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Electroporation – IRE

The NanoKnife™ process

The NanoKnife Soft Tissue Ablation procedure uses IRE (Irreversible Electroporation) to destroy cancer cells. The surrounding tissue is not injured in the process. For the first time, prostate cancer can be treated with this method in such a way that continence is preserved and there is only a low risk of impotence. In addition, the NanoKnife procedure has a very low probability of pain or scarring.

Here at VITUS, we are proud of the pioneering work we have done with the NanoKnife process. We are among the world’s leading experts in the use of IRE in the treatment of prostate cancer.

Through our close collaboration with the inventor of IRE for medical purposes, Prof. Boris Rubinsky of the University of Berkeley in the USA, we have had the opportunity to study and understand IRE at all stages of development, from laboratory to animal studies to human application. Our physicists and physicians are thus among the pioneers and the world’s leading experts in electroporation processes – both in the scientific and technical field and as well as in the clinical use.

Irreversible electroporation (IRE) treatment can avoid side effects such as impotence and incontinence with comparable efficacy

While modern, gentle treatments have long been established in other areas of medicine, in urology it is still a long time coming. In the case of breast cancer, the entire breast is not longer amputated for a long time, but the tumor is removed focally. In the case of renal cell carcinoma, the healthy part of the kidney is preserved instead of removing the entire kidney (if possible). The prostate is still removed “radically”, i.e. completely, unnecessarily in most cases.

This has changed since the successful introduction of Irreversible Electroporation (IRE) for the treatment of prostate cancer. With IRE, prostate cancer can be focally destroyed, with a lower likelihood of side effects.

The wide range of IRE treatments :

From focal therapy of small carcinomas to a problem solver for unresectable T4 carcinomas.

RE – also known by the product name NanoKnife – enables the gentle treatment of prostate cancer while avoiding impotence and incontinence.

IRE can be used to treat the full range of prostate cancers – from small focal carcinomas to T4 tumors that have already infiltrated the bladder or rectum – inoperable, usually advanced cases.


* Urinary incontinence, as it is called, is the lack or inability of the body to safely store and self-directly empty the contents of the bladder. This leads to involuntary loss of urine. While there are several possible definitions of incontinence, a long-term study of incontinence after prostatectomy** concludes that a reasonable definition of incontinence is when a patient requires 2 or more pads per day 12 months after prostate surgery.

** Sacco E, Prayer-Galetti T, Pinto F, et al. Urinary incontinence after radical prostatectomy: incidence by definition, risk factors, and temporal trend in a large series with a long-term follow-up. BJU Int. 2006;97:1234-41.

*** Syan, Raveen, and Victor W. Nitti. “Post-prostatectomy Incontinence Initial Evaluation.” Urinary Dysfunction in Prostate Cancer. Springer, Cham, 2016. 15-30.

NanoKnife technology

ideal for the treatment of prostate cancer

The NanoKnife process is based on ultra-short pulses that generate strong electric fields. The pulses are 100 microseconds long – i.e. 0.0001 seconds. Compared to standard procedures, this new technology has unique features that make it ideal for treating the prostate.

Precision crucial for therapeutic success with NanoKnife

Since 2007, the IRE technique has been approved by the FDA in the USA and CE marking in Europe. This was done because corresponding studies prove that all cells within the treatment area can be killed with this method. In order to achieve this and carry out a successful IRE treatment, two factors are crucial:

The first condition is met by multiparametric MRI examination, 3D biopsy or, if necessary, other procedures. The second condition is fulfilled by a minimally invasive procedure under general anesthesia. Sterile needles with variable exposure lengths are inserted. “Exposure length” refers to the area of the needle that exposes the tissue to electrical current. We have experience with this procedure since 2011 and have performed the most prostate treatments worldwide. This makes us one of the leading experts worldwide, while other clinics are just getting started.

Clinical application of IRE in prostate cancer.

Correct Technique decisive for good or bad results

As with many other medical treatments, the technical details of IRE treatment determine its success, i.e., the reliability with which the tumor is destroyed and the side effects triggered by the treatment.

Unfortunately, no technical standards have been established for IRE treatment of the prostate. That is, each physician performs IRE treatments at his or her discretion using his or her technique. Most urologists, therefore use a grid, also known as a brachytherapy grid, for the placement of the electrodes, which they know from brachytherapy and which is used there for the insertion of the radioactive seeds.

Placement of IRE electrodes with a brachytherapy grid is too imprecise for good treatment results

And that’s where the problems begin. This is because the use of a grid significantly reduces the accuracy with which the IRE electrodes can be placed. This is illustrated below.

Figure 7 shows the problem with using a brachytherapy grid to place the electrodes.

Since the electrodes are made of thin metal rods about 1 mm thick, they are flexible. Leg insertion into the prostate via a hole in the grid, they are more or less bent by the tissue layers of the pelvic floor and deflected from the intended path. With a penetration depth of 6 cm (typical position of the prostate), a bending of only 2 degrees is sufficient for the electrode tip to miss the desired position by 2 mm.

