title: Impact of tumour differentiation to select patients before liver transplantation for hepatocellular carcinoma.
abstract: OBJECTIVE
  To generate a new score with improved accuracy compared with Milan criteria to select patients.
  
  
  METHODS
  The training cohort comprised 373 patients transplanted for hepatocellular carcinoma (HCC) between 1988 and 1998 (cohort 1). An algorithm was derived from the analysis of patient data by the proportional hazard Cox regression model. The area under the receiver operating characteristic (AUROC) was used to determine a cut-off value. The validation cohort comprised 140 patients transplanted between 1999 and 2001 (cohort 2).
  
  
  RESULTS
  Multivariate analysis identified three predictors of 5-year tumour-free survival: tumour differentiation (P=0.02), diameter (P<0.0001) and number of nodules (P=0.04). A cut-off value of 4 was derived from the AUROC of the final score. Five-year tumour-free survival was 60.2 ± 3.1% in patients with as score <4 and 36.4 ± 4.7% in individuals with a score ≥4, P<0.0001. In the validation cohort, 5-year tumour-free survival was 82.8 ± 3.6% (score <4) and 50.0 ± 10.7% (score ≥4), P=0.0003. In patients with a score <4, there was no significant difference in 5-year tumour-free survival between Milan+ and Milan- patients, either in cohort 1 or 2. Five-year tumour-free survival of Milan- patients was significantly better in individuals with a score <4 compared with those with a score ≥4, both in cohort 1 (61.5 ± 9.1 vs 31.4 ± 4.6%, P=0.009) and in cohort 2 (P=0.02).
  
  
  CONCLUSIONS
  A novel score taking into account tumour differentiation shows higher accuracy than Milan criteria in predicting 5-year tumour-free survival following liver transplantation for HCC. Prospective studies should validate these findings.
authors.affiliation: AP-HP, Department of Hepatology, Groupe Henri-Mondor Albert-Chenevier, Creteil, France. thomas.decaens@hmn.aphp.fr
authors.forename: Thomas
authors.initials: T
authors.lastname: Decaens
authors.forename: Françoise
authors.initials: F
authors.lastname: Roudot-Thoraval
authors.forename: Hanaa
authors.initials: H
authors.lastname: Badran
authors.forename: Philippe
authors.initials: P
authors.lastname: Wolf
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.forename: Rene
authors.initials: R
authors.lastname: Adam
authors.forename: Olivier
authors.initials: O
authors.lastname: Boillot
authors.forename: Claire
authors.initials: C
authors.lastname: Vanlemmens
authors.forename: Jean
authors.initials: J
authors.lastname: Gugenheim
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dharancy
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Bernard
authors.forename: Karim
authors.initials: K
authors.lastname: Boudjema
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.forename: Jean
authors.initials: J
authors.lastname: Hardwigsen
authors.forename: Christian
authors.initials: C
authors.lastname: Ducerf
authors.forename: Georges Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Hilleret
authors.forename: Olivier
authors.initials: O
authors.lastname: Chazouillères
authors.forename: Daniel
authors.initials: D
authors.lastname: Cherqui
authors.forename: Ariane
authors.initials: A
authors.lastname: Mallat
authors.forename: Christophe
authors.initials: C
authors.lastname: Duvoux
mesh_terms: D000328:Adult; D000465:Algorithms; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D005260:Female; D005602:France; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome