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The Effect of Irreversible Electroporation on Blood Vessels, Bile Ducts, Urinary Tract, Intestines, and Nerves

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Irreversible Electroporation in Clinical Practice

Abstract

Surgical resection is the definitive treatment option for patients with primary or metastatic cancers, resulting in the best possible patient outcomes when resection is achieved with negative margins. However, involvement of vital structures such as blood vessels and genitourinary or gastrointestinal tract often poses a contraindication to safe and successful surgical resection.

J.A. Vogel and L.G.P.H. Vroomen contributed equally

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References

  1. Long G, Bakos G, Shires PK, Gritter L, Crissman JW, Harris JL, Clymer JW. Histological and finite element analysis of cell death due to irreversible electroporation. Technol Cancer Res Treat. 2014;13(6):561–9. doi:10.7785/tcrtexpress.2013.600253.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Date RS, Siriwardena AK. Radiofrequency ablation of the pancreas. II: Intra-operative ablation of non-resectable pancreatic cancer. A description of technique and initial outcome. JOP. 2005;6(6):588–92.

    PubMed  Google Scholar 

  3. Tanabe KK, Curley SA, Dodd GD, Siperstein AE, Goldberg SN. Radiofrequency ablation: the experts weigh in. Cancer. 2004;100(3):641–50. doi:10.1002/cncr.11919.

    Article  PubMed  Google Scholar 

  4. Howard JH, Tzeng CW, Smith JK, Eckhoff DE, Bynon JS, Wang T, Arnoletti JP, Heslin MJ. Radiofrequency ablation for unresectable tumors of the liver. Am Surg. 2008;74(7):594–600. discussion 600-591

    PubMed  Google Scholar 

  5. Goldberg SN, Hahn PF, Tanabe KK, Mueller PR, Schima W, Athanasoulis CA, Compton CC, Solbiati L, Gazelle GS. Percutaneous radiofrequency tissue ablation: does perfusion-mediated tissue cooling limit coagulation necrosis? J Vasc Interv Radiol. 1998;9(1 Pt 1):101–11.

    Article  CAS  PubMed  Google Scholar 

  6. Lu DS, Raman SS, Vodopich DJ, Wang M, Sayre J, Lassman C. Effect of vessel size on creation of hepatic radiofrequency lesions in pigs: assessment of the heat sink effect. AJR Am J Roentgenol. 2002;178(1):47–51. doi:10.2214/ajr.178.1.1780047.

    Article  PubMed  Google Scholar 

  7. Rubinsky B. Irreversible electroporation in medicine. Technol Cancer Res Treat. 2007;6(4):255–60.

    Article  PubMed  Google Scholar 

  8. Scheffer HJ, Nielsen K, van Tilborg AA, Vieveen JM, Bouwman RA, Kazemier G, Niessen HW, Meijer S, van Kuijk C, van den Tol MP, Meijerink MR. Ablation of colorectal liver metastases by irreversible electroporation: results of the COLDFIRE-I ablate-and-resect study. Eur Radiol. 2014;24(10):2467–75. doi:10.1007/s00330-014-3259-x.

    Article  CAS  PubMed  Google Scholar 

  9. Phillips MA, Narayan R, Padath T, Rubinsky B. Irreversible electroporation on the small intestine. Br J Cancer. 2012;106(3):490–5. doi:10.1038/bjc.2011.582.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Au JT, Kingham TP, Jun K, Haddad D, Gholami S, Mojica K, Monette S, Ezell P, Fong Y. Irreversible electroporation ablation of the liver can be detected with ultrasound B-mode and elastography. Surgery. 2013;153(6):787–93. doi:10.1016/j.surg.2012.11.022.

    Article  PubMed  Google Scholar 

  11. Ben-David E, Appelbaum L, Sosna J, Nissenbaum I, Goldberg SN. Characterization of irreversible electroporation ablation in in vivo porcine liver. AJR Am J Roentgenol. 2012;198(1):W62–8. doi:10.2214/ajr.11.6940.

