Epidemiology and Etiology
Recent studies have shown a conspicuous increase in the incidence of Hepatocellular Carcinoma (HCC) in the United States (NEJM 1999; 340: 845-50). This increase is a reflection of predisposing conditions and represents a change in the mode of presentation of these lesions. In the past, many of these lesions were discovered when they were large and/or disseminated in a clinically compensated patient. Now, however, these lesions are detected with increasing frequency when they are small. It is at this stage that several therapeutic options are available. These options include ablation therapy, surgical resection, and liver transplantation.

Figure 1: Gross specimen of resected liver demonstrating the surface nodularity, regenerating nodules, and fibrotic changes of cirrhosis. Note the brownish, well-circumscribed HCC. Such a lesion would be amenable to ablation therapy.

Most hepatomas arise in the adults with cirrhosis (Figure 1). Cirrhosis can be considered a precancerous condition. The rate of development of HCC in cirrhosis is from 1 to 3% per year (J Hepatol 2000; 32:255–337). Hemochromatosis can be a cause of cirrhosis, but hepatitis–related cirrhosis is by far the most common. Recent reports have linked increased iron deposition in cirrhotic livers with increased incidence of HCC (Radiology 1999; 212:235–240). Hepatitis B has known oncogenic properties, but the rate of HCC related to HBV has remained relatively stable; in fact it has actually shown a decline in certain populations where vaccinations have been used. It is hepatitis C– related cirrhosis that has been the main contributor to the increased incidence of HCC worldwide. Today, about 1.8% of the US population (3.9 million people) is infected with HBC.

Diagnosis
There is no serological marker that is sensitive and specific for the diagnosis of HCC. Alpha–fetoprotein (AFP) can be normal or non–diagnostic in a sizable number of patients with HCC. Mild elevations may be seen in patients with chronic inflammation and cirrhosis.

Figure 2a: Arterial injection during CT demonstrates the typical hypervascular nature of this peripheral HCC. Figure 2b: Due to its location, this lesion was amenable to surgical resection.

Radiological diagnosis often depends on the presence of early arterial supply to the tumor. This is often a size related phenomenon, such that lesions one centimeter or less in diameter have the most variable vascular supply. Most lesions that reach a size of about 3 cm. are clearly discernable due to their hypervascularity (Figure 2). Helical CT offers assessment of arterial and portal circulations. MR signal intensity can be used with similar reliability. Most HCC’s larger than one centimeter will demonstrate increased signal intensity on T2–weighted images (Figure 3, below). High signal intensity on T1–weighted images and low signal on T2–weighted images suggests adenomatous hyperplasic nodules, some of which may undergo malignant transformation (Hepatology 1995; 17:27). These concepts are guidelines, not rules, and not all lesions abide by them. It is the smaller lesions that are difficult to diagnosis, but it is only when the tumor is small that most therapeutic options are plausible.

Therapeutic Options
Surgery remains the only curative therapy for HCC. Presurgical assessment requires imaging to determine the extent of the intrahepatic disease and to exclude the presence of metastatic disease. It is also imperative to determine the amount of liver reserve and comorbid conditions. In non–cirrhotic patients, surgical resection is the treatment of choice. In cirrhotic patients, surgery is usually reserved for those patients with peripheral lesions and preserved liver function (Figure 2). Liver transplantation is most appropriate in individuals with advanced cirrhosis and small tumors (less than 5 cm).

Interventional therapies are reserved for unresectable lesions or inoperable patients and patients awaiting liver transplantation. Local tumor ablation may involve injectables/chemicals (ethanol, acetic acid, hot saline, CDDP/epinephrine) or thermal ablation (radio–frequency ablation, laser, freezing).

Figure 3: T2–weighted MR of patient with liver cirrhosis and multifocal HCC demonstrating characteristic increased signal intensity of lesions. Figure 4: Lipiodol injection used in TACE of HCC demonstrates the hyperdense localized oil uptake with the HCC

Percutaneous ethanol injection therapy (PEIT) is the most commonly utilized of the interventional therapies and therefore clinicians have wide experience with it. It is best used in situations where the disease is confined to the liver, there is limited liver deterioration, the lesion has well–defined margins, is easy to detect, and is less than 3–4cm. (Child A or B). PEIT may be performed with a single– or multiple–hole needle and often requires several sessions. Biliary and vascular reflux should be avoided. PEIT offers improved survival. Recurrence (local and distant) parallels surgical resection in cirrhosis (51% to 98%).

Transarterial chemoembolization (TACE) can also be used alone or in concert with PEIT. Prognostic factors affecting the success of TACE include the size of the tumor, the hepatic functional reserve, and the oil retention of the tumor (Figure 4). There are, however, no randomized clinical trials comparing these treatments.

Radio–frequency ablation (RFA) uses high frequency alternating current to produce frictional heat and thermal coagulation of tissues. The electrode is NOT the source of the heat. Factors that contribute to the heating of tissue include distance from the electrode, RF current intensity, and duration of the current. There are three RFA probes presently available as follows: Rita (expandable, multiple, seven electrodes), the RTC (expandable, ten electrodes), and the Radionics (single or cluster of three electrodes). The selection criteria for RFA ablation include disease confined to the liver, well defined margins, size and number of lesions, and adequate hepatic reserve. One of the advantages of RFA over PEIT is that RFA does not damage larger vessels due to heat dissipation from the flowing blood. However both RFA and PEIT cause damage to bile ducts. The location of the lesion becomes an important factor in choosing between these theraputic modalities.

When one compares PEIT to RFA (Radiology 1999; 210:655–661) in the treatment of small HCC’s, one finds that there is a higher rate of complete necrosis (90% vs. 80%), a reduction in the number of sessions required for successful ablation (1.2 vs. 4.8), and a higher complication rate with PEIT.

Cryoablation (freezing) appears to have a higher complication rate and greater incidence of local reccurrence when compared to RFA (Am J Surg 1999; 178:592–599).