Currently, pancreatic cancer has become the 4th leading cause of death among cancer patients. Since pancreatic cancer grows rapidly and wraps around surrounding blood vessels, pancreatic ducts and nerve tissues, about 80% of patients are unable to receive surgical treatment at the time of detection, and symptoms such as abdominal pain, biliary system obstruction and gastrointestinal emptying disorder are already obvious. The treatment of pancreatic cancer is still a worldwide challenge. Nanoblade ablation has made a breakthrough in the treatment of pancreatic cancer, creating an effective and safe treatment opportunity for most of the pancreatic cancer patients who have lost the chance of surgery, especially for locally advanced pancreatic carcinoma (LAPC) patients.

Clinical Application and Principled Parameter Setting of Nanoknife for Pancreatic Cancer was published on Chin J Interv Imaging Ther,Vol 14,No 4

【Citation of literature】 WEI Yingtian, XIAO Yueyong, ZHANG Xiao, ZHANG Xiaobo, HE Xiaofeng,ZHANG Xin,LI Jie, YANG Jie.Chin J Interv Imaging Ther,Vol 14,No 4

WEI Yingtian, XIAO Yueyong, ZHANG Xiao, ZHANG Xiaobo

HE Xiaofeng,ZHANG Xin,LI Jie, YANG Jie

[Department of Radiology,Chinese PLA General Hospital]

Abstract

Nanoknife(irreversible electroporation)has demonstrated to be a safe and effective approach to tumor ablation，and plays a prominent r01e in application of treatment of pancreatic carcinoma， specifically locally advanced pancreatic carcinoma(LAPC)． The complicated parameters of Nanoknife comparatively is still difficult.The advantage，optimal selection，adequate parameters regarding Nanoknife were reviewed in this article．

1、Nanoknife ablation principle and advantages

Nanoknife ablation, also known as irreversible electroporation (IRE), is a new type of tumor ablation treatment based on microsecond high voltage electrical pulse release causing irreversible perforation of tumor cell membranes, thus causing apoptosis. Since there is no temperature change in the ablation area during the ablation process, it is also called  normothermic ablation compared to cold or thermal ablation commonly used in clinical practice. At present, there are three basic clinical ablation methods: ablation under direct vision in open surgery, percutaneous percutaneous ablation under imaging guidance (CT, ultrasound) and lumpectomy-assisted ablation.

For pancreatic cancer, especially tumors located in the head of the pancreas, because they are adjacent to important structures such as superior mesenteric artery, duodenum, common bile duct and abdominal cavity trunk, and rich in nerve tissue, the tumors are prone to invade these tissues during the growth process, causing obstruction and pain in the pancreas, bile duct and duodenum. In the past, tumor ablation, such as radiofrequency, microwave, cryopreservation and radioactive particle implantation, can cause damage to the above tissues during the process of puncture and ablation, so it is easy to cause complications such as bleeding and pancreatic fluid leakage, and the tumor recurrence rate is high. The efficacy of radiotherapy or radiotherapy combined with surgical resection for pancreatic cancer is also unsatisfactory, with a 5-year survival rate of less than 5%.

The advantage of nano-knife ablation lies in its high-voltage electric pulse method, which only perforates the lipid bilayer of the cell membrane in the ablation area and does not cause serious extracellular matrix damage. The blood vessels, bile ducts and nerve tissues will not be irreversibly damaged because they are rich in collagen tissue and elastic fibers, and there is no heat sink effect, so the important structures are preserved and the occurrence of bleeding and pancreatic and biliary leakage is reduced.

2、Pancreatic tumor Nanoknife ablation parameters setting

The effects of electric pulse release on the cell membrane are reversible and irreversible, depending on the ablation voltage, and when the electric field strength is 50-1000 V/cm, it produces reversible perforation of the cell membrane, which usually closes after 180 min. When the electric field strength is 1000-3000 V/cm, it can produce irreversible damage to the cell membrane and cause apoptosis. Due to the different electrical conductivity of different tissue structures, the voltage required for ablation is also different, and too high a voltage can cause tissue damage. Changes in cell permeability can increase the electrical conductivity of the tissue. In animal experiments, Garcia et al. found that prolonged ablation time can also cause thermal damage to tissues, because thermal damage can occur at temperatures below the normal tissue denaturation when the ablation time is too long.

The current clinical studies at home and abroad for pancreatic tumor ablation use a needle tip exposure length of 1.5 cm, a voltage of 1200-1800 V/cm, a wavelength of 70-100 μs, and a pulse number of 90; there are no standard treatment parameters for pancreatic tumor ablation, and the operator can adjust them according to the patient's own condition and the size and location of the tumor.

Avoidance of local heat generation due to high current Although the nanoknife is a non-thermal ablation method, due to the influence of local current and the conductivity of the tissue itself, there is an actual temperature change in the ablation area during the pulse release process, which is mainly related to the ablation parameter settings. The heat generation in the ablation area of nanoknife is mainly related to the pulse release time and the length of needle tip exposure, etc. Dunki-Jacobs et al. tested the temperature variation of nanoknife ablation of pig liver at 1.5 cm, 2.0 cm and 3.0 cm of needle tip exposure, and found that the temperature of the ablation area was highest at 3.0 cm of needle tip exposure length, but the difference was not The difference was not statistically significant when compared with other tip exposure lengths. Therefore, the length of the exposed end of the needle tip of nanosaber ablation was not positively correlated with the increase in temperature in the ablation zone, and further studies are needed.

For whether the pulse release between electrode needles can achieve good ablation effect, the ablation should be pre-tested before the pulse release, that is, after the electrode needles are in place, 10-20 pulses should be tested with the parameters of 1.0-1.5 cm at the exposed end of each group of electrode needles, voltage 1500 V/cm and wavelength 90 μs. After the test and ablation, the ablation effect can be evaluated by the change of voltage and current waveform. The test current is usually 20-35A to start the formal ablation, if the current is too low, it will lead to incomplete ablation, which can be adjusted by increasing the length of the exposed end or raising the voltage.

The effect of pulse number on local temperature increase In nanosaber ablation therapy, the number of pulses can be increased appropriately to improve the ablation efficiency, but it should be noted that increasing the number of pulses too much will lead to the increase of local current in the ablation area and increase the risk of tissue protein denaturation and thermal damage. At present, it is safer to choose 90-100 pulses for nanosaber ablation treatment of pancreatic tumors.

Conclusion

With the continuous exploration of the effectiveness and safety of Nanoknife ablation for the treatment of LAPC, its advantages are becoming more and more prominent, but there is still no uniform standard for the selection of patients, ablation parameters setting, ablation scope and ablation modality selection for Nanoknife ablation for pancreatic cancer. Nanoknife can be used not only for the treatment of LAPC alone, but also in combination with radiotherapy and chemotherapy or as a means of tumor reduction to create opportunities for surgical procedures.

Currently, a multi-center clinical registration trial of the Steep Pulse Therapeutic Apparatus (Nanoknife) for the ablation treatment of pancreatic malignant tumors is underway in several hospitals across the country. For more information, please leave a message in the background or contact the following person by phone.

Contact person:Manage Zuo from Alpmed

Tel:022-23788188 Ext 7206