    Article  PubMed  Google Scholar 

  12. Charpentier KP, Wolf F, Noble L, Winn B, Resnick M, Dupuy DE. Irreversible electroporation of the liver and liver hilum in swine. HPB: Off J Int Hepato Pancreato Biliary Assoc. 2011;13(3):168–73. doi:10.1111/j.1477-2574.2010.00261.x.

    Article  Google Scholar 

  13. Lee YJ, Lu DSK, Osuagwu F, Lassman C. Irreversible electroporation in porcine liver: short-and long-term effect on the hepatic veins and adjacent tissue by ct with pathological correlation. Investig Radiol. 2012;47(11):671–5.

    Article  Google Scholar 

  14. Golberg A, Bruinsma BG, Uygun BE, Yarmush ML. Tissue heterogeneity in structure and conductivity contribute to cell survival during irreversible electroporation ablation by electric field sinks. Sci Rep. 2015;5:8485. doi:10.1038/srep08485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Appelbaum L, Ben-David E, Sosna J, Nissenbaum Y, Goldberg SN. US findings after irreversible electroporation ablation: radiologic-pathologic correlation. Radiology. 2012;262(1):117–25. doi:10.1148/radiol.11110475.

    Article  PubMed  Google Scholar 

  16. Lee EW, Chen C, Prieto VE, Dry SM, Loh CT, Kee ST. Advanced hepatic ablation technique for creating complete cell death: irreversible electroporation. Radiology. 2010;255(2):426–33. doi:10.1148/radiol.10090337.

    Article  PubMed  Google Scholar 

  17. Lee EW, Loh CT, Kee ST. Imaging guided percutaneous irreversible electroporation: ultrasound and immunohistological correlation. Technol Cancer Res Treat. 2007;6(4):287–94.

    Article  PubMed  Google Scholar 

  18. Liu Y, Xiong Z, Zhou W, Hua Y, Li C, Yao C. Percutaneous ultrasound-guided irreversible electroporation: a goat liver study. Oncol Lett. 2012;4(3):450–4. doi:10.3892/ol.2012.781.

    PubMed  PubMed Central  Google Scholar 

  19. Edd JF, Horowitz L, Davalos RV, Mir LM, Rubinsky B. In vivo results of a new focal tissue ablation technique: irreversible electroporation. IEEE Trans Biomed Eng. 2006;53(7):1409–15. doi:10.1109/tbme.2006.873745.

    Article  PubMed  Google Scholar 

  20. Chen X, Ren Z, Zhu T, Zhang X, Peng Z, Xie H, Zhou L, Yin S, Sun J, Zheng S. Electric ablation with irreversible electroporation (IRE) in vital hepatic structures and follow-up investigation. Sci Rep. 2015;5:16233. doi:10.1038/srep16233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Choi YS, Kim HB, Chung J, Kim HS, Yi JH, Park JK. Preclinical analysis of irreversible electroporation on rat liver tissues using a microfabricated electroporator. Tissue Eng Part C Methods. 2010;16(6):1245–53. doi:10.1089/ten.TEC.2009.0803.

    Article  PubMed  Google Scholar 

  22. Maor E, Ivorra A, Leor J, Rubinsky B. The effect of irreversible electroporation on blood vessels. Technol Cancer Res Treat. 2007;6(4):307–12.

    Article  PubMed  Google Scholar 

  23. Maor E, Ivorra A, Leor J, Rubinsky B. Irreversible electroporation attenuates neointimal formation after angioplasty. IEEE Trans Biomed Eng. 2008;55(9):2268–74. doi:10.1109/tbme.2008.923909.

    Article  PubMed  Google Scholar 

  24. Narayanan G, Bhatia S, Echenique A, Suthar R, Barbery K, Yrizarry J. Vessel patency post irreversible electroporation. Cardiovasc Intervent Radiol. 2014;37(6):1523–9. doi:10.1007/s00270-014-0988-9.

