Irreversible electroporation ablation technique in treatment of esophageal cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XIA Yanmin ¹ , ZHU Jianfei ² , WANG Wenchen ¹ ,  JIANG Tao ¹

1. Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, P.R.China;
2. Department of Thoracic Surgery, Shaanxi People’s Hospital, Xi'an, 710068, P.R.China;

Corresponding author：

JIANG Tao, Email: jiangtaotd@163.com

Keywords：

Esophageal cancer; ablation; irreversible electroporation; therapy; animal experiment

DOI：

10.7507/1007-4848.202010066

Video：

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Objective To explore the therapeutic effect and safety of irreversible electroporation (IRE) ablation technique on esophageal cancer.Methods An ECM830 electroporator was used for IRE treatment on esophageal cancer cells EC109 and KYSE30. According to the different electric field intensity, five groups were assigned: a control group, a 500 V/cm group, a 1000 V/cm group, a 1500 V/cm group, and a 2 000 V/cm group. After 24 h, methyl thiazolyltetrazolium (MTT) was used to detect the cell proliferation of each group. Western blotting was performed to evaluate the expression of apoptosis proteins in cells before or after IRE treatment. Eight healthy BALB/c nude mice were equally divided into two groups: a control group (n=4) and an IRE group (n=4). EC109 was used to establish subcutaneous transplantation tumors and subsequently the mice in the IRE group were treated with flat electrode. The weight and volume of tumors were measured after 14 days. Ten healthy New Zealand white rabbits were equally divided into two groups: a control group (n=5) and an IRE group (n=5). After exposing the abdominal cavity, the abdominal esophagus of the IRE group was treated with flat electrode. Seven days later, the esophagus was extracted for HE and Masson staining.Results When the electric field intensity was low (500 V/cm), there was no change in esophageal cancer cells proliferation after IRE treatment compared to the control group (EC109: P=0.385, KYSE30: P=0.600). With the increase of electric field intensity, the influence of IRE on the proliferation of esophageal cancer cell gradually increased. When it reached 2 000 V/cm, there was basically no cell viability after IRE treatment (P<0.001). The results of Western blotting showed that the expression of cleaved caspase-3 increased after IRE treatment (P<0.01). Animal experiments indicated that the weight and volume of tumors in nude mice reduced (P<0.05) and the growth of tumors was slowed down after IRE treatment. In addition, the parenchymal cells of rabbit esophagus were largely damaged, while interstitial tissues such as fibers were well preserved.Conclusion IRE ablation has the potential to inhibit the proliferation of esophageal cancer cell and slow down the tumor growth.What’s more, it is safe for the esophagus.

Citation： XIA Yanmin, ZHU Jianfei, WANG Wenchen, JIANG Tao. Irreversible electroporation ablation technique in treatment of esophageal cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2021, 28(9): 1095-1101. doi: 10.7507/1007-4848.202010066 Copy

