Nanoknife ablation in pancreatic cancer.

Nanoknife is the trade name of a new ablation method called irreversible electroporation (IRE). In this method, short-duration but very high electrical current is given to the tissue to open holes in the cell wall. These openings disrupt the internal structure of the cell and lead to a non-aggressive tissue death called "apoptosis".

The idea of opening holes in the cell wall with electric current is not new; it was already applied in the 1980s, to get large molecules such as certain antibiotics and chemotherapeutic agents into the cell (reversible electroporation). In this method, electroporation is temporary and when the electrical current is interrupted, the cell wall returns to normal and the cells maintain their vitality. Irreversible electroporation (nanoknife) has been used for ablation purposes in the 2000s. In this method, the cell wall permeability is increased irreversibly by using a very high and short pulsed electrical current (average 3000 volts), and consequently the cell loses its viability. The needles used in the Nanoknife are called electrodes and an average of 3-4 electrodes should be placed around the tumor during the procedure. There should be 1-2 cm distance between these electrodes, which should be parallel to each other and should not pass through critical structures such as intestines, vessels and nerves. Once the needles have been properly placed, each pair of these needles is sequentially given a high (3000 volt, 50 amperes) electric current in order. As a result, a cubic-shaped ablation area is obtained. During the procedure, the Nanoknife device is connected to an ECG device to ensure that the electric current is given only in a certain part of the heart contraction, thereby preventing high electrical current from damaging the heart. Nevertheless, the support of an experienced anesthesia team is very important as blood pressure and arrhythmia may develop during the procedure.

Nanoknife ablation has some significant differences from heat-based (thermal) ablation methods such as radiofrequency, microwave, laser and cryoablation: 1. Thermal ablation may not kill tumors adjacent to large vessels. Because, the blood flowing through the vessel may prevent the areas adjacent to the vessel wall from reaching enough heat or coldness. Because of this effect which is called "heat sink", live tumor cells may remain in the adjacent parts of the vessels, leading to local recurrences. In Nanoknife ablation, there is no such effect as no temperature or coldness is used for ablation. The tumor tissue adjacent to the large vessels can be completely killed. 2. Thermal ablation methods and chemical ablation methods (alcohol ablation, etc.) make an aggressive ablation called necrosis in tumor tissue. In the area of necrosis, structures such as blood vessels, nerves, bile and urinary canals are often damaged besides the tumor tissue . Nanoknife causes a less aggressive tissue death which is called apoptosis, and structures such as vessels, nerves, bile ducts and urine channels containing connective tissue (collagen) are less damaged. Therefore, Nanoknife ablation may be a safer method in tumors close to the critical structures such as vessels, nerves, bile and urine channels.

However, besides these advantages, Nanoknife has also important limitations; the procedure should be performed under general anesthesia since there are muscle contractions and blood pressure increases during the ablation. Nanoknife ablation also lasts longer and costs more than other ablations. Nanoknife ablation is now mostly used in pancreatic and prostate cancer. When the tumor is diagnosed in pancreatic cancer, 85% of the tumors are not suitable for surgery. Nanoknife has been shown to kill tumor cells around the vessels, stomach and bowels without damaging these structures. However, in order to make Nanoknife ablation safe in pancreatic cancer, 3-4 needles should be placed parallel to each other without passing through the vessels and intestines. For this, it is very important that the imaging methods are used at maximum and the practicing physician is very experienced in image-guided pancreatic interventions. It has been shown in several studies that nanoknife ablation may prolong survival and the quality of life when performed ideally.

It has also been shown in some studies that nanoknife ablation does not cause permanent damage to bile ducts. Therefore, in patients with tumors near or adjacent to bile ducts, Nanoknife ablation may be a good option. In a few series in the literature, successful results have been reported in some tumors such as colon cancer metastases and cholangiocarcinoma adjacent to the main bile duct.

Nanoknife has also the potential to be a good ablation method in the prostate. Although some ablation methods such as cryoablation and laser have been successfully applied in prostate cancer, impotence and urinary problems may develop in the patient since the nerves that cause urinary retention and penile erection may be damaged. In Nanoknife ablation, nerve damage may also occur, but it is reported to be temporary at least in animal studies. Therefore, Nanoknife ablation may be good option in prostate cancer patients who wish to preserve their urinary and sexual functions.