First Human Trial of High-Frequency Irreversible Electroporation Therapy for Prostate Cancer (2024)

Abstract

Irreversible electroporation, as a nonthermal therapy of prostate cancer, has been usedin clinic for several years. The mechanism of irreversible electroporation ablation isthermal independent; thus, the main structures (eg, rectum, urethra, and neurovascularbundle) in prostate are spared during the treatment, which leads to the retention ofprostate function. However, various clinical trials have shown that muscle contractionsoccur during this therapy, which warrants deep muscle anesthesia. Use of high-frequencybipolar pulses has been proposed to reduce muscle contractions during treatment, which hasalready triggered a multitude of studies at the cellular and animal scale. In this study,we first investigated the efficacy and safety of high-frequency bipolar pulses in humanprostate cancer ablation. There are 40 male patients with prostate cancer aged between 51and 85 years involved in this study. All patients received 250 high-frequency bipolarpulse bursts with the repeat frequency of 1 Hz. Each burst comprised 20 individual pulsesof 5 microseconds, so one burst total energized time was 100 microseconds. The number ofthe electrodes ranged 2 to 6, depending on tumor size. A small amount of muscle relaxantwas still needed, so there were no visible muscle contractions during the pulse deliveryprocess. Four weeks after treatment, it was found that the ablation margins were distinctin magnetic resonance imaging scans, and the prostate capsule and urethra were retained.Eight patients underwent radical prostatectomy for pathological analysis after treatment,and the results of hematoxylin and eosin staining revealed that the urethra and majorvasculature in prostate have been preserved. By overlaying the electric field contour onthe ablation zone, the electric field lethality threshold is determined to be 522 ± 74V/cm. This study is the first to validate the feasibility of tumor ablation byhigh-frequency bipolar pulses and provide valuable experience of irreversibleelectroporation in clinical applications.

Keywords: irreversible electroporation, high-frequency bipolar pulses, prostate cancer, muscle contractions, cancer ablation

Introduction

Prostate cancer is one of the most common malignancies in men, and its morbiditysignificantly increases with age. Prostate cancer has the highest mortality rate among thecancers occurring in males, except for lung carcinoma in China.1 There are many important structures proximal to the prostate, such as the rectum,urethra, and neurovascular bundle (NVB). Radical prostatectomy,2 a conventional treatment technique for prostate cancer, wreaks havoc on the blood,NVB, and urethra, causing severe trauma and impotence. Newer minimally invasivethermal-based therapies, including cryoablation,3 radiofrequency ablation,4,5 and microwave ablation, ablate the tumor when the temperature is higher or lower thana critical value. However, the ablation of tumors near blood vessels is affected because ofthe heat-sink effect. Another limitation of these thermal-based therapies is that they arenonselective because the aforementioned proximal structures can be damaged, leading to somecomplications.

Irreversible electroporation (IRE) is a new nonthermal ablation modality that employsintensitive and narrow electric pulses to create permanent defects on the cell membrane,resulting in cell death.6,7 Contrast to thermal therapies, the mechanism of IRE is thermal independent, making itpossible to ablate the tumors near the heat-sensitive structures. Optimization of pulseparameters and the arrangement of electrodes allow the vessels and nerves to be sparedduring treatment, which is beneficial for the patients’ recovery and retaining prostatefunction. Additionally, the ablation results of IRE remain unaffected by blood perfusionbecause of its nonthermal mechanism.8,9 These characteristics enable the wide application of IRE in clinics. Following thefirst clinical trial of IRE on prostate cancer treatment, IRE has been found to be useful invarious clinical applications.1013

Typically, IRE utilizes 80 to 120 unipolar pulses applied for a duration of 50 to 100microseconds and at a voltage-to-distance ratio of >1000 V/cm. The pulses are deliveredin synchrony with the patient’s heartbeat to minimize adverse cardiac events or at afrequency of 0.1 to 5 Hz.1416 However, this protocol can evoke muscle contractions during the pulse deliveryprocess, which may cause pain to the patients and bring about a displacement of theelectrodes, thereby adversely affecting the ablation outcome.9,17 Therefore, a deep neuromuscular blockade is necessary to ensure that the IREtreatment goes smoothly.

