Low Recurrence Rate of Hepatocellular Carcinoma after Liver Transplantation: Better Patient Selection or Lower Immunosuppression?

Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma

“…Recent publications have questioned the utility of the Milan criteria in stratifying for risk of posttransplant recurrence of HCC. 6,18 The original Milan series 4 contains a group of patients with more advanced tumors. A total of 13 of their original patients qualified for transplantation by initial imaging studies, but were found on examination of the explanted liver to have more extensive disease.…”

“…Our "Tumor Protocol" was planned to minimize the potential impact of steroids 12 and calcineurin-inhibitors 6 on HCC recurrence, and to allow for benefits of the previously reported antitumor activity of sirolimus. [13][14][15] In the absence of a control group, we cannot conclude that our protocol prevented tumor recurrence or prolonged survival in cases with tumor recurrence.…”

“…These results indicate that cyclosporine could exacerbate tumor growth in patients with existing tumors. 30 Vivarelli et al 6 reported that patients with HCC receiving a high dosage of cyclosporine A during post -liver transplant months 3 to 12 experienced a significantly lower recurrence-free survival. A cutoff in the cumulative cyclosporine A dosage was determined by applying a receiver-operating characteristic curve.…”

“…Excellent outcomes after liver transplantation for patients with HCC within the Milan criteria have subsequently been reported from other centers. [5][6][7][8] Our initial experience with 9 consecutive patients transplanted with HCC, in whom no recurrences were seen, suggested that the criteria may be too restrictive and that patients with more advanced disease may also benefit from liver transplantation. Other groups have further investigated the impact of tumor characteristics on tumor recurrence and patient survival.…”

“…5,9,10 Among various parameters that influence tumor-free survival after liver transplantation, steroid and calcineurininhibitor based immunosuppression has been shown to have an adverse effect on recurrence of hepatic malignancies. 6,11,12 In contrast, sirolimus had been reported to have antitumor activity in malignant cell lines and in animal models carrying human tumors. 13 -16 In December 1996, we initiated a prospective cohort evaluation of liver transplantation in patients with tumors meeting and extending beyond the Milan criteria in the context of a sirolimus-based immunosuppressive protocol (Tumor Protocol) that sought to minimize exposure to calcineurin inhibitors and steroids.…”