Feasibility and effectiveness of endoscopic irreversible electroporation for the upper gastrointestinal tract: an experimental animal study

Han Jo Jeon,Eun Sun Kim,Kang Won Lee,Jong Hyuk Kim,Hoon Jai Chun,Hyuk Soon Choi,Jae Min Lee,Yeon Seok Seo,Eun Joo Bang,Sang Hyun Kim,Hong Sik Lee,Yoon Tae Jeen,Sun Young Yim,Bora Keum,Hong Bae Kim

doi:10.1038/s41598-021-94583-w

Abstract

Irreversible electroporation (IRE) is a local non-thermal ablative technique currently used to treat solid tumors. Here, we investigated the clinical potency and safety of IRE with an endoscope in the upper gastrointestinal tract. Pigs were electroporated with recently designed endoscopic IRE catheters in the esophagus, stomach, and duodenum. Two successive strategies were introduced to optimize the electrical energy for the digestive tract. First, each organ was electroporated and the energy upscaled to confirm the upper limit energy inducing improper tissue results, including bleeding and perforation. Excluding the unacceptable energy from the first step, consecutive electroporations were performed with stepwise reductions in energy to identify the energy that damaged each layer. Inceptive research into inappropriate electrical intensity contributed to extensive hemorrhage and bowel perforation for each tissue above a certain energy threshold. However, experiments performed below the precluded energy accompanying hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays showed that damaged mucosal area and depth significantly decreased with decreased energy. Relevant histopathology showed infiltration of inflammatory cells with pyknotic nuclei at the electroporated lesion. This investigation demonstrated the possibility of endoscopic IRE in mucosal dysplasia or early malignant tumors of the hollow viscus.

Highlights

Irreversible electroporation (IRE) is a local non-thermal ablative technique currently used to treat solid tumors
In our two consecutive experiments, we successfully demonstrated that in vivo irreversible electroporation (IRE) ablation of the upper GI tract was both feasible and effective
While phase 1 of our study demonstrated adverse effects such as perforation and bleeding after the application of high electrical intensity, phase 2 showed that the electroporation could be accomplished safely if optimized energy was administered

Summary

Introduction

Irreversible electroporation (IRE) is a local non-thermal ablative technique currently used to treat solid tumors. Each organ was electroporated and the energy upscaled to confirm the upper limit energy inducing improper tissue results, including bleeding and perforation. Relevant histopathology showed infiltration of inflammatory cells with pyknotic nuclei at the electroporated lesion. This investigation demonstrated the possibility of endoscopic IRE in mucosal dysplasia or early malignant tumors of the hollow viscus. With the efficacy of perioperative chemotherapy depending on the surgical procedure remaining insufficient, the standard treatment for locally advanced gastric cancer remains unclear[5]. A new ablation technique called irreversible electroporation (IRE) was developed and includes electropermeabilization, which induces cell membrane perforation by an external electric field[8]. Of the cell membrane changes the transmembrane potential and increases conductivity and permeability, resulting in permanent nano-sized aqueous pores on the cell membrane that eventually cause cell d eath[9]

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Conclusion