Arena et al18 proposed a new-generation IRE technique to mitigate the impact of musclecontractions, namely, high-frequency IRE (also called as H-FIRE). This new type of pulseconsists of a set of bipolar pulse bursts, and each burst comprises a number of individualpulses of duration ranging between 0.5 and 10 microseconds, and the total energized time ofeach burst is in the order of 100 microseconds. Some experiments involving the use of HFbipolar pulses have previously been conducted on cells and animals to verify the efficacy ofHF bipolar pulses on the tumor-killing effect and reduction in muscle contraction.19,20 The studies showed that the muscle contraction inhibition and tissue ablationcharacteristics are closely related to the duration of individual HF bipolar pulses.

Although several studies have been conducted regarding the effects of HF bipolar pulses oncells and tissues and there is strong evidence that such pulses can be used for tumortherapy, the efficacy and safety of their clinical application have not yet been studied.Our group has developed a tumor therapy apparatus that can generate both regular IRE pulsesand HF bipolar pulses, and it has passed the registration test at the Shanghai Testing andInspection Institute for Medical Devices. This article details the first human trial of HFbipolar pulses for treating prostate cancer using the apparatus developed by our group, andmagnetic resonance imaging (MRI) and ultrasound were combined to locate the tumor in theprostate and guide electrode insertion during treatment. Four weeks after the treatment, MRIwas used to image the ablation zone and the prostate was resected for pathologicalexamination. The electric field threshold of ablation could be determined by overlaying theelectric field contours on the ablation zone. This clinical trial validated the feasibilityof the clinical use of HF bipolar pulses for prostate cancer treatment, thereby promotingvarious clinical applications of our technique.

Methods

Patient Information

Clinical trials were performed after obtaining patients’ consent and approval from theShanghai Changhai Hospital Ethics Committee (CHEC2017-075) and Good Clinical Practices.Forty patients received therapeutic HF bipolar pulses, and their ages were in the range 51to 85 years. The patients were treated at Shanghai Changhai Hospital in Shanghai, China.Significantly elevated prostate-specific antigen level was detected in patients, and thepatients then underwent multiparametric MRI to detect the suspected tumor in theirprostate; the maximum tumor size in all patients was 1 to 3 cm. The patients’ treatmentinformation is listed in Table1. A needle biopsy was performed before the IRE procedure to demonstrate theclinical significance of prostate cancer through histological analysis.

Table 1.

The Patients Treatment Information.

NoNumber of ElectrodesMaximum Size of Tumor, cmNumber of PatientsPatients AgeTreatment Time, min
12<1364, 76, 79<8
231.0-1.51381, 71, 59, 71, 82, 74, 69, 59, 79, 67, 51, 58, 63<20
341.5-2.01076, 68, 73, 57, 65, 81, 84, 85, 73, 78<30
452.0-2.5868, 51, 65, 74, 68, 76, 82, 75<40
562.5-3.0675, 66, 75, 64, 72, 77<45

Open in a new tab

Therapeutic Equipment

A composite steep pulse therapeutic apparatus was used to generate HF bipolar pulses, asshown in Figure 1A. The apparatuscan produce bursts of HF bipolar pulses, constituting of individual pulses of durationranging from 1 to 100 microseconds; the interburst delay is 1 second, and the rise time isless than 100 nanoseconds. The schematic of bipolar HF pulse bursts applied in this studyis shown in Figure 1B.

Figure 1.

Open in a new tab

In each trial, 2 to 6 needle electrodes were inserted into the tumor region, and thedistance between 2 electrodes was <2 cm. The diameter of the electrodes was 1 mm, andthe exposure length was set to 1.0 to 3.0 cm (Figure 1B), depending on the tumor’s size.

