**4.2. Advantages and disadvantages of MWA**

shown to mediate the rejection of metastatic lesions, when combined with CTLA-4 blockade,

While cryoablation has been strongly shown to activate the immune system, the opposite has also been seen. Multiple animal models have shown susceptibility to rechallenge and increased metastasis post ablation [73–75]. A possible explanation for these results is variation in the technical factors of cryoablation. Differing animal models, methods of freezing, length, number of freeze-thaw cycles, differences in minimum temperature achieved as well as differing ablation zone size and position all contribute to different clinical outcome and immunologic stimulation or anergy [73]. Sabel et al. established that variation in the technical parameters of cryoablation indeed affect the ratio of apoptosis to necrosis and subsequent immune response. Sabel et al. investigated the rate of freezing in an animal model using either a low or high rate of freezing. They found that a high rate of freezing induced a higher amount of necrosis when compared to a low rate of freezing. The high rate induced more danger signals stimulating a strong anti-tumor response [73]. A high ratio of apoptosis to necrosis has been shown to downregulate the immunologic response and even induce anergy [76]. When apoptotic cells are presented to DCs, a lower amount of TNF-α, IL-1β, IL-8, IL-10, IL-12, and granulocyte macrophage colony-stimulating factor (GM-CSF) produce inhibitory effects on these cells [77, 78]. The ablation zone size and percentage of tumor encompassed may play a role in the immunologic response. An experiment conducted in a murine metastatic liver tumor model demonstrated that smaller volume ablations show a significant decrease

Microwave ablation (MWA) is a hyperthermic ablative technique that is similar in many ways to RFA. MWA was introduced in the 1980s and 1990s and showed potential, but suffered from problems controlling the emitted field. There was a relatively high complication rate with MWA, thus RFA became the dominant ablative technique [80, 81]. While the early MWA systems had higher complication rates, since then newer designs have significantly decreased the complication rates. Recent retrospective and prospective studies have proven the efficacy

From a procedural point of view, MWA and RFA are performed similarly under image guidance. The operator guides a MWA antenna toward the targeted lesion using their favored imaging modality (**Figure 2**). Unlike RFA, MWA does not require the use of grounding pads to establish an electrical circuit. MWA uses dielectric hysteresis to produce heat. An oscillating field, typically 900–2500 MHZ, is applied forcing polar molecules (such as water) to continuously move and realign in the field creating kinetic energy and ultimately raising the temperature of the tissue. Microwaves are able to propagate through a variety of tissues, even those with low electrical conductivity, high impedance, or low thermal conductivity. This

and safety of MWA for not only HCC lesions but also other hepatic lesions [82–85].

it can mediate rejection of metastatic lesions and prevent disease recurrence [72].

160 Hepatocellular Carcinoma - Advances in Diagnosis and Treatment

in metastasis [79].

**4.1. Overview**

**4. Microwave ablation**

makes MWA more versatile [86].

MWA has the distinct advantage of being able to penetrate through high impedance tissues, meaning that even if charred or desiccated tissues build up near the probe, the field is able to penetrate and continue enlarging the ablation zone. Since MWA does not rely on conduction of tissue, heat is able to penetrate tissues with a high impedance such as lung or bone [86].

Multiple MWA antennas are able to be used synergistically to enlarge the ablation zone, achieve higher temperatures, or concomitantly ablate multiple lesions [87]. While RFA using multiple probes requires the probes to be used in series, MWA with multiple antennas can be used simultaneously with one power source. Due to the properties of MWA, there is future potential use ablating larger lesions than is currently possible.

The peak temperatures achieved in the central zone can readily exceed 100°C. The ability to achieve higher temperatures and use multiple probes simultaneously means shorter treatment times and larger area of coagulative necrosis and lethal hyperthermia. Higher temperatures and larger central zone lessen the effect of nearby heat sinks. It has been shown that large vessels <10 mm in size will not affect the ablation, making it possible to ablate lesions in regions that are not possible with RFA [88].

