Image guided ablation.

Ablation refers to the local application of optical, acoustic or electrical energy and cold as to induce irreversible cell injury, apoptosis and coagulative necrosis of tissues. By contrast to surgical excision, ablation is a minimally invasive treatment option, whereby the scarified tissue remains in situ and is being absorbed over several months and transformed to a scar. Clinical use of ablation encompasses the treatment of various tumors, including liver, lung, kidney, pancreatic, head and neck cancer and bone metastasis. Additionally, neurological disorders, particularly essential tremor and Parkinson’s disease, can be treated by ablation of brain tissue or neuronal structures. Relatively novel is the use electrical energy in a certain pattern that induces cell apoptosis without coagulation, referred to irreversible electroporation (IRE), see Rui Chen et al. in this issue of SMJ. In order to decide which kind of local cell destruction is useful and can be applied safely a thorough understanding of the underlying principles is essential. In addition, it is required to use an appropriate imaging technology to monitor and control the process of tissue destruction. The process of energy-induced cell/tissue destruction consists of two phases through direct and indirect mechanisms. The direct damage of cells occurs rapidly after exposure of the target tissue to high temperature, alteration of the cell membrane, dysfunction of mitochondrial and inhibition of DNA replication. Changes of cell membrane fluidity and permeability are considered as the major cause of cell injury, leading to dysfunction of actin filaments and microtubules and impairment of facilitated diffusion across the cell membrane. Mitochondria are affected by high temperature, increasing leakage of protons through the inner mitochondrial membrane and changing the ultrastructure in minutes. Besides the changes in cellular level, heatinduced denaturation of key replication enzymes DNA polymerase a and b, which is responsible for semiconservative DNA replication and DNA repair synthesis respectively, thereby inhibiting DNA replication. Denaturation of polymerase substrate chromatin, abnormal condensation of non-histone nuclear matrix proteins, disruption of RNA synthesis and the release of lysosomal enzymes are believed the mechanisms of heat-mediated reproductive cell death. The indirect mechanism occurs via several mechanisms, including induction of apoptosis, the release of cytokines and stimulation of immune response. Apoptosis is increased in the peripheral zone of the central ablated lesion, which undergoes coagulative necrosis. Expression of essential apoptotic protein p53 was upregulated and bcl-2 was downregulated in human liver cancer tissues after ablation treatment. Release of pro-inflammatory cytokines such as interleukin-1b (IL-1b), IL-6, IL-8, IL-18 and tumor necrosis factor-a (TNF-a) increase in several hours to days after ablation maximize the anti-tumor response. Heat shock proteins (HSPs) are a large family of stressinduced proteins and play a key role in cell survival and development. Recently, HSP70 attracts interest in research and is concerned as a biomarker and potential anti-tumor targets. Preclinical and clinical evidences indicate that the upregulation of HSP70 expression may stimulate anti-tumor immunity by inducing various immunological processes and regulation of multiple pathways including stress-activated kinases pathway JNK, extracellular signal-regulated kinases ERK and cell cycle inhibitor p21. Energy transmitted into target tumor lesion and induces local tumor destruction. According to the energy sources, the clinical techniques can be categorized as radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA), irreversible electroporation (IRE) and high-intensity focused ultrasound (HIFU/FUS). Each of the technologies shows strengths and weaknesses in the ablation of various tissues and organs. Radiofrequency ablation (RFA) is the most accepted modality for tumor ablation using an electromagnetic energy source with frequencies at 200–1200Hz