Abstract

Background and AimIrreversible electroporation (IRE) is a method of targeted cell ablation which has been suggested as a potential cancer therapy as it leaves structures such as blood vessels and the extracellular matrix intact, thereby allowing the rapid recovery of healthy tissue. Here, we investigated the effects of IRE on the colon in vivo in a porcine model.MethodsIRE ablation was performed on the colon walls of 12 female Tibet mini-pigs, creating a total of 24 lesions. Lesions were monitored periodically by endoscopy. The pigs were euthanized 7, 14, 21 or 28 days after IRE ablation and the colons harvested for gross and histological analysis. Sections were stained with hematoxylin and eosin (H&E), Masson’s trichrome (MT) stain and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.ResultsAll pigs tolerated the ablation procedure without serious clinical symptoms or complications. There was no evidence of perforation by endoscopy or gross postmortem examination. All lesions were characterized by necrotic cell death with mild inflammation and hyperemia, with a sharp demarcation between ablated and adjacent normal tissue. A fibrous scar was observed in the ablated colon tissue. Histological analysis revealed damage to each layer of the colon. Histopathology findings also showed the preservation of extracellular structures and the recovery of the ablated colon.ConclusionsThe complete ablation of the target area, its rapid recovery and the lack of posttreatment symptoms suggest that IRE ablation may be a promising therapy for tumors located adjacent to or violating the colon wall.

Highlights

  • Colon cancer is one of the most common malignant tumors in the world, accounting for approximately 1.2 million incident cases and over 600,000 deaths annually[1]

  • Sections were stained with hematoxylin and eosin (H&E), Masson’s trichrome (MT) stain and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay

  • The complete ablation of the target area, its rapid recovery and the lack of posttreatment symptoms suggest that Irreversible electroporation (IRE) ablation may be a promising therapy for tumors located adjacent to or violating the colon wall

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Summary

Introduction

Colon cancer is one of the most common malignant tumors in the world, accounting for approximately 1.2 million incident cases and over 600,000 deaths annually[1]. Collateral damage to the colon often occurs after radiotherapy for pelvic or abdominal malignancies or as a side effect of chemotherapy, resulting in bloating, abdominal cramping, severe diarrhea, nausea, and vomiting. These side effects are seen as the limiting factor in increasing both chemotherapy and radiotherapy dosage and can force discontinuation of treatment[5]. In the treatment of abdominal cancer, IRE has the ability to avoid collateral damage even in tissues within the electric field[5, 6] This method of targeted induction of cell death has proved effective in destroying cancer in animal models[7,8,9,10,11,12]. We investigated the effects of IRE on the colon in vivo in a porcine model

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