While MWA has many advantages, its ability to deliver a high amount of energy comes with several trade-offs. Coaxial cables have excellent properties for this application and are thus used to connect the antenna to the microwave generator. However, the coaxial cables used have a large diameter in order to avoid dangerous cable overheating. Larger diameter decreases the risk of overheating but becomes cumbersome and inflexible leading to difficulties while manipulating the antennas and performing the procedure [89]. The microwave antennas are likewise made using coaxial cable and also suffer from the same problem. In order for the antenna to handle higher power levels, the diameter must be increased or an active cooling system needs to be employed [86, 89].

**Figure 2.** Hepatic microwave ablation. Pre-procedure imaging demonstrates a focal HCC lesion at the hepatic dome (left, arrow). Two microwave needles were advanced into the lesion, with gas bubbles developing during the ablation (middle). Follow-up imaging demonstrates a focal defect without enhancing viable tissue consistent with a complete ablation (right).

Active cooling systems have helped eliminate several problems. They allow a smaller diameter antenna to handle higher power and eliminate the risk of ablating healthy tissues along the proximal antenna tract, increase the size of the ablation, increase the amount of power delivered, and can prevent the probe from backing out. Various cooling methods have been employed from chilled saline to cooling with compressed gas utilizing the Joule-Thomson phenomenon [86]. Some newer probes that use the Joule-Thompson phenomenon are able to be locked into place by freezing the antenna tract to prevent it from moving or backing out.

OK-432 is able to induce pro-inflammatory cytokines and activate the T-cell–mediated immunity. Li et al. demonstrated that MWA and OK-432 used in combination resulted in prolonged survival and a strong immunologic response to rechallenge in a murine model of breast cancer. The results showed that a dominant Th1 response is generated. The cytokines IL-12, IL-2, and IFN-γ were significantly increased with no effect on Th2-type cytokines. Additionally, immunohistochemical analysis showed that a predominance of CD8+ T cells infiltrating the

Minimally Invasive Therapies for Hepatocellular Carcinoma: Mechanisms of Local Control…

http://dx.doi.org/10.5772/intechopen.72275

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Immunotherapy combined with MWA for the treatment of HCC has been investigated in both phase I and phase II trials [93, 96]. This combination was shown to increase the absolute number of circulating lymphocytes. When analyzed for specific subgroups, patients showed increased levels of cytotoxic subsets of T cells and decreased suppressive subsets. Additionally, patients treated with immunotherapy had significantly improved liver function. However,

CTLA-4 blockade holds great promise when combined with cryoablation, but could also be used in with MWA. CTLA-4 blocking antibodies and GM-CSF combined with MWA were shown to induce tumor-specific cellular immune response in a murine model [94]. The combination of the three resulted in a 90% rejection upon tumor rechallenge and 50% of the animals treated showed distant tumor regression. Since both of these drugs are currently available for

Minimally invasive thermal-based therapy has become a reliable method for the treatment of HCC. Many advances in ablative therapy have occurred since their initial implementation ranging from design to technical implementation. The most promising of these advances is combination therapies that create a tumor-specific immunologic response. Combination therapy has shown great promise in the treatment and prevention of not only HCC, but also other malignancies. There is much more to learn about the immunologic reaction to ablative

and Rahul A. Sheth2

1 University of Texas Health Science Center Houston – McGovern Medical School, Houston,

\*

the disease-free survival and overall survival rate were not significantly improved.

human use, this combination represents one that could be clinically used today.

therapy creating an exciting time of investigation and discovery.

, Joshua D. Kuban<sup>2</sup>

\*Address all correspondence to: rasheth@mdanderson.org

2 MD Anderson Cancer Center, Houston, Texas, USA

treated tumors.

**5. Conclusion**

**Author details**

Andrew W. Ritchey1

Texas, USA

Since the primary advantage of MWA is the ability to deliver, a significant amount of power safety concerns arises. With MWA, it is harder to predict the size of the ablation zone, which can lead to damage of surrounding structures. The shape of the ablation zone produced can be relatively thin and long increasing this risk. While problems with MWA exist, currently these issues should not limit its use ablating HCC and other lesions in the liver. MWA has been proven effective and comparatively safe to RFA when measuring complication rates [82–85].
