group. An alpha-fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups.
  
  
  
  Tumor differentiation and cancer-related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha-fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077-2088).
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Sapisochin
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goldaracena
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Laurence
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Dib
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barbas
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Anand
authors.initials: A
authors.lastname: Ghanekar
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Cleary
authors.affiliation: Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.|Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Les
authors.initials: L
authors.lastname: Lilly
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cattral
authors.affiliation: Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Max
authors.initials: M
authors.lastname: Marquez
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Selzner
authors.affiliation: Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.|Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Renner
authors.affiliation: Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada.|Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Nazia
authors.initials: N
authors.lastname: Selzner
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Ian D
authors.initials: ID
authors.lastname: McGilvray
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Greig
authors.affiliation: Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada.|Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Grant
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011446:Prospective Studies