    Article  PubMed  Google Scholar 

  25. Scheffer HJ, Melenhorst MC, Vogel JA, van Tilborg AA, Nielsen K, Kazemier G, Meijerink MR. Percutaneous irreversible electroporation of locally advanced pancreatic carcinoma using the dorsal approach: a case report. Cardiovasc Intervent Radiol. 2015;38(3):760–5. doi:10.1007/s00270-014-0950-x.

    Article  PubMed  Google Scholar 

  26. Martin RC 2nd, Kwon D, Chalikonda S, Sellers M, Kotz E, Scoggins C, McMasters KM, Watkins K. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg. 2015;262(3):486–494.; discussion 492-484. doi:10.1097/SLA.0000000000001441.

    Article  PubMed  Google Scholar 

  27. Philips P, Hays D, Martin RC. Irreversible electroporation ablation (IRE) of unresectable soft tissue tumors: learning curve evaluation in the first 150 patients treated. PLoS One. 2013;8(11):e76260. doi:10.1371/journal.pone.0076260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Silk MT, Wimmer T, Lee KS, Srimathveeravalli G, Brown KT, Kingham PT, Fong Y, Durack JC, Sofocleous CT, Solomon SB. Percutaneous ablation of peribiliary tumors with irreversible electroporation. J Vasc Interv Radiol: JVIR. 2014;25(1):112–8. doi:10.1016/j.jvir.2013.10.012.

    Article  PubMed  Google Scholar 

  29. van den Bos W, Scheffer HJ, Vogel JA, Wagstaff PG, de Bruin DM, de Jong MC, van Gemert MJ, de la Rosette JJ, Meijerink MR, Klaessens JH, Verdaasdonk RM. Thermal energy during irreversible electroporation and the influence of different ablation parameters. J Vasc Interv Radiol. 2016;27(3):433–43. doi:10.1016/j.jvir.2015.10.020.

    Article  PubMed  Google Scholar 

  30. Trueba-Arguinarena FJ, de Prado-Otero DS, Poves-Alvarez R. Pancreatic adenocarcinoma treated with irreversible electroporation case report: first experience and outcome. Medicine. 2015;94(26):e946. doi:10.1097/md.0000000000000946.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Scheffer HJ, Nielsen K, de Jong MC, van Tilborg AA, Vieveen JM, Bouwman AR, Meijer S, van Kuijk C, van den Tol PM, Meijerink MR. Irreversible electroporation for nonthermal tumor ablation in the clinical setting: a systematic review of safety and efficacy. J Vasc Interv Radiol. 2014;25(7):997–1011.; quiz 1011. doi:10.1016/j.jvir.2014.01.028.

    Article  PubMed  Google Scholar 

  32. Kingham TP, Karkar AM, D'Angelica MI, Allen PJ, Dematteo RP, Getrajdman GI, Sofocleous CT, Solomon SB, Jarnagin WR, Fong Y. Ablation of perivascular hepatic malignant tumors with irreversible electroporation. J Am Coll Surg. 2012;215(3):379–87. doi:10.1016/j.jamcollsurg.2012.04.029.

    Article  PubMed  Google Scholar 

  33. Hosein PJ, Echenique A, Loaiza-Bonilla A, Froud T, Barbery K, Rocha Lima CM, Yrizarry JM, Narayanan G. Percutaneous irreversible electroporation for the treatment of colorectal cancer liver metastases with a proposal for a new response evaluation system. J Vasc Interv Radiol. 2014;25(8):1233–1239. e1232. doi:10.1016/j.jvir.2014.04.007.

    Article  PubMed  Google Scholar 

  34. Cannon R, Ellis S, Hayes D, Narayanan G, Martin RC 2nd. Safety and early efficacy of irreversible electroporation for hepatic tumors in proximity to vital structures. J Surg Oncol. 2013;107(5):544–9. doi:10.1002/jso.23280.

