Modifications to IRE: Are we there yet?

In an upcoming issue of JVIR, researchers from Stanford University present their experience in producing spherical ablation using irreversible electroporation (IRE) using a single electrode and a grounding pad. The drawbacks to IRE are evident to any interventionalist that regularly uses this treatment technique in clinical practice and any research that addresses these shortcomings should come as welcome news. In short, IRE has some limitations as an ablative tool including cardiac arrhythmias, requirement for chemical paralysis to prevent muscle contractions, and need for placing probes close together. This study investigated two modifications to attempt to address these issues. One is the use of high-frequency IRE (H-FIRE). Besides sounding awesome, H-FIRE uses a rapid burst of 0.25-5-µs alternating-polarity pulses instead of the long-duration monopolar IRE pulse. This produces less susceptibility to distortions in the magnetic field distribution created by tissue heterogeneities and produces more predictable treatment zones. Further, H-FIRE inhibits stimulation of action potentials and treats without inducing muscles contractions. However, H-FIRE has been limited by the small size and “peanut” shape of the ablation zone. This study included a modified probe design to include a single electrode at the target site and a distal grounding pad. This differs from the traditional design with two separate electrical conductors co-located in the same tumor volume. Computed simulations were performed by using varying voltages, electrode exposure lengths, and tissue types. A vegetable (potato) tissue model was then used to compare ablations created by conventional and high-frequency IRE protocols by using the two collinear electrodes or a single electrode configured with a grounding pad. In addition, the new electrode configuration was evaluated in ex vivo liver tissue. Researchers found that the new probe + grounding pad configuration produced larger and more spherical ablation volumes than the traditional configuration in computed simulations and tissue models. Potato model studies verify that the probe + grounding pad configuration produces larger and more spherical ablations than those produced by the traditional method. The researchers made no comment regarding the flavor of the ablated potato.

Commentary:

This paper does a very good job at identifying an existing treatment modification (H-FIRE) and modifying that further with creating a single probe system with the use of a grounding pad. As many interventional oncologists would attest, it would be very advantageous in clinical practice to have an IRE system that used a single probe and was able to create spherical ablation zones. There are some additional hurdles for this technical modification. As mentioned in the paper, the creation of large ablations is theoretically possible with the new configuration if voltages are between 3,000 and 5,000 V. However, 3,000 V is the highest voltage reported for clinical IRE treatments, and the thermal implications of these higher voltages are not fully understood. In addition, in the new configuration, the electrical current will travel between the single electrode and the grounding pad. There is the potential for nontarget thermal and electrical effects. Despite these obstacles, many interventionalists will be looking forward to seeing this technology progress through development to the market.

Click here for abstract

Sano MB, Fan RE, Hwang GL, Sonn GA, Xing L. Production of Spherical Ablations Using Nonthermal Irreversible Electroporation: A Laboratory Investigation Using a Single Electrode and Grounding Pad. J Vasc Interv Radiol. doi: 10.1016/j.jvir.2016.05.032

Post Author:
Luke R. Wilkins, MD
University of Virginia

Results from the RENOVA study show superiority of stent graft to balloon angioplasty in the treatment of arteriovenous graft stenosis

A national team of researchers led by Dr. Ziv Haskal of the University of Virginia have recently published their 2-yr results from the Prospective, Randomized, Concurrently-Controlled Study of an ENdOVAscular Stent Graft. The RENOVA trial, was conducted at 28 clinical sites in the U.S. and was designed to compare the use of an ePTFE stent graft to PTA alone for the revision of AV access graft-venous anastomotic stenosis through 2 years. A total of 270 patients were enrolled with malfunctioning AVG anastomotic stenoses of ≥50%. 138 patients underwent placement of a stent graft (SG) and 132 received angioplasty (PTA) alone. At 12 months, treatment area primary patency (TAPP) was: SG 47.6% vs. PTA 24.8% (p< 0.001) and access circuit primary patency (ACPP) was SG 24% vs. PTA 11% (p=0.007). At 24 months, TAPP was: SG 26.9% vs. PTA 13.5% (p<0.001) and ACPP was SG 9.5% vs. PTA 5.5% (p=0.01). The estimated number of re-interventions before graft abandonment was 3.4 for the SG group vs. 4.3 for PTA group. There were no significant differences in the adverse events (p>0.05) excepting restenosis requiring reintervention rates of 82.6% in PTA patients vs. 63.0% in SG (p<0.001). The authors concluded that at 2 years, Stent graft use provided a “sustained, greater than two-fold advantage over angioplasty in treatment area and overall access patency.”

Discussion

The FLAIR trial from 2010 showed 6-month superiority of the SG for both prolonging uninterrupted access function and patency of the target stenosis and led to FDA approval of the device. The RENOVA study has replicated and affirmed the pivotal trial results, extending the follow up to 2 years, and establishing the long-term superiority of this stent-graft for revision of failing anastomoses in prosthetic grafts as compared to repeated PTA. As detailed in the paper, the healthcare costs of maintaining a failed AV access are substantial. Further, given the burden associated repeat interventions upon patients, the use of SGs in this clinical scenario may offer significant advantages to the dialysis patient population and to the healthcare system as a whole.

Click here for full text

Haskal, Ziv J., et al. "Prospective, Randomized, Concurrently-Controlled Study of a Stent Graft versus Balloon Angioplasty for Treatment of Arteriovenous Access Graft Stenosis: 2-Year Results of the RENOVA Study." Journal of Vascular and Interventional Radiology 27.8 (2016): 1105-1114.

Post Author:
Luke R. Wilkins, MD
University of Virginia