Objective: To determine the long-term results of liver transplantation for well- or moderately differentiated hepatocellular carcinoma (HCC).
Summary Background Data: HCC patient selection for liver transplantation remains controversial, and deciding exclusively on the strength of criteria such as number and size of nodules appears prognostically inaccurate.
Methods: Since 1991, preoperative tumor grading has been used at our center to establish whether a patient with HCC is fit for transplantation. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. Thirty-three patients with moderately or well-differentiated HCC were prospectively studied after liver transplantation. A group of 15 patients with incidental HCC transplanted during the same period were also evaluated and compared with the 33 patients with preoperatively diagnosed HCC.
Results: On histologic examination, 38% of the entire group of 48 patients did not meet the Milan criteria and 42% were pTNM stages III and IV. The median follow-up was 44 months. The 5-year actuarial survival rate was 75% and recurrence-free survival was 92%. HCC recurred in only 3 patients (6%). The only histomorphologic variable differing significantly between incidental and nonincidental HCC was nodule size. The timing of diagnosis (incidental vs. nonincidental HCC), the Milan criteria, and the TNM stage revealed no statistically significant impact on overall and recurrence-free survival rates.
Conclusions: The routine pre-orthotopic liver transplantation tumor grading may represent a valid tool in the selection of unresectable HCC patients for transplantation.
Over the last decade, the disappointing results reported in early publications on transplantation for hepatocellular carcinoma (HCC)1-3 and the scarce availability of liver donors4 have favored the introduction at many centers5-7 of stringent morphologic criteria (solitary nodule <5 cm, 3 nodules <3 cm) for listing HCC patients for orthotopic liver transplantation (OLT). Many papers8-13 have shown, however, that adopting these criteria carries the risk of a significant number of patients being refused a potentially curative solution. Conversely, a significant proportion of patients assumed to be good transplant candidates are actually at high risk of tumor recurrence.
Recent studies have shown that tumor grade and microscopic vascular invasion represent a much more direct indicator of the biologic progression of HCC and hence of posttransplant tumor recurrence risk.8,14-22 Only tumor grade can be routinely determined preoperatively, however, and may thus be a worthwhile criterion for selecting candidates for OLT.8,9,15,23-26 Several works published in the 1980s had already pointed out the relevance of the histologic features of HCC, and grade in particular, to the prognosis of patients undergoing resection or transplantation.27-31 Since 1991, our center has adopted a protocol for selecting HCC patients for OLT that considers preoperative grading as a means for excluding the biologically most aggressive cases, while size and number of nodules were not considered absolute selection criteria.
The aim of the present study was to evaluate the efficacy of OLT in a group of HCC patients selected on the basis of specific criteria, which excluded the biologically most aggressive cases according to grade. A group of patients with incidentally detected HCC transplanted during the same interval was also prospectively observed.