Liver Transplantation for Hepatocellular Carcinoma: Beyond the Milan Criteria

Division of Gastroenterology, University of California, San Francisco, CA 94143-0538, USA.
American Journal of Transplantation (Impact Factor: 5.68). 09/2008; 8(10):1982-9. DOI: 10.1111/j.1600-6143.2008.02351.x
Source: PubMed


Liver transplantation represents a cornerstone in the management of early-stage hepatocellular carcinoma (HCC). Expansion beyond the Milan criteria for liver transplantation (1 lesion <or= 5 cm, or 2 to 3 lesions each <or= 3 cm) remains controversial. This review covers several key areas: (1) Recent developments and published data on expanded criteria for deceased donor and live-donor liver transplantation, with emphasis on criteria that have been applied to preoperative imaging. (2) Independent testing of expanded criteria, where published data are largely limited to the proposed University of California, San Francisco criteria (1 lesion <or= 6.5 cm, 2-3 lesions each <or= 4.5 cm with total tumor diameter <or= 8 cm). (3) Response to loco-regional therapy and tumor downstaging. (4) The fundamental questions and answers in resolving the controversy over expanded criteria. The key issue pertains to whether acceptable outcome can be achieved on a broader scale beyond single center experience, which appears to support modest expansion beyond the Milan criteria. The foundation of the debate over expanded criteria may rest upon what the transplant community would consider to be the acceptable threshold for patient survival using expanded criteria, without causing significant harm to other transplant candidates without HCC.

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    • "Carcinomas occurring in transplant recipients after LTx have been increasingly reported. Tumor recurrence after LTx for hepatocellular carcinoma (HCC) in end-stage liver cirrhosis is frequently encountered, especially with advanced HCC patients [2]. However, de novo HCC originating from liver allograft in a patient who received LTx for benign disease has only rarely been reported. "
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    ABSTRACT: Post-transplant malignancy is the major cause of later death of recipients after liver transplantation. Tumor recurrence after liver transplantation for patients with hepatocellular carcinoma in the end stage of cirrhosis has been frequently encountered. However, de novo hepatocellular carcinoma originating from the liver allograft has only rarely been reported. Here we reported a case of de novo hepatocellular carcinoma developed 2 years after living donor liver transplantation for hepatitis B-related liver cirrhosis with viral YMDD mutation. To the best of our knowledge, this is the first report of de novo hepatocellular carcinoma in a liver graft with recurrent hepatitis B virus infection after liver transplantation for hepatitis B-related liver cirrhosis with YMDD mutation. Moreover, the de novo cancer first presented as a lung mass with minimal liver involvement and was obscured by a pulmonary fungal infection.
    Full-text · Article · Aug 2013 · World Journal of Surgical Oncology
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    • "The rate of rejection was of 30%, but no case of graft loss occurred. Yao et al. [5] reported an overall 11% rate of recurrence (8 patients) in 70 liver transplant recipients meeting or not the Milan criteria, on treatment with cyclosporine or tacrolimus; 3 of them, about 4% of the entire population, met the Milan criteria. As noted in an interesting editorial by Wall [83], in patients meeting the Milan criteria, Kneteman results where almost the same of those obtained by Yao in the same group of patients receiving CNI-based immunosuppression; on the other hand, there was a consistent gain in tumor-free survival in patients beyond the Milan criteria. "

    Preview · Article · May 2011 · The Open Transplantation Journal
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    • "A pre-transplant evaluation is essential to obtain better posttransplant outcome. The Milan criteria have been successfully used to evaluate the necessity of LT for patients with HCC, and have contributed to predicting the post-transplant outcome [6] [7]. However, the predictive factors of the progression of fibrosis and graft loss due to re-infected HCV have not been fully elucidated [8]. "
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    ABSTRACT: The results of post-transplant antiviral therapy for recurrent hepatitis C virus (HCV) are poor, and significant pre-transplant predictors for sustained viral response (SVR) have not yet been identified. Pegylated interferon/ribavirin therapy was performed for more than 48 weeks in 50 patients who underwent liver transplantation (LT) for HCV genotype 1-related liver disease. Of these, 22 patients achieved SVR. The predictive potential of the viral mutations, including amino acids (aa) 70 and 91 in the Core region, interferon sensitivity-determining region (ISDR, aa 2209-2248) and interferon/ribavirin resistance-determining region (IRRDR, aa 2334-2379) in NS5A, was evaluated. In 16 patients, the sequences in the pre- and post-transplant samples were the same, except for aa 70 in the Core of 1 patient. The SVR achievement percentage was significantly lower in the Non-double wild (DW) at aa 70 and 91, the ISDR<2 and IRRDR<6 groups than in the DW (30% vs. 65%, p=0.015), the ISDR2 (35% vs. 69%, p=0.035) and IRRDR6 (25% vs. 78%, p<0.001) groups, respectively. Predictive scoring with these three items provides a newly established and significant predictor for SVR after LT (p=0.015). DW, ISDR2 and IRRDR6 were found to be significant predictors for SVR after LT. In addition, it is possible that the establishment of a new scoring system consisting of these three factors may be a useful marker to predict interferon sensitivity for recurrent HCV after LT.
    Full-text · Article · Mar 2010 · Journal of Hepatology
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