    Article  PubMed  Google Scholar 

  35. Dollinger M, Zeman F, Niessen C, Lang SA, Beyer LP, Muller M, Stroszczynski C, Wiggermann P. Bile duct injury after irreversible electroporation of hepatic malignancies: evaluation of MR imaging findings and laboratory values. J Vasc Interv Radiol. 2015; doi:10.1016/j.jvir.2015.10.002.

  36. Scheffer HJ, Vroomen LG, de Jong MC, Melenhorst MC, Zonderhuis BM, Daams F, Vogel JA, Besselink MG, van Kuijk C, Witvliet J, de van der Schueren MA, de Gruijl TD, Stam AG, van den Tol PM, van Delft F, Kazemier G, Meijerink MR. Ablation of locally advanced pancreatic cancer with percutaneous irreversible electroporation: Results of the phase I/II PANFIRE study. Radiology. 2017;282(2):585–597. doi:10.1148/radiol.2016152835. Epub 2016 Sep 6

  37. Bower M, Sherwood L, Li Y, Martin R. Irreversible electroporation of the pancreas: definitive local therapy without systemic effects. J Surg Oncol. 2011;104(1):22–8. doi:10.1002/jso.21899.

    Article  PubMed  Google Scholar 

  38. Charpentier KP, Wolf F, Noble L, Winn B, Resnick M, Dupuy DE. Irreversible electroporation of the pancreas in swine: a pilot study. HPB (Oxford). 2010;12(5):348–51. doi:10.1111/j.1477-2574.2010.00174.x.

    Article  Google Scholar 

  39. Fritz S, Sommer CM, Vollherbst D, Wachter MF, Longerich T, Sachsenmeier M, Knapp J, Radeleff BA, Werner J. Irreversible electroporation of the pancreas is feasible and safe in a porcine survival model. Pancreas. 2015;44(5):791–8. doi:10.1097/mpa.0000000000000331.

    Article  PubMed  Google Scholar 

  40. Wimmer T, Srimathveeravalli G, Gutta N, Ezell PC, Monette S, Kingham TP, Maybody M, Durack JC, Fong Y, Solomon SB. Comparison of simulation-based treatment planning with imaging and pathology outcomes for percutaneous CT-guided irreversible electroporation of the porcine pancreas: a pilot study. J Vasc Intervent Radiol: JVIR. 2013;24(11):1709–18. doi:10.1016/j.jvir.2013.05.056.

    Article  Google Scholar 

  41. Martin RC 2nd, McFarland K, Ellis S, Velanovich V. Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma. J Am Coll Surg. 2012;215(3):361–9. doi:10.1016/j.jamcollsurg.2012.05.021.

    Article  PubMed  Google Scholar 

  42. Paiella S, Butturini G, Frigerio I, Salvia R, Armatura G, Bacchion M, Fontana M, D’Onofrio M, Martone E, Bassi C. Safety and feasibility of irreversible electroporation (IRE) in patients with locally advanced pancreatic cancer: results of a prospective study. Dig Surg. 2015;32(2):90–7. doi:10.1159/000375323.

    Article  PubMed  Google Scholar 

  43. Kluger MD, Epelboym I, Schrope BA, Mahendraraj K, Hecht EM, Susman J, Weintraub JL, Chabot JA. Single-institution experience with irreversible electroporation for T4 pancreatic cancer: first 50 patients. Ann Surg Oncol. 2016;23(5):1736–43. doi:10.1245/s10434-015-5034-x.

    Article  PubMed  Google Scholar 

  44. Vogel JA, Rombouts SJ, de Rooij T, van Delden OM, Dijkgraaf MG, van Gulik TM, van Hooft JE, van Laarhoven HW, Martin RC, Schoorlemmer A, Wilmink JW, van Lienden KP, Busch OR, Besselink MG. Induction Chemotherapy followed by resection or irreversible electroporation in locally advanced pancreatic cancer (IMPALA): A prospective cohort study. Ann Surg Oncol. 2017. doi:10.1245/s10434-017-5900-9. [Epub ahead of print]

  45. Deodhar A, Monette S, Single GW Jr, Hamilton WC Jr, Thornton R, Maybody M, Coleman JA, Solomon SB. Renal tissue ablation with irreversible electroporation: preliminary results in a porcine model. Urology. 2011;77(3):754–60. doi:10.1016/j.urology.2010.08.036.

    Article  PubMed  Google Scholar 

  46. Olweny EO, Kapur P, Tan YK, Park SK, Adibi M, Cadeddu JA. Irreversible electroporation: evaluation of nonthermal and thermal ablative capabilities in the porcine kidney. Urology. 2013;81(3):679–84. doi:10.1016/j.urology.2012.11.026.

    Article  PubMed  Google Scholar 

  47. Srimathveeravalli G, Silk M, Wimmer T, Monette S, Kimm S, Maybody M, Solomon SB, Coleman J, Durack JC. Feasibility of catheter-directed intraluminal irreversible electroporation of porcine ureter and acute outcomes in response to increasing energy delivery. J Vasc Intervent Radiol: JVIR. 2015;26(7):1059–66. doi:10.1016/j.jvir.2015.01.020.

    Article  Google Scholar 

  48. Tracy CR, Kabbani W, Cadeddu JA. Irreversible electroporation (IRE): a novel method for renal tissue ablation. BJU Int. 2011;107(12):1982–7. doi:10.1111/j.1464-410X.2010.09797.x.

    Article  PubMed  Google Scholar 

  49. Wimmer T, Srimathveeravalli G, Silk M, Monette S, Gutta N, Maybody M, Erinjery JP, Coleman JA, Solomon SB, Sofocleous CT. Feasibility of a modified biopsy needle for irreversible electroporation ablation and periprocedural tissue sampling. Technol Cancer Res Treat. 2015; doi:10.1177/1533034615608739.

  50. Wendler JJ, Pech M, Porsch M, Janitzky A, Fischbach F, Buhtz P, Vogler K, Huhne S, Borucki K, Strang C, Mahnkopf D, Ricke J, Liehr UB. Urinary tract effects after multifocal nonthermal irreversible electroporation of the kidney: acute and chronic monitoring by magnetic resonance imaging, intravenous urography and urinary cytology. Cardiovasc Intervent Radiol. 2012;35(4):921–6. doi:10.1007/s00270-011-0257-0.

    Article  PubMed  Google Scholar 

  51. Thomson KR, Cheung W, Ellis SJ, Federman D, Kavnoudias H, Loader-Oliver D, Roberts S, Evans P, Ball C, Haydon A. Investigation of the safety of irreversible electroporation in humans. J Vasc Interv Radiol. 2011;22(5):611–21. doi:10.1016/j.jvir.2010.12.014.

    Article  PubMed  Google Scholar 

  52. Trimmer CK, Khosla A, Morgan M, Stephenson SL, Ozayar A, Cadeddu JA. Minimally invasive percutaneous treatment of small renal tumors with irreversible electroporation: a single-center experience. J Vasc Interv Radiol. 2015;26(10):1465–71. doi:10.1016/j.jvir.2015.06.028.

    Article  PubMed  Google Scholar 

  53. Valerio M, Strickert PD, Ahmed HU, Dickinson L, Ponsky L, Shnier R, Allen C, Emberton M. Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer. Prostate Cancer Prostatic Dis. 2014;17(4):343–7. doi:10.1038/pcan.2014.33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ting F, Tran M, Bohm M, Siriwardana A, Van Leeuwen PJ, Haynes AM, Delprado W, Shnier R, Stricker PD. Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control. Prostate Cancer Prostatic Dis. 2016;19(1):46–52. doi:10.1038/pcan.2015.47.

    Article  CAS  PubMed  Google Scholar 

  55. Li W, Fan Q, Ji Z, Qiu X, Li Z. The effects of irreversible electroporation (IRE) on nerves. PLoS One. 2011;6(4):e18831.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wong SSM, Hui JWY, Chan AWH, Chu CM, Rowlands DK, Yu SCH. Irreversible electroporation of the femoral neurovascular bundle: imaging and histologic evaluation in a swine model. J Vasc Interv Radiol. 2015;26(8):1212–1220.e1211.

