ABSTRACT
BACKGROUND/AIMS: The Up7 criteria for HCC have recently emerged to identify potential candidates for OLT. The aim of this study was to assess the validity of the Up7 criteria according to the pathological analysis of the explanted livers. METHODOLOGY: For recurrence risk calculation 669 HCC transplanted patients were classified according to both the pathological Milan and Up7 criteria. In order to identify potential predictors of recurrence, selected biological tumor markers and morphological features were then tested by Cox regression. RESULTS: The 5-year HCC recurrence rate for the Milan out/Up7 in subgroup (n=87), was significantly higher than patients meeting Milan criteria (n=299), 15.8% vs. 9.4% (p=0.0290). For patients within the Up7 criteria (n=383), only pre-OLT AFP level >1000ng/mL and microvascular invasion were significant predictors for recurrence, and for those beyond the Up7 criteria (n=286), pre-OLT AFP level >1000ng/mL, poor differentiation grade and microvascular invasion remained significant. CONCLUSIONS: Compared to the current Milan staging system, HCC patients within the pathological Up7 criteria were associated with a higher, but acceptable risk of recurrence after OLT, and along with tumor burden, other parameters can potentially be used for further refinement of HCC staging, such as AFP levels and microvascular invasion.
Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Liver Transplantation , Neoplasm Recurrence, Local/pathology , Patient Selection , Female , France , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment , Survival RateABSTRACT
Orthotopic liver transplantation (OLT) indication for hepatocellular carcinoma (HCC) is currently based on the Milan criteria. The University of California, San Francisco (UCSF) recently proposed an expansion of the selection criteria according to tumors characteristics on the explanted liver. This study: 1) assessed the validity of these criteria in an independent large series and 2) tested for the usefulness of these criteria when applied to pre-OLT tumor evaluation. Between 1985 and 1998, 479 patients were listed for liver transplantation (LT) for HCC and 467 were transplanted. According to pre-OLT (imaging at date of listing) or post-OLT (explanted liver) tumor characteristics, patients were retrospectively classified according to both the Milan and UCSF criteria. The 5-yr survival statistics were assessed by the Kaplan-Meier method and compared by the log-rank test. Pre-OLT UCSF criteria were analyzed according to an intention-to-treat principle. Based on the pre-OLT evaluation, 279 patients were Milan+, 44 patients were UCSF+ but Milan- (subgroup of patients that might benefit from the expansion), and 145 patients were UCSF- and Milan-. With a short median waiting time of 4 months, 5-yr survival was 60.1 +/- 3.0%, 45.6 +/- 7.8%, and 34.7 +/- 4.0%, respectively (P < 0.001). The 5-yr survival was arithmetically lower in UCSF+ Milan- patients compared to Milan+ but this difference was not significant (P = 0.10). Based on pathological features of the explanted liver, 5-yr survival was 70.4 +/- 3.4%, 63.6 +/- 7.8%, and 34.1 +/- 3.1%, in Milan+ patients (n = 184), UCSF+ Milan- patients (n = 39), and UCSF- Milan- patients (n = 238), respectively (P < 0.001). However, the 5-yr survival did not differ between Milan+ and UCSF+ Milan- patients (P = 0.33). In conclusion, these results show that when applied to pre-OLT evaluation, the UCSF criteria are associated with a 5-yr survival below 50%. Their applicability is therefore limited, despite similar survival rates compared to the Milan criteria, when the explanted liver is taken into account.
