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the HCC recurrence-free survival of patients, besides light absorption, temperatures of up to 150 °C are reached within
immunosuppression by MDSCs, the memory phenotype the tumor, leading to substantial coagulative necrosis.
and lifetime of TAA-specific T-cells are not sufficient to The most commonly used device for laser ablation is the
prevent HCC recurrence completely. Additional treatments Nd-YAG laser. The optical fibers are inserted directly into
by the vaccine or immunomodulatory drugs might be the lesion under MRI guidance through a percutaneously
useful to improve the immunological effect of RFA. [61] placed needle, which is removed after localization. A
multi-needle approach is essential to treat large lesions
Microwave coagulation therapy successfully (> 5 cm). In such tumors, treatment time
Microwave ablation is the term used for all electromagnetic can approach 1 h. Thermocoagulation is monitored in
methods of inducing tumor destruction by using devices real time under MRI, allowing accurate estimation of the
with frequencies greater than or equal to 900 kHz. The actual extent of the thermal damage. The indications
passage of microwaves into cells or other materials and contraindications of laser ablation are the same as
containing water results in the rotation of individual those for RFA and microwave ablation. Laser ablation
[69]
molecules. This rapid molecular rotation generates and has been shown to be effective in inducing complete
uniformly distributes heat, which is instantaneous and necrosis in HCC. Because with other ablative techniques,
continuous until the radiation is stopped. Microwave long-term success rates are related to tumor size, and an
irradiation creates an ablation area around the needle 82% complete response rate has been reported for lesions
in a column or round shape, depending on the type of measuring 3.2 cm in diameter. In a series of 74 patients
needle used and the generating power. The local with small HCCs, survival rates at 1, 3, and 5 years were
[62]
effect of treatment in HCC was assessed by examining 99%, 48%, and 15%, respectively. [70]
the histological changes of the tumor after microwave
ablation. [63,64] In one study, 89% of 18 small tumors were Percutaneous cryoablation
ablated completely. Coagulative necrosis with faded Cryotherapy can destroy tumors directly. With different
[63]
nuclei and eosinophilic cytoplasm were the predominant physical and chemical mechanisms of the therapy, cell
findings in the ablated areas. There were also areas in death depends on the rate of cooling, absolute depth of
which the tumors maintained their native morphological hypothermia, the rate of thawing, the number of freeze-
features as if the area was fixed, but their cellular activity thaw cycles and delayed effects of post-thaw ischemia.
was destroyed as demonstrated by succinic dehydrogenase Most tumor cells die at -40 °C; repeated freezing can
staining. One study compared microwave ablation and PEI improve the efficacy. The larger diameter of current
in a retrospective evaluation of 90 patients with small cryoprobes and the location of tumors within the liver still
HCC. The overall 5-year survival rates for patients with limit its application. Guo et al. reported of 26 patients
[65]
[71]
well-differentiated HCC treated with microwave ablation with HCCs of 10-14 cm in diameter receiving argon-helium
and PEI were not significantly different. However, among cryotherapy after TACE. After this therapy, the average
the patients with moderately or poorly differentiated HCC, neoplasm necrosis rate was 28.7%, significantly higher
overall survival with microwave ablation was significantly than that of TACE only.
better than with PEI. In a large series including 234
patients, the 3- and 5-year survival rates were 73% and High-intensity focused ultrasound ablation
57%, respectively. At multivariate analysis, tumor size, High-intensity focused ultrasound ablation (HIFU) as a
[66]
the number of nodules, and Child-Pugh classification had a new modality for the treatment of HCC has been applied
significant effect on survival. Only one randomized trial clinically. In the treatment area, all tumor cells seem to
[67]
compared the effectiveness of microwave ablation with be irreversibly dead in the forms of nuclear pyknosis,
that of RFA. Seventy-two patients with 94 HCC nodules debris, and dissolution. Blood sinusoids were collapsed
[68]
[72]
were randomly assigned to RFA and microwave ablation with endothelial cell damage. In combination with
groups. Unfortunately, the data in this study were analyzed TACE, HIFU gives a 1-year survival rate of 42.9% for IVa
with respect to lesions and not to patients. Although no stage patients (P < 0.05 compared to patients receiving
statistically significant differences were observed with TACE only) and median reduction rates of 28.6%, 35.0%,
respect to the efficacy of the two procedures, a tendency 50.0%, and 50.0% of tumor sizes at 1, 3, 6, and 12 months,
[73]
of favoring RFA was recognized with respect to local respectively. However, the need for general anesthesia
recurrences and complications rates. [68] and high expenses are its disadvantages.

Laser-induced interstitial thermotherapy COMBINATION THERAPIES
Laser-induced thermotherapy uses optical fibers to deliver
high-energy laser radiation to the target lesion. Because of Both TACE and RFA have well-known limitations in terms

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