Liver Transplantation for Hepatocellular Carcinoma: Expanding Frontiers and Building Bridges
Section snippets
HCC surveillance, liver transplantation, and organ allocation
Because curative interventions are currently only possible in early-stage disease, early detection of HCC is a critical component of successful treatment. The current screening protocol in patients with cirrhosis involves abdominal ultrasound every 6 months combined with serum α-fetoprotein (AFP) level (see article elsewhere in this issue by Morris Sherman). The majority of patients with cirrhosis, however, do not undergo regular surveillance for HCC. One series from the United States found
The Milan and recently expanded liver transplantation criteria
Liver transplantation was initially performed for patients with large, unresectable, and advanced-staged HCC, and results were disappointing. Five-year survival rates were only approximately 25% for patients who underwent transplantation during the period from 1987 to 1991.3
In their landmark study, Mazzaferro and colleagues4 reported much better survival for patients with early compared with late-stage HCC. They defined criteria now known as the Milan criteria: a single lesion less than 5 cm or
Bridging/Ablative therapies
The risk of dropout (ie, removal from the transplant waiting list because of disease progression beyond transplant criteria) is approximately 20% during the first 6 months after listing. Dropout of patients due to progression of tumor beyond criteria has become a significant clinical problem, especially for patients at transplant centers with long waiting times. Within 1 year of diagnosis, at least 70% of patients with untreated HCC have tumor growth, 20% develop vascular invasion, and 9%
Chemotherapy
Several chemotherapeutic regimens have been used in the treatment of HCC and are described in detail in the article elsewhere in this issue by Wrzesinski and coworkers. Despite some significant advances in recent years, the development of truly effective chemotherapy for this cancer remains elusive. One of the most promising agents is the multikinase inhibitor, sorafenib, which has antiangiogenic and antiproliferative properties. It is the first agent to demonstrate a modest but statistically
Surgical resection and salvage transplantation
Surgical resection has been the gold standard treatment of patients with HCC. Resection requires that a tumor is in a location amenable to resection and that patients have adequate hepatic function immediately afterward. The best resection candidates are those with a single lesion in a noncirrhotic background or in well-compensated cirrhosis with a normal bilirubin and no portal hypertension.
Unfortunately, surgical resection is associated with a high rate of both early recurrence (likely due to
Tumor pathology and molecular profiling
Commonly used selection criteria do not consider tumor histology or molecular characteristics. Tumor characteristics, such as size and number, are actually surrogates for molecular characteristics and the presence of microvascular invasion. Poor differentiation has been shown to be a predictor of microvascular invasion and is an independent risk factor for tumor recurrence.26, 27 There is a poor correlation between the tumor grade on pretransplant percutaneous fine-needle biopsy, however, and
Immunosuppression after transplantation
Immunosuppression after transplantation may be a factor in disease progression for patients with recurrent disease. The addition or substitution of an agent with antiproliferative effects may slow the rate of tumor growth. Mammalian target of rapamycin inhibitors, such as sirolimus and everolimus, have been used at some centers due to their potential antiproliferative effect. Controlled trials, however, are necessary to demonstrate actual efficacy for routine use of mammalian target of
Assessing the risk of progression or recurrence and monitoring for recurrent disease
Transplant criteria, such as the Milan criteria, have been designed to select individuals least likely to develop recurrent disease after transplantation. Unknown is whether other characteristics, such as recipient or donor factors, might have prognostic value for predicting dropout while awaiting transplantation or recurrence after transplantation. Risk factors for dropout might enable better adjustment of transplant priority or MELD exception points.
There has been little published in regards
Building bridges
It is an exciting era in liver transplantation for HCC. Results for patients transplanted within Milan criteria are excellent. There are many critical questions still awaiting answers, however. In particular, when should bridging therapies be used? At the authors’ institution, bridging therapies have been used with excellent outcomes in patients within Milan criteria. Because the mean waiting time for patients exceeds 6 months, the authors use bridging therapy for all patients with HCC amenable
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