The primary goal of most ablation procedures is to eradicate all viable malignant cells within a designated target volume. Similar to the surgical approach of metastasectomy, tumor ablation therapies attempt to include at least a 0.5 to 1.0 cm ablative margin of seemingly normal tissue for the liver and the lung, though less may be needed for some tumors in the kidney. While complete tumor eradication is of primary importance, sparing normal surrounding tissues and accuracy of therapy are also important clinical considerations. As such, one significant advantage of percutaneous ablative therapies over conventional standard surgical resection is the potential to remove or destroy only a minimal amount of normal tissue. For example, in primary liver tumors, where functional hepatic reserve is a primary predictive factor in long-term patient survival outcomes, ablation therapies can minimize iatrogenic damage to surrounding cirrhotic parenchyma. This is also useful when nephron-sparing treatments are needed in patients with von Hippel-Lindau, who are prone to the development of multiple renal cell carcinomas, and in patients with primary lung malignancies in the setting of extensive underlying emphysema and limited lung function. Other clinical circumstances in which high specificity and accuracy of targeting have proven useful include providing symptomatic relief for patients with symptomatic osseous metastases or hormonally active neuroendocrine tumors, and in using percutaneous therapies to improve focal interstitial drug delivery. Percutaneous thermal therapies are limited, however, by the quality of imaging guidance, and in some cases, by complex anatomy and difficult access. Another important factor is that the amount of tumor destruction is determined by the pattern of temperature, energy, or chemical distribution within treated tissues. This means that for larger tumors (usually defined to be larger than 3 cm in diameter), a single ablation treatment may not be sufficient to entirely encompass the desired ablative margins. In these instances, multiple overlapping ablations or simultaneous use of multiple applicators may be required to successfully treat the entire tumor and ablative margin, though accurate targeting and applicator placement can often be technically challenging in this scenario.

Ethanol instillation has been used mainly for treating hepatocellular carcinoma in patients with cirrhosis. Ethanol destroys tissue by causing dehydration of the cytoplasm and protein denaturation. Furthermore, alcohol entering the local tumor circulation leads to necrosis of the vascular endothelium, subsequent vascular thrombosis, and ultimately ischemic tissue necrosis. The treatment of primary hepatocellular carcinoma with ethanol injection has been considerably more successful than the treatment of liver metastases because of tumor characteristics, including softer tissue composition compared to the heterogeneous and dense fibrous nature of metastases, and a capsule or pseudo-capsule surrounded by cirrhotic liver, which limits diffusion and increases concentration within the target (Fig. 1).

Intratumoral administration of chemically ablative substances such as ethanol and acetic acid is the ablation modality that has the longest experience and clinical follow-up, particularly in the treatment of hepatocellular carcinoma. Chemical ablation is an attractive option in many developing regions because it is inexpensive and simple. However, success of chemical ablation therapies in more solid adenocarcinomas has been limited by reported difficulty in achieving uniform diffusion of percutaneously injected drugs over larger tumor volumes, due to poor diffusion of chemical agents throughout the tumor. As a result, focal thermal ablation has replaced chemical ablation in many cases. Chemical ablation is now more typically used for tumors difficult to treat with thermal therapies (mostly due to tumor proximity to heat sensitive adjacent structures), and for small tumors such as locally recurrent thyroid cancer or benign lesions such as bronchogenic cysts, thyroglossal duct cysts, or endometriomas.

Thermal ablation strategies attempt to destroy tumor tissue by increasing or decreasing temperatures sufficiently to induce irreversible cellular injury. These strategies can be broadly divided into cryoablation or hyperthermic ablation, where heat may be generated by ultrasound or electromagnetic (RF, microwave, and laser) energy. Other techniques to generate heat or otherwise induce cellular necrosis have been reported; however, none have found widespread utility to date.

By far, the most well-studied and clinically relevant percutaneous ablation source to date has been RF energy. During RF ablation, electrical current from the generator oscillates between electrodes through ion channels present in most biological tissues. In this way, the RF ablation setup can be thought of as a simple electrical circuit, where the current loop comprises a generator, cabling, electrodes, and tissues as the resistive element. Tissues are imperfect conductors of electricity (i.e., they have electrical impedance), so current flow leads to frictional agitation at the ionic level and heat generation, known as the Joule effect. Heating occurs most rapidly in areas of high current density; tissues nearest to an electrode are heated most effectively while more peripheral areas receive heat by thermal conduction.

Ablative heating leads to tissue dehydration and water vaporization, which cause dramatic increases in circuit impedance. These rapid and often sudden increases in impedance can be used as a feedback signal in RF generators, which will be covered in more detail later. When these effects begin to inhibit current flow from a generator, alternative methods to decrease circuit impedance such as expanding the electrode surface area, pulsing the input power, and injections of saline can be used to augment RF current flow.

Irreversible cellular injury occurs when cells are heated to 46°C for 60 minutes, and occurs more rapidly as the temperature rises. Immediate cellular damage centers on protein coagulation of cytosolic and mitochondrial enzymes and nucleic acid–histone protein complexes. The exact temperature at which cell death occurs is multifactorial and tissue specific. Based upon prior studies demonstrating that tissue coagulation can be induced by focal tissue heating to ∼50°C for <5 minutes, this has become the standard surrogate endpoint for thermal ablation therapies (Fig. 2).