If electrodes are inserted through two adjacent grid holes 5 mm apart, the tips of the electrodes can be positioned in the prostate at a distance of 1 to 9 mm. The probability that they achieve a distance of 5 mm is low and would be pure coincidence. With a typical spacing of the electrodes of 15 to 20 mm and a typical size of the prostate of 30 – 40 mm transverse diameter, an inaccuracy of 5 ± 4 mm is completely unacceptable. Insertion of the electrodes via a standard brachytherapy grid is therefore unsuitable.

Figure. 6: – IRE generator from Angiodynamics (left) with which the most IRE treatments of the prostate have been performed worldwide. The generator is connected to the electrodes, which here are inserted through the pelvic floor into the prostate via a brachytherapy grid (a plastic perforated plate) (image above). According to the information provided by the manufacturer Angiodynamics, the electrodes (in green, 1 – 4) should be placed so that they surround the tumor (magenta).
Figure. 7: Estimated inaccuracy of electrode insertion using a brachytherapy grid.
Figure. 8: Even tests with a grid specially made for VITUS with 2.5 mm hole spacing did not provide the desired accuracy.

The VITUS method

Highest accuracy due to manual insertion of the electrodes into the prostate gland

Not only because of the inaccuracy in the X-Y plane of the brachytherapy grid (described in Figures 6, 7 and 8), at the VITUS Prostate Center, we have developed the manual insertion of the electrodes (Fig. 9) perfected. This method allows the placement of electrodes with 1 -2 mm precision.

The figures in this section illustrate the advantages of manual electrode placement using the VITUS method.

Figure 9A shows a cross-section through a prostate with a fictitious prostate carcinoma (in magenta) in the right (radiological orientation, left on the image) outer zone. Also shown are the various portions of the neurovascular bundle (NVB), in and on the prostatic capsule as well as extrafascial. More externally located, anatomically poorly defined portions of the NVB are not shown.

Figure 9B shows the superimposition of a standard brachytherapy grid with 5 mm hole spacing over the prostate. According to the technique recommended by the manufacturer Angiodynamics, the electrodes (green dots) should be placed so that the tumor is surrounded by electrodes. The localization of the electrodes results from the nearest grid points, respectively holes in the grid. The figure shows the IRE ablation fields resulting from an application using Grid.

Two facts stand out:

This leads to unnecessary damage in the right NVB. This is because the electrodes become hot during pulse emission, so they can cause thermal damage if they are in close proximity to sensitive structures. Although these only affect an area of about 1 – 2 mm around each electrode, this is sufficient to damage the right NVB as the electrodes are in direct contact with it. In addition, electrolysis products such as H+ and OH- with an acidic and basic environment are formed around the electrodes during the electrical pulses, which also cause damage to nerves and vessels.

Figure 9 A: Cross-section through a prostate with a fictitious prostatic carcinoma (in magenta).
Figure 9 B: Overlay of a standard brachytherapy grid with 5 mm hole spacing over the prostate.
Figure 9 C: IRE ablation fields resulting from pairs of electrodes inserted manually.

Advantages of manual
Electrode placement
in der x-y-Ebene mit der
VITUS Methode

Figure 9C shows the advantages of manual placement of IRE electrodes using the VITUS method. With no predetermined grid points, the electrodes can all be placed within the prostate capsule. Direct damage to the neurovascular bundle (NVB) from heat or electrolysis products emitted from the electrodes is thus avoided.

By placing the electrodes freely, an IRE ablation field can be generated that optimally follows the contour of the prostate so that the tumor (magenta) is safely destroyed, but the NVB is spared.

Advantages of manual electrode placement in the z-plane
(longitudinal direction)
mit der VITUS Methode

However, electrode placement with the VITUS method brings advantages not only in the x-y plane, but also in the z-direction, the longitudinal axis of the prostate. This is illustrated in Figure 10.

When placing the electrodes through a brachytherapy grid, all electrodes are aligned parallel in the z-direction, except for minor deviations.

However, because the shape of the prostate resembles a pyramid standing on its apex (apex caudal/bottom, base cranial/top), parallel insertion of the electrodes with equal length of the conductive electrode portion results in the caudal/bottom portions of the electrically conductive electrode lying outside the capsule, directly in the NVB, damaging it by heat and electrolysis products (Figure 10 left, red area).

This can be prevented with the VITUS method by inserting the electrodes at an angle, following the prostate capsule. This is only possible manually, i.e. without a grid. By adjusting the “exposure length”, i.e. the electrically conductive electrode portion, it can be achieved that the NBI is protected from heat and electrolysis products (Figure 11). Simulations of the electric field performed by VITUS physicists show that the IRE ablation field in the VITUS method conforms to the prostate capsule even in the third spatial direction (z-direction), thus providing optimal results.

Fig.10 : Forced parallel insertion of needles through brachytherapy grid may result in unnecessary damage to sensitive tissue (red area).
Figure. 11: Manual adjustment of needle positions leads to maximum protection of healthy surrounding tissue while maintaining the effectiveness of the therapy.