    Article  PubMed  Google Scholar 

  57. Schoellnast H, Monette S, Ezell PC, Deodhar A, Maybody M, Erinjeri JP, Stubblefield MD, Single GW Jr, Hamilton WC Jr, Solomon SB. Acute and subacute effects of irreversible electroporation on nerves: experimental study in a pig model. Radiology. 2011;260(2):421–7. doi:10.1148/radiol.11103505.

    Article  PubMed  Google Scholar 

  58. Schoellnast H, Monette S, Ezell PC, Maybody M, Erinjeri JP, Stubblefield MD, Single G, Solomon SB. The delayed effects of irreversible electroporation ablation on nerves. Eur Radiol. 2013;23(2):375–80. doi:10.1007/s00330-012-2610-3.

    Article  PubMed  Google Scholar 

  59. Tam AL, Abdelsalam ME, Gagea M, Ensor JE, Moussa M, Ahmed M, Goldberg SN, Dixon K, McWatters A, Miller JJ, Srimathveeravalli G, Solomon SB, Avritscher R, Wallace MJ, Gupta S. Irreversible electroporation of the lumbar vertebrae in a porcine model: is there clinical-pathologic evidence of neural toxicity? Radiology. 2014;272(3):709–19. doi:10.1148/radiol.14132560.

    Article  PubMed  Google Scholar 

  60. Niessen C, Jung EM, Schreyer AG, Wohlgemuth WA, Trabold B, Hahn J, Rechenmacher M, Stroszczynski C, Wiggermann P. Palliative treatment of presacral recurrence of endometrial cancer using irreversible electroporation: a case report. J Med Case Rep. 2013;7:128. doi:10.1186/1752-1947-7-128.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Vroomen LGPH, Scheffer HJ, Melenhorst MCAM, van Grieken N, van den Tol MP, Meijerink MR. Irreversible Electroporation to Treat Malignant Tumor Recurrences Within the Pelvic Cavity: A Case Series. Cardiovasc Intervent Radiol. 2017 May 3. doi:10.1007/s00270-017-1657-6.

  62. Marshall RH, Avila EK, Solomon SB, Erinjeri JP, Maybody M. Feasibility of intraoperative nerve monitoring in preventing thermal damage to the “Nerve at Risk” during image-guided ablation of tumors. Cardiovasc Intervent Radiol. 2015; doi:10.1007/s00270-015-1287-9.

  63. Faroja M, Ahmed M, Appelbaum L, Ben-David E, Moussa M, Sosna J, Nissenbaum I, Goldberg SN. Irreversible electroporation ablation: is all the damage nonthermal? Radiology. 2013;266(2):462–70. doi:10.1148/radiol.12120609.

    Article  PubMed  Google Scholar 

  64. Dunki-Jacobs EM, Philips P, Martin RC 2nd. Evaluation of thermal injury to liver, pancreas and kidney during irreversible electroporation in an in vivo experimental model. Br J Surg. 2014;101(9):1113–21. doi:10.1002/bjs.9536.

    Article  CAS  PubMed  Google Scholar 

  65. Scheffer HJ, Vogel JA, van den Bos W, Neal RE 2nd, van Lienden KP, Besselink MG, van Gemert MJ, van der Geld CW, Meijerink MR, Klaessens JH, Verdaasdonk RM. The influence of a metal stent on the distribution of thermal energy during irreversible electroporation. PLoS One. 2016;11(2):e0148457. doi:10.1371/journal.pone.0148457.

    Article  PubMed  PubMed Central  Google Scholar 

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Vogel, J.A., Vroomen, L.G.P.H., Srimathveeravalli, G. (2018). The Effect of Irreversible Electroporation on Blood Vessels, Bile Ducts, Urinary Tract, Intestines, and Nerves. In: Meijerink, M., Scheffer, H., Narayanan, G. (eds) Irreversible Electroporation in Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-55113-5_5

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