Clin Endosc.  2021 May;54(3):413-419. 10.5946/ce.2020.126.

Novel Ablation Therapy Using Endoscopic Irreversible Electroporation in the Bile Duct: A Pilot Animal Study

Affiliations
  • 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
  • 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea
  • 3Department of Biosystems and Biomaterials Science and Engineering, Seoul National University, Seoul, Korea

Abstract

Background/Aims
Irreversible electroporation (IRE) is a relatively new ablation method. However, the application of IRE ablation in the treatment of biliary disease has not been attempted. A minimally invasive approach using endoscopic retrograde cholangiopancreatography (ERCP) can be a novel therapeutic modality for IRE ablation. In this study, we aimed to investigate the feasibility of endoscopic IRE for the biliary tract using an animal model.
Methods
A new catheter-type electrode was developed for endoscopic IRE ablation of the biliary tract. We performed ERCP and endoscopic IRE ablations in the normal common bile duct of Yorkshire pigs. The experimental setting of IRE was 500 V/cm (50 pulses, 100-µs length). The animals were sacrificed after 24 hr, and the ablated bile duct was examined.
Results
Well-demarcated focal color changes were observed on the mucosa of the common bile duct. The depth of change after IRE was confined to the mucosal and submucosal layers. Apoptotic changes in the bile duct were observed only around the IRE ablation area. Immunohistochemistry assay showed cell death in the bile duct along the electrode.
Conclusions
Endoscopic IRE ablation using ERCP was successfully performed in the common bile duct. It can be a potential option for the treatment of biliary tumors.

Keyword

Ablation; Bile duct; Endoscopic retrograde cholangiopancreatography; Irreversible electroporation

Figure

  • Fig. 1. Components of the newly designed endoscopic catheter-type irreversible electroporation electrode. Catheter-type irreversible electroporation (A) connecting to the main generator system. The Gemini Twin Wave BTX electroporation system (BTX Genetronics, San Diego, CA, USA) (B) consists of the banana connector (C) along with insulated wires (D) and two electrodes arranged at 5-mm intervals on the tip (E) transmitting energy to the tissue.

  • Fig. 2. Process of endoscopic retrograde cholangiopancreatography-guided endoscopic irreversible electroporation ablation. (A) After inserting the duodenoscope and targeting the ampulla of Vater, (B) cannulation was performed. (C) The guidewire was inserted, and (D) the electrode was inserted through the guidewire.

  • Fig. 3. Gross specimen of the bile duct after endoscopic retrograde cholangiopancreatography-guided endoscopic irreversible electroporation (IRE). In the red circle, the ablated region in the bile duct was 1 cm long and 5 mm wide. Well-demarcated focal color changes were observed on the mucosa of the bile duct where IRE was applied. No evidence of burn, bleeding, or any mucosal damage was observed in areas where IRE ablation was not applied.

  • Fig. 4. Specimen with formalin fixation. In the yellow circle, the boundary of the ablated region was also visually apparent, as seen after formalin fixation.

  • Fig. 5. Histopathologic findings of the bile duct in hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate digoxigenin nick end labeling (TUNEL) assay (×40, ×100). In the areas where irreversible electroporation was applied, the nucleus inside the cells were not observed (left). The area where irreversible electroporation was applied could be seen as a dark brown area in immunohistopathology with the TUNEL assay (right).

  • Fig. 6. Magnified images of the irreversible electroporation ablation area and the nonablated area in hematoxylin and eosin-stained sections (×40, ×400). Intracellular nuclei were observed in normal cells (right). However, the nuclei were not observed in the irreversible electroporation-ablated area (left).


Cited by  1 articles

Large Animal Models in Pancreas and Biliary Disease
Seok Jeong, Jin-Seok Park, Don Haeng Lee
Korean J Gastroenterol. 2021;77(3):99-103.    doi: 10.4166/kjg.2021.031.


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