Irreversible electroporation and the nanoknife

Written by: Mr Nicola de´ Liguori-Carino
Published: | Updated: 13/05/2019
Edited by: Cal Murphy

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.

Spotting 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.


Are there any serious side-effects of IRE?

Whether delivered percutaneously or with open surgery, IRE can potentially cause a number of side-effects of different severity. Some of the most serious are:

  • Blood clots in big vessels close to the pancreas
  • Internal organ perforations
  • Bleeding
  • Internal infections
  • Cardiac arrhythmia

Although very low, there is also a risk of mortality.


Could this treatment be used in other types of cancer in the future?

IRE can possibly be used in other cancers. For liver cancers like HCC and colorectal metastases, it can be used instead of radiofrequency ablation (RFA) and microwave ablation (MWA) when the tumour cannot be surgically resected and is very close to major blood vessels. Some research is also ongoing to see if it can be safe and useful in unresectable hilar cholangiocarcinomas (bile duct cancer). It is also used for certain kidney and prostate cancers.

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

By Mr Nicola de´ Liguori-Carino

Mr Nicola de’ Liguori-Carino is highly experienced consultant general surgeon with a special interest in conditions affecting the liver, gallbladder, biliary system and pancreas. He has an extensive experience with groins and abdominal wall hernias. He is available to see patients at short notice and his private practice is embedded in an efficient, multidisciplinary team which can provide comprehensive treatment to patients in a quick and timely manner.

Mr de’ Liguori-Carino completed his surgical training in Italy then spent a period of time studying under some of the USA’s leading surgeons at the Ohio University Hospital, Columbus. Following this, he moved to the UK to complete higher subspeciality training in hepatobiliary and pancreatic (HPB) surgery at the University of Liverpool and Leeds. In 2009 Mr de’ Liguori-Carino was appointed Consultant at HPB, Laparoscopic and General Surgeon at Manchester.

Mr de’ Ligouri-Carino’s unit at Manchester Royal Infirmary is one of the largest HPB units in Europe. It covers a local population of 3.5 million and regularly handles referrals from the rest of the UK and abroad. Mr de' Liguori-Carino’s work at the hospital is internationally recognised for innovation and excellent results, and he is actively involved in a number of clinical trials focussed on new treatments for liver and pancreatic cancer.

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