**5. Conclusion**

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. 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].

The immunologic response to MWA is less well characterized compared to other methods of ablation, such as RFA and cryoablation. The vast majority of the research regarding the immune response and immunologic stimulation has been studied with either RFA or cryoablation. Recently specific immunologic mechanisms and the effects following MWA have been studied in more detail. It has been assumed that the immunologic response to MWA is similar to the mechanism and response to RFA [90, 91]. Currently, our knowledge about the immune response to MWA comes from both animal and clinical trials of various tumor types from

In regards to patient management and future treatment, the goal of therapy is to generate a lasting immune response that results in regression of distant lesions and generate protection from disease recurrence. As detailed in previous sections, the aim of treatment is to generate specific cytokines triggering the Th1 response and activating the cellular immune system. Similar to other ablative techniques, MWA alone is not powerful enough to trigger the desired

The specific immune response to MWA in patients with HCC has been analyzed by Zhang et al. In their study, 45 patients with HCC treated with MWA had peripheral blood analysis following treatment. The results showed significant increases in IL-12 and decreases in IL-4 and IL-10 [91]. These results are promising since IL-12 is involved in the differentiation of Th1 cells and generation of cellular immunity. Furthermore, patients showed decreased levels of IL-4 and IL-10, which are involved in activation of humoral immunity. While MWA alone is not enough to create a significantly different clinical response, the cytokine profile produced

Various combination therapies have been studied ranging from OK-432, immunotherapy, GM-CSF, and CTLA-4 blockade [92–94]. OK-432, also known as picibanil, is a low virulence mixture of *Streptococcus pyogenes* that has been used as an antitumor agent since 1975 [95].

immune response, but holds potential with combination therapy [90, 91].

**4.3. Immunologic response to MWA**

162 Hepatocellular Carcinoma - Advances in Diagnosis and Treatment

breast to hepatic carcinomas [92–94].

is advantageous.

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 therapy creating an exciting time of investigation and discovery.
