br Local ablative therapies This broad category

Local ablative therapies
This broad category includes those modalities that employ different forms of energy, delivered “in situ”, with the common goal of targeted tissue destruction. Chemical, thermal and electrical energy sources have been vigorously used, researched, developed, improved and clinically deployed in the last several years. Chemical ablation is the oldest percutaneous technique that has been broadly performed using agents such as ethanol or acetic niclosamide (percutaneous ethanol injection, PEI), which destroys tumor cells within the targeted tissue by induction of coagulative necrosis. However, such chemical substances, when injected percutaneously through thin needles, can diffuse into nearby tissues, which may increase the risk of drug diffusion into the arterial system and cause harmful complications. Neverthless, this technique has had low procedural complication rate and very promising results in terms of local control for treating capsulated HCC nodules that are less than 5cm. 5-year overall survical (OS) is at 47% and 29% respectively, for Child A and B cirrhotic patients. In the treatment of single infiltrating or multiple encapsulated tumors, the injection of chemical substances has shown least efficacy, mainly due to the absence of a peripheral capsule which can retain the chemical agents within tumor tissues [4]. The same issue could probably account for the unsatisfactory results when this technique is employed for treating liver metastases.
Chemical ablation has been replaced by newer technologies, based on induction of temperature variations: both increase and decrease, until the desired cytotoxic level is achieved within the targeted tissues. When heat is applied and maintained for sufficient time, over a target temperature, tissue ablation is achieved. Usually, a temperature less than −40°C or higher than 60°C, the onset of cell destruction is almost instantaneously via the induction of proteins denaturation or plasma membrane collapse due to ice crystal formation. Complete necrosis can be induced in almost all tissue types at such extreme temperatures. When reaching a temperature near to 50°C, cell death related to microvascular thrombosis, ischemia, and hypoxia may occur [5]. At temperatures slightly more than −40°C cells cool off slower and are susceptible to cell death from osmotic shock. Ice formation outside the cells, induces a hyperosmotic extracellular space with cell dehydration and, upon thawing, a reversal flux inward the cell, inducing cell swelling and membrane rupture [6].

Radiofrequency ablation
Radiofrequency energy represents the most well studied technology and the main reference for the evaluation of other more recently developed ablative techniques. When RF energy is applied, an oscillating electrical current flows through the body between electrodes in a simple circuit in which tissues, being weak electrical conductors, represent the resistive element. Thus, ionic agitation is induced in tissues around interstitial electrode and resistive heating is produced in the areas closest to the interstitial probe. As a result, tissues in proximity to the electrode are subjected to the highest current and thus a greater rise in temperature than tissues further away from the probe that are heated mostly via thermal conduction [7]. Radiofrequency ablation has emerged as the standard technique for local tumor treatment and has demonstrated better survival than PEI. Cho et al. in a recent meta-analysis of RCTs on small HCC treatment reported better local control and significant improvement in 3-year survival with RFA when compared to PEI (odds ratio 0.477, 95% confidence interval 0.340–0.670; P<0.001) [8]. The main limitations of RFA are the dimension of lesions to be treated, the “heat sink effect” produced by main vessels close to the tumor and the possibility of high major complication rate when used for sub-capsular lesions and when bile duct is in the proximity. Livraghi et al. [9] reported the safety of RFA in liver malignancies in a multicenter study involving 3500 patients: low mortality (0.3%) and low morbidity rate with major and minor complications were observed in 2.2% and less than 5% of patients, respectively. This large cohort study has established percutaneous RFA as a safe and relatively low-risk procedure.