Irreversible Electroporation for Nonthermal Tumor Ablation in the Clinical Setting: A Systematic Review of Safety and Efficacy

doi:10.1016/j.jvir.2014.01.028

Journal of Vascular and Interventional Radiology

Volume 25, Issue 7, July 2014, Pages 997-1011

https://doi.org/10.1016/j.jvir.2014.01.028 Get rights and content

Abstract

Purpose

To provide an overview of current clinical results of irreversible electroporation (IRE), a novel, nonthermal tumor ablation technique that uses electric pulses to induce cell death, while preserving structural integrity of bile ducts and vessels.

Methods

All in-human literature on IRE reporting safety or efficacy or both was included. All adverse events were recorded. Tumor response on follow-up imaging from 3 months onward was evaluated.

Results

In 16 studies, 221 patients had 325 tumors treated in liver (n = 129), pancreas (n = 69), kidney (n = 14), lung (n = 6), lesser pelvis (n = 1), and lymph node (n = 2). No major adverse events during IRE were reported. IRE caused only minor complications in the liver; however, three major complications were reported in the pancreas (bile leak [n = 2], portal vein thrombosis [n = 1]). Complete response at 3 months was 67%–100% for hepatic tumors (93%–100% for tumors < 3 cm). Pancreatic IRE combined with surgery led to prolonged survival compared with control patients (20 mo vs 13 mo) and significant pain reduction.

Conclusions

In cases where other techniques are unsuitable, IRE is a promising modality for the ablation of tumors near bile ducts and blood vessels. This articles gives an extensive overview of the available evidence, which is limited in terms of quality and quantity. With the limitations of the evidence in mind, IRE of central liver tumors seems relatively safe without major complications, whereas complications after pancreatic IRE appear more severe. The available limited results for tumor control are generally good. Overall, the future of IRE for difficult-to-reach tumors appears promising.

Section snippets

Materials and Methods

This review was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for reporting systematic reviews (17). The reviewers agreed to the terminology suggested by the Society of Interventional Radiology (SIR) in “Image-Guided Tumor Ablation: Standardization of Terminology and Reporting Criteria” (18).

Results

The searches identified 232 hits in PubMed and 353 in EMBASE. After removal of duplicates and exclusion based on title and abstract, 26 remaining articles were reviewed. The final analysis included 16 full-text articles (Fig 2). The articles were published between August 2010 and November 2013. Six articles were case reports and 10 were case series. The quality assessment summary scores of the included studies are shown in Figure 3. The entire list of ratings for each study is available in

Discussion

Intentional cell death induced by IRE for tumor ablation has been studied in recent years. Extensive preclinical testing of the potential advantage of preservation of extracellular matrix structures in the absence of thermal coagulation was performed before IRE was introduced in the clinical setting. The results found in this review are discussed further here.

References (55)

K.P. Charpentier et al.
Irreversible electroporation of the liver and liver hilum in swine
HPB
(2011)
A. José et al.
Irreversible electroporation shows efficacy against pancreatic carcinoma without systemic toxicity in mouse models
Cancer Lett
(2012)
K.P. Charpentier et al.
Irreversible electroporation of the pancreas in swine: a pilot study
HPB
(2010)
A. Deodhar et al.
Renal tissue ablation with irreversible electroporation: preliminary results in a porcine model
Urology
(2011)
D. Moher et al.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
J Clin Epidemiol
(2009)
S.N. Goldberg et al.
Image-guided tumor ablation: standardization of terminology and reporting criteria
J Vasc Interv Radiol
(2009)
R.C.G. Martin et al.
Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma
J Am Coll Surg
(2012)
K. Thomson et al.
Investigation of the safety of irreversible electroporation in humans
J Vasc Interv Radiol
(2011)
T.P. Kingham et al.
Ablation of perivascular hepatic malignant tumors with irreversible electroporation
J Am Coll Surg
(2012)
M.T. Silk et al.
Percutaneous ablation of peribiliary tumors with irreversible electroporation
J Vasc Interv Radiol
(2014)

G. Narayanan et al.

Percutaneous irreversible electroporation for downstaging and control of unresectable pancreatic adenocarcinoma

J Vasc Interv Radiol

(2012)

S. Bagla et al.

Percutaneous irreversible electroporation of surgically unresectable pancreatic cancer: a case report

J Vasc Interv Radiol

(2012)

P. Hadjicostas et al.

Radiofrequency ablation in pancreatic cancer

HPB

(2006)

E.W. Lee et al.

