Irreversible Electroporation - Nanoknife Surgery

Some tumors wrap around the vessels and ducts that keep a patient alive. Heat would destroy both. Irreversible electroporation kills the tumor and spares the pipes. Electricity does it. Nothing is cut.

Irreversible electroporation, or IRE, marketed as NanoKnife, destroys a tumor with short, high-voltage electrical pulses delivered between thin needle electrodes placed around it. The pulses open permanent holes in the membranes of the cells, which die over the following days, while the collagen framework of blood vessels, bile ducts and nerves survives. Despite the name, no cutting takes place. In a registry of 200 patients with locally advanced pancreatic cancer treated after chemotherapy, median survival was 24.9 months and local recurrence occurred in 3 percent (Martin and colleagues, Annals of Surgery, 2015). A prospective phase II trial of the percutaneous technique reached a median of 17 months from diagnosis (Ruarus and colleagues, Radiology, 2020). This page explains what IRE is and how it differs from heat ablation, which tumors it treats, what the studies show and what they do not, the procedure itself, the risks, the follow-up, and how patients from abroad arrange it at Biruni Hospital in Istanbul.

What IRE is

Every ablation method on the market before this one killed tumors with temperature. Radiofrequency and microwave probes heat tissue past 60 degrees. Cryoablation freezes it past minus 40. Both work, and both have the same limit, which is that heat and cold do not know the difference between a tumor and the artery running through it. A tumor pressed against the portal vein, the bile duct, the ureter or the nerves of the pelvis could not be ablated without risking the structure beside it, and a tumor surrounding those structures could not be ablated at all.

What it needs

Four things.

General anesthesia with complete muscle relaxation, because each pulse contracts every muscle in its path. Every pulse timed to the heartbeat, since one delivered at the wrong moment of the cardiac cycle can trigger an arrhythmia. Electrodes parallel to one another and within millimeters of the plan. And a team that has done it before, since the learning curve is steep and the organs involved forgive little.

Which tumors it treats

The ones heat cannot reach safely. That is the whole indication.

By organ

1. Pancreas. Locally advanced cancer that has grown around the celiac or superior mesenteric arteries and cannot be removed, in a patient who has responded to or at least not progressed on several months of chemotherapy. The largest use and the one with the most data. Also used during surgery to treat the margin where the tumor cannot be fully separated from a vessel.
2. Liver. Tumors, primary or metastatic, within a centimeter of the main bile ducts or the major veins, where a heat probe would cause a stricture or a thrombosis. IRE treats them and leaves the ducts open.
3. Prostate. Focal treatment of a cancer confined to one part of the gland, and salvage treatment of cancer that has returned after radiation, where surgery and further radiation carry high rates of incontinence and rectal injury.
4. Kidney. Tumors at the hilum, where the vessels and the collecting system enter, that partial nephrectomy and heat ablation would both endanger.
5. Other. Selected tumors of the pelvis near nerves, tumors of the adrenal near the vena cava, and lung tumors near the hilum, in specialist centers and small numbers.

What the studies show

No randomized trial has compared IRE with anything. What exists is one large registry, one prospective phase II trial and several single-center series, and a patient should read the numbers with that in mind.

1. PANFIRE-2, the prospective trial. Fifty patients, 40 with locally advanced and 10 with recurrent pancreatic cancer, treated by CT-guided percutaneous IRE at Amsterdam. Median survival was 17 months from diagnosis and 10 months from the procedure. Local recurrence developed in 46 percent. Major complications occurred in 21 patients, and one death was probably related to the procedure. The trial met its survival target and the authors noted that a tumor volume over 37 milliliters and a very high CA 19-9 level predicted worse outcomes (Ruarus and colleagues, 2020).
2. Salvage prostate IRE. Seventy-four men whose prostate cancer had returned after radiation were treated with focal IRE in Sydney. At a median of four years, 77 percent had needed no further treatment, 91 percent were free of metastases, one rectal fistula had occurred, and 93 percent of those who answered questionnaires remained continent (Geboers and colleagues, BJU International, 2023).
3. The gap between them. The registry included patients selected by surgeons and treated in the operating room. The trial treated sicker patients through the skin. The difference in survival, 24.9 against 17 months, reflects selection as much as technique, and the honest range for a patient with locally advanced pancreatic cancer who responds to chemotherapy and then has IRE is somewhere between the two.

