Page 14 - Read Online

[59]
Thermal ablative therapies resection. Liver transplantation for HCC remains the
Radiofrequency ablation best treatment option and offers the longest survival for
Radio frequencies are the part of the electromagnetic the approximately 10% of patients who are candidates.
spectrum that are bound by a low oscillation of 3 Hz Treatment with RFA, while a patient is awaiting for liver
and a high of 300 GHz. RFA refers to the coagulative transplantation, has been shown to be an independent
necrosis of tissue as a result of heat deposition around prognostic factor for longer survival. Although Child-
[56]
a probe generating electromagnetic radiation within the Pugh class C patients may be safely treated with RFA, a
radiofrequency spectrum. The probe (energy source) is survival benefit is unlikely as life expectancy is determined
inserted within the target lesion, and the circuit is closed by the progression of cirrhosis. On the other hand,
by placing grounding pads on the patient’s body, usually although prospective, randomized trials are lacking, there
the thighs. A generator modulates the radio frequency is strong evidence that Child-Pugh class A and B patients
amplitude, and the energy is locally deposited as a result may benefit from RFA of unresectable HCC.
of molecular frictional loss resulting in heating of the
tissues around the probe tip. The eventual ablated zone Percutaneous RFA for HCC carries certain unique risks. The
geometry is a result of complex interactions that includes mortality of percutaneous liver RFA is extremely low (<
the type and shape of the probe, the duration of ablation, 1%). However, this assumes preserved liver function and
the maximum temperature reached, and the proximity small ablation volumes. Because most deaths after RFA are
[52]
of the target lesion to vessels. Computed tomographic attributed to liver failure, this risk increases with larger
scanning or ultrasound is used for percutaneous probe ablation volumes and diminished liver reserve (resulting
guidance, although magnetic resonance imaging (MRI) from prior hepatectomy, cirrhosis, previous ablations,
is emerging as a possible alternative. Effective ablation and other). The overall major risks associated with liver
depends on good tissue conductivity, which allows heat RFA are on the order of 4-5%. [56-58,60] Most patients treated
transfer farther away from the probe and a larger ablation with RFA for HCC may be discharged home on the day
zone. Counterintuitively, a fast power increase will result of the procedure after a 3- to 6-h observation unless a
in the tissue around the probe being desiccated, which complication.
limits heat conduction and the ablation zone. Therefore,
slow and methodical ablation with a gradual power RFA is also known to enhance host immune response.
increase is desired. RFA of liver lesions usually takes from However, the epitopes at which enhanced immune
10 to 30 min per lesion. responses occur, the impact on patient prognosis, and
the functions and phenotypes of T-cells induced are
The efficacy of RFA depends on technical aspects and to still unclear. To address these issues, Mizukoshi et al.
[61]
a lesser extent, on patient selection. Lesion size is the analyzed immune responses before and after RFA in 69
most important determinant of RFA success. Lesions up HCC patients using 11 tumor-associated antigens (TAA)-
to 3 cm can be treated effectively with reported complete derived peptides that were identified to be appropriate
ablation rates of about 90%. [53-56] For lesions > 3 cm, [53,57,58] for analyzing HCC-specific immune responses. The
the efficacy of RFA decreases with increasing lesion size. immune responses were analyzed using enzyme-linked
Complete ablation is possible with favorable anatomy immunospot (ELISPOT) assays and tetramer assays using
for lesions of 3-5 cm; however, beyond the 5 cm size, a peripheral blood mononuclear cells. An increase in the
complete response is unlikely. The rate of recurrence is number of TAA-specific T-cells detected by interferon-γ
nearly 0% for smaller lesions and > 50% for lesions > 5 ELISPOT assays occurred in 62.3% of patients after RFA.
cm. Another determinant of success is lesion location. The antigens and its epitope at which enhanced T cell
Central (near the hilum) lesions should be avoided responses occur were diverse, and some of them were
because of the risk of the central bile duct and vascular newly induced. The number of TAA-specific T cells after
injury. Additionally, the lesions bordering a large (> 3 mm) RFA was associated with the prevention of HCC recurrence,
vessel may not respond because of thermal protection and it was clarified to be predictive of HCC recurrence
provided by the adjacent blood flow, a phenomenon after RFA by univariate and multivariate analyzes. The
termed “heat-sink”. Survival of patients with unresectable number of TAA-specific T cells after RFA was inversely
HCC treated with RFA is reportedly 75-92% at 1 year, 80% at correlated with the frequency of CD14+ HLA-DR(-/low)
2 years, 37-59% at 3 years, and 28% at 5 years. [53,55] Even for myeloid-derived suppressor cells (MDSCs). Modification
resectable tumors, RFA appears to offer the same benefit of the T cell phenotype was observed after RFA. The
as resection in selected patients. Survival rates for Child- number of TAA-specific T-cells at 24 weeks after RFA was
Pugh class A or B patients with lesions up to 3 cm are decreased. Although RFA can enhance various TAA-specific
not different between groups treated with RFA vs. surgical T-cell responses and the T-cells induced contribute to

Hepatoma Research | Volume 2 | Issue 1 | January 15, 2016 5