1.	Hur C, Miller M, Kong CY, et al. Trends in esophageal adenocarcinoma incidence and mortality. Cancer, 2013, 119(6): 1149-1158.
2.	Zhang Y, Zhou M, Bai L, et al. Radiofrequency ablation combined with esophageal stent in the treatment of malignant esophageal stenosis: A single-center prospective study. Oncol Lett, 2018, 16(3): 3157-3161.
3.	Lal P, Thota PN. Cryotherapy in the management of premalignant and malignant conditions of the esophagus. World J Gastroenterol, 2018, 24(43): 4862-4869.
4.	Niemeier RC, Etoz S, Gil DA, et al. Quantifying optical properties with visible and near-infrared optical coherence tomography to visualize esophageal microwave ablation zones. Biomed Opt Express, 2018, 9(4): 1648-1663.
5.	Ringel-Scaia VM, Beitel-White N, Lorenzo MF, et al. High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity. EBio Medicine, 2019, 44: 112-125.
6.	Simmerman E, Chung J, Lawson A, et al. Application of irreversible electroporation abltation as adjunctive treatment for margin enhancement: Safety and efficacy. J Surg Res, 2020, 246: 260-268.
7.	Cohen EI, Field D, Lynskey GE, et al. Technology of irreversible electroporation and review of its clinical data on liver cancers. Expert Rev Med Devices, 2018, 15(2): 99-106.
8.	Ruarus AH, Vroomen LGPH, Geboers B, et al. Percutaneous irreversible electroporation in locally advanced and recurrent pancreatic cancer (PANFIRE-2): A multicenter, prospective, single-arm, phase Ⅱ study. Radiology, 2020, 294(1): 212-220.
9.	Karagiannis A, Varkarakis J. Irreversible electroporation for the ablation of prostate cancer. Curr Urol Rep, 2019, 20(10): 63.
10.	Blazevski A, Scheltema MJ, Amin A, et al. Irreversible electroporation (IRE): A narrative review of the development of IRE from the laboratory to a prostate cancer treatment. BJU Int, 2020, 125(3): 369-378.
11.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
12.	蔡杰, 倪彭智, 王文凭, 等. 淋巴化疗在食管癌治疗中的应用现状. 中国胸心血管外科临床杂志, 2017, 24(8): 635-639.
13.	Takaki H, Cornelis F, Kako Y, et al. Thermal ablation and immunomodulation: From preclinical experiments to clinical trials. Diagn Interv Imaging, 2017, 98(9): 651-659.
14.	叶挺, 夏阳, 宗刚军. 阵发性心房颤动射频消融术后并发食管溃疡伴穿孔一例. 中华心血管病杂志, 2020, 48(1): 72-73.
15.	Song Z, Xu X, Liu M, et al. Efficacy and mechanism of steep pulse irreversible electroporation technology on xenograft model of nude mice: a preclinical study. World J Surg Oncol, 2018, 16(1): 84.
16.	Wasson EM, Alinezhadbalalami N, Brock RM, et al. Understanding the role of calcium-mediated cell death in high-frequency irreversible electroporation. Bioelectrochemistry, 2020, 131: 107369.
17.	Scheck J, Bruners P, Schindler D, et al. Comparison of chronologic change in the size and contrast-enhancement of ablation zones on CT images after irreversible electroporation and radiofrequency ablation. Korean J Radiol, 2018, 19(4): 560-567.
18.	Ren F, Li Q, Gao X, et al. Electrical and thermal analyses of catheter-based irreversible electroporation of digestive tract. Int J Hyperthermia, 2019, 36(1): 854-867.
19.	Sugimoto K, Kakimi K, Takeuchi H, et al. Irreversible electroporation versus radiofrequency ablation: Comparison of systemic immune responses in patients with hepatocellular carcinoma. J Vasc Interv Radiol, 2019, 30(6): 845-853.
20.	Distelmaier M, Barabasch A, Heil P, et al. Midterm safety and efficacy of irreversible electroporation of malignant liver tumors located close to major portal or hepatic veins. Radiology, 2017, 285(3): 1023-1031.
21.	陈军周, 周宁新. 肿瘤微创消融新技术— 不可逆性电穿孔. 中国普外基础与临床杂志, 2016, 23(3): 365-368.
22.	Vaessen EMJ, Timmermans RAH, Tempelaars MH, et al. Reversibility of membrane permeabilization upon pulsed electric field treatment in Lactobacillus plantarum WCFS1. Sci Rep, 2019, 9(1): 19990.
23.	Neven K, van Es R, van Driel V, et al. Acute and long-term effects of full-power electroporation ablation directly on the porcine esophagus. Circ Arrhythm Electrophysiol, 2017, 10(5): e004672.