Procedure

The patients were placed in the dorsal lithotomy position and were operated under asepticconditions and general anesthesia. In order to administer a lower concentration of musclerelaxant to patients, a muscle relaxant (cisatracurium besylate) at a dose of only 0.001mg/kg·min was injected, which was lower than the dose used during a conventional surgery(0.0015 mg/kg·min).21

Then, the therapeutic electrodes were punctured transperineally at the margin of thecancer lesion under transrectal ultrasound guidance, and the space between electrodes wasmeasured using ultrasound images.

High-frequency bipolar pulses were delivered after the position of the needle electrodeswas determined. The burst of HF bipolar pulses, consisting of 20 pulses each of 5microseconds, had a total energized time of 100 microseconds, with a 10-µs delay timebetween the positive and the negative pulses. The schematic of HF bipolar pulses is givenin Figure 1C. The initialvoltage-to-distance ratio applied was 1500 V/cm between the pairs of electrodes. Thevoltage was adjusted during the trial to avoid a very large pulse current (>40 A).Pulses were delivered at a repetition rate of 1 burst/second in sets of 50 pulses,following a 10-second delay to avoid an increase in temperature in the tissues; this cyclewas repeated for a total number of 250 bursts that were delivered between each pair ofelectrodes. The electrodes were removed after treatment, and the patient was inserted witha urethral catheter and left to wake up.

Therapeutic Effect Evaluation

Four weeks after treatment, MRI was used to estimate the ablation area. In addition, theposition of the electrodes in MRI image, which would be used to analyze the electric fieldthreshold of ablation, was determined by matching the MRI image and the ultrasound imagewith the location of electrodes.

The efficacy of ablation at the cellular level was analyzed in 8 patients who underwentcomplete resection of the prostate after 4 weeks based on voluntary principles. Theseprostates were sectioned and processed for histology analysis using hematoxylin and eosinstaining. Color images of each tissue section were acquired using the Aperio LV1 DigitalPathology Slide Scanner (Leica Biosystems Inc, Buffalo Grove, Illinois).

Numerical Simulations

It was difficult to reconstruct an accurate 3D model because only low-resolution MRIslices were acquired. Therefore, a 2D finite element model of the prostate tissue wasestablished using COMSOL Multiphysics software (version 4.2a; COMSOL Inc, Burlington,Massachusetts). As shown in Figure2, the ellipse represents the prostate and the 3 small circles represent theelectrodes. The diameter of the needle electrode was set at 1 mm, and the electrodespacing was set according to the measured distance in the ultrasound image. The tumorswere not considered in the model because the dielectric parameters of prostate cancer werenot clear when HF bipolar pulses were applied.

Figure 2.

Open in a new tab

The electric field distribution in the biological tissue was closely related to theelectrical conductivity and permittivity. The electrical conductivity and permittivitychanges during the process of electroporation, but the dynamic response of tissue to HFbipolar pulses has been poorly researched; thus, in this study, the static model was usedfor an initial analysis. The fundamental frequency of the burst in this study was 33.3kHz, and the corresponding permittivity and conductivity of the prostate tissues, whichcould be found from the reference,22 were 7162.9 and 0.43292 S/m, respectively.

The Laplace equation was used to solve the electric field distribution in the tissueregion. Within the solution domain, the electric current module was used to solve thefollowing equations:

J=Q[Am3],1
J=(σ+0rt)E[Am2],2
E=U[Vm],3

where U is the electric potential, E is the electricfield, J is the current density, Q is the currentsource, σ is the conductivity, ∊r is the relative permittivity, and ∊0 is the permittivity of freespace. The boundaries surrounding 1 electrode were assigned a constant electricalpotential:

U=U[V].4

The boundaries of the other electrode were assigned as a relative ground:

U=0[V].5

The remaining boundaries were defined as electrical insulation:

nJ=0[Am],6

where n is the normal vector to the surface and J isthe electrical current density.

The electric field distribution with isocontours can be determined using COMSOL softwarethrough electric field simulation. The electric field lethality threshold can bedetermined preliminarily by comparing the calculated electric field intensity contours andthe ablation zone in MRI section and finding the electric field intensity closest to theablation boundary.

Results

The number of electrodes used in this clinical trial was 2 to 6 as shown in Table 1. The treatment time for eachpatient was <45 minutes, and there were no abnormalities during the pulse deliveryprocess. Physiological indexes were monitored during treatment (including heart rate, bloodoxygen level, and respiration rate), and all were found to be within the normal range.Low-dose muscle relaxants were injected before treatment; hence, muscle contractions did notoccur during treatment. This is important because any major movements performed by thepatients could potentially damage the nearby structures owing to the movement ofelectrodes.

After treatment, the patients felt well and could move around after approximately 10 hours.All patients were discharged from the hospital on the next day, and none required furtherhospitalization.

After 4 weeks, lesions were clearly visible in MRI scans. As shown in Figure 3, the areas surrounded by the red curve,namely, the darker regions, are the ablation areas. The areas surrounded by the blue curvesare the prostate. In some cases, the electrode needles were positioned very close to theprostate capsule, but MRI scans revealed that the HF bipolar pulses had not damaged theprostate capsule. Figure 3B alsoshowed that the prostate capsule was intact, which could inhibit the metastasis of prostatecancer cells.

Figure 3.

Open in a new tab

The location of prostate cancer was determined using MRI prior to treatment (Figure 4A). The therapeutic electrodeswere then punctured transperineally at the margin of the cancer lesion under transrectalultrasound guidance (Figure 4B).Comparing MRIs with ultrasound images facilitated the determination of electrodes positionsin MRI scans as shown in Figure 4C.The electrode needles are all positioned in the ablation area, and the tissue between theelectrodes has been completely ablated. The shape of the ablation area is closely related tothe position of electrodes.

Figure 4.

Open in a new tab

After determining the position of electrodes in MRI scans, the contours of the electricfield distributions between each pair of electrodes were drawn as shown in Figure 5. Comparing the ablationboundaries and electric field distribution allows the preliminary determination of theelectric field lethality threshold in the case of constant conductivity, and the averagelethality threshold of the treatment protocol used in this trial was 522 ± 74 V/cm.

Figure 5.

Open in a new tab

The prostates of 8 patients were excised and used for histological analysis 4 weeks aftertreatment. Histological examination showed that the ablated area had diffuse necroticglandular tissue without any obvious viable tissue within the ablated zone (Figure 6A). Although Figure 6B showed that large vessels inthe tissue were intact, some amount of bleeding was observed near the electrodes with theappearance of scattered blood cells in the tissue, which may have been caused by capillarydamage. The ablated zone was demarcated well from the immediately adjacent unaffectedprostate parenchyma and the transition zone between the necrotic glandular tissue in theablation area and the adjacent normal glandular tissue was abrupt (Figure 6C). In addition, necrotic glandular tissue wasnoted adjacent to the urethra as shown in Figure 6D. However, the urethral structural integrity remained intact withoutevidence of necrosis within the submucosa, even when the urethra was subjected to directablation during the safety portion of the study.

Figure 6.

Open in a new tab

Patients were followed up for 6 months; in summary, the overall outcomes of our clinicaltreatment of patients with prostate cancer were that 8 of 40 patients underwent radicalprostatectomy 4 weeks later, and 32 of 40 patients retained their prostates. Sexual functionwas preserved in 14 (100%) of 14 patients, 40 (100%) of 40 patients could control urinationand did not require urinal pads, and 0 of 40 patients had urinary incontinence duringsurgery. The average hospitalization duration was 2 days, and the use time of urination was2 to 10 days. Of the 40 patients, 15 (37.5%) presented hematuria 2 weeks after surgery and 5(12.5%) presented hematuria 4 weeks after treatment. None presented hematuria after 6months.

Discussion

Prostate cancer is one of the most common malignancies in older males. There are importantblood vessels and NVB around the prostate. A radical prostatectomy can cause severe traumaand impotence, while thermal ablation therapies can also injure adjacent structures, such asthe rectum, urethra, and NVB, thereby causing some complications. Prostate cancer treatmentneeds to guarantee that tumor cells have been completely killed to prolong the patientsurvival. Moreover, it is preferable to preserve the function of the prostate because thiswill improve the quality of life.

Irreversible electroporation has several demonstrated advantages over well-known,thermal-based ablation methods. Many of these advantages stem from the mechanism ofpermanent destruction of the cell membrane, resulting in cell death in a nonthermalmanner.

The first clinical trial of IRE for the treatment of prostate cancer published in 2010showed good therapeutic effect.23 However, during treatment, unipolar electric pulses can induce muscle contractions,unless deep muscle paralysis is maintained.

Arena et al18 proposed a new type of pulse that utilizes an HF bipolar pulse burst to replace thetraditional single monopolar pulse for tumor ablation. They also conducted ablationexperiments on murine tumors to verify the effects of inhibition of muscle contraction andtumor growth.19 Subsequently, Yao et al20 systemically researched the ablation effect and muscle contractions by applying HFbipolar pulses to liver tissues in vivo and recommended 2 and 5microseconds as the ideal width for individual pulses; this became an important parameterfor clinical treatment. They also studied the difference between the dielectric propertyvariations caused by traditional IRE pulses and HF bipolar pulses,24 and pointed out that the HF bipolar pulse mitigates dielectric property variation toa higher extent than the conventional IRE pulses when fitting the dielectric spectrum datato the Cole–Cole model. In addition, Bhonsle et al25,26 found that the area ablated by HF bipolar pulses is more consistent with the fielddistribution of the simulation, which helps doctors predict the ablation area. Siddiquiet al27 carried out a series of experiments on pig liver, the results of which showed thatincreasing the number of bursts could improve the ablation area. Recently, Zhao etal showed the dynamic change in conductivity induced by HF bipolar pulses andcompared it to conventional IRE.28

Ablation efficacy to a certain extent and muscle contraction outcomes were achieved in thepresent study using HF bipolar pulses with an individual pulse width of 5 microseconds, atotal number of 250 bursts, and an applied voltage-to-distance ratio of 1500 V/cm. Inaddition, muscle paralysis was induced in HF bipolar pulse treatment to guarantee patientsafety, but the muscle relaxant dosage was less than that used during traditional IRE.21,29

Here, the electric field threshold of ablation for HF bipolar pulses in human prostatecancer treatment was studied, and it was determined by comparing the electric field contoursfrom simulation to the ablation area in MRI scans. The ultrasound imaging was recorded whenthe patients were placed in the dorsal lithotomy position, which is different from theposition of patients while undergoing an MRI. Therefore, there may be some errors in thedetermination of the electrode position by matching the ultrasound and MRI scans. Inaddition, the conductivity is set at a constant value, but during the treatment, theconductivity of the tissue will increase with the pulse applied, and the ablation area also changes30; hence, more accurate models that consider the dynamic conductivity should be builtfor multiparameter optimization in the future to predict the optimal ablation range.

Thermal ablation methods such as cryoablation,3 radiofrequency ablation,31 and microwave ablation,32 have limitations caused by vessel heat-sink effect, which means that the tumors nearthe vessels cannot be completely ablated and thereby result in high local recurrence rates.In contrast, histological analysis demonstrated that lesions caused by HF bipolar pulsesshowed complete destruction, even extending to the vessel wall, without sparing the tissuesadjacent to the vessel. Although an appearance of bleeding showed that the tissues had acapillary injury, the larger vessels in the tissues were intact. The preservation of thelarge vessels raises the possibility that there could be tissue regeneration in the ablated area.32,33

Preservation of the surrounding functional structures is very important during prostatecancer ablation. Although previous studies have has demonstrated that urethra could bepreserved without sloughing or major damage, some clinical cases showed that IRE has thepotential to affect the urethra if it is located in the lethal electric field.34 The pathological analysis conducted in this study revealed that the urethra remainsintact, and this result may imply that HF bipolar pulses have advantages over IRE.

After treatment, the patients could recover quickly, and they were able to move about 10hours after treatment without any uneasiness. The result that sexual function was preservedin 14 (100%) of 14 patients showed that the NVB was preserved during treatment, which madethe patients more willing to accept this therapy.

Conclusion

This study describes the first trial conducted in humans involving administration of HFbipolar pulses therapy for prostate cancer; HF bipolar pulse is a minimally invasivenonthermal therapy in tumor ablation that can reduce the dose of muscle relaxant duringtreatment. Compared to radical prostatectomy and thermal therapy, it can preserve the NVB,urethra, and major vasculature in the prostate, which is beneficial to patient recovery. Thepostoperative effect of such a treatment on patients was very encouraging, that is, sexualfunction was preserved in 14 (100%) of 14 patients, 40 (100%) of 40 patients could controlurination and did not require urinal pads, and 0 of 40 patients had urinary incontinenceduring surgery. The clinical trials were conducted successfully, and they provide valuableinsights regarding the treatment of prostate cancer using HF bipolar pulses, which willpromote the ablation of solid tumors by IRE.

Abbreviations

HF

high frequency

IRE

irreversible electroporation

MRI

magnetic resonance imaging

NVB

neurovascular bundle.

Footnotes

Authors’ Note: S.D., H.W., and C.Y. contributed equally to this work. Shanghai Changhai Hospital EthicsCommittee, Ethical approval NO.: CHEC2017-075. All patients consented to the clinicaltrial verbally.

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research,authorship, and/or publication of this article.

Funding: The author(s) disclosed receipt of the following financial support for the research,authorship, and/or publication of this article: This work was supported in part by theNatural Science Foundation Project of CQ CSTC (cstc2014jcyjjq90001), the GraduateScientific Research and Innovation Foundation of Chongqing (CYB17011), the FundamentalResearch Funds for the Central Universities (106112017CDJZRPY0103, 106112017CDJQJ158835),Key Industrial Generic Technology Innovation Special Project of CQ CSTC(cstc2015zdcy-ztzxX0003), and the National Natural Science Foundation of China(51321063).

ORCID iD: Chenguo Yao, PhD First Human Trial of High-Frequency Irreversible Electroporation Therapy for Prostate Cancer (7)http://orcid.org/0000-0002-1781-2756

References

  • 1.Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015.CA Cancer J Clin.2016;66(2):115–132. [DOI] [PubMed] [Google Scholar]
  • 2.Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevationfollowing radical prostatectomy. JAMA.1999;28(1):1591–1597. [DOI] [PubMed] [Google Scholar]
  • 3.Hale Z, Miyake M, Palacios DA, Rosser CJ.Focal cryosurgical ablation of the prostate: a singleinstitute’s perspective. BMC Urol.2013;13:1–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Minami Y, Kudo M, Kawasaki T, et al. Percutaneous ultrasound-guided radiofrequency ablationwith artificial pleural effusion for hepatocellular carcinoma in the hepaticdome. J Gastroenterol.2003;38(11):1066–1070. [DOI] [PubMed] [Google Scholar]
  • 5.Lau WY, Lai EC.The current role of radiofrequency ablation in themanagement of hepatocellular carcinoma: a systematic review. AnnSurg.2009;249(1):20–25. [DOI] [PubMed] [Google Scholar]
  • 6.Davalos RV, Mir IL, Rubinsky B.Tissue ablation with irreversibleelectroporation. Ann Biomed Eng.2005;33(2):223–231. [DOI] [PubMed] [Google Scholar]
  • 7.Yao C, Sun C, Mi Y, Xiong L.Experimental studies on Killing and inhibiting effects ofsteep pulsed electric field (SPEF) to target cancer cell and solidtumor. IEEE Trans Plasma Sci.2004;32(4):1626–1633. [Google Scholar]
  • 8.Rubinsky B.Irreversible electroporation in medicine.Technol Cancer Res Treat.2007;6(4):255–260. [DOI] [PubMed] [Google Scholar]
  • 9.Maor E, Ivorra A, Rubinsky B.Non thermal irreversible electroporation: novel technologyfor vascular smooth muscle cells ablation. PLoS One.2009;4(3):e4757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Rossmeisl JH, Jr, Garcia PA, Pancotto TE, et al. Safety and feasibility of the NanoKnife system forirreversible electroporation ablative treatment of canine spontaneous intracranialgliomas. J Neurosurg.2015;123(4):1008–1025. [DOI] [PubMed] [Google Scholar]
  • 11.Bos WVD, Bruin DMD, Muller BG, et al. The safety and efficacy of irreversible electroporationfor the ablation of prostate cancer: a multicentre prospective human in vivo pilot studyprotocol. BMJ Open.2014;4(10):e6382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Olweny EO, Kapur P, Tan YK, Park SK, Adibi M, Cadeddu JA.Irreversible electroporation: evaluation of nonthermal andthermal ablative capabilities in the porcine kidney.Urology.2013;81(3):679–684. [DOI] [PubMed] [Google Scholar]
  • 13.Wendler JJ, Pech M, Blaschke S, et al. Angiography in the isolated perfused kidney: radiologicalevaluation of vascular protection in tissue ablation by nonthermal irreversibleelectroporation. Cardiovasc Intervent Radiol.2012;35(2):383–390. [DOI] [PubMed] [Google Scholar]
  • 14.Dunki-Jacobs EM, Philips P, Martin RC., IIEvaluation of resistance as a measure of successful tumorablation during irreversible electroporation of the pancreas. JAm Coll Surg.2014;218(2):179–187. [DOI] [PubMed] [Google Scholar]
  • 15.Bertacchini C, Margotti PM, Bergamini E, Ronchetti M, Cadossi R.Irreversible Electroporation Systems for Clinical Use.Berlin, Germany:Springer;2010:255–272. [Google Scholar]
  • 16.Zager Y, Kain D, Landa N, Leor J, Maor E.Optimization of irreversible electroporation protocols forin-vivo myocardial decellularization. PLoS One.2016;11(11):e165475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Yao C, Zhao Y, Chengxiang LI, Yan MI, Liao R.Recent advances in tissue minimally invasive ablation withirreversible electroporation. High Volt Eng.2014;40:3725–3737. [Google Scholar]
  • 18.Arena CB, Sano MB, Rossmeisl JH, et al. High-frequency irreversible electroporation (H-FIRE) fornon-thermal ablation without muscle contraction. Biomed EngOnline.2011;10:9144–9153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Sano MB, Arena CB, Bittleman KR, et al. Bursts of bipolar microsecond pulses inhibit tumorgrowth. Sci Rep.2015;5:14999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Yao C, Dong S, Zhao Y, et al. Bipolar microsecond pulses and insulated needle electrodesfor reducing muscle contractions during irreversible electroporation.IEEE Trans Biomed Eng.2017;64(12):2924–2937. [DOI] [PubMed] [Google Scholar]
  • 21.ChemicalBook. Cisatracurium Besylate Basicinformation. 2017. http://www.chemicalbook.com/ProductChemicalPropertiesCB7855410_EN.htm.Accessed December 20, 2017.
  • 22.Italian National Research Council.Dielectric Properties of Body Tissues. 2018. http://niremf.ifac.cnr.it/tissprop/. Accessed January 5,2018.
  • 23.Onik G, Rubinsky B.Irreversible Electroporation: First Patient Experience FocalTherapy of Prostate Cancer. Berlin, Germany:Springer;2010:235–247. [Google Scholar]
  • 24.Yao C, Zhao Y, Liu H, Dong S, Lv Y, Ma J.Dielectric variations of potato induced by irreversibleelectroporation under different pulses based on the cole-cole model.IEEE Trans Dielectr Electr Insul.2017;24(4):2225–2233. [Google Scholar]
  • 25.Bhonsle SP, Arena CB, Sweeney DC, Davalos RV.Mitigation of impedance changes due to electroporationtherapy using bursts of high-frequency bipolar pulses. BiomedEng Online. 2015;14(suppl3):1–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Ivey JW, Latouche EL, Sano MB, Rossmeisl JH, Davalos RV, Verbridge SS.Targeted cellular ablation based on the morphology ofmalignant cells. Sci Rep.2015;5:17157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Siddiqui IA, Latouche EL, Dewitt MR, et al. Induction of rapid, reproducible hepatic ablations usingnext-generation, high frequency irreversible electroporation (H-FIRE) invivo. HPB (Oxford). 2016;18(9):726–734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Zhao Y, Bhonsle S, Dong S, et al. Characterization of conductivity changes duringhigh-frequency irreversible electroporation for treatment planning.IEEE Trans Biomed Eng.2017;99:1–1. [DOI] [PubMed] [Google Scholar]
  • 29.Cheung W, Kavnoudias H, Roberts S, Szkandera B, Kemp W, Thomson KR.Irreversible electroporation for unresectablehepatocellular carcinoma: initial experience and review of safety andoutcomes. Technol Cancer Res Treat.2013;12(3):233–241. [DOI] [PubMed] [Google Scholar]
  • 30.Campelo S, Valerio M, Ahmed HU, et al. An evaluation of irreversible electroporation thresholdsin human prostate cancer and potential correlations to physiologicalmeasurements. APL Bioeng.2017;1(1):16101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Calkins H, Reynolds MR, Spector P, et al. Treatment of atrial fibrillation with antiarrhythmic drugsor radiofrequency ablation: two systematic literature reviews andmeta-analyses. Circ Arrhythm Electrophysiol.2009;2(4):349. [DOI] [PubMed] [Google Scholar]
  • 32.Simon CJ, Dupuy DE, Mayosmith WW.Microwave ablation: principles andapplications. Radiographics.2005;25(suppl1):S69. [DOI] [PubMed] [Google Scholar]
  • 33.Onik G, Mikus P, Rubinsky B.Irreversible electroporation: implications for prostateablation. Technol Cancer Res Treat.2007;6(4):295. [DOI] [PubMed] [Google Scholar]
  • 34.Bos WVD, Bruin DMD, Jurhill RR, et al. The correlation between the electrode configuration andhistopathology of irreversible electroporation ablations in prostate cancerpatients. World J Urol.2016;34(5):657–664. [DOI] [PMC free article] [PubMed] [Google Scholar]
First Human Trial of High-Frequency Irreversible Electroporation Therapy for Prostate Cancer (2024)
Top Articles
Latest Posts
Recommended Articles
Article information

Author: Wyatt Volkman LLD

Last Updated:

Views: 5717

Rating: 4.6 / 5 (46 voted)

Reviews: 85% of readers found this page helpful

Author information

Name: Wyatt Volkman LLD

Birthday: 1992-02-16

Address: Suite 851 78549 Lubowitz Well, Wardside, TX 98080-8615

Phone: +67618977178100

Job: Manufacturing Director

Hobby: Running, Mountaineering, Inline skating, Writing, Baton twirling, Computer programming, Stone skipping

Introduction: My name is Wyatt Volkman LLD, I am a handsome, rich, comfortable, lively, zealous, graceful, gifted person who loves writing and wants to share my knowledge and understanding with you.