Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2018; 10(12): 476-486
Published online Dec 15, 2018. doi: 10.4251/wjgo.v10.i12.476
Histological analysis of human pancreatic carcinoma following irreversible electroporation in a nude mouse model
Jun-Jun Su, Kai Xu, Peng-Fei Wang, Hao-Yun Zhang, Yong-Liang Chen
Jun-Jun Su, Kai Xu, Peng-Fei Wang, Hao-Yun Zhang, Yong-Liang Chen, Department of Hepatobiliary Surgery, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
Jun-Jun Su, Division of Gastroenterological Surgery, Department of Surgery, Shanxi Provincial People’s Hospital, Taiyuan 030012, Shanxi Province, China
Author contributions: All authors helped perform the study; Su JJ, Xu K and Zhang HY analyzed and interpreted the data; Su JJ wrote the manuscript; all authors have read and approved the final version of the manuscript.
Institutional animal care and use committee statement: The study was reviewed and approved by the Department of Hepatobiliary Surgery of Chinese People’s Liberation Army General Hospital, China.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at chenyongl301@163.com. All participants provided informed consent for data sharing.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Yong-Liang Chen, MD, PhD, Professor, Department of Hepatobiliary Surgery, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. chenyongl301@163.com
Telephone: +86-10-66875531
Received: September 14, 2018
Peer-review started: September 14, 2018
First decision: October 3, 2018
Revised: October 15, 2018
Accepted: November 23, 2018
Article in press: November 24, 2018
Published online: December 15, 2018
Abstract
AIM

To determine changes in the morphology and function of pancreatic cancer cells after irreversible electroporation (IRE) treatment, and to explore the clinical significance of IRE treatment for pancreatic cancer providing an experimental basis for the clinical application of IRE treatment.

METHODS

IRE was carried out in an athymic nude mouse model of pancreatic carcinoma generated with human pancreatic cancer cells 1. In therapy groups, IRE electrodes were inserted with 90 pulses per second at 800 V/cm applied to ablate the targeted tumor tissues. Histological assessment of the affected tissue was performed by hematoxylin and eosin staining (HE). Quantification of cell proliferation and apoptosis was performed by evaluating Ki67 and caspase-3 levels, respectively. Flow cytometry was used to assess cell apoptosis. Ultrasound imaging was carried out to evaluate IRE treatment results. Pathological correlation studies showed IRE is effective for the targeted ablation of pancreatic tumors in an orthotopic mouse model.

RESULTS

IRE was efficacious in removing tumors in the orthotopic mouse model. The IRE-ablated zone displays characteristics of nude mouse models at different time-points as assessed by hematoxylin and eosin staining. Immunohistochemical analysis of samples from the pancreatic cancer models showed significantly enhanced caspase-3 cleavage and Ki67. Flow cytometry data corroborated the above findings that apoptosis in tumor cells was observed immediately on the first postoperative day, and with time the middle and late stages of apoptosis were observed. For ultrasound imaging studies, the IRE ablation zone became a hyperechoic area due to increasing inflammatory and immunologic cellular contents.

CONCLUSION

IRE is a promising new approach for pancreatic cancer, with many potential advantages over conventional ablation techniques.

Keywords: Irreversible electroporation, Pancreatic carcinoma, Pathological evaluation, Transplantation model, Nude mouse

Core tip: Patients with pancreatic cancer have a poor prognosis. It often quickly develops into locally advanced pancreatic cancer that is considered to be surgically unresectable. Irreversible electroporation represents a novel tumor ablation method that induces cell apoptosis with no thermal coagulation effects. This study aimed to assess the clinical significance of irreversible electroporation treatment in pancreatic cancer, and to provide an experimental basis for the clinical application of irreversible electroporation treatment.