Predicting recurrence after liver transplantation in patients with hepatocellular carcinoma exceeding the up-to-seven criteria

Authors

  • Francesco D'Amico,

    Corresponding author
    1. Hepatobiliary Surgery and Liver Transplant Unit, Department of General Surgery and Organ Transplantation, University of Padua, Padua, Italy
    2. Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY
    • Hepatobiliary Surgery and Liver Transplant Unit, Department of General Surgery and Organ Transplantation, University of Padua, Padua, Italy
    Search for more papers by this author
  • Myron Schwartz,

    1. Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY
    Search for more papers by this author
  • Alessandro Vitale,

    1. Unità di Chirurgia Oncologica, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy
    Search for more papers by this author
  • Parissa Tabrizian,

    1. Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY
    Search for more papers by this author
  • Sasan Roayaie,

    1. Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY
    Search for more papers by this author
  • Swan Thung,

    1. Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY
    Search for more papers by this author
  • Maria Guido,

    1. Pathology Section, Department of Medical and Diagnostic Sciences, University of Padua, Padua, Italy
    Search for more papers by this author
  • Juan del Rio Martin,

    1. Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY
    Search for more papers by this author
  • Thomas Schiano,

    1. Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY
    Search for more papers by this author
  • Umberto Cillo

    1. Hepatobiliary Surgery and Liver Transplant Unit, Department of General Surgery and Organ Transplantation, University of Padua, Padua, Italy
    2. Pathology Section, Department of Medical and Diagnostic Sciences, University of Padua, Padua, Italy
    3. Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY
    4. Unità di Chirurgia Oncologica, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy
    Search for more papers by this author

Abstract

The up-to-seven (Up-to-7) criteria [with 7 being the sum of the size and number of tumors for any given hepatocellular carcinoma (HCC)] have been recently proposed to identify potential candidates for liver transplantation (LT) among patients exceeding the Milan criteria. The aim of this study was to compare the ability of the available pathologic staging systems (the Milan, University of California San Francisco, and Up-to-7 criteria) to predict recurrence. A study population of 479 HCC transplanted patients was identified from prospectively collected databases at Mount Sinai Medical Center (New York, NY) and the University of Padua (Padua, Italy). The best pathologic staging system was identified with log rank, proportion separation index (PSEP), and Cox analyses. Pathologic tumor characteristics (tumor number, tumor size, sum of diameters, macroscopic and microscopic vascular invasion, and grading) were then tested by univariate and multivariate Cox analyses in the prognostic subgroups within and beyond the calculated criteria. The Up-to-7 criteria performed as the best pathologic staging system, the calculated 1-, 3-, and 5-year recurrence probabilities being 4%, 8%, and 14% within the criteria (n = 355) and 22%, 45%, 51% beyond the criteria (n = 124; P < 0.0001) and the calculated PSEP being 0.27 (95% confidence interval = 0.23-0.31). In multivariate analysis, only biological variables (vascular invasion and tumor grade) significantly predicted recurrence beyond the Up-to-7 criteria. A 3-stage pathologic staging system with a potential to be applied in the preoperative setting was thus created: within the Up-to-7 criteria (recurrence rate = 8%), beyond the Up-to-7 criteria without macrovascular invasion and poorly differentiated grade (recurrence rate = 24%), and beyond the Up-to-7 criteria with macrovascular invasion and/or poorly differentiated grade (recurrence rate = 45%). In conclusion, HCC patients within the pathologic Up-to-7 criteria were associated with a low risk of recurrence after LT. Beyond these criteria, however, a significant proportion of patients with a good HCC biological profile had an acceptable risk of recurrence. Liver Transpl 15:1278–1287, 2009. © 2009 AASLD.

Ancillary