1. Hur C, Miller M, Kong CY, et al. Trends in esophageal adenocarcinoma incidence and mortality. Cancer, 2013, 119(6): 1149-1158.
2. Zhang Y, Zhou M, Bai L, et al. Radiofrequency ablation combined with esophageal stent in the treatment of malignant esophageal stenosis: A single-center prospective study. Oncol Lett, 2018, 16(3): 3157-3161.
3. Lal P, Thota PN. Cryotherapy in the management of premalignant and malignant conditions of the esophagus. World J Gastroenterol, 2018, 24(43): 4862-4869.
4. Niemeier RC, Etoz S, Gil DA, et al. Quantifying optical properties with visible and near-infrared optical coherence tomography to visualize esophageal microwave ablation zones. Biomed Opt Express, 2018, 9(4): 1648-1663.
5. Ringel-Scaia VM, Beitel-White N, Lorenzo MF, et al. High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity. EBio Medicine, 2019, 44: 112-125.
6. Simmerman E, Chung J, Lawson A, et al. Application of irreversible electroporation abltation as adjunctive treatment for margin enhancement: Safety and efficacy. J Surg Res, 2020, 246: 260-268.
7. Cohen EI, Field D, Lynskey GE, et al. Technology of irreversible electroporation and review of its clinical data on liver cancers. Expert Rev Med Devices, 2018, 15(2): 99-106.
8. Ruarus AH, Vroomen LGPH, Geboers B, et al. Percutaneous irreversible electroporation in locally advanced and recurrent pancreatic cancer (PANFIRE-2): A multicenter, prospective, single-arm, phase Ⅱ study. Radiology, 2020, 294(1): 212-220.
9. Karagiannis A, Varkarakis J. Irreversible electroporation for the ablation of prostate cancer. Curr Urol Rep, 2019, 20(10): 63.
10. Blazevski A, Scheltema MJ, Amin A, et al. Irreversible electroporation (IRE): A narrative review of the development of IRE from the laboratory to a prostate cancer treatment. BJU Int, 2020, 125(3): 369-378.
11. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
12. 蔡杰, 倪彭智, 王文凭, 等. 淋巴化疗在食管癌治疗中的应用现状. 中国胸心血管外科临床杂志, 2017, 24(8): 635-639.
13. Takaki H, Cornelis F, Kako Y, et al. Thermal ablation and immunomodulation: From preclinical experiments to clinical trials. Diagn Interv Imaging, 2017, 98(9): 651-659.
14. 叶挺, 夏阳, 宗刚军. 阵发性心房颤动射频消融术后并发食管溃疡伴穿孔一例. 中华心血管病杂志, 2020, 48(1): 72-73.
15. Song Z, Xu X, Liu M, et al. Efficacy and mechanism of steep pulse irreversible electroporation technology on xenograft model of nude mice: a preclinical study. World J Surg Oncol, 2018, 16(1): 84.
16. Wasson EM, Alinezhadbalalami N, Brock RM, et al. Understanding the role of calcium-mediated cell death in high-frequency irreversible electroporation. Bioelectrochemistry, 2020, 131: 107369.
17. Scheck J, Bruners P, Schindler D, et al. Comparison of chronologic change in the size and contrast-enhancement of ablation zones on CT images after irreversible electroporation and radiofrequency ablation. Korean J Radiol, 2018, 19(4): 560-567.
18. Ren F, Li Q, Gao X, et al. Electrical and thermal analyses of catheter-based irreversible electroporation of digestive tract. Int J Hyperthermia, 2019, 36(1): 854-867.
19. Sugimoto K, Kakimi K, Takeuchi H, et al. Irreversible electroporation versus radiofrequency ablation: Comparison of systemic immune responses in patients with hepatocellular carcinoma. J Vasc Interv Radiol, 2019, 30(6): 845-853.
20. Distelmaier M, Barabasch A, Heil P, et al. Midterm safety and efficacy of irreversible electroporation of malignant liver tumors located close to major portal or hepatic veins. Radiology, 2017, 285(3): 1023-1031.
21. 陈军周, 周宁新. 肿瘤微创消融新技术— 不可逆性电穿孔. 中国普外基础与临床杂志, 2016, 23(3): 365-368.
22. Vaessen EMJ, Timmermans RAH, Tempelaars MH, et al. Reversibility of membrane permeabilization upon pulsed electric field treatment in Lactobacillus plantarum WCFS1. Sci Rep, 2019, 9(1): 19990.
23. Neven K, van Es R, van Driel V, et al. Acute and long-term effects of full-power electroporation ablation directly on the porcine esophagus. Circ Arrhythm Electrophysiol, 2017, 10(5): e004672.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Irreversible electroporation ablation technique in treatment of esophageal cancer

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