Only 5%-10% of patients with cirrhosis and HCC seen at tertiary care centers will be candidates for surgical resection. Surgery is restricted to patients with solitary HCC, usually less than 5 cm in diameter, without evidence of vascular invasion or extrahepatic spread, and preserved liver function. The presence of significant portal hypertension or an abnormal bilirubin level should be considered contraindications to surgical resection. This would avoid significant postoperative impairment of liver function. However, HCC recurrence after hepatectomy has a negative impact on long-term survival, and adjuvant chemotherapy or preoperative chemoembolization has not been shown to reduce the risk of recurrence or to improve survival. OLT has several advantages over surgical resection for patients with HCC: (1) It can be used in patients with all stages of liver disease and (2) it simultaneously treats the cancer and addresses the neoplastic potential of the remaining liver as well as the liver disease itself. The current guidelines for eligibility are 1 lesion < 5 cm or ≤ 3 lesions, each < 3 cm. In patients who are candidates for both resection and transplantation, the best outcomes are currently obtained with transplantation. However, organ shortage limits the availability of OLT. For patients who are not candidates for surgical approaches, locoregional forms of treatment are available. Percutaneous ethanol ablation is currently considered the standard form of direct ablation. It is safe, simple, and inexpensive. To be suitable for this technique, HCCs must be less than 3 cm in size and have fewer than 3 nodules. The results could be comparable to those of surgery in a selected group of patients with small solitary tumors and mild liver dysfunction. PEI entails less procedure-related morbidity and mortality than surgery and fewer complications. As with surgical resection, tumor recurrences occur in one half of the patients; repeat therapy is often feasible in these cases. The experience with RFA is still limited, but its results appear promising. It appears to be an effective technique for the ablation of small liver tumors. RFA has some advantages over PEI, but prospective controlled studies are needed to determine which should be considered the method of choice for local ablation. The experience with other forms of local therapy (MCT, laser coagulation therapy, and cryotherapy) remains limited. TACE provides a survival advantage for patients not amenable to ablation therapies, Childs A and B cirrhosis, no vascular invasion, and lack of systemic symptoms. TACE is, therefore, only indicated in approximately 15% of patients with HCC. There is no convincing evidence that cytotoxic chemotherapy prolongs survival or improves the quality of life of these patients. Similarly, hormonal therapy with antiandrogens or antiestrogens has not demonstrated any benefit. Other forms of treatment such as with octreotide, interferons, radiation, or gene therapy are still experimental. In the United States, survival of patients with HCC has not changed significantly during the past 20 years. A limited proportion of patients with HCC are eligible for potentially curative forms of treatment. Despite improvements in early diagnosis, most patients still present with advanced disease. There is currently no treatment option that provides an unequivocal survival benefit for such patients. Important efforts should therefore be directed toward the development of effective screening, surveillance, and prevention strategies, along with prompt referral of cases to specialized centers for optimal multidisciplinary evaluation and management. Universal vaccination against HBV has the potential to reduce significantly the worldwide incidence of HCC. Other strategies, including chemoprevention, need better assessment.
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