title: Predictive value of nodule size and differentiation in HCC recurrence after liver transplantation.
abstract: BACKGROUND
  Liver transplantation (LT) is considered the best treatment option for HCC patients with cirrhosis. However, the scarce availability of liver donors and the risk of dropout from the waiting list due to the tumor progression severely limit LT for HCC. In this study, we evaluate the survival and recurrence in a cohort of patients undergoing LT for HCC fulfilling "Milan Criteria" (MC) pre-LT. In this study, we propose the development of a new prognostic score which could improve the accuracy in predicting recurrence post-LT.
  
  
  METHODS
  Between 1997 and 2011, out of 1010 LT performed in our unit, 131 patients had T2 staged HCC (inside MC). The prognostic model predicting HCC recurrence post-LT was derived from Cox regression analysis. The performance of this model was validated in an external cohort of 198 HCC patients transplanted at another center.
  
  
  RESULTS
  Overall survival at 1-3-5 years was 87%, 74.4%, 68.2%, whereas recurrence-free survival was 94.1%, 81.4%, 77.6%, respectively. Predictive factors for recurrence-free survival included high tumor grading (HR 5.01; p = 0.006) and tumor diameter (HR 1.46; p = 0.045). According to this model, the estimated relative risk of HCC recurrence after LT is given by this formula: 0.382 × (Tumor size [cm]) + 1.613 × (if Grading 3-4). The ROC curve was 0.878 (p < 0.001) in predicting HCC recurrence.
  
  
  CONCLUSIONS
  In conclusion, our study showed that the use of this new prognostic score, taking into account maximal tumor diameter and tumor differentiation, improves the accuracy of Milan criteria in predicting HCC recurrence.
authors.affiliation: Department of Surgery, HPB and General Surgery Unit, Ravenna Hospital, Viale Randi 5, 48121 Ravenna, Italy.
authors.forename: Gian Piero
authors.initials: GP
authors.lastname: Guerrini
authors.affiliation: Department of Surgery, General Surgery and Abdominal Transplant Unit, "Papa Giovanni XXIII" Hospital, Piazza Organizzazione Mondiale della Sanità, 24127 Bergamo, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Pinelli
authors.affiliation: Hepato-Pancreato-Biliary and Liver Transplant Unit, Department of Surgery, University Hospital of Modena, Via Del Pozzo 71, 41125 Modena, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Di Benedetto
authors.affiliation: Department of Surgery, General Surgery and Abdominal Transplant Unit, "Papa Giovanni XXIII" Hospital, Piazza Organizzazione Mondiale della Sanità, 24127 Bergamo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Marini
authors.affiliation: Department of Surgery, General Surgery and Abdominal Transplant Unit, "Papa Giovanni XXIII" Hospital, Piazza Organizzazione Mondiale della Sanità, 24127 Bergamo, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Corno
authors.affiliation: Department of Surgery, General Surgery and Abdominal Transplant Unit, "Papa Giovanni XXIII" Hospital, Piazza Organizzazione Mondiale della Sanità, 24127 Bergamo, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Guizzetti
authors.affiliation: Department of Surgery, General Surgery and Abdominal Transplant Unit, "Papa Giovanni XXIII" Hospital, Piazza Organizzazione Mondiale della Sanità, 24127 Bergamo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aluffi
authors.affiliation: Department of Surgery, General Surgery and Abdominal Transplant Unit, "Papa Giovanni XXIII" Hospital, Piazza Organizzazione Mondiale della Sanità, 24127 Bergamo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zambelli
authors.affiliation: Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Piazza Organizzazione Mondiale della Sanità, 24128 Bergamo, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fagiuoli
authors.affiliation: Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Piazza Organizzazione Mondiale della Sanità, 24128 Bergamo, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Lucà
authors.affiliation: Department of Surgery, General Surgery and Abdominal Transplant Unit, "Papa Giovanni XXIII" Hospital, Piazza Organizzazione Mondiale della Sanità, 24127 Bergamo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lucianetti
authors.affiliation: Department of Surgery, General Surgery and Abdominal Transplant Unit, "Papa Giovanni XXIII" Hospital, Piazza Organizzazione Mondiale della Sanità, 24127 Bergamo, Italy. Electronic address: mcolledan@hpg23.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Colledan
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000601:surgery*; D002454:Cell Differentiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects*; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology* / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate
keywords: Hepatocellular carcinoma; Liver biopsy; Liver resection; Liver transplantation; Liver tumor; Milan criteria; Up-to-Seven criteria