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Interventional management of hepatocellular carcinoma
Key points
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Image guided techniques are the most common invasive therapy for unresectable hepatocellular carcinoma (HCC).
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Level 1 evidence supports survival benefit chemoembolization.
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New embolic devices may offer benefits not currenlty realized.
Background
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer-related death. Although the highest prevalence is still in sub-Saharan Africa and Asia, the incidence in the United States is rising along with the rise in hepatitis B and C and the longer survival of cirrhotic patients. As novel therapeutic options have emerged and been refined, the manner in which HCC is treated has changed dramatically compared with just two decades ago. The approach to a patient with HCC has been reasonably standardized as a result of several international guidelines. Now, there is a reproducible algorithm that determines whether a patient undergoes transplantation, surgical resection, ablation, transarterial treatment, or systemic chemotherapy ( Figure 8-1 ). It should be noted that a minorty of HCC patients can be treated with resection or transplantation, and percutaneous ablation and transarterial techniques have emerged as essential therapies in the treatment algorithm for HCC.
This chapter focuses on these ablative and transarterial techniques. Percutaneous ethanol injection (PEI) was introduced in the 1980s as the first effective ablative technique. Since then, the thermal systems radiofrequency (RF), microwave (MW), and cryoablation have gained wide acceptance, with the most data having been gathered for RF ablation (RFA). The newest method, though largely experimental in the treatment of HCC, is irreversible electroporation (IRE).
Transarterial therapy for HCC was first reported in the late 1970s. In the 1980s, several reports discussed the feasibility of combining embolic and chemotherapeutic agents. Two seminal randomized controlled trials in 2002 were the first to demonstrate a survival benefit in patients with unresectable HCC treated with transarterial chemoembolization. , Phase 1 and 2 clinical trials on doxorubicin eluting embolic beads in the treatment of unresectable HCC were conducted in the mid 2000s in an attempt to standardize the procedure and improve the pharmacokinetic profile of chemoembolization. During the past 10 years, nonocclusive alternatives to transarterial embolization (TAE)/transarterial chemoembolization (TACE) have received growing interest. The following pages discuss the technical details of these approaches, their indications, complications, and their relative value in the treatment of unresectable HCC.
Percutaneous ablation
The technical details of the various percutaneous ablative techniques named above can be found in Chapter 2 . The discussion here will focus on workup and preoperative imaging, data-based patient selection, complications, and postprocedural care and imaging.
Patient preparation and preoperative imaging
Either magnetic resonance imaging (MRI) or computed tomography (CT) with arterial and portal contrast phases should be obtained to identify the location, number, and size of tumors to be treated. The imaging is essential to determine whether the lesions are amenable to ablation. The case should be explicitly discussed with the referring physician or tumor board, and the patient’s disease stage should be characterized by the combination of imaging findings, laboratory results, and functional status. Blood product replacement should be performed if the international normalized ratio (INR) is >1.5 and the platelets are <50,000/mm . Aspirin and/or clopidogrel should be held at least 5 days prior to the procedure if possible. Imaging will also guide whether ultrasonography, CT, or a combination will be used to ablate the lesion(s).
Ablative techniques
Radiofrequency ablation
As stated above, most of the data on percutaneous techniques has been generated for radiofrequency ablation (RFA), so the current recommendations primarily apply to this ablative modality ( Figure 8-2 ). RFA relies on thermal heat created by an electrical current passing through the electrode embedded in the tumor. Patients who should be considered for RFA are those with very-early-stage and early-stage HCC. Very early stage is defined as having a performance status of 0, being Child-Pugh Class A, and having a single tumor <2 cm in size. The treatment options for these patients are surgical resection and ablation, and the decision is made based largely on anatomic location. Lesions that should be resected include those in a subcapsular or perivascular distribution, as ablation is occasionally unsafe and less effective in these respective locations. Presuming the patient is a good surgical candidate (normal liver function, absence of portal hypertension), the 5-year survival rate following anatomic resection is >75%. , Livraghi et al. conducted a retrospective analysis of 218 very-early-stage HCC patients treated with RFA and found an overall 55% 5-year survival rate, which climbed to 68% in patients whose initial tumor was deemed resectable, indicating a favorable comparison to surgery. Cho et al. simulated a randomized trial between resection and RFA based on previous data and concluded that RFA followed by resection (if necessary, in the event of local failure) had a nearly identical survival to primary resection. In conclusion, the current recommendations favor surgical resection in patients with very-early-stage disease; however, for nonresectable tumors, RFA offers excellent 5-year survival and spares significantly more hepatic parenchyma than anatomic resection.
Early-stage HCC patients, defined as having intact liver function (Child-Pugh Class A or B) and a solitary tumor 2–5 cm or 3 tumors <3 cm, can undergo resection, transplantation, or ablation. The decision as to which to pursue is highly patient and tumor specific. Head-to-head comparisons between RFA and resection have been conflicting, with one randomized trial demonstrating essentially no difference, and the other favoring resection. Other factors to consider are the size of the tumor; lesions greater than 3 cm are not as effectively treated at the margins by RFA. As stated above, the heat-sink effect caused by vessels adjacent to the lesion limit the effectiveness of RFA. Other technologies, including MW ablation, may overcome some of these limitations of RFA, but further studies are required for confirmation.
Contraindications include diffuse or infiltrative tumors, those with vascular invasion, and distant disease. Relative contraindications include proximity to the gallbladder and gastrointestinal viscera, and a central location. Iatrogenic cholecystitis is usually temporary. The colon is most susceptible to thermal damage, possibly because of its fixed position and thin wall. A central tumor position has a higher risk for biliary tract violation.
The estimated mortality rate is 0.1%–0.5%, with major complication rates ranging from 2% to 3%. Complications include thermal burns, intraperitoneal hemorrhage, bile duct injury, and visceral injury. Special note should be made of tumor tract seeding, estimated to have a 0.5% incidence, for which many practitioners ablate the tract itself.
Percutaneous chemical injection
PEI is the oldest of the percutaneous ablative techniques. It relies on the dispersion of ethanol within the lesion, which results in coagulation necrosis. When compared to RFA for early-stage HCC, PEI shows a less favorable survival profile. It also has been shown to have higher recurrence rates, postulated to be secondary to inhomogeneous infiltration of a lesion and the inability to create an ablation margin that would encompass satellite lesions. However, in patients with very-early-stage HCC, PEI can be effective when tumor location makes the lesion unresectable or suboptimal for RFA. It is also much less costly than the thermal ablative technologies.
Percutaneous acetic acid injection works on a similar principle to PEI, with the theoretical benefit compared to PEI of being able to dissolve intratumoral septations and achieve higher homogeneity. It compares favorably with PEI, but has not been widely adopted.
Microwave ablation
MW technology causes local excitation of water molecules to generate tissue heat via friction, and is capable of creating much higher intratumoral temperatures than RFA ( Figure 8-3 ). Moreover, MW ablation is capable of creating a larger ablation zone and is not affected by adjacent vasculature. That being said, the one randomized trial that compared MW ablation with RFA failed to demonstrate a survival benefit. However, MW technology has improved markedly since this trial, and those results may be obsolete.
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