Clinical Pearls & Morning Reports
With a 5-year survival of 18%, liver cancer is the second most lethal tumor, after pancreatic cancer. Read the Review Article here.
A: Hepatocellular carcinoma is rare among patients without liver disease and is twice as common in men as in women. Cirrhosis of any cause increases the risk of hepatocellular carcinoma. In Western countries and Japan, the main cause of hepatocellular carcinoma is hepatitis C virus infection. Hepatocellular carcinoma can also arise in patients who have chronic liver disease but do not have established cirrhosis or marked inflammation (e.g., patients with hepatitis B virus infection). Worldwide, hepatitis B virus infection is the main cause of hepatocellular carcinoma. Alcoholic cirrhosis is another frequent cause of hepatocellular carcinoma. The increase in nonalcoholic fatty liver disease, which together with metabolic syndrome and obesity amplifies the risk of liver cancer, will soon become a leading cause of liver cancer in Western countries. Smoking and coinfection with the human immunodeficiency virus can also contribute to the development of hepatocellular carcinoma.
A: Abdominal ultrasonography every 6 months is the recommended method for surveillance, with or without measurement of serum levels of alpha-fetoprotein. The results are operator-dependent, with a sensitivity of 47 to 84% and a specificity higher than 90%. The performance of ultrasound surveillance is problematic in obese patients.
A: Liver transplantation can be performed in patients with a limited tumor burden who are not candidates for resection. The Milan criteria for liver transplantation (i.e., a single nodule ≤5 cm in diameter or up to three nodules, none larger than 3 cm in diameter) are the benchmark in patients with hepatocellular carcinoma. Macrovascular tumor invasion or extrahepatic spread is a contraindication for transplantation because of the high risk of tumor recurrence. Transplantation in patients with tumors that meet the Milan criteria is associated with survival of 60 to 80% at 5 years and 50% at 10 years, with post-transplantation tumor recurrence lower than 15%. Neoadjuvant treatments administered while patients are on the waiting list, generally ablation or transarterial therapies, are a cost-effective means of reducing the number of dropouts due to tumor progression when the median waiting time is longer than 6 months. The use of these therapies to down-stage some tumors exceeding the Milan criteria (i.e., reducing the tumor burden to meet the criteria) is a way of making formerly ineligible patients eligible for transplantation.
A: Patients with intermediate-stage tumors should be considered for transarterial therapies. The main treatment method is transarterial chemoembolization (TACE), which entails intraarterial infusion of a cytotoxic agent, followed immediately by embolization of the vessels that feed the tumor. Adjacent nontumoral liver tissue is generally protected from TACE because, unlike the tumor, its blood supply comes mainly from the portal vein. Systemic therapies are recommended for patients who have advanced disease or who have intermediate-stage disease and progression with transarterial therapies. Sorafenib was the first systemic drug approved by the Food and Drug Administration for the treatment of hepatocellular carcinoma and is the standard of care for frontline therapy. As the number of systemic agents found to be effective in phase 3 trials continues to grow, the challenge is to determine the order of sequential systemic therapy that maximizes the clinical benefit with minimal toxic effects and cost.