Irreversible electroporation

Irreversible electroporation is a soft tissue ablation technique using ultra short but strong electrical fields to create permanent and hence lethal nanopores in the cell membrane, to disrupt cellular homeostasis. The resulting cell death results from induced apoptosis or necrosis induced by either membrane disruption or secondary breakdown of the membrane due to transmembrane transfer of electrolytes and adenosine triphosphate.[1][2][3][4] The main use of IRE lies in tumor ablation in regions where precision and conservation of the extracellular matrix, blood flow and nerves are of importance. The first generation of IRE for clinical use, in the form of the NanoKnife System, became commercially available for research purposes in 2009, solely for the surgical ablation of soft tissue tumors.[5] Cancerous tissue ablation via IRE appears to show significant cancer specific immunological responses which are currently being evaluated alone and in combination with cancer immunotherapy.[6][7][8][9]

Irreversible electroporation
Other names	Non-thermal irreversible electroporation
Specialty	oncology

History

First observations of IRE effects go back to 1898.[10] Nollet reported the first systematic observations of the appearance of red spots on animal and human skin that was exposed to electric sparks.[11] However, its use for modern medicine began in 1982 with the seminal work of Neumann and colleagues.[12] Pulsed electric fields were used to temporarily permeabilize cell membranes to deliver foreign DNA into cells. In the following decade, the combination of high-voltage pulsed electric fields with the chemotherapeutic drug bleomycin and with DNA yielded novel clinical applications: electrochemotherapy and gene electrotransfer, respectively.[13][14][15][16][17]

Mechanism

Further information: Electroporation § Physical mechanism

Utilizing ultra short pulsed but very strong electrical fields, micropores and nanopores are induced in the phospholipid bilayers which form the outer cell membranes. Two kinds of damage can occur:

1. Reversible electroporation (RE): Temporary and limited pathways for molecular transport via nanopores are formed, but after the end of the electric pulse, the transport ceases and the cells remain viable. Medical applications are, for example, local introduction of intracellular cytotoxic pharmaceuticals such as bleomycin (electroporation and electrochemotherapy).
2. Irreversible electroporation (IRE): After a certain degree of damage to the cell membranes by electroporation, the leakage of intracellular contents is too severe or the resealing of the cellular membrane is too slow, leaving healthy and/or cancerous cells irreversibly damaged. They die by either apoptosis or via cell-internally induced necrotic pathways, which is unique to this ablation technique.

It should be stated that even though the ablation method is generally accepted to be apoptosis, some findings seem to contradict a pure apoptotic cell death, making the exact process by which IRE causes cell death unclear.[18][4] In any case, all studies gree that the cell death is an induced one with the cells dying over a varying time period of hours to days and does not rely on local extreme heating and melting of tissue via high energy deposition like most ablation technologies (see radiofrequency ablation, microwave ablation, High-intensity focused ultrasound).

When an electrical field of more than 0.5 V/nm[19] is applied to the resting trans-membrane potential, it is proposed that water enters the cell during this dielectric breakdown. Hydrophilic pores are formed.[20][21] A molecular dynamics simulation by Tarek[22] illustrates this proposed pore formation in two steps:[23]

1. After the application of an electrical field, water molecules line up in single file and penetrate the hydrophobic center of the bilayer lipid membrane.
2. These water channels continue to grow in length and diameter and expand into water-filled pores, at which point they are stabilized by the lipid head groups that move from the membrane-water interface to the middle of the bilayer.

It is proposed that as the applied electrical field increases, the greater is the perturbation of the phospholipid head groups, which in turn increases the number of water filled pores.[24] This entire process can occur within a few nanoseconds.[22] Average sizes of nanopores are likely cell-type specific. In swine livers, they average around 340-360 nm, as found using SEM.[23]

A secondary described mode of cell death was described to be from a breakdown of the membrane due to transmembrane transfer of electrolytes and adenosine triphosphate.[3] Other effects like heat[25] or electrolysis[26][27] were also shown to play a role in the currently clinically applied IRE pulse protocols.

Potential advantages and disadvantages

Advantages of IRE

1. Tissue selectivity - conservation of vital structures within the treatment field. Its capability of preserving vital structures within the IRE-ablated zone. In all IRE ablated liver tissues, critical structures, such as the hepatic arteries, hepatic veins, portal veins and intrahepatic bile ducts were all preserved. In IRE the cell death is mediated by apoptosis. Structures mainly consisting of proteins like vascular elastic and collagenous structures, as well as peri-cellular matrix proteins are not affected by the currents. Vital and scaffolding structures (like large blood vessels, urethra or intrahepatic bile ducts) are conserved.[28] The electrically insulating myelin layer, surrounding nerve fibers, protects nerve bundles from the IRE effects to a certain degree. Up to what point nerves stay unaffected or can regenerate is not completely understood.[29]
2. Sharp ablation zone margins- The transition zone between reversible electroporated area and irreversible electroporated area is accepted to be only a few cell layers. Whereas, the transition areas as in radiation or thermal based ablation techniques are non-existent. Further, the absence of the heat sink effect, which is a cause of many problems and treatment failures, is advantageous and increases the predictability of the treatment field. Geometrically, rather complex treatment fields are enabled by the multi-electrode concept.[30]
3. Absence of thermally induced necrosis - The short pulse lengths relative to the time between the pulses prevents joule heating of the tissue. Hence, by design, no necrotic cell damage is to be expected (except possibly in very close proximity to the needle). Therefore, IRE has none of the typical short and long term side-effects associated with necrosis.[31][32]
4. Short treatment time - A typical treatment takes less than 5 minutes. This does not include the possibly complicated electrode placement which might requie the use of many electrode and re-position of the electrodes during the procedure.
5. Real time monitoring - The treatment volume can be to a certain degree be visualized, both during and after the treatment. Possible visualization methods are ultrasound, MRI, and CT.[30]
6. Immunological response - IRE appreas to provoke a stronger immunlogical response than other ablation methods[8] which is currently being studied for use in conjunction with cancer immunotheraputic approaches.[6]

Disadvantages of IRE

1. Strong muscle contractions - The strong electric fields created by IRE, due to direct stimulation of the neuromuscular junction, cause strong muscle contractions requiring special anesthesia and total body paralysis.[33]
2. Incomplete ablation within targeted tumors - The originally threshold for IRE of cells was approximately 600 V/cm with 8 pulses, a pulse duration of 100 μs, and a frequency of 10 Hz.[34] Qin et al. later discovered that even at 1,300 V/cm with 99 pulses, a pulse duration of 100 μs, and 10 Hz, there were still islands of viable tumor cells within ablated regions.[35] This suggests that tumor tissue may respond differently to IRE than healthy parenchyma. The mechanism of cell death following IRE relies on cellular apoptosis, which results from pore formation in the cellular membrane. Tumor cells, known to be resistant to apoptotic pathways, may require higher thresholds of energy to be adequately treated. However, the recurrence rated found in clinical studies suggest a rather low recurrence rate and ofen superior overall survival when compared with other ablation modalities.[36][37]
3. Local environment - The electric fields of IRE are strongly influenced by the conductivity of the local environment. The presence of metal, for example with biliary stents, can result in variances in energy deposition. Various organs, such as the kidneys, are also subject to irregular ablation zones, due to the increased conductivity of urine.[38]

Use in medical practice

A number of electrodes, in the form of long needles, are placed around the target volume. The point of penetration for the electrodes is chosen according to anatomical conditions. Imaging is essential to the placement and can be achieved by ultrasound, magnetic resonance imaging or tomography. The needles are then connected to the IRE-generator, which then proceeds to sequentially build up a potential difference between two electrodes. The geometry of the IRE-treatment field is calculated in real time and can be influenced by the user. Depending on the treatment-field and number of electrodes used, the ablation takes between 1 and 10 minutes. In general muscle relaxants are administered, since even under general anesthetics, strong muscle contractions are induced by excitation of the motor end-plate.

