Colorectal cancer is one of the most common gastrointestinal cancers associated with substantial morbidity and mortality. A alternative treatment modality for local symptom control, including tumor bleeding and colonic obstruction, is needed, especially in non-surgical candidates. Electroporation is a non-thermal ablative therapy that delivers a series of electrical pulses to increase cell membrane permeability. The use of a high-frequency biphasic pulse reduces painful muscle contraction associated with traditional electroporation. The reversible calcium electroporation has been investigated in the lower gastrointestinal tract. With an adjustment of electrical parameters, electroporation can be irreversible and lead to substantial cell apoptosis, promising for use as a monotherapy. We are demonstrating the use of endoscopic irreversible electroporation therapy for the treatment of colorectal cancer for the first time in a porcine model. After two weeks following viral vector injection in an experimental colorectal cancer porcine model, a follow-up colonoscopy showed a tumor with extensive mucosal involvement. Histopathology showed pleomorphic malignant cells with a high nucleus-to-cytoplasm ratio and prominent nuclei compatible with poorly differentiated carcinoma. The pig underwent a colonoscopy under general anesthesia. The electroporation device was easily attached to the distal end of the endoscope and secured with adhesive tape. The chamber was oriented to 6 o'clock position. The electrical pulse was delivered from the lateral wall of the chamber from side to side alternatively. The ablative area is non-thermal and located within the 5 mm height of the chamber with an additional distance deep down. The minimum ablation volume is 1.5 cubic centimeters. The scope was advanced until the target lesion was reached. The electroporation device was placed directly onto the tumor. A vacuum feature assists in drawing tumor tissue into direct contact with the electrodes. The pulse generator delivers a series of pulse bursts of biphasic waves with a frequency of 10 Hz and an electric field intensity of 1 kV per centimeter. After a short period of energy delivery, the chamber was flushed with distilled water to control the temperature and prevent thermal injury. The negative pressure was then reapplied. Energy delivery can result in vibrations as seen here. Endoscopists maintain the scope position to ensure good tissue contact with the chamber for the entire period of energy delivery. After a complete single session, the probe is repositioned to treat the residual area. One tumor showed blood oozing. Electroporation chamber was placed over the friable mucosa. Vascularity was markedly decreased during the application of opposing suction force. Mucosal discoloration can be appreciated in time of electrical energy delivery. Electroporation provided an effective hemostasis. The bleeding completely stopped after the electroporation session. Progressive reduction in tumor size, chronic ulceration, and scarring were noted during follow-up endoscopy. There were no procedure-related adverse outcomes. In summary, initial in vivo experience with irreversible electroporation monotherapy as a tumor ablative therapy in an experimental colorectal cancer porcine model was promising. Electroporation as an alternative modality may be considered for palliation and adjunct therapy in colorectal cancer.

Irreversible electroporation therapy

colorectal cancer

non-thermal ablative therapy

electrical pulses

cell apoptosis