title: Sirolimus-based immunosuppression therapy in liver transplantation for patients with hepatocellular carcinoma exceeding the Milan criteria.
abstract: OBJECTIVE
  Sirolimus (SRL) acts as a primary immunosuppressant or antitumor agent. The aim of the present study was to evaluate the influence of SRL on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) exceeding the Milan criteria.
  
  
  METHODS
  We retrospectively examined 73 consecutive patients who underwent OLT for HCC exceeding the Milan criteria from March 2004 through December 2005. Among them, 27 patients were treated with SRL-based immunosuppressive protocols after OLT, and 46 patients by an FK506-based protocol. Statistical analysis was based on the intent-to-treat method.
  
  
  RESULTS
  The 2 groups were comparable in all clinicopathologic parameters. The mean overall survival was 594 +/- 35 days in the SRL group and 480 +/- 42 days in the FK506 group (P = .011); the mean disease-free survival period was 519 +/- 43 days in the SRL group and 477 +/- 48 days in the FK506 group (P = .234). Multivariate analysis revealed Child's status (P = .004) and immunosuppressive protocol (P = .015) were the significant factors affecting overall survival. Only microvascular invasion (P = .004) was significantly associated with disease-free survival. Among 24 surviving patient in the SRL group, 2 patients had SRL discontinued for toxicity; 10 had SRL monotherapy immunosuppression.
  
  
  CONCLUSIONS
  The SRL-based immunosuppressive protocol improved the overall survival of patients after OLT for HCC exceeding the Milan criteria, probably by postponing recurrence and with better tolerability.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: Z-Q
authors.initials: ZQ
authors.lastname: Wu
authors.forename: S-J
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: X-W
authors.initials: XW
authors.lastname: Huang
authors.forename: Z-Y
authors.initials: ZY
authors.lastname: Tang
authors.forename: J
authors.initials: J
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D018579:Patient Selection; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D017741:Survivors; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus