Abstract

Our objective was to develop a technique for performing irreversible electroporation (IRE) of esophageal tumors while mitigating thermal damage to the healthy lumen wall. We investigated noncontact IRE using a wet electrode approach for tumor ablation in a human esophagus with finite element models for electric field distribution, joule heating, thermal flux, and metabolic heat generation. Simulation results indicated the feasibility of tumor ablation in the esophagus using an catheter mounted electrode immersed in diluted saline. The ablation size was clinically relevant, with substantially lesser thermal damage to the healthy esophageal wall when compared to IRE performed by placing a monopolar electrode directly into the tumor. Additional simulations were used to estimate ablation size and penetration during noncontact wet-electrode IRE (wIRE) in the healthy swine esophagus. A novel catheter electrode was manufactured and wIRE evaluated in seven pigs. wIRE was performed by securing the device in the esophagus and using diluted saline to isolate the electrode from the esophageal wall while providing electric contact. Computed tomography and fluoroscopy were performed post-treatment to document acute lumen patency. Animals were sacrificed within four hours following treatment for histologic analysis of the treated esophagus. The procedure was safely completed in all animals; post-treatment imaging revealed intact esophageal lumen. The ablations were visually distinct on gross pathology, demonstrating full thickness, circumferential regions of cell death (3.52 ± 0.89 mm depth). Acute histologic changes were not evident in nerves or extracellular matrix architecture within the treatment site. Catheter directed noncontact IRE is feasible for performing penetrative ablations in the esophagus while avoiding thermal damage.

References

1.
Njei
,
B.
,
Mccarty
,
T. R.
, and
Birk
,
J. W.
,
2016
, “
Trends in Esophageal Cancer Survival in United States Adults From 1973 to 2009: A SEER Database Analysis
,”
J. Gastroenterol. Hepatol.
,
31
(
6
), pp.
1141
1146
.10.1111/jgh.13289
2.
Khangura
,
S. K.
, and
Greenwald
,
B. D.
,
2013
, “
Endoscopic Management of Esophageal Cancer After Definitive Chemoradiotherapy
,”
Dig. Dis. Sci.
,
58
(
6
), pp.
1477
1485
.10.1007/s10620-012-2554-0
3.
Haefner
,
M. F.
,
Lang
,
K.
,
Krug
,
D.
,
Koerber
,
S. A.
,
Uhlmann
,
L.
,
Kieser
,
M.
,
Debus
,
J.
, and
Sterzing
,
F.
,
2015
, “
Prognostic Factors, Patterns of Recurrence and Toxicity for Patients With Esophageal Cancer Undergoing Definitive Radiotherapy or Chemo-Radiotherapy
,”
J. Radiat. Res
,
56
(
4
), pp.
742
749
.10.1093/jrr/rrv022
4.
Dallal
,
H. J.
,
Smith
,
G. D.
,
Grieve
,
D. C.
,
Ghosh
,
S.
,
Penman
,
I. D.
, and
Palmer
,
K. R.
,
2001
, “
A Randomized Trial of Thermal Ablative Therapy Versus Expandable Metal Stents in the Palliative Treatment of Patients With Esophageal Carcinoma
,”
Gastrointest. Endosc.
,
54
(
5
), pp.
549
557
.10.1067/mge.2001.118947
5.
Akhtar
,
K.
,
Byrne
,
J. P.
,
Bancewicz
,
J.
, and
Attwood
,
S. E. A.
,
2000
, “
Argon Beam Plasma Coagulation in the Management of Cancers of the Esophagus and Stomach
,”
Surg. Endosc.
,
14
(
12
), pp.
1127
1130
.10.1007/s004640000266
6.
Lightdale
,
C. J.
,
Heier
,
S. K.
,
Marcon
,
N. E.
,
McCaughan
,
J. S.
,
Gerdes
,
H.
,
Overholt
,
B. F.
,
Sivak
,
M. V.
, et al.,
1995
, “
Photodynamic Therapy With Porfimer Sodium Versus Thermal Ablation Therapy With Nd:YAG Laser for Palliation of Esophageal Cancer: A Multicenter Randomized Trial
,”
Gastrointest. Endosc.
,
42
(
6
), pp.
507
512
.10.1016/S0016-5107(95)70002-1
7.
Al-Sakere
,
B.
,
André
,
F.
,
Bernat
,
C.
,
Connault
,
E.
,
Opolon
,
P.
,
Davalos
,
R. V.
,
Rubinsky
,
B.
, and
Mir
,
L. M.
,
2007
, “
Tumor Ablation With Irreversible Electroporation
,”
PLoS One
,
2
(
11
), p.
e1135
.10.1371/journal.pone.0001135
8.
Rubinsky
,
B.
,
2007
, “
Irreversible Electroporation in Medicine
,”
Technol. Cancer Res. Treat.
,
6
(
4
), pp.
255
259
.10.1177/153303460700600401
9.
Garcia
,
P. A.
,
Davalos
,
R. V.
, and
Miklavcic
,
D.
,
2014
, “
A Numerical Investigation of the Electric and Thermal Cell Kill Distributions in Electroporation-Based Therapies in Tissue
,”
PLoS One
,
9
(
8
), p.
e103083
.10.1371/journal.pone.0103083
10.
Deodhar
,
A.
,
Monette
,
S.
,
Single
,
G. W.
,
Hamilton
,
W. C.
,
Thornton
,
R.
,
Maybody
,
M.
,
Coleman
,
J. A.
, and
Solomon
,
S. B.
,
2011
, “
Renal Tissue Ablation With Irreversible Electroporation: Preliminary Results in a Porcine Model
,”
Urology
,
77
(
3
), pp.
754
760
.10.1016/j.urology.2010.08.036
11.
Wendler
,
J. J.
,
Porsch
,
M.
,
Hühne
,
S.
,
Baumunk
,
D.
,
Buhtz
,
P.
,
Fischbach
,
F.
,
Pech
,
M.
, et al.,
2013
, “
Short- and Mid-Term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model
,”
Cardiovasc. Interventional Radiol.
,
36
(
2
), pp.
512
520
.10.1007/s00270-012-0452-7
12.
Wah
,
T. M.
,
Lenton
,
J.
,
Smith
,
J.
,
Bassett
,
P.
,
Jagdev
,
S.
,
Ralph
,
C.
,
Vasudev
,
N.
, et al.,
2021
, “
Irreversible Electroporation (IRE) in Renal Cell Carcinoma (RCC): a Mid-Term Clinical Experience
,”
Eur. Radiol.
,
31
(
10
), pp.
7491
7499
.10.1007/s00330-021-07846-5
13.
Hsiao
,
C. Y.
,
Yang
,
P. C.
,
Li
,
X.
, and
Huang
,
K. W.
,
2020
, “
Clinical Impact of Irreversible Electroporation Ablation for Unresectable Hilar Cholangiocarcinoma
,”
Sci. Rep.
10
(
1
), pp.
1
6
.10.1038/s41598-020-67772-2
14.
Silk
,
M. T.
,
Wimmer
,
T.
,
Lee
,
K. S.
,
Srimathveeravalli
,
G.
,
Brown
,
K. T.
,
Kingham
,
P. T.
,
Fong
,
Y.
, et al.,
2014
, “
Percutaneous Ablation of Peribiliary Tumors With Irreversible Electroporation
,”
J. Vasc. Interventional Radiol.
,
25
(
1
), pp.
112
118
.10.1016/j.jvir.2013.10.012
15.
Reddy
,
V. Y.
,
Koruth
,
J.
,
Jais
,
P.
,
Petru
,
J.
,
Timko
,
F.
,
Skalsky
,
I.
,
Hebeler
,
R.
, et al.,
2018
, “
Ablation of Atrial Fibrillation With Pulsed Electric Fields: An Ultra-Rapid, Tissue-Selective Modality for Cardiac Ablation
,”
JACC Clin. Electrophysiol.
,
4
(
8
), pp.
987
995
.10.1016/j.jacep.2018.04.005
16.
Faroja
,
M.
,
Ahmed
,
M.
,
Appelbaum
,
L.
,
Ben-David
,
E.
,
Moussa
,
M.
,
Sosna
,
J.
,
Nissenbaum
,
I.
, and
Nahum Goldberg
,
S.
,
2013
, “
Irreversible Electroporation Ablation: Is All the Damage Nonthermal?
,”
Radiology
,
266
(
2
), pp.
462
470
.10.1148/radiol.12120609
17.
Agnass
,
P.
,
van Veldhuisen
,
E.
,
Vogel
,
J. A.
,
Kok
,
H. P.
,
de Keijzer
,
M. J.
,
Schooneveldt
,
G.
,
de Haan
,
L. R.
, et al.,
2020
, “
Thermodynamic Profiling During Irreversible Electroporation in Porcine Liver and Pancreas: A Case Study Series
,”
J. Clin. Transl. Res.
,
5
(
3
), pp.
109
132
.10.18053/jctres.05.202003.004
18.
van den Bos
,
W.
,
Scheffer
,
H. J.
,
Vogel
,
J. A.
,
Wagstaff
,
P. G. K.
,
de Bruin
,
D. M.
,
de Jong
,
M. C.
,
van Gemert
,
M. J. C.
, et al.,
2016
, “
Thermal Energy During Irreversible Electroporation and the Influence of Different Ablation Parameters
,”
J. Vasc. Interventional Radiol.
,
27
(
3
), pp.
433
443
.10.1016/j.jvir.2015.10.020
19.
Ivorra
,
A.
,
2008
, “
Use of Conductive Gels for Electric Field Homogenization Increases the Antitumor Efficacy of Electroporation Therapies
,”
Phys. Med. Biol.
, 53(22), pp.
6605
6618
.10.1088/0031-9155/53/22/020
20.
Edd
,
J. F.
, and
Davalos
,
R. V.
,
2007
, “
Mathematical Modeling of Irreversible Electroporation for Treatment Planning
,”
Technol. Cancer Res Treat.
,
6
(
4
), pp.
275
286
.10.1177/153303460700600403
21.
Patti
,
M. G.
,
Gantert
,
W.
, and
Way
,
L. W.
,
1997
, “
Surgery of the Esophagus: Anatomy and Physiology
,”
Surg. Clin. North Am.
,
77
(
5
), pp.
959
970
.10.1016/S0039-6109(05)70600-9
22.
Corovic
,
S.
,
Lackovic
,
I.
,
Sustaric
,
P.
,
Sustar
,
T.
,
Rodic
,
T.
, and
Miklavcic
,
D.
,
2013
, “
Modeling of Electric Field Distribution in Tissues During Electroporation
,”
Biomed. Eng. Online
,
12
(
1
), p.
1
.10.1186/1475-925X-12-16
23.
Šel
,
D.
,
Cukjati
,
D.
,
Batiuskaite
,
D.
,
Slivnik
,
T.
,
Mir
,
L. M.
, and
Miklavčič
,
D.
,
2005
, “
Sequential Finite Element Model of Tissue Electropermeabilization
,”
IEEE Trans. Biomed. Eng.
,
52
(
5
), pp.
816
827
.10.1109/TBME.2005.845212
24.
Beitel-White
,
N.
,
Bhonsle
,
S.
,
Ii
,
R. C. G. M.
, and
Davalos
,
R. V.
,
2018
, “
Electrical Characterization of Human Biological Tissue for Irreversible Electroporation Treatments
,”
40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
,
Honolulu, HI
,
July 17–21
, pp.
4170
4173
.10.1109/EMBC.2018.8513341
25.
Song
,
Y.
, and
Zheng
,
J.
,
2020
, “
The Esophagus Survives Non-Thermal Irreversible Electroporation Ablation and Gradually Rehabilitates
,” Research Square.10.21203/rs.3.rs-18960/v1
26.
Jeon
,
H. J.
,
Choi
,
H. S.
,
Park
,
J. Y.
,
Yoon
,
J. Y.
,
Park
,
G.
,
Sim
,
J. Y.
,
Bang
,
E. J.
, et al.,
2022
, “
Applicability of Advanced Endoscopic Balloon-Type Irreversible Electroporation Catheter on the Esophagus: Preclinical Animal Study
,”
J. Clin. Oncol.
40
(
4_suppl
), pp.
339
339
.10.1200/JCO.2022.40.4_suppl.339
27.
Egeland
,
C.
,
Baeksgaard
,
L.
,
Johannesen
,
H.
,
Löfgren
,
J.
,
Plaschke
,
C.
,
Svendsen
,
L.
,
Gehl
,
J.
, and
Achiam
,
M.
,
2018
, “
Endoscopic Electrochemotherapy for Esophageal Cancer: A Phase I Clinical Study
,”
Endosc. Int. Open
,
6
(
6
), pp.
E727
E734
.10.1055/a-0590-4053
28.
Rodriguez
,
S. A.
,
Adler
,
D. G.
,
Chand
,
B.
,
Conway
,
J. D.
,
Diehl
,
D. L.
,
Kantsevoy
,
S. V.
,
Kwon
,
R. S.
, et al.,
2008
, “
Mucosal Ablation Devices
,”
Gastrointest. Endosc.
,
68
(
6
), pp.
1031
1042
.10.1016/j.gie.2008.06.018
29.
Phillips
,
M.
,
Maor
,
E.
, and
Rubinsky
,
B.
,
2010
, “
Nonthermal Irreversible Electroporation for Tissue Decellularization
,”
ASME J. Biomech. Eng.
,
132
(
9
) p.
091003
.10.1115/1.4001882
30.
Phillips
,
M. A.
,
Narayan
,
R.
,
Padath
,
T.
, and
Rubinsky
,
B.
,
2012
, “
Irreversible Electroporation on the Small Intestine
,”
Br. J. Cancer
,
106
(
3
), pp.
490
495
.10.1038/bjc.2011.582
31.
Srimathveeravalli
,
G.
,
Wimmer
,
T.
,
Monette
,
S.
,
Gutta
,
N. B.
,
Ezell
,
P. C.
,
Maybody
,
M.
,
Weiser
,
M. R.
, and
Solomon
,
S. B.
,
2013
, “
Evaluation of an Endorectal Electrode for Performing Focused Irreversible Electroporation Ablations in the Swine Rectum
,”
J. Vasc. Interventional Radiol.
,
24
(
8
), pp.
1249
1256
.10.1016/j.jvir.2013.04.025
32.
Ueshima
,
E.
,
Schattner
,
M.
,
Mendelsohn
,
R.
,
Gerdes
,
H.
,
Monette
,
S.
,
Takaki
,
H.
,
Durack
,
J. C.
,
Solomon
,
S. B.
, and
Srimathveeravalli
,
G.
,
2018
, “
Transmural Ablation of the Normal Porcine Common Bile Duct With Catheter-Directed Irreversible Electroporation is Feasible and Does Not Impact Duct Patency
,”
Gastrointest. Endosc.
, 87(1), pp. 300.e1–300.e6.10.1016/j.gie.2017.05.004
33.
Srimathveeravalli
,
G.
,
Silk
,
M.
,
Wimmer
,
T.
,
Monette
,
S.
,
Kimm
,
S.
,
Maybody
,
M.
,
Solomon
,
S. B.
,
Coleman
,
J.
, and
Durack
,
J. C.
,
2015
, “
Feasibility of Catheter-Directed Intraluminal Irreversible Electroporation of Porcine Ureter and Acute Outcomes in Response to Increasing Energy Delivery
,”
J. Vasc. Interventional Radiol.
,
26
(
7
), pp.
1059
1066
.10.1016/j.jvir.2015.01.020
34.
Neven
,
K.
,
van Es
,
R.
,
van Driel
,
V.
,
van Wessel
,
H.
,
Fidder
,
H.
,
Vink
,
A.
,
Doevendans
,
P.
, and
Wittkampf
,
F.
,
2017
, “
Acute and Long-Term Effects of Full-Power Electroporation Ablation Directly on the Porcine Esophagus
,”
Circ. Arrhythm Electrophysiol.
,
10
(
5
), p. e004672.10.1161/CIRCEP.116.004672
35.
Song
,
Y.
,
Zheng
,
J.
, and
Fan
,
L.
,
2021
, “
Nonthermal Irreversible Electroporation to the Esophagus: Evaluation of Acute and Long-Term Pathological Effects in a Rabbit Model
,”
J. Am. Heart Assoc.
,
10
(
22
), p.
20731
.10.1161/JAHA.120.020731
36.
Tholakanahalli
,
V. N.
,
2020
, “
Epicardial Ablation Via Arterial and Venous Systems
,”
Card Electrophysiol. Clin.
,
12
(
3
), pp.
391
399
.10.1016/j.ccep.2020.06.006
37.
Geboers
,
B.
,
Scheffer
,
H. J.
,
Graybill
,
P. M.
,
Ruarus
,
A. H.
,
Nieuwenhuizen
,
S.
,
Puijk
,
R. S.
,
van den Tol
,
P. M.
, et al.,
2020
, “
High-Voltage Electrical Pulses in Oncology: Irreversible Electroporation, Electrochemotherapy, Gene Electrotransfer, Electrofusion, and Electroimmunotherapy
,”
Radiology
,
295
(
2
), pp.
254
272
.10.1148/radiol.2020192190
38.
Lee
,
R. C.
,
2005
, “
Cell Injury by Electric Forces
,”
Ann. N Y Acad. Sci.
,
1066
(
1
), pp.
85
91
.10.1196/annals.1363.007
39.
Vogel
,
J. A.
,
van Veldhuisen
,
E.
,
Alles
,
L. K.
,
Busch
,
O. R.
,
Dijk
,
F.
,
van Gulik
,
T. M.
,
Huijzer
,
G. M.
, et al.,
2019
, “
Time-Dependent Impact of Irreversible Electroporation on Pathology and Ablation Size in the Porcine Liver: A 24-Hour Experimental Study
,”
Technol. Cancer Res. Treat.
,
18
, p. 1533033819876899.10.1177/1533033819876899
40.
Schoellnast
,
H.
,
Monette
,
S.
,
Ezell
,
P. C.
,
Deodhar
,
A.
,
Maybody
,
M.
,
Erinjeri
,
J. P.
,
Stubblefield
,
M. D.
, et al.,
2011
, “
Acute and Subacute Effects of Irreversible Electroporation on Nerves: Experimental Study in a Pig Model
,”
Radiology
,
260
(
2
), pp.
421
427
.10.1148/radiol.11103505
41.
Schoellnast
,
H.
,
Monette
,
S.
,
Ezell
,
P. C.
,
Maybody
,
M.
,
Erinjeri
,
J. P.
,
Stubblefield
,
M. D.
,
Single
,
G.
, and
Solomon
,
S. B.
,
2013
, “
The Delayed Effects of Irreversible Electroporation Ablation on Nerves
,”
Eur. Radiol.
,
23
(
2
), pp.
375
380
.10.1007/s00330-012-2610-3
42.
Surowiec
,
A. J.
,
Stuchly
,
S. S.
,
Barr
,
J. R.
, and
Swarup
,
A.
,
1988
, “
Dielectric Properties of Breast Carcinoma and the Surrounding Tissues
,”
IEEE Trans. Biomed. Eng.
,
35
(
4
), pp.
257
263
.10.1109/10.1374
43.
Hasgall
,
P. A.
,
Di Gennaro
,
F.
,
Baumgartner
,
C.
,
Neufeld
,
E.
,
Lloyd
,
B.
,
Gosselin
,
M. C.
,
Payne
,
D.
, and
Klingenböck
,
A.
,
2022
, “
IT'IS Database for Thermal and Electromagnetic Parameters of Biological Tissues
,”.
44.
COMSOL AB
, “
COMSOL Multiphysics®
,”
COMSOL AB
,
Stockholm, Sweden
.
45.
MatWeb, LLC
,
1996
, “
MatWeb Material Property Data
,”
MatWeb, LLC
.
46.
Deng
,
Z. S.
, and
Liu
,
J.
,
2001
, “
Blood Perfusion-Based Model for Characterizing the Temperature Fluctuation in Living Tissues
,”
Phys. A (Amsterdam, Neth.)
,
300
(
3–4
), pp.
521
530
.10.1016/S0378-4371(01)00373-9
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