Irreversible electroporation in eradication of rabbit VX2 liver tumor

J Vasc Interv Radiol

(2012)

M. Pavlin et al.

Effect of cell electroporation on the conductivity of a cell suspension

Biophys J

(2005)

M. Ahmed et al.

Principles of and advances in percutaneous ablation

Radiology

(2011)

E.W. Lee et al.

Irreversible electroporation: a novel image-guided cancer therapy

Gut Liver

(2010)

M.A. Phillips et al.

Irreversible electroporation on the small intestine

Br J Cancer

(2012)

G. Onik et al.

Irreversible electroporation: implications for prostate ablation

Technol Cancer Res Treat

(2007)

H. Schoellnast et al.

Irreversible electroporation adjacent to the rectum: evaluation of pathological effects in a pig model

Cardiovasc Intervent Radiol

(2012)

J.J. Wendler et al.

Urinary tract effects after multifocal nonthermal irreversible electroporation of the kidney: acute and chronic monitoring by magnetic resonance imaging, intravenous urography and urinary cytology

Cardiovasc Intervent Radiol

(2012)

M. Bower et al.

Irreversible electroporation of the pancreas: definitive local therapy without systemic effects

J Surg Oncol

(2011)

W. Li et al.

The effects of irreversible electroporation (IRE) on nerves

PloS One

(2011)

H. Schoellnast et al.

The delayed effects of irreversible electroporation ablation on nerves

Eur Radiol

(2013)

E.W. Lee et al.

Advanced hepatic ablation technique for creating complete cell death: irreversible electroporation

Radiology

(2010)

Y. Guo et al.

Irreversible electroporation therapy in the liver: longitudinal efficacy studies in a rat model of hepatocellular carcinoma

Cancer Res

(2010)

A. Deodhar et al.

Irreversible electroporation near the heart: ventricular arrhythmias can be prevented with ECG synchronization

AJR Am J Roentgenol

(2011)

Cited by (327)

Progress on pulsed electrocatalysis for sustainable energy and environmental applications
2023, Chemical Engineering Journal
Electrocatalysis processes play an important role in the research and development of sustainable energy and environmental applications. However, the utilization of a constant voltage in steady-state operations can sometimes limit the current electrocatalysis process due to unsatisfactory efficiency and limited selectivity behaviors. In comparison, dynamically tuneable pulsed electrocatalysis presents a promising alternative for achieving higher process control, enhanced efficiency, and improved selectivity during certain electrochemical processes when compared to its constant current counterpart. This article presents a comprehensive overview of pulsed electrocatalysis as a valuable tool within electrocatalysis. This includes an overview of the mechanistic details along with a thorough discussion regarding the facile process parameter optimization. Moreover, the contemporary catalyst manipulation and unique electrolytic conditions offered by pulsed electrocatalysis are demonstrated in tandem with other considerations such as mass transfer, long-term stability, and system designs. The potential of it is manifested in cutting-edge applications such as CO₂ conversion, water splitting, and other environmental and biomedical applications. It appears that we are entering a new era in electrocatalysis, where adjustable pulse patterns can be employed to achieve enhanced efficiency and unmatched selectivity.
Catheter-Based Electroporation: A Novel Technique for Catheter Ablation of Cardiac Arrhythmias
2023, JACC: Clinical Electrophysiology
Catheter ablation of arrhythmias is now standard of care in invasive electrophysiology. Current ablation strategies are based on the use of thermal energy. With continuous efforts to optimize thermal energy delivery, effectiveness has greatly improved; however, safety concerns persist. This review focuses on a novel ablation technology, irreversible electroporation (IRE), also known as pulsed-field ablation which may be a safer alternative for arrhythmia management. Pulsed-field ablation is thought to be a nonthermal ablation that applies short-duration high-voltage electrical fields to ablate myocardial tissue with high selectivity and durability while sparing important neighboring structures such as the esophagus and phrenic nerves. There are multiple ongoing studies investigating the potential superior outcomes of IRE compared to radiofrequency ablation in treating patients with atrial and ventricular arrhythmias. In this review, we describe the current evidence of preclinical and clinical trials that have shown promising results of catheter-based IRE.
Engineering high post-electroporation viabilities and transfection efficiencies for elongated cells on suspended nanofiber networks
2023, Bioelectrochemistry
The impact of cell shape on cell membrane permeabilization by pulsed electric fields is not fully understood. For certain applications, cell survival and recovery post-treatment is either desirable, as in gene transfection, electrofusion, and electrochemotherapy, or is undesirable, as in tumor and cardiac ablations. Understanding of how morphology affects cell viability post-electroporation may lead to improved electroporation methods. In this study, we use precisely aligned nanofiber networks within a microfluidic device to reproducibly generate elongated cells with controlled orientