Top

Published in:

01-05-2017 | ORIGINAL ARTICLE

Successful ablation of lymph nodes using irreversible electroporation (IRE) in a porcine survival model

Authors: Stefan Fritz, Christof M. Sommer, Thomas Longerich, Clemens Kuhn-Neureuther, Boris Radeleff, Jens Werner, Thilo Hackert

Published in: Langenbeck's Archives of Surgery | Issue 3/2017

Abstract

Background

Irreversible electroporation (IRE), a nonthermal injury ablation technique, has been shown to be effective and safe in various organs, such as in the kidney, liver, prostate, or in pancreas. In contrast to radiofrequency or microwave ablation, IRE is also effective in the neighborhood of major vessels. Many human cancers reveal lymphatic spread. The present study aimed to evaluate technical feasibility and safety of IRE in lymphatic tissue. To our knowledge, this is the first report showing successful IRE of lymph nodes in a standardized porcine survival model.

Methods

A total of ten pigs were divided into two study groups. Five animals received ECG-gated IRE of mesenteric lymph nodes of the small bowel and were sacrificed 2 h after ablation. Another five animals were followed up for 7 days. Clinical parameters, laboratory and abdominal imaging by contrast-enhanced computed tomography, as well as histology were obtained from all animals at different time points.

Results

During and after IRE ablation, no cardiocirculatory side effects were noted in any of the animals. In the acute phase experiments, no damage to adjacent organs and no thermal injuries were seen following IRE. One hundred twenty minutes after ablation, no significant laboratory changes were observed. In the survival group, all animals recovered quickly and showed normal activity and feeding habits indicating a minimal pain level. Seven days after IRE ablation, a significant increase in white blood cell count was observed, while creatinine, urea, or hemoglobin remained unchanged. Computed tomography revealed a hypodense lesion following IRE already at 2 h. Histopathology showed coagulation necrosis of the treated lymph nodes with preservation of the lymph node capsule.

Conclusions

This porcine survival model shows that IRE can safely and effectively be performed in lymph nodes. Thus, IRE might display a novel approach for therapy of lymph node metastasis. Further clinical studies are needed to evaluate the oncologic outcome of IRE ablation in lymph node metastasis.

Davalos RV, Mir IL, Rubinsky B (2005) Tissue ablation with irreversible electroporation. Ann Biomed Eng 33(2):223–231CrossRefPubMed

Golberg A, Yarmush ML (2013) Nonthermal irreversible electroporation: fundamentals, applications, and challenges. IEEE Trans Biomed Eng 60(3):707–714CrossRefPubMed

Yachida S, Iacobuzio-Donahue CA (2009) The pathology and genetics of metastatic pancreatic cancer. Arch Pathol Lab Med 133(3):413–422PubMed

Kingham TP, Karkar AM, D'Angelica MI et al (2012) Ablation of perivascular hepatic malignant tumors with irreversible electroporation. J Am Coll Surg 215(3):379–387CrossRefPubMed

Ting F, Tran M, Bohm M, et al. (2015) Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control. Prostate Cancer Prostatic Dis

Martin RC 2nd, Kwon D, Chalikonda S et al (2015) Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg 262(3):486–494 discussion 492-4 CrossRefPubMed

Fritz S, Sommer CM, Vollherbst D et al (2015) Irreversible electroporation of the pancreas is feasible and safe in a porcine survival model. Pancreas 44(5):791–798CrossRefPubMed

Narayanan G, Hosein PJ, Arora G et al (2012) Percutaneous irreversible electroporation for downstaging and control of unresectable pancreatic adenocarcinoma. J Vasc Interv Radiol 23(12):1613–1621CrossRefPubMed

Rombouts SJ, Vogel JA, van Santvoort HC et al (2015) Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer. Br J Surg 102(3):182–193CrossRefPubMed

10.

Narayanan G, Bhatia S, Echenique A et al (2014) Vessel patency post irreversible electroporation. Cardiovasc Intervent Radiol 37(6):1523–1529CrossRefPubMed

11.

Vogel JA, van Veldhuisen E, Agnass P et al (2016) Time-dependent impact of irreversible electroporation on pancreas, liver, blood vessels and nerves: a systematic review of experimental studies. PLoS One 11(11):e0166987CrossRefPubMedPubMedCentral

12.

Silk M, Tahour D, Srimathveeravalli G et al (2014) The state of irreversible electroporation in interventional oncology. Semin Intervent Radiol 31(2):111–117CrossRefPubMedPubMedCentral

13.

Scheffer HJ, Nielsen K, de Jong MC et al (2014) Irreversible electroporation for nonthermal tumor ablation in the clinical setting: a systematic review of safety and efficacy. J Vasc Interv Radiol 25(7):997–1011 quiz 1011 CrossRefPubMed

14.

Deipolyi AR, Golberg A, Yarmush ML et al (2014) Irreversible electroporation: evolution of a laboratory technique in interventional oncology. Diagn Interv Radiol 20(2):147–154PubMedPubMedCentral

15.

Neal RE 2nd, Davalos RV (2009) The feasibility of irreversible electroporation for the treatment of breast cancer and other heterogeneous systems. Ann Biomed Eng 37(12):2615–2625CrossRefPubMed

16.

Shimizu Y, Yamaue H, Maguchi H et al (2013) Predictors of malignancy in intraductal papillary mucinous neoplasm of the pancreas: analysis of 310 pancreatic resection patients at multiple high-volume centers. Pancreas 42(5):883–888CrossRefPubMed

17.

Arena CB, Rylander MN, Davalos RV (2009) Theoretical study for the treatment of pancreatic cancer using electric pulses. Conf Proc IEEE Eng Med Biol Soc 2009:5997–6000PubMed

18.

Krassowska W, Filev PD (2007) Modeling electroporation in a single cell. Biophys J 92(2):404–417CrossRefPubMed

19.

Marchegiani G, Mino-Kenudson M, Sahora K, et al. (2014) IPMN involving the main pancreatic duct: biology, epidemiology, and long-term outcomes following resection. Ann Surg

20.

Thomson KR, Cheung W, Ellis SJ et al (2011) Investigation of the safety of irreversible electroporation in humans. J Vasc Interv Radiol 22(5):611–621CrossRefPubMed

21.

Wagstaff PG, Buijs M, van den Bos W et al (2016) Irreversible electroporation: state of the art. Onco Targets Ther 9:2437–2446CrossRefPubMedPubMedCentral

22.

Shen H, Yu Z, Zhao J et al (2016) Early diagnosis and treatment of gastrointestinal neuroendocrine tumors. Oncol Lett 12(5):3385–3392PubMedPubMedCentral

23.

Strobel O, Hartwig W, Hackert T et al (2013) Re-resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with encouraging survival. Ann Surg Oncol 20(3):964–972CrossRefPubMed

24.

Bower M, Sherwood L, Li Y et al (2011) Irreversible electroporation of the pancreas: definitive local therapy without systemic effects. J Surg Oncol 104(1):22–28CrossRefPubMed

25.

Tracy CR, Kabbani W, Cadeddu JA (2011) Irreversible electroporation (IRE): a novel method for renal tissue ablation. BJU Int 107(12):1982–1987CrossRefPubMed

26.

Swindle MM Second edition: swine in the laboratory—surgery, anesthesia, imaging, and experimental techniques. Taylor & Francis Group, Boca Raton, London, New York, 2007, Medical University of South Carolina, Charleston, SC 2007

27.

Sommer CM, Fritz S, Vollherbst D et al (2015) CT-guided irreversible electroporation in an acute porcine liver model: effect of previous transarterial iodized oil tissue marking on technical parameters, 3D computed tomographic rendering of the electroporation zone, and histopathology. Cardiovasc Intervent Radiol 38(1):191–200CrossRefPubMed

28.

Sommer CM, Fritz S, Wachter MF et al (2013) Irreversible electroporation of the pig kidney with involvement of the renal pelvis: technical aspects, clinical outcome, and three-dimensional CT rendering for assessment of the treatment zone. J Vasc Interv Radiol 24(12):1888–1897CrossRefPubMed

29.

Cannon R, Ellis S, Hayes D et al (2013) Safety and early efficacy of irreversible electroporation for hepatic tumors in proximity to vital structures. J Surg Oncol 107(5):544–549CrossRefPubMed

30.

Trueba-Arguinarena FJ, de Prado-Otero DS, Poves-Alvarez R (2015) Pancreatic adenocarcinoma treated with irreversible electroporation case report: first experience and outcome. Medicine (Baltimore) 94(26):e946CrossRef

31.

Bagla S, Papadouris D (2012) Percutaneous irreversible electroporation of surgically unresectable pancreatic cancer: a case report. J Vasc Interv Radiol 23(1):142–145CrossRefPubMed

32.

Deodhar A, Dickfeld T, Single GW et al (2011) Irreversible electroporation near the heart: ventricular arrhythmias can be prevented with ECG synchronization. AJR Am J Roentgenol 196(3):W330–W335CrossRefPubMedPubMedCentral

33.

Ierardi AM, Lucchina N, Duka E et al (2014) “Vascular lock” causing splenic perfusion defects during irreversible electroporation of a locally advanced pancreatic tumor. JOP 15(6):604–608PubMed

34.

Dollinger M, Muller-Wille R, Zeman F et al (2015) Irreversible electroporation of malignant hepatic tumors—alterations in venous structures at subacute follow-up and evolution at mid-term follow-up. PLoS One 10(8):e0135773CrossRefPubMedPubMedCentral

35.

Al-Sakere B, Andre F, Bernat C et al (2007) Tumor ablation with irreversible electroporation. PLoS One 2(11):e1135CrossRefPubMedPubMedCentral

36.

Daniels C, Rubinsky B (2009) Electrical field and temperature model of nonthermal irreversible electroporation in heterogeneous tissues. J Biomech Eng 131(7):071006CrossRefPubMed

37.

Andre FM, Gehl J, Sersa G et al (2008) Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin. Hum Gene Ther 19(11):1261–1271CrossRefPubMed

38.

Wimmer T, Srimathveeravalli G, Gutta N et al (2013) 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 Interv Radiol 24(11):1709–1718CrossRefPubMed

39.

Zhang Z, Li W, Procissi D, et al. (2013) Rapid dramatic alterations to the tumor microstructure in pancreatic cancer following irreversible electroporation ablation. Nanomedicine (Lond)

40.

Lee EW, Chen C, Prieto VE et al (2010) Advanced hepatic ablation technique for creating complete cell death: irreversible electroporation. Radiology 255(2):426–433CrossRefPubMed

41.

Dunki-Jacobs EM, Philips P, Martin RC 2nd (2014) Evaluation of thermal injury to liver, pancreas and kidney during irreversible electroporation in an in vivo experimental model. Br J Surg 101(9):1113–1121CrossRefPubMed

42.

van den Bos W, Scheffer HJ, Vogel JA et al (2016) Thermal energy during irreversible electroporation and the influence of different ablation parameters. J Vasc Interv Radiol 27(3):433–443CrossRefPubMed

43.

Bhutiani N, Agle S, Li Y et al (2016) Irreversible electroporation enhances delivery of gemcitabine to pancreatic adenocarcinoma. J Surg Oncol 114(2):181–186CrossRefPubMed

44.

Brown DB, Narayanan G (2012) Interventional radiology and the pancreatic cancer patient. Cancer J 18(6):591–601CrossRefPubMed

45.

Au JT, Wong J, Mittra A et al (2011) Irreversible electroporation is a surgical ablation technique that enhances gene transfer. Surgery 150(3):474–479CrossRefPubMedPubMedCentral

46.

Edd JF, Horowitz L, Davalos RV et al (2006) In vivo results of a new focal tissue ablation technique: irreversible electroporation. IEEE Trans Biomed Eng 53(7):1409–1415CrossRefPubMed

47.

Faroja M, Ahmed M, Appelbaum L et al (2013) Irreversible electroporation ablation: is all the damage nonthermal? Radiology 266(2):462–470CrossRefPubMed

48.

Wagstaff PG, de Bruin DM, van den Bos W et al (2015) Irreversible electroporation of the porcine kidney: temperature development and distribution. Urol Oncol 33(4):168 e1-7CrossRefPubMed

49.

Ball C, Thomson KR, Kavnoudias H (2010) Irreversible electroporation: a new challenge in “out of operating theater” anesthesia. Anesth Analg 110(5):1305–1309CrossRefPubMed

Title: Successful ablation of lymph nodes using irreversible electroporation (IRE) in a porcine survival model
Authors: Stefan Fritz
Christof M. Sommer
Thomas Longerich
Clemens Kuhn-Neureuther
Boris Radeleff
Jens Werner
Thilo Hackert
Publication date: 01-05-2017
Publisher: Springer Berlin Heidelberg
Published in: Langenbeck's Archives of Surgery / Issue 3/2017
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-017-1579-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Successful ablation of lymph nodes using irreversible electroporation (IRE) in a porcine survival model

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2017

Effects of a preoperative immune-modulating diet in patients with esophageal cancer: a prospective parallel group randomized study

Gut microbiota and bacterial translocation in digestive surgery: the impact of probiotics

Esophagectomy for cancer in octogenarians: should we do it?

A surgical department for intensified care

Combined hepatic arterial resection in pancreatic resections for locally advanced pancreatic cancer

Intensive care and health outcomes of open abdominal treatment: long-term results of vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM)