Irreversible electroporation and the nanoknife

Cancer is an ever-present danger to our health, affecting thousands of people in the UK, and capable of appearing in almost any part of the body. New treatments are always being researched and developed to combat cancer. Could electrical pulses provide an answer to those cancers that are difficult to treat with surgery or chemotherapy? We asked expert surgeon Mr Nicola de’ Liguori Carino.

What is irreversible electroporation?

Irreversible electroporation, also known as IRE, is a non-thermal ablative technique used to destroy cancer cells. It is a relatively new technique that has been used in medicine for over a decade, and its use is not widespread, as research is still being done into its efficacy. It is potentially a way to stop the growth or even reduce the size of stage III pancreatic cancer and prevent it from spreading (metastasis).

What types of cancer is it currently used for?

Although irreversible electroporation has been used in medicine for over a decade, interest in this technique has increased in recent years.

Today, the cancer most commonly treated with irreversible electroporation is stage III pancreatic cancer. Its safety in this setting was reported in the scientific literature between 2009 and 2018.

Irreversible electroporation can also be used in some cases for liver cancers (colorectal liver metastases, hepatocellular carcinoma (HCC), and neuroendocrine tumours) that cannot be treated with surgical resection (liver resection).

Some urological cancers including prostate cancer and renal cell cancer may also benefit from treatment with irreversible electroporation.

Learn more about how to spot the signs of pancreatic cancer

How does irreversible electroporation work?

IRE is based on pulses of electrical energy delivered between two electrodes. These electric pulses affect the membranes (outer surface) of the cancerous cells, changing the existing cellular membrane potential. This results in nanoscale (tiny) defects in the lipid bilayer of the membrane, which disrupts the stability of the cells and leads to a phenomenon known as apoptosis – cell death controlled by the body itself.

The extent of cell damage and death depends on the amplitude, duration, frequency and number of pulses applied. Because IRE causes cell death through apoptosis, structures formed by proteins, such as vascular elastin and collagenous structures, are not affected, and therefore surrounding blood vessels are preserved. This allows for the ablation of malignancies (cancers) that are surrounded by these structures, which is typically the case for locally advanced pancreatic cancer.

Unlike thermal-induced methods, such as microwave and radiofrequency ablation, which result in fibrosis and scarring, the apoptotic cells are phagocytosed (destroyed) by cells of the immune system and replaced by innate cellular degeneration.

The procedure

Irreversible electroporation is most commonly performed using the AngioDynamics NanoKnife™ system. This has been commercially available since 2009, and is approved by the Food and Drug Administration. The Nanoknife system consists of a computer-controlled pulse generator that delivers 90 (3000 V) direct current (25-45 A) electrical pulses to the IRE probes. The pulses last for 20-100 microseconds each. Pulses are usually given in a train of 6-20 bursts, with 10-20 pulses in each burst and a pause of a few seconds between bursts.

IRE can be delivered percutaneously or with open surgery, both requiring general anaesthesia.

In the percutaneous technique, 2-6 IRE needles are inserted through the skin and the muscles of the abdominal wall, deep into the pancreatic tumour. The procedure is performed in the radiology department, where the placement of the needles is guided by CT scan images.

The open technique is performed in the operating theatre. An incision (known as laparotomy) is made in the abdominal wall to expose the pancreas. The needles are placed by direct view and with the help of the ultrasound scan into the pancreas.

The open technique is most commonly used because it is probably safer than the percutaneous approach, and allows for more accurate needle placement. Moreover, the open surgical technique allows for a precise assessment on the degree of infiltration into blood vessels, which might mean that a tumour that was diagnosed as inoperable based on scans (CT and MRI scans) is in fact potentially resectable.

Despite being more invasive, the experience reported in clinical studies suggests that the open technique does not add significant perioperative complications when compared to the percutaneous technique.

To find out more or to book an appointment, visit Mr Nicola de’ Liguori Carino’s profile.