Reading the numbers as a patient

Three conditions. No spread beyond the pancreas on a scan taken within the last month. At least three to four months of chemotherapy completed, with the tumor no larger than before it started. And a tumor smaller than about four centimeters, since larger volumes were the strongest predictor of failure in the trial. Meeting all three gives a reasonable expectation of local control and of a survival measured in a year or two rather than months. Meeting none of them means chemotherapy should continue instead, and the file review will say so plainly.

The procedure

Ninety minutes to three hours. General anesthesia. Two to six nights.

The electrodes are placed one at a time under CT, each checked against the plan, and the generator delivers its pulses between every pair in turn while the anesthesiologist watches the heart rhythm on the monitor and the muscle relaxant keeps the patient still. The whole delivery takes minutes. The placement takes most of the time.

Risks

Higher than for heat ablation of a simple tumor. The tumors IRE treats sit against the most dangerous structures in the abdomen.

What lowers the risk

A team that does the procedure regularly. Tumors under four centimeters. Recovery from chemotherapy, with a good blood count and no infection. A plastic rather than a metal stent. And restraint. The commonest serious harm from IRE in the published series came from treating patients who should not have been treated, whose disease had already spread or whose tumors were too large, and the file review exists to prevent that.

After the procedure

Two things happen in the first weeks. Pain eases. The scan looks worse before it looks better.

Local recurrence developed in 23 of 50 participants, 46 percent, after percutaneous IRE (Ruarus and colleagues, 2020). Local recurrence occurred in 3 percent in the surgical registry (Martin and colleagues, 2015). Both numbers are true, for different patients treated by different routes, and a patient should ask which group resembles his own case.

Repeat treatment

Recurrence at the edge of the treated zone can be treated again, by IRE or by radiation, if the disease elsewhere remains controlled. Spread in the meantime sends the patient back to drug treatment, and the IRE has bought the months in between.

Coming from abroad

IRE is a treatment patients travel for because few centers offer it and fewer offer it with the surgical and interventional experience the pancreas demands. The length of stay is ten to fourteen days, which covers the tumor board, the scan, the cardiac assessment, the procedure, three to six nights in hospital and a week of recovery near the hospital before the flight, since the risk of a delayed pancreatic leak makes an early departure unwise. Patients are fit to fly when the surgeon or the interventional radiologist confirms that the drain, if one was placed, is out and the blood tests are stable, in the second week for most. What the team needs before travel is the CT or MRI as image files, the pathology, the chemotherapy record with dates and response, the most recent CA 19-9, the list of medicines, an ECG and a note of any heart condition or implanted device. The tumor board reviews the file without charge and replies with whether IRE is appropriate, by which route, or whether continued chemotherapy, radiation or surgery would serve the patient better.

One coordinator from the international patients office handles arrangements from the first message through discharge and answers the same WhatsApp number once you are back home. The office works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and books interpreters for other languages, and it arranges the visa invitation letter, airport transfers, daily transport and accommodation near the hospital for the patient and a companion for the full stay. Halal, vegetarian and diabetic meals, a prayer room on site, and a female physician on request wherever the rota allows. The follow-up scans are reviewed by the same team wherever they are taken, and the oncologist at home receives the procedure report and the plan for restarting chemotherapy before the patient lands.

Cost

One figure, after the file review.

It depends on the route, percutaneous or surgical, the number of electrodes, the anesthesia, the monitored bed and the hospital stay. Hospitals in this market quote IRE as a package for the procedure with the single-use electrodes, which are a large part of the cost, included, and the pre-procedure scans, chemotherapy and any longer stay for complications priced separately.

Confirm what the figure includes. Confirm, too, what a longer stay would add, since the stay after IRE varies more than after any other ablation, from three nights for an uncomplicated percutaneous case to two weeks or more for a patient who develops a pancreatic leak and needs a drain, antibiotics and time.