Athermal technique for ablating renal tumors looks promising

August 1, 2010

Irreversible electroporation appears to be a promising nonthermal technique for renal tissue ablation.

Key Points

San Francisco-Irreversible electroporation (IRE) appears to be a promising nonthermal technique for renal tissue ablation. Findings from an initial evaluation performed in a porcine model support undertaking further animal studies to more fully characterize the efficacy and safety of this minimally invasive modality, researchers reported at the AUA annual meeting.

The experiments were performed using a commercially available platform known as NanoKnife IRE (AngioDynamics, Latham, NY) that is FDA-cleared for ablation of soft tissue. Its probe is inserted into the tissue, where a high-voltage (~2300 V) direct current passing between two electrodes induces an electrical field that creates nano-scale pores within the cell membrane, leading to cellular lysis.

A total of 24 ablations were performed via laparoscopy using either a monopolar or bipolar probe in a series of eight Yorkshire pigs. Groups of two animals each were sacrificed at 10 minutes, 1 hour, 7 days, and 14 days post-treatment for histologic evaluation by gross microscopic examination and using both hematoxylin and eosin and nicotinamide adenine dinucleotide tetrazolium reductase (NADH) staining to determine cell viability.

The results showed that IRE predictably resulted in immediate histologic changes characteristic of cell death. The urothelium was completely spared in 20% of cases despite direct contact with the probe, and in another 60% of ablations, there was only partial urothelial erosion. In addition, there was evidence of some regrowth and repopulation of the collecting system by 14 days, reported first author Chad R. Tracy, MD, who was an endourology fellow at the University of Texas Southwestern Medical Center, Dallas, working with Jeffrey A. Cadeddu, MD, at the time of the study.

"Compared with radiofrequency or cryotherapy-based ablative modalities that cause cell death via thermal injury, IRE has a potential benefit as a nonthermal technique in that it would avoid energy loss via a 'heat sink' effect," Dr. Tracy said. "Therefore, it may allow treatment of small renal tumors in the proximity of large vessels.

"In addition, the fact that IRE spares the urothelium in the majority of cases suggests that this technology may be useful in the treatment of tumors that are in close proximity to the renal collecting system. Finally, because the area of cellular damage progresses from the point of probe insertion inward, IRE may have a benefit for minimizing collateral tissue damage.

"However, further studies in animal models are needed to determine if IRE may be used safely and reproducibly for renal tissue ablation in humans and how it may best be applied," added Dr. Tracy, who is currently a clinical assistant professor of urology at the University of Iowa, Iowa City.

Gross examination of the tissue samples from animals sacrificed after 10 minutes and 1 hour showed the early lesions were diffusely hemorrhagic, and staining for NADH showed sharp delineation between treated and nontreated tissue.

The areas of hemorrhage resolved by 7 days and there was minimal inflammation noted at that follow-up. Lesion size progressively decreased over time, consistent with the development of fibrosis and cellular contraction at day 14.

Bipolar treatment more damaging

Comparisons of the histologic findings from use of the bipolar and monopolar probes showed there was more variability in the size of the lesions created with the bipolar probe, and the bipolar treatment was also more damaging to the collecting system.

Dr. Tracy noted that considering the proximity between the kidneys and the heart and the high-voltage electrical current used in IRE, there is a potential concern about an adverse effect on cardiac conduction. Although these initial animal models were designed to study the evolution of the ablative lesions and did not include extensive safety evaluations, all of the animals lived to the time of sacrifice without exhibiting any treatment-related adverse effects, and no urinomas were noted at the time of animal sacrifice.