What is electrochemotherapy ?

Electrochemotherapy is a new technique for the treatment of skin tumors.

Electrochemotherapy is easy to use, fast, with excellent results that are scientifically proven. It combines intratumoral injections of a cytotoxic agent and the application of brief, high-intensity electric pulses.

Electrochemotherapy permits the selective increase in membrane permeability of tumor cells. It uses both chemical – a chemotherapeutic agent – and physical – electroporation – methods.

This causes a rapid and significant increase in the concentration of drugs, and therefore cytotoxicity, in the tumor cells.

Electric pulses on living cells

This physical process affects all cells within the vicinity of the electric pulses. However, the increased effectiveness of the cytotoxic drug up-take is restricted to tumor cells.

The electric pulses significantly increase the efficiency of cytotoxic drugs, while decreasing the side effects.

Electrochemotherapy also has a major impact at the tissue level, known as the vascular lock.

The application of electrical pulses to tissue causes a temporary cessation of blood flow in the electrified areas.

The mechanism is based in part on response-dependent histamine.

The duration of the interruption of blood flow in healthy tissues (one to two minutes in the muscle) is insufficient to produce a harmful hypoxia or other side effect (Gehl et al. 2002).

Within tumors, this vessel occlusion lasts several hours. Additionally, vascular endothelial cells divide to constantly produce new vessels in the tumor and are also sensitive to electrochemotherapy.

The subsequent vascular lock reduces blood flow in the tumor, which enhances the efficacy of electrochemotherapy (Sersa et al. 2008).

Proof of this effect of the vascular lock were observed on histological, physiological, and digital models.

The safety and efficacy of electrochemotherapy was recently demonstrated in nearby tumors that are irrigated by large blood vessels and in the treatment of liver metastases located near major hepatic vessels (Miklavčič, 2014).

Finally, an activation of the immune system occurs.

According to preliminary studies, this activation involves IL-2 and TLR.

Experiments were performed on immunodeficient mice in which tumors were implanted experimentally; the delay in tumor growth is twice as fast in immunodeficient mice compared to immunocompetent mice.

Furthermore, no immunodeficient mouse has recovered while 80% of immunocompetent mice were able to eliminate the tumor (Bretonneau, 2012).

Cytotoxic drug injections

An essential prerequisite for effective electrochemotherapy is the injection of the correct concentration of drug.

Application of electric pulses

The physiochemical principle explains why electrochemotherapy is effective for all types of tumors.

Every living cell is isolated from the external environment by a membrane whose permeability is changed by electric pulses.

Electrochemotherapy is effective on all tumor types, but its level of effectiveness seems to vary depending on the tumor type.

Several reasons can account for this: inherent variability in sensitivity of tumor cells to drugs; ineffective membrane permeability; drug distribution; or immunogenicity of tumor cells.

The electric field is not applied to kill the cells, but to create temporary permeabilization.

Genes expressed in the cells exposed to the electric field were analyzed using a DNA chip; electric pulses resulted in a stress response, characterized by the presence of the HSP70 protein (Miklavcic, 2004).

Healing of the tumor

After treatment, a first phase, characterized by inflammation (neutrophils, lymphocytes, plasma cells) takes place, and is followed by a necrosis in 80% of tumors.

Two weeks following treatment, there is a decrease in the number of apoptotic cells without inflammation.

The high level of tumor cell necrosis is generally a positive sign.

The necrosis remains localized since electrochemotherapy only affects the cycle cells (by mitotic death), not cells in a quiescence state, such as muscle and nerve cells.

Principle of electrochemotherapy

Anticancer drug surrounding the cell.

Electroporation exposes a cell to a high-intensity electric field that temporarily destabilizes the membrane. During this time the membrane is permeable to the anticancer drug surrounding the cell.

When the field is turned off, the pores in the membrane reseal, enclosing drugs inside.

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electrochemotherapy in your clinic ?