Typical parameters (1st generation IRE system):

• Number of pulses per treatment: 90
• Pulse length: 100 μs
• Intermission between pulses: 100 to 1000 ms
• Field strength: 1500 volt/cm
• Current: ca. 50 A (tissue- and geometry dependent)
• Max ablation volume using two electrodes: 4 × 3 × 2 cm³

The shortly pulsed, strong electrical fields are induced through thin, sterile, disposable electrodes. The potential differences are calculated and applied by a computer system between these electrodes in accordance to a previously planned treatment field.

One specific device for the IRE procedure is the NanoKnife system manufactured by AngioDynamics, which received FDA 510k clearance on October 24, 2011.[39] The NanoKnife system has also received an Investigational Device Exemption (IDE) from the FDA that allows AngioDynamics to conduct clinical trials using this device.[39] The Nanoknife system transmits a low-energy direct current from a generator to electrode probes placed in the target tissues for the surgical ablation of soft tissue. In 2011, AngioDynamics received an FDA warning letter for promoting the device for indications for which it had not received approval.[40]

In 2013, the UK National Institute for Health and Clinical Excellence issued a guidance that the safety and efficacy of the use of irreversible electroporation of the treatment of various types of cancer has not yet been established.[41]

Newer generations of Electroporation-based ablation systems are being developed specifically to address the shortcomings of the first generation of IRE but, as of June 2020, none of the technologies are available as a medical device.[27][42][43]

Clinical data

Potential organ systems, where IRE might be of significant impact due to its properties, pancreas, liver, prostate and the kid were in the main focus wit studes listed in Table 1 -3 (state: June 2020).

None of the potential organ systems, which may be treated for various conditions and tumors, are covered by randomized multicenter trials or long-term follow-ups (state. June 2020).

Liver

Table 1: Irreversible Electroporation Clinical Data in the Liver[36]

Author, Year	No. of Patients / Lesions	Tumor Type and median size	Approach	Median follow-up (mo)	Primary efficacy [44] (%)	Secondary efficacy [44] (%)
Bhutiani et al., 2016[45]	30 / 30	HCC (n = 30), 3.0 cm	Open (n = 10), laparoscopic (n = 20)	6	97	NS
Cannon et al., 2013[46]	44 / 48	HCC (n = 14), CRLM (n = 20), Other (n = 10); 2.5 cm	Percutaneous (n = 28), open (n = 14), laparoscopic (n = 2)	12	59.5	NS
Frühling et al., 2017[47]	30 / 38	HCC (n = 8), CRLM (n = 23), other (n = 7); 2.4 cm	Percutaneous (n = 30)	22,3	65.8 (at 6 months)	NS
Hosein et al., 2014[48]	28 / 58	CRLM (n = 58), 2.7 cm	Percutaneous (n = 28)	10,7	97	NS
Kingham et al., 2012[49]	28 / 65	HCC (n = 2), CRLM (n = 21), other (n = 5); 1.0 cm	Percutaneous (n = 6), open (n = 22)	6	93.8	NS
Narayanan et al., 2014[50]	67 / 100	HCC (n = 35), CRLM (n = 20), CCC (n = 5); 2.7 cm	Percutaneous (n = 67)	10,3	NS	NS
Niessen et al., 2015[51]	25 / 59	HCC (n = 22), CRLM (n = 16), CCC (n = 6), other (n = 4); 1.7 cm	Percutaneous (n = 25)	6	70.8	NS
Niessen et al., 2016[52]	34 / 59	HCC (n = 33), CRLM (n = 22), CCC (n = 5), other (n = 5); 2.4 cm	Percutaneous (n = 34)	13,9	74.8	NS
Niessen et al., 2017[53]	71 / 64	HCC (n = 31), CRLM (n = 16), CCC (n = 6), other (n = 4); 2.3 cm	Percutaneous (n = 71)	35,7	68.3	NS
Philips et al., 2013[54]	60 / 62	HCC (n = 13), CRLM (n = 23), CCC (n = 2), other (n = 22); 3.8 cm	Percutaneous (NS) open (NS)	18	NS	NS
Scheffer et al., 2014[55]	10 / 10	CRLM (n = 10), 2.4 cm	Open (n = 10)	0	88.9	NS
Thomson et al., 2011[56]	25 / 63	HCC (n = 17), CRLM (n = 15), other (n = 31); 2.5 cm	Percutaneous (n = 25)	3	51.6	56.5

Hepatic IRE appears to be safe, even when performed near vessels and bile ducts[57][58] with an overall complication rate of 16%, with most complications being needle related (pneumothorax and hemorrhage).The COLDFIRE-2 trial with 50 patients showed 76% local tumor progression-free survival after 1 year.[59] Whilst there are no studies comparing IRE to other ablative therapies yet, thermal ablations have shown a higher efficacy in that matter with around 96% progression free survival. Therefor Bart et al.[36] concluded that IRE should currently only be performed for only truly unresectable and unablatable tumors.

Pancreas

Table 2: Irreversible Electroporation Clinical Data in the Pancreas[36]

Author, Year	No. of Patients	Stage of Disease and Median Largest Tumor Diameter	Approach	Median Follow-up (mo)	Median Overall Survival (mo)	Local Recurrence (%)	Tumor Downstaging Caused by IRE
Belfiore et al., 2017[60]	29	LAPC, NS	Percutaneous	29	14.0	3	3 patients
Flak et al., 2019[61]	33	LAPC, 3.0 cm (88% after chemotherapy or radiation therapy)	Percutaneous (n = 32), open (n = 1)	9	18.5 (diagnosis), 10.7 (IRE)	NS	3 patients
Kluger et al., 2016[62]	50	LAPC T4, 3.0 cm	Open	8,7	12.0 (IRE)	11	NS
Lambert et al., 2016[63]	21	LAPC, 3.9 cm	Open (n = 19), percutaneous (n = 2)	NS	10.2	NS	NS
Leen et al., 2018[64]	75	LAPC, 3.5 cm (after chemotherapy)	Percutaneous	11.7	27.0 (IRE)	38	3 patients
Månsson et al., 2016[65]	24	LAPC, NS (after chemotherapy)	Percutaneous	NS	17.9 (diagnosis), 7.0 (IRE)	58	2 patients
Månsson et al., 2019[66]	24	LAPC, 3.0 cm (before chemotherapy)	Percutaneous	NS	13.3 (diagnosis)	33	0
Martin et al., 2015[67]	150	LAPC, 2.8 cm (after chemo- or radiation therapy)	Open	29	23.2 (diagnosis), 18 (IRE)	2	NS
Narayanan et al., 2016[68]	50	LAPC, 3.2 cm 6 1.3 (after chemo- or radiation therapy)	Percutaneous	NS	27 (diagnosis), 14.2 (IRE)	NS	3 patients
Paiella et al., 2015[69]	10	LAPC, 3.0 cm	Open	7.6	15.3 (diagnosis), 6.4 (IRE)	NS	NS
Ruarus et al., 2019[70]	50	LAPC (n = 40) and local recurrence (n = 10), 4.0 cm (68% after chemotherapy)	Percutaneous	NS	17.0 (diagnosis), 9.6 (IRE)	46	0 patients
Scheffer et al., 2017[71]	25	LAPC, 4.0 cm (52% after chemotherapy)	Percutaneous	12 (7–16)	17.0 (diagnosis), 11.0 (IRE)	NS	NS
Sugimoto et al., 2018[72]	8	LAPC, 2.9 cm	Open or percutaneous, NS	17.5	17.5 (diagnosis)	38	0 patients
Vogel et al., 2017[73]	15	LAPC, NS	Open	24	16 (diagnosis)	NS	NS
Yan et al., 2016[74]	25	LAPC, 4.2 cm	Open	3	NS	2	NS
Zhang et al., 2017[75]	21	LAPC, 3.0 cm	Percutaneous	1	NS	NS	NS

The overall survival rates in studies on the use of IRE for pancreatic cancer provide an encouraging nonvariable endpoint and show an additive beneficial effect of IRE compared with standard-of care chemotherapeutic treatment with FOLFIRINOX (a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) (median OS, 12–14months).[76][77] However, IRE apreas to be more effective in conjunction with systemic therapy and is not suggested as first-line treatment.[66] Despite that IRE makes adjuvant tumor mass reduction therapy for LAPC possible for the first time, IRE remains, in its current state, a high risk and high side effect procedure which is justifyied only due to the high mortality and the lack of alternatives.

Prostate

Table 3: Irreversible Electroporation Clinical Data in the Prostate[36]

Author, Year	No. of Patients	Gleason Score	Pretreatment or Concurrent Treatment	Adverse events, 1/2/3/4/5	Functional Outcome (% of patients)	Oncologic Efficacy (no. of patients)	Comments
Onik and Rubinsky (2010)[78]	16	3+3: n = 7 3+4: n = 6 4+4: n = 3	NS	NR	At 6 months: urinary incontinence 0% erectile dysfunction 0%	Local recurrence, n = 0; out-of-field occurrence, n = 1	Adequate flow in NVB postoperative
Van den Bos et al. (2016)[79]	16	3+3: n = 8 4+3: n = 3 4+4: n = 2	Radical prostatectomy 4 weeks after IRE	15/8/1/0/0	NS	15 patients showed complete fibrosis or necrosis of ablation zone	Electrode configuration completely enveloped ablation, leaving no viable cells in 15 patients
Van den Bos et al. (2018)[80]	63	3+3: n = 9 3+4: n = 38 4+3: n = 16	Concurrent TURP (n = 10)	Grade 1: 24% Grade 2: 11% Grade 3–5: 0%	At 12 months: urinary incontinence 0%; erectile dysfunction 23%	Local recurrence, n = 7; out-of-field recurrence, n = 4	Safe and effective
Guenther et al. (2019)[81]	429/471	3+3: n = 82 3+4/4+3: n = 225 4+4: n = 68 5+3/3+5: n = 3 >4+4 = 42	Pretreated with: radical prostatectomy (n = 21), radiation therapy (n = 28), TURP (n = 17), HIFU (n = 8) ADT (n = 29)	93/17/7/0/0	At >=12 months: urinary incontinence 0%; erectile dysfunction 3%	after up to 6y: local recurrence, n = 20; out-of-field recurrence, n = 27	Comparable 5-year Recurrence Free Survival to radical prostatectomy with improved urogenital outcomes
Valerio et al. (2014)[82]	34	3+3: n = 9 3+4: n = 19 4+3: n = 5 4+4: n = 1	NS	12/10/0/0/0	At 6 months: urinary incontinence 0%; erectile dysfunction 5%	Local residual disease, n = 6; only one histologic verification. Out-of-field recurrence, NS	Average ablation volume of 12mL
Ting et al. (2016)[83]	25	3+3: n = 2 3+4: n = 15 4+3: n = 8 4+4: n = 0	None	Grade 1: 35% Grade 2: 29% Grade 3–5: 0%	At 6 months: urinary incontinence 0%; erectile dysfunction, unknown	Local recurrence, n = 0; out-of-fieldrecurrence, n = 5 (with histologic verification)	Good oncological control achieved with low toxicity
Blazevski et al. (2020)[84]	50	3+3: n = 5 3+4: n = 37 4+3: n = 6 4+4: n = 2	NS	Grade 1: 10 Grade 2: 9 Grade 3–5: 0%	incontinence 2% (study only focused apical lesions); erectile dysfunction 6%	Local recurrence, n=1 out-of-fieldrecurrence, NS	Study only focused on apical lesions (difficult to treat with other methods without causing impotence and incontinence). Focal ablation using IRE for PCa in the distal apex appears safe and feasible.

The concept of treating prostate cancer with IRE was first proposed by Gary Onik and Boris Rubinsky in 2007.[85] Prostate carcinomas are frequently located near sensitive structures which might be permanently damaged by thermal treatments or radiation therapy. The applicability of surgical methods is often limited by accessibility and precision. Surgery is also associated with a long healing time and high rate of side effects.[86] Using IRE, the urethra, bladder, rectum and neurovascular bundle and lower urinary sphincter can potentially be included in the treatment field without creating (permanent) damage.

IRE has been in use against prostate cancer since 2011, partly in form of clinical trials, compassionate care or individualized treatment approach. As for all other ablation technologies and also most conventional methods, no studies employed a randomized multi-center approach or targeted cancer-specific mortality as endpoint. Cancer-specific mortality or overall survival are notoriously hard to assess for prostate cancer, as the trials require more than a decade and usually several treatment types are performed during the years making treatment spcific survival advantages difficult to quantify. Therefor the results of ablation-based treatments and focal treatments in general usually use local recurrences and functional outcome (quality of life) as endpoint. In that regard, the clinical results collected so far and listed in Table 3 shown encouraging results and uniformly state IRE as a safe and effective tretment (at least for focal ablation) but all warrant further studies. The largest cohort presented by Guenther et al.[81] with up to 6 year follow-up is limited as a heterogeneous retrospective analysis an no prospecitve clinical trial. Therefore, despite that several hospitals in Europe have been employing the method for many years with one private clinic even listing more than one thousand treatments as of June 2020,[87] IRE for prostate cancer is currently not recommended in treatment guidelines.

Kidney

While nephron-sparing surgery is the gold standard treatment for small, malignant renal masses, ablative therapies are considered a viable option in patients who are poor surgical candidates. Radiofrequency ablation (RFA) and cryoablation have been used since the 1990s; however, in lesions larger than 3 cm, their efficacy is limited. The newer ablation modalities, such as IRE, microwave ablation (MWA), and high-intensity focused ultrasound, may help overcome the challenges in tumor size.[88]

The first human studies have proven the safety of IRE for the ablation of renal masses; however, the effectiveness of IRE through histopathological examination of an ablated renal tumor in humans is yet to be known. Wagstaff et al. have set out to investigate the safety and effectiveness of IRE ablation of renal masses and to evaluate the efficacy of ablation using MIR and contrast-enhanced ultrasound imaging. In accordance with the prospective protocol designed by the authors, the treated patients will subsequently undergo radical nephrectomy to assess IRE ablation success.[89]

Later phase 2 prospective trials showed good results in terms of safety and feasibility [90][91] for small renal masses but the cohort was limited in numbers (7 and 10 patients respectively), hence efficacy is not yet sufficiently determined. IRE appears safe for small renal masses up to 4 cm. However, the consensus is that current evidence is still inadequate in quality and quantity.[36]

Lung

In a prospective, single-arm, multi-center, phase II clinical trial, the safety and efficacy of IRE on lung cancers were evaluated. The trial included patients with primary and secondary lung malignancies and preserved lung function. The expected effectiveness was not met at interim analysis and the trial was stopped prematurely. Complications included pneumothoraces (11 of 23 patients), alveolar hemorrhage not resulting in significant hemoptysis, and needle tract seeding was found in 3 cases (13%). Disease progression was seen in 14 of 23 patients (61%). Stable disease was found in 1 (4%), partial remission in 1 (4%) and complete remission in 7 (30%) patients. The authors concluded that IRE is not effective for the treatment of lung malignancies.[92] Similarly poor treatment outcomes have been observed in other studies.[93][94]

A major obstacle of IRE in the lung is the difficulty in positioning the electrodes; placing the probes in parallel alignment is made challenging by the interposition of ribs. Additionally, the planned and actual ablation zones in the lung are dramatically different due to the differences in conductivity between tumor, lung parenchyma, and air.[95]

Coronary arteries

Maor et el have demonstrated the safety and efficiency of IRE as an ablation modality for smooth muscle cells in the walls of large vessels in rat model.[96] Therefore, IRE has been suggested as preventive treatment for coronary artery re-stenosis after percutaneous coronary intervention.

Pulmonary veins

Numerous studies in animals have demonstrated the safety and efficiency of IRE as a non-thermal ablation modality for pulmonary veins in context of atrial fibrillation treatment. IRE's advantages in comparison with RF-ablation and cryoablation are: well defined ablation area and the lack of peripheral thermal damage. Therefore, IRE has been suggested as a part of novel treatment for atrial fibrillation.[97]

Other organs

IRE has also been investigated in ex-vivo human eye models for treatment of uveal melanoma[98] and in thyroid cancer.[99]

Successful ablations in animal tumor models have been conducted for lung,[100][101] brain,[102][103] heart,[104] skin,[105][106] bone,[107][108] head and neck cancer,[109] and blood vessels.[110]

References

1. Rubinsky B, Onik G, Mikus P (February 2007). "Irreversible electroporation: a new ablation modality--clinical implications". Technology in Cancer Research & Treatment. 6 (1): 37–48. doi:10.1177/153303460700600106. PMID 17241099. S2CID 46010434.
2. Ringel-Scaia VM, Beitel-White N, Lorenzo MF, Brock RM, Huie KE, Coutermarsh-Ott S, et al. (June 2019). "High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity". EBioMedicine. 44: 112–125. doi:10.1016/j.ebiom.2019.05.036. PMC 6606957. PMID 31130474.
3. Gissel H, Lee RC, Gehl J (2011). "Electroporation and Cellular Physiology". In Kee ST, Gehl J, Lee EW (eds.). Clinical Aspects of Electroporation. New York, NY: Springer New York. pp. 9–17. doi:10.1007/978-1-4419-8363-3_2. ISBN 978-1-4419-8362-6.
4. Zhang Y, Lyu C, Liu Y, Lv Y, Chang TT, Rubinsky B (June 2018). "Molecular and histological study on the effects of non-thermal irreversible electroporation on the liver". Biochemical and Biophysical Research Communications. 500 (3): 665–670. doi:10.1016/j.bbrc.2018.04.132. PMC 5990035. PMID 29678581.
5. Clinical trial number NCT02041936 for "Outcomes of Ablation of Unresectable Pancreatic Cancer Using the NanoKnife Irreversible Electroporation (IRE) System" at ClinicalTrials.gov
6. Calvet CY, Mir LM (June 2016). "The promising alliance of anti-cancer electrochemotherapy with immunotherapy". Cancer Metastasis Reviews. 35 (2): 165–77. doi:10.1007/s10555-016-9615-3. PMC 4911376. PMID 26993326.
7. Pandit H, Hong YK, Li Y, Rostas J, Pulliam Z, Li SP, Martin RC (March 2019). "Evaluating the Regulatory Immunomodulation Effect of Irreversible Electroporation (IRE) in Pancreatic Adenocarcinoma". Annals of Surgical Oncology. 26 (3): 800–806. doi:10.1245/s10434-018-07144-3. PMID 30610562. S2CID 57428676.
8. Bulvik BE, Rozenblum N, Gourevich S, Ahmed M, Andriyanov AV, Galun E, Goldberg SN (August 2016). "Irreversible Electroporation versus Radiofrequency Ablation: A Comparison of Local and Systemic Effects in a Small-Animal Model". Radiology. 280 (2): 413–24. doi:10.1148/radiol.2015151166. PMID 27429143.
9. Scheffer HJ, Stam AG, Geboers B, Vroomen LG, Ruarus A, de Bruijn B, et al. (2019-11-02). "Irreversible electroporation of locally advanced pancreatic cancer transiently alleviates immune suppression and creates a window for antitumor T cell activation". Oncoimmunology. 8 (11): 1652532. doi:10.1080/2162402X.2019.1652532. PMC 6791414. PMID 31646081.
10. Fuller GW (1898). Report on the investigations into the purification of the Ohio River water: at Louisville, Kentucky, made to the president and directors of the Louisville Water Company (Report). Louisville Ky.: Louisville Water Company.
11. Nollet JA (1754). Recherches sur les causes particulieres des phe ́nome ́nes e ́lectriques. Paris: Guerin & Delatour.
12. Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH (1982). "Gene transfer into mouse lyoma cells by electroporation in high electric fields". The EMBO Journal. 1 (7): 841–5. doi:10.1002/j.1460-2075.1982.tb01257.x. PMC 553119. PMID 6329708.
13. Mir LM, Belehradek M, Domenge C, Orlowski S, Poddevin B, Belehradek J, Schwaab G, Luboinski B, Paoletti C (1991). "[Electrochemotherapy, a new antitumor treatment: first clinical trial]". Comptes Rendus de l'Académie des Sciences, Série III. 313 (13): 613–8. PMID 1723647.
14. Okino M, Mohri H (December 1987). "Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors". Japanese Journal of Cancer Research. 78 (12): 1319–21. PMID 2448275.
15. Orlowski S, Belehradek J, Paoletti C, Mir LM (December 1988). "Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs". Biochemical Pharmacology. 37 (24): 4727–33. doi:10.1016/0006-2952(88)90344-9. PMID 2462423.
16. Daud AI, DeConti RC, Andrews S, Urbas P, Riker AI, Sondak VK, Munster PN, Sullivan DM, Ugen KE, Messina JL, Heller R (December 2008). "Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma". Journal of Clinical Oncology. 26 (36): 5896–903. doi:10.1200/JCO.2007.15.6794. PMC 2645111. PMID 19029422.
17. Titomirov AV, Sukharev S, Kistanova E (January 1991). "In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1088 (1): 131–4. doi:10.1016/0167-4781(91)90162-f. PMID 1703441.
18. Golberg A, Yarmush ML (March 2013). "Nonthermal irreversible electroporation: fundamentals, applications, and challenges". IEEE Transactions on Bio-Medical Engineering. 60 (3): 707–14. doi:10.1109/TBME.2013.2238672. PMID 23314769. S2CID 16034684.
19. Tieleman DP, Leontiadou H, Mark AE, Marrink SJ (May 2003). "Simulation of pore formation in lipid bilayers by mechanical stress and electric fields". Journal of the American Chemical Society. 125 (21): 6382–3. doi:10.1021/ja029504i. PMID 12785774.
20. Weaver JC (May 1994). "Molecular basis for cell membrane electroporation". Annals of the New York Academy of Sciences. 720 (1): 141–52. Bibcode:1994NYASA.720..141W. doi:10.1111/j.1749-6632.1994.tb30442.x. PMID 8010633.
21. Neumann E, Kakorin S, Toensing K (February 1999). "Fundamentals of electroporative delivery of drugs and genes". Bioelectrochemistry and Bioenergetics. 48 (1): 3–16. doi:10.1016/s0302-4598(99)00008-2. PMID 10228565.
22. Tarek M (June 2005). "Membrane electroporation: a molecular dynamics simulation". Biophysical Journal. 88 (6): 4045–53. Bibcode:2005BpJ....88.4045T. doi:10.1529/biophysj.104.050617. PMC 1305635. PMID 15764667.
23. Lee EW, Wong D, Prikhodko SV, Perez A, Tran C, Loh CT, Kee ST (January 2012). "Electron microscopic demonstration and evaluation of irreversible electroporation-induced nanopores on hepatocyte membranes". Journal of Vascular and Interventional Radiology. 23 (1): 107–13. doi:10.1016/j.jvir.2011.09.020. PMID 22137466.
24. Chen C, Smye SW, Robinson MP, Evans JA (March 2006). "Membrane electroporation theories: a review". Medical & Biological Engineering & Computing. 44 (1–2): 5–14. doi:10.1007/s11517-005-0020-2. PMID 16929916. S2CID 6039291.
25. van Gemert MJ, Wagstaff PG, de Bruin DM, van Leeuwen TG, van der Wal AC, Heger M, van der Geld CW (February 2015). "Irreversible electroporation: just another form of thermal therapy?". The Prostate. 75 (3): 332–5. doi:10.1002/pros.22913. PMC 4305196. PMID 25327875.
26. Rubinsky L, Guenther E, Mikus P, Stehling M, Rubinsky B (October 2016). "Electrolytic Effects During Tissue Ablation by Electroporation". Technology in Cancer Research & Treatment. 15 (5): NP95–NP103. doi:10.1177/1533034615601549. PMID 26323571. S2CID 31700711.
27. Klein N, Mercadal B, Stehling M, Ivorra A (June 2020). "In vitro study on the mechanisms of action of electrolytic electroporation (E2)". Bioelectrochemistry. 133: 107482. doi:10.1016/j.bioelechem.2020.107482. PMID 32062417.
28. Maor E, Rubinsky B (March 2010). "Endovascular nonthermal irreversible electroporation: a finite element analysis". Journal of Biomechanical Engineering. 132 (3): 031008. doi:10.1115/1.4001035. PMID 20459196.
29. Schoellnast H, Monette S, Ezell PC, Maybody M, Erinjeri JP, Stubblefield MD, Single G, Solomon SB (February 2013). "The delayed effects of irreversible electroporation ablation on nerves". European Radiology. 23 (2): 375–80. doi:10.1007/s00330-012-2610-3. PMID 23011210. S2CID 19251168.
30. Lee EW, Thai S, Kee ST (September 2010). "Irreversible electroporation: a novel image-guided cancer therapy". Gut and Liver. 4 Suppl 1 (Suppl.1): S99–S104. doi:10.5009/gnl.2010.4.s1.s99. PMC 2989557. PMID 21103304.
31. Neal RE, Davalos RV (December 2009). "The feasibility of irreversible electroporation for the treatment of breast cancer and other heterogeneous systems". Annals of Biomedical Engineering. 37 (12): 2615–25. CiteSeerX 10.1.1.679.1068. doi:10.1007/s10439-009-9796-9. PMID 19757056. S2CID 985854.
32. Edd JF, Horowitz L, Davalos RV, Mir LM, Rubinsky B (July 2006). "In vivo results of a new focal tissue ablation technique: irreversible electroporation". IEEE Transactions on Bio-Medical Engineering. 53 (7): 1409–15. doi:10.1109/TBME.2006.873745. PMID 16830945. S2CID 8269394.
33. Arena CB, Sano MB, Rossmeisl JH, Caldwell JL, Garcia PA, Rylander MN, Davalos RV (November 2011). "High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction". BioMedical Engineering OnLine. 10 (1): 102. doi:10.1186/1475-925x-10-102. PMC 3258292. PMID 22104372.
34. Rubinsky B, Onik G, Mikus P (February 2007). "Irreversible electroporation: a new ablation modality--clinical implications". Technology in Cancer Research & Treatment. 6 (1): 37–48. doi:10.1177/153303460700600106. PMID 17241099.
35. Qin Z, Jiang J, Long G, Lindgren B, Bischof JC (March 2013). "Irreversible electroporation: an in vivo study with dorsal skin fold chamber". Annals of Biomedical Engineering. 41 (3): 619–29. doi:10.1007/s10439-012-0686-1. PMID 23180025. S2CID 9514520.
36. Geboers B, Scheffer HJ, Graybill PM, Ruarus AH, Nieuwenhuizen S, Puijk RS, et al. (May 2020). "High-Voltage Electrical Pulses in Oncology: Irreversible Electroporation, Electrochemotherapy, Gene Electrotransfer, Electrofusion, and Electroimmunotherapy". Radiology. 295 (2): 254–272. doi:10.1148/radiol.2020192190. PMID 32208094.
37. Aycock KN, Davalos RV (2019-12-01). "Irreversible Electroporation: Background, Theory, and Review of Recent Developments in Clinical Oncology". Bioelectricity. 1 (4): 214–234. doi:10.1089/bioe.2019.0029.
38. Ben-David E, Ahmed M, Faroja M, Moussa M, Wandel A, Sosna J, Appelbaum L, Nissenbaum I, Goldberg SN (December 2013). "Irreversible electroporation: treatment effect is susceptible to local environment and tissue properties". Radiology. 269 (3): 738–47. doi:10.1148/radiol.13122590. PMC 4228712. PMID 23847254.
39. "FDA Grants Prostate IDE Approval for AngioDynamics' NanoKnife System". Press Release. AngioDynamics. 13 June 2013.
40. "Angiodynamics, Inc. Enforcement Actions: Warning Letter" (PDF). Public Health Service. United States Food and Drug Administration. 2011-01-21.
41. Vroomen LG, Petre EN, Cornelis FH, Solomon SB, Srimathveeravalli G (September 2017). "Irreversible electroporation and thermal ablation of tumors in the liver, lung, kidney and bone: What are the differences?". Diagnostic and Interventional Imaging. 98 (9): 609–617. doi:10.1016/j.diii.2017.07.007. PMID 28869200. Current evidence on the safety and efficacy of irreversible electroporation for treating primary lung cancer and metastases in the lung is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research.
42. Siddiqui IA, Kirks RC, Latouche EL, DeWitt MR, Swet JH, Baker EH, et al. (June 2017). "High-Frequency Irreversible Electroporation: Safety and Efficacy of Next-Generation Irreversible Electroporation Adjacent to Critical Hepatic Structures". Surgical Innovation. 24 (3): 276–283. doi:10.1177/1553350617692202. PMID 28492356. S2CID 4056858.
43. Nuccitelli R (2017). "Tissue Ablation Using Nanosecond Electric Pulses". In Miklavčič D (ed.). Handbook of Electroporation. Cham: Springer International Publishing. pp. 1787–1797. doi:10.1007/978-3-319-32886-7_93. ISBN 978-3-319-32885-0.
44. Ahmed M, Solbiati L, Brace CL, Breen DJ, Callstrom MR, Charboneau JW, et al. (October 2014). "Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update". Radiology. 273 (1): 241–60. doi:10.1148/radiol.14132958. PMC 4263618. PMID 24927329.
45. Bhutiani N, Philips P, Scoggins CR, McMasters KM, Potts MH, Martin RC (July 2016). "Evaluation of tolerability and efficacy of irreversible electroporation (IRE) in treatment of Child-Pugh B (7/8) hepatocellular carcinoma (HCC)". HPB. 18 (7): 593–9. doi:10.1016/j.hpb.2016.03.609. PMC 4925804. PMID 27346140.
46. Cannon R, Ellis S, Hayes D, Narayanan G, Martin RC (April 2013). "Safety and early efficacy of irreversible electroporation for hepatic tumors in proximity to vital structures". Journal of Surgical Oncology. 107 (5): 544–9. doi:10.1002/jso.23280. PMID 23090720.
47. Frühling P, Nilsson A, Duraj F, Haglund U, Norén A (April 2017). "Single-center nonrandomized clinical trial to assess the safety and efficacy of irreversible electroporation (IRE) ablation of liver tumors in humans: Short to mid-term results". European Journal of Surgical Oncology. 43 (4): 751–757. doi:10.1016/j.ejso.2016.12.004. PMID 28109674.
48. Hosein PJ, Echenique A, Loaiza-Bonilla A, Froud T, Barbery K, Rocha Lima CM, et al. (August 2014). "Percutaneous irreversible electroporation for the treatment of colorectal cancer liver metastases with a proposal for a new response evaluation system". Journal of Vascular and Interventional Radiology. 25 (8): 1233–1239.e2. doi:10.1016/j.jvir.2014.04.007. PMID 24861662.
49. Kingham TP, Karkar AM, D'Angelica MI, Allen PJ, Dematteo RP, Getrajdman GI, et al. (September 2012). "Ablation of perivascular hepatic malignant tumors with irreversible electroporation". Journal of the American College of Surgeons. 215 (3): 379–87. doi:10.1016/j.jamcollsurg.2012.04.029. PMID 22704820.
50. Narayanan G, Bhatia S, Echenique A, Suthar R, Barbery K, Yrizarry J (December 2014). "Vessel patency post irreversible electroporation". Cardiovascular and Interventional Radiology. 37 (6): 1523–9. doi:10.1007/s00270-014-0988-9. PMID 25212418. S2CID 24354742.
51. Niessen C, Igl J, Pregler B, Beyer L, Noeva E, Dollinger M, et al. (May 2015). "Factors associated with short-term local recurrence of liver cancer after percutaneous ablation using irreversible electroporation: a prospective single-center study". Journal of Vascular and Interventional Radiology. 26 (5): 694–702. doi:10.1016/j.jvir.2015.02.001. PMID 25812712.
52. Niessen C, Beyer LP, Pregler B, Dollinger M, Trabold B, Schlitt HJ, et al. (April 2016). "Percutaneous Ablation of Hepatic Tumors Using Irreversible Electroporation: A Prospective Safety and Midterm Efficacy Study in 34 Patients". Journal of Vascular and Interventional Radiology. 27 (4): 480–6. doi:10.1016/j.jvir.2015.12.025. PMID 26922979.
53. Niessen C, Thumann S, Beyer L, Pregler B, Kramer J, Lang S, et al. (March 2017). "Percutaneous Irreversible Electroporation: Long-term survival analysis of 71 patients with inoperable malignant hepatic tumors". Scientific Reports. 7 (1): 43687. Bibcode:2017NatSR...743687N. doi:10.1038/srep43687. PMC 5339813. PMID 28266600.
54. Philips P, Hays D, Martin RC (2013-11-01). Zhang Z (ed.). "Irreversible electroporation ablation (IRE) of unresectable soft tissue tumors: learning curve evaluation in the first 150 patients treated". PLOS ONE. 8 (11): e76260. Bibcode:2013PLoSO...876260P. doi:10.1371/journal.pone.0076260. PMC 3815199. PMID 24223700.
55. Scheffer HJ, Nielsen K, van Tilborg AA, Vieveen JM, Bouwman RA, Kazemier G, et al. (October 2014). "Ablation of colorectal liver metastases by irreversible electroporation: results of the COLDFIRE-I ablate-and-resect study". European Radiology. 24 (10): 2467–75. doi:10.1007/s00330-014-3259-x. PMID 24939670. S2CID 8251595.
56. Thomson KR, Cheung W, Ellis SJ, Federman D, Kavnoudias H, Loader-Oliver D, et al. (May 2011). "Investigation of the safety of irreversible electroporation in humans". Journal of Vascular and Interventional Radiology. 22 (5): 611–21. doi:10.1016/j.jvir.2010.12.014. PMID 21439847.
57. Kourounis G, Paul Tabet P, Moris D, Papalambros A, Felekouras E, Georgiades F, et al. (2017). "Irreversible electroporation (Nanoknife® treatment) in the field of hepatobiliary surgery: Current status and future perspectives" (PDF). Journal of B.U.On. 22 (1): 141–149. PMID 28365947.
58. Silk MT, Wimmer T, Lee KS, Srimathveeravalli G, Brown KT, Kingham PT, et al. (January 2014). "Percutaneous ablation of peribiliary tumors with irreversible electroporation". Journal of Vascular and Interventional Radiology. 25 (1): 112–8. doi:10.1016/j.jvir.2013.10.012. PMID 24262034.
59. Scheffer HJ, Vroomen LG, Nielsen K, van Tilborg AA, Comans EF, van Kuijk C, et al. (October 2015). "Colorectal liver metastatic disease: efficacy of irreversible electroporation--a single-arm phase II clinical trial (COLDFIRE-2 trial)". BMC Cancer. 15 (1): 772. doi:10.1186/s12885-015-1736-5. PMC 4619419. PMID 26497813.
60. Belfiore G, Belfiore MP, Reginelli A, Capasso R, Romano F, Ianniello GP, et al. (March 2017). "Concurrent chemotherapy alone versus irreversible electroporation followed by chemotherapy on survival in patients with locally advanced pancreatic cancer". Medical Oncology. 34 (3): 38. doi:10.1007/s12032-017-0887-4. PMID 28161827. S2CID 21975227.
61. Flak RV, Stender MT, Jensen TM, Andersen KL, Henriksen SD, Mortensen PB, et al. (February 2019). "Treatment of locally advanced pancreatic cancer with irreversible electroporation - a Danish single center study of safety and feasibility". Scandinavian Journal of Gastroenterology. 54 (2): 252–258. doi:10.1080/00365521.2019.1575465. PMID 30907286. S2CID 85498704.
62. Kluger MD, Epelboym I, Schrope BA, Mahendraraj K, Hecht EM, Susman J, et al. (May 2016). "Single-Institution Experience with Irreversible Electroporation for T4 Pancreatic Cancer: First 50 Patients". Annals of Surgical Oncology. 23 (5): 1736–43. doi:10.1245/s10434-015-5034-x. PMID 26714959. S2CID 12668014.
63. Lambert L, Horejs J, Krska Z, Hoskovec D, Petruzelka L, Krechler T, et al. (2016-01-16). "Treatment of locally advanced pancreatic cancer by percutaneous and intraoperative irreversible electroporation: general hospital cancer center experience". Neoplasma. 63 (2): 269–73. doi:10.4149/213_150611n326. PMID 26774149.
64. Leen E, Picard J, Stebbing J, Abel M, Dhillon T, Wasan H (April 2018). "Percutaneous irreversible electroporation with systemic treatment for locally advanced pancreatic adenocarcinoma". Journal of Gastrointestinal Oncology. 9 (2): 275–281. doi:10.21037/jgo.2018.01.14. PMC 5934146. PMID 29755766.
65. Månsson C, Brahmstaedt R, Nilsson A, Nygren P, Karlson BM (September 2016). "Percutaneous irreversible electroporation for treatment of locally advanced pancreatic cancer following chemotherapy or radiochemotherapy". European Journal of Surgical Oncology. 42 (9): 1401–6. doi:10.1016/j.ejso.2016.01.024. PMID 26906114.
66. Månsson C, Brahmstaedt R, Nygren P, Nilsson A, Urdzik J, Karlson BM (May 2019). "Percutaneous Irreversible Electroporation as First-line Treatment of Locally Advanced Pancreatic Cancer". Anticancer Research. 39 (5): 2509–2512. doi:10.21873/anticanres.13371. PMID 31092446. S2CID 155101619.
67. Martin RC, Kwon D, Chalikonda S, Sellers M, Kotz E, Scoggins C, et al. (September 2015). "Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy". Annals of Surgery. 262 (3): 486–94, discussion 492–4. doi:10.1097/sla.0000000000001441. PMID 26258317.
68. Narayanan G, Hosein PJ, Beulaygue IC, Froud T, Scheffer HJ, Venkat SR, et al. (March 2017). "Percutaneous Image-Guided Irreversible Electroporation for the Treatment of Unresectable, Locally Advanced Pancreatic Adenocarcinoma". Journal of Vascular and Interventional Radiology. 28 (3): 342–348. doi:10.1016/j.jvir.2016.10.023. PMID 27993507.
69. Paiella S, Butturini G, Frigerio I, Salvia R, Armatura G, Bacchion M, et al. (2015). "Safety and feasibility of Irreversible Electroporation (IRE) in patients with locally advanced pancreatic cancer: results of a prospective study". Digestive Surgery. 32 (2): 90–7. doi:10.1159/000375323. PMID 25765775. S2CID 25093235.
70. Ruarus AH, Vroomen LG, Geboers B, van Veldhuisen E, Puijk RS, Nieuwenhuizen S, et al. (January 2020). "Percutaneous Irreversible Electroporation in Locally Advanced and Recurrent Pancreatic Cancer (PANFIRE-2): A Multicenter, Prospective, Single-Arm, Phase II Study". Radiology. 294 (1): 212–220. doi:10.1148/radiol.2019191109. PMID 31687922.
71. Scheffer HJ, Vroomen LG, Zonderhuis BM, Daams F, Vogel JA, Besselink MG, et al. (April 2016). "Ablation of locally advanced pancreatic carcinoma by percutaneous irreversible electroporation: Results of the phase I/II PANFIRE-study". HPB. 18: e115. doi:10.1016/j.hpb.2016.02.269.
72. Sugimoto K, Moriyasu F, Tsuchiya T, Nagakawa Y, Hosokawa Y, Saito K, et al. (November 2018). "Irreversible Electroporation for Nonthermal Tumor Ablation in Patients with Locally Advanced Pancreatic Cancer: Initial Clinical Experience in Japan". Internal Medicine. 57 (22): 3225–3231. doi:10.2169/internalmedicine.0861-18. PMC 6287993. PMID 29984761.
73. Vogel JA, Rombouts SJ, de Rooij T, van Delden OM, Dijkgraaf MG, van Gulik TM, et al. (September 2017). "Induction Chemotherapy Followed by Resection or Irreversible Electroporation in Locally Advanced Pancreatic Cancer (IMPALA): A Prospective Cohort Study". Annals of Surgical Oncology. 24 (9): 2734–2743. doi:10.1245/s10434-017-5900-9. PMID 28560601. S2CID 21656974.
74. Yan L, Chen YL, Su M, Liu T, Xu K, Liang F, et al. (December 2016). "A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma". Chinese Medical Journal. 129 (24): 2920–2925. doi:10.4103/0366-6999.195476. PMC 5198526. PMID 27958223.
75. Zhang Y, Shi J, Zeng J, Alnagger M, Zhou L, Fang G, et al. (February 2017). "Percutaneous Irreversible Electroporation for Ablation of Locally Advanced Pancreatic Cancer: Experience From a Chinese Institution". Pancreas. 46 (2): e12–e14. doi:10.1097/mpa.0000000000000703. PMID 28085755.
76. Rombouts SJ, Walma MS, Vogel JA, van Rijssen LB, Wilmink JW, Mohammad NH, et al. (December 2016). "Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer". Annals of Surgical Oncology. 23 (13): 4352–4360. doi:10.1245/s10434-016-5373-2. PMC 5090009. PMID 27370653.
77. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M (August 2011). "Pancreatic cancer". Lancet. 378 (9791): 607–20. doi:10.1016/S0140-6736(10)62307-0. PMC 3062508. PMID 21620466.
78. Onik G, Rubinsky B (2010). "Irreversible Electroporation: First Patient Experience Focal Therapy of Prostate Cancer". In Rubinsky B (ed.). Irreversible Electroporation. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 235–247. doi:10.1007/978-3-642-05420-4_10. ISBN 978-3-642-05419-8.
79. van den Bos W, Jurhill RR, de Bruin DM, Savci-Heijink CD, Postema AW, Wagstaff PG, et al. (August 2016). "Histopathological Outcomes after Irreversible Electroporation for Prostate Cancer: Results of an Ablate and Resect Study". The Journal of Urology. 196 (2): 552–9. doi:10.1016/j.juro.2016.02.2977. PMID 27004693.
80. van den Bos W, Scheltema MJ, Siriwardana AR, Kalsbeek AM, Thompson JE, Ting F, et al. (May 2018). "Focal irreversible electroporation as primary treatment for localized prostate cancer". BJU International. 121 (5): 716–724. doi:10.1111/bju.13983. PMID 28796935. S2CID 25747416.
81. Guenther E, Klein N, Zapf S, Weil S, Schlosser C, Rubinsky B, Stehling MK (2019-04-15). Ahmad A (ed.). "Prostate cancer treatment with Irreversible Electroporation (IRE): Safety, efficacy and clinical experience in 471 treatments". PLOS ONE. 14 (4): e0215093. Bibcode:2019PLoSO..1415093G. doi:10.1371/journal.pone.0215093. PMC 6464181. PMID 30986263.
82. Valerio M, Stricker PD, Ahmed HU, Dickinson L, Ponsky L, Shnier R, et al. (December 2014). "Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer". Prostate Cancer and Prostatic Diseases. 17 (4): 343–7. doi:10.1038/pcan.2014.33. PMC 4227889. PMID 25179590.
83. Ting F, Tran M, Böhm M, Siriwardana A, Van Leeuwen PJ, Haynes AM, et al. (March 2016). "Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control". Prostate Cancer and Prostatic Diseases. 19 (1): 46–52. doi:10.1038/pcan.2015.47. PMID 26458959. S2CID 6206548.
84. Blazevski, Alexandar; Amin, Amer; Scheltema, Matthijs J.; Balakrishnan, Anjali; Haynes, Anne-Maree; Barreto, Daniela; Cusick, Thomas; Thompson, James; Stricker, Phillip D. (2020-06-02). "Focal ablation of apical prostate cancer lesions with irreversible electroporation (IRE)". World Journal of Urology. doi:10.1007/s00345-020-03275-z. ISSN 0724-4983.
85. Onik G, Mikus P, Rubinsky B (August 2007). "Irreversible electroporation: implications for prostate ablation". Technology in Cancer Research & Treatment. 6 (4): 295–300. doi:10.1177/153303460700600405. PMID 17668936.
86. Kasivisvanathan V, Emberton M, Ahmed HU (August 2013). "Focal therapy for prostate cancer: rationale and treatment opportunities". Clinical Oncology. 25 (8): 461–73. doi:10.1016/j.clon.2013.05.002. PMC 4042323. PMID 23759249.
87. Stehling, Michael M.D. Ph.D. "Vitus Prostate Center - Privatly owned Radiology Clinic".
88. Olweny EO, Cadeddu JA (September 2012). "Novel methods for renal tissue ablation". Current Opinion in Urology. 22 (5): 379–84. doi:10.1097/mou.0b013e328355ecf5. PMID 22706069.
89. Wagstaff PG, de Bruin DM, Zondervan PJ, Savci Heijink CD, Engelbrecht MR, van Delden OM, et al. (March 2015). "The efficacy and safety of irreversible electroporation for the ablation of renal masses: a prospective, human, in-vivo study protocol". BMC Cancer. 15 (1): 165. doi:10.1186/s12885-015-1189-x. PMC 4376341. PMID 25886058.
90. Wendler JJ, Pech M, Köllermann J, Friebe B, Siedentopf S, Blaschke S, et al. (March 2018). "Upper-Urinary-Tract Effects After Irreversible Electroporation (IRE) of Human Localised Renal-Cell Carcinoma (RCC) in the IRENE Pilot Phase 2a Ablate-and-Resect Study". Cardiovascular and Interventional Radiology. 41 (3): 466–476. doi:10.1007/s00270-017-1795-x. PMID 28929209. S2CID 5024881.
91. Buijs M, Zondervan PJ, de Bruin DM, van Lienden KP, Bex A, van Delden OM (March 2019). "Feasibility and safety of irreversible electroporation (IRE) in patients with small renal masses: Results of a prospective study". Urologic Oncology. 37 (3): 183.e1–183.e8. doi:10.1016/j.urolonc.2018.11.008. PMID 30509869.
92. Ricke J, Jürgens JH, Deschamps F, Tselikas L, Uhde K, Kosiek O, De Baere T (April 2015). "Irreversible electroporation (IRE) fails to demonstrate efficacy in a prospective multicenter phase II trial on lung malignancies: the ALICE trial". Cardiovascular and Interventional Radiology. 38 (2): 401–8. doi:10.1007/s00270-014-1049-0. PMID 25609208. S2CID 34055662.
93. Thomson KR, Cheung W, Ellis SJ, Federman D, Kavnoudias H, Loader-Oliver D, Roberts S, Evans P, Ball C, Haydon A (May 2011). "Investigation of the safety of irreversible electroporation in humans". Journal of Vascular and Interventional Radiology. 22 (5): 611–21. doi:10.1016/j.jvir.2010.12.014. PMID 21439847.
94. Usman M, Moore W, Talati R, Watkins K, Bilfinger TV (June 2012). "Irreversible electroporation of lung neoplasm: a case series". Medical Science Monitor. 18 (6): CS43-7. doi:10.12659/msm.882888. PMC 3560719. PMID 22648257.
95. Srimathveeravalli G, Wimmer T, Silk M, et al. (2013). "Treatment planning considerations for IRE in the lung: placement of needle electrodes is critical". J Vasc Interv Radiol. 24 (4): S22. doi:10.1016/j.jvir.2013.01.047.
96. Maor E, Ivorra A, Rubinsky B (2009-03-09). "Non thermal irreversible electroporation: novel technology for vascular smooth muscle cells ablation". PLOS ONE. 4 (3): e4757. Bibcode:2009PLoSO...4.4757M. doi:10.1371/journal.pone.0004757. PMC 2650260. PMID 19270746.
97. Xie F, Varghese F, Pakhomov AG, Semenov I, Xiao S, Philpott J, Zemlin C (2015-12-14). "Ablation of Myocardial Tissue With Nanosecond Pulsed Electric Fields". PLOS ONE. 10 (12): e0144833. Bibcode:2015PLoSO..1044833X. doi:10.1371/journal.pone.0144833. PMC 4687652. PMID 26658139.
98. Mandel Y, Laufer S, Belkin M, Rubinsky B, Pe'er J, Frenkel S (2013-01-01). "Irreversible electroporation of human primary uveal melanoma in enucleated eyes". PLOS ONE. 8 (9): e71789. Bibcode:2013PLoSO...871789M. doi:10.1371/journal.pone.0071789. PMC 3764134. PMID 24039721.
99. Meijerink MR, Scheffer HJ, de Bree R, Sedee RJ (August 2015). "Percutaneous Irreversible Electroporation for Recurrent Thyroid Cancer--A Case Report". Journal of Vascular and Interventional Radiology. 26 (8): 1180–2. doi:10.1016/j.jvir.2015.05.004. PMID 26210244.
100. Deodhar A, Monette S, Single GW, Hamilton WC, Thornton RH, Sofocleous CT, Maybody M, Solomon SB (December 2011). "Percutaneous irreversible electroporation lung ablation: preliminary results in a porcine model". Cardiovascular and Interventional Radiology. 34 (6): 1278–87. doi:10.1007/s00270-011-0143-9. PMID 21455641. S2CID 13294844.
101. Dupuy DE, Aswad B, Ng T (April 2011). "Irreversible electroporation in a Swine lung model". Cardiovascular and Interventional Radiology. 34 (2): 391–5. doi:10.1007/s00270-010-0091-9. PMID 21191587. S2CID 1233259.
102. Garcia PA, Pancotto T, Rossmeisl JH, Henao-Guerrero N, Gustafson NR, Daniel GB, Robertson JL, Ellis TL, Davalos RV (February 2011). "Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient". Technology in Cancer Research & Treatment. 10 (1): 73–83. doi:10.7785/tcrt.2012.500181. PMC 4527477. PMID 21214290.
103. Garcia PA, Rossmeisl JH, Neal RE, Ellis TL, Olson JD, Henao-Guerrero N, Robertson J, Davalos RV (July 2010). "Intracranial nonthermal irreversible electroporation: in vivo analysis". The Journal of Membrane Biology. 236 (1): 127–36. CiteSeerX 10.1.1.679.527. doi:10.1007/s00232-010-9284-z. PMID 20668843. S2CID 10958480.
104. Lavee J, Onik G, Mikus P, Rubinsky B (2007). "A novel nonthermal energy source for surgical epicardial atrial ablation: irreversible electroporation". The Heart Surgery Forum. 10 (2): E162-7. doi:10.1532/hsf98.20061202. PMID 17597044.
105. Al-Sakere B, André F, Bernat C, Connault E, Opolon P, Davalos RV, Rubinsky B, Mir LM (November 2007). "Tumor ablation with irreversible electroporation". PLOS ONE. 2 (11): e1135. Bibcode:2007PLoSO...2.1135A. doi:10.1371/journal.pone.0001135. PMC 2065844. PMID 17989772.
106. Calmels L, Al-Sakere B, Ruaud JP, Leroy-Willig A, Mir LM (December 2012). "In vivo MRI follow-up of murine tumors treated by electrochemotherapy and other electroporation-based treatments". Technology in Cancer Research & Treatment. 11 (6): 561–70. doi:10.7785/tcrt.2012.500270. PMID 22712607.
107. Fini M, Tschon M, Ronchetti M, Cavani F, Bianchi G, Mercuri M, Alberghini M, Cadossi R (November 2010). "Ablation of bone cells by electroporation". The Journal of Bone and Joint Surgery. British Volume. 92 (11): 1614–20. doi:10.1302/0301-620X.92B11.24664. hdl:11380/646548. PMID 21037363.
108. Fini M, Tschon M, Alberghini M, Bianchi G, Mercuri M, Campanacci L, et al. (2011). "Cell electroporation in bone tissue.". In Lee E, Kee S, Gehl J (eds.). Clinical aspects of electroporation. New York, NY.: Springer. pp. 115–127. ISBN 978-1-4419-8362-6.
109. Wong D, Lee EW, Kee ST (2011). "Translational research on irreversible electroporation: VX2 rabbit head and neck.". In Lee E, Kee S, Gehl J (eds.). Clinical Aspects of Electroporation. Berlin: Springer. pp. 231–236. ISBN 978-1-4419-8362-6.
110. Maor E, Ivorra A, Rubinsky B (2009-01-01). "Non thermal irreversible electroporation: novel technology for vascular smooth muscle cells ablation". PLOS ONE. 4 (3): e4757. Bibcode:2009PLoSO...4.4757M. doi:10.1371/journal.pone.0004757. PMC 2650260. PMID 19270746.

Further reading

• Rubinsky B (2009). Irreversible Electroporation (Series in Biomedical Engineering). Berlin: Springer. ISBN 978-3-642-05419-8.