Date Published: February 4, 2016
Publisher: Public Library of Science
Author(s): Hester J. Scheffer, Jantien A. Vogel, Willemien van den Bos, Robert E. Neal, Krijn P. van Lienden, Marc G. H. Besselink, Martin J. C. van Gemert, Cees W. M. van der Geld, Martijn R. Meijerink, John H. Klaessens, Rudolf M. Verdaasdonk, Maria Rosaria Scarfi.
Irreversible electroporation (IRE) uses short duration, high-voltage electrical pulses to induce cell death via nanoscale defects resulting from altered transmembrane potential. The technique is gaining interest for ablations in unresectable pancreatic and hepatobiliary cancer. Metal stents are often used for palliative biliary drainage in these patients, but are currently seen as an absolute contraindication for IRE due to the perceived risk of direct heating of the metal and its surroundings. This study investigates the thermal and tissue viability changes due to a metal stent during IRE.
IRE was performed in a homogeneous tissue model (polyacrylamide gel), without and with a metal stent placed perpendicular and parallel to the electrodes, delivering 90 and 270 pulses (15–35 A, 90 μsec, 1.5 cm active tip exposure, 1.5 cm interelectrode distance, 1000–1500 V/cm, 90 pulses/min), and in-vivo in a porcine liver (4 ablations). Temperature changes were measured with an infrared thermal camera and with fiber-optic probes. Tissue viability after in-vivo IRE was investigated macroscopically using 5-triphenyltetrazolium chloride (TTC) vitality staining.
In the gel, direct stent-heating was not observed. Contrarily, the presence of a stent between the electrodes caused a higher increase in median temperature near the electrodes (23.2 vs 13.3°C [90 pulses]; p = 0.021, and 33.1 vs 24.8°C [270 pulses]; p = 0.242). In-vivo, no temperature difference was observed for ablations with and without a stent. Tissue examination showed white coagulation 1mm around the electrodes only. A rim of vital tissue remained around the stent, whereas ablation without stent resulted in complete tissue avitality.
IRE in the vicinity of a metal stent does not cause notable direct heating of the metal, but results in higher temperatures around the electrodes and remnant viable tissue. Future studies should determine for which clinical indications IRE in the presence of metal stents is safe and effective.
Irreversible electroporation (IRE) is a relatively novel ablation modality that uses electrical energy to induce cell death . Electrodes are placed around a tumor, through which high-voltage, but sub-millisecond electrical pulses are applied at a low frequency (0.5–2 Hz). As opposed to thermal ablation techniques, the electrical pulses are designed to distort the pre-existing cellular membrane potential, leading to disruption of the lipid bilayer, after which the cell loses its homeostatic properties and dies [2–5]. Preclinical studies have shown that within the ablation zone IRE mostly affects cells, leaving the supporting extracellular matrix structures relatively intact [6–8]. This preservation of gross anatomic architecture allows tumors near vascular and biliary structures that are otherwise unresectable or unamenable to thermal-based modalities, to be ablated safely [9,10].
It was never disputed that every electric field, including a field for irreversible electroporation, produces a thermal effect . Yet, from 2005 onwards, scientists showed that IRE could be isolated from thermal effects and used by itself to produce substantial volumes of tissue ablation in vivo, with negligible thermal effects [3,8,27–29]. The application of IRE for the therapeutic ablation of tumors however, has evolved to use more aggressive energy regimens, with higher voltage and higher pulse number protocols. These high-energy regimens have shown to generate potentially harmful thermal effects [11,15,16,30], which is reaffirmed in the present study. Much effort should therefore be put in the development of clinical pulse protocols that mitigate these thermal effects and maintain IRE as the vastly predominant modality of tissue death.
IRE in the vicinity of a metal stent does not cause notable increased heating of the metal stent, but results in higher temperatures around the electrodes. In vivo, a remnant viable tissue region immediately adjacent to the stent was observed. These findings reinforce the appeal to either place plastic biliary endoprostheses or to remove of metal stents prior to IRE whenever possible. Future studies should determine for which clinical indications IRE in the presence of metal stents is safe and effective.