Pancreatic ductal adenocarcinoma is extremely aggressive and is the 4th most frequent tumor-related cause of death in the Western world. The one-year survival rate is 20 percent and the 5-year overall survival rate is only 5 percent. Pancreatic ductal adenocarcinoma often become symptomatic at very advanced stages with only 15 to 20 percent of patients being able to undergo a therapeutic local resection. Patients who do not meet the criteria for local consolidative resection may either have advanced locoregional disease and/or distant metastases. Advanced locoregional pancreatic ductal adenocarcinoma without metastatic disease has a survival rate of 6 to 12 months. Those with distant metastases have a survival rate of only 3 to 6 months.

Locally advanced pancreatic adenocarcinoma is defined by the involvement of the superior mesenteric artery, the celiac axis, and/or long segment portal vein occlusion on cross-sectional imaging. Resectable tumors will be free from the superior mesenteric vein, superior mesenteric artery and celiac axis, with no nodal involvement outside of the area of resection. Unresectable disease will have occlusion, thrombosis or encasement that extends for several centimeters of superior mesenteric vein and portal vein. Tumor abutment, encasement or thrombosis of the superior mesenteric artery is also considered unresectable disease. Involvement of lymph nodes outside of the area of resection also indicates that the patient is not resectable.

For patients who have unresectable pancreatic ductal adenocarcinoma, chemotherapy and radiation can only provide short-term disease control. Chemotherapy and radiation regimens have not been shown to prolong survival significantly in this disease, and therefore, there is a need for additional adjunctive or consolidative treatment to provide improved local control, pain relief and possibly impact survival. Image guided ablation technique like irreversible electroporation has shown promise as a new treatment option for patients with stage III locally advanced pancreatic cancer.

A unique advantage of Nanoknife is that it does not require heat to ablate tumor cells, rather it works by using high voltage but low energy direct current. The process in which low energy direct current ablates tissue is called irreversible electroporation. In order to understand how this process works, the investigators have to understand some background cell biology. The cell membrane separates the intracellular space and the extracellular space/fluid, and controls transport processes between the two compartments of the cell. Electroporation increases cell membrane permeability by subjecting it to an electrical field and uses rapid series of short electrical pulses delivered using high voltage but low energy direct current to create defects (pores) in the cell membrane that result in loss of homeostasis and cell death. The result is a well demarcated area of ablation. The Nanoknife system comes with 19 gauge needles that have depth markings. The needle surface is echogenic. The active electrode length is adjustable in 0.5 cm increments from zero to 4 cm. There is an external electrocardiogram synchronization device that automatically detects the R wave and energy is delivered synchronously to the R wave. The electrodes can be arranged in multiple configurations using two to six electrodes. The spacing between the electrodes can be from 0.5 cm to 2.0 cm, and electrode exposure can be from 0.5 cm to 4.0 cm. Energy is delivered between the electrode pairs, and this results in an area of ablated tissue.

Nanoknife is particularly useful in patients with pancreatic ductal adenocarcinoma because of the proximity of pancreatic tumors to critical surrounding structures such as bile ducts and major blood vessels. Because it does not use heat to ablate tissue (which induces necrosis) but rather uses cell apoptosis, it theoretically has no impact on the surrounding structures that mainly consist of proteins like vascular elastic and collagenous structures as well as peri-cellular matrix proteins (protecting large blood vessels and bile ducts). Further study of Nanoknife is needed to see if this therapy can potentially impact survival and/or provide adequate local palliation to improve quality of life in patients with locally advanced unresectable pancreatic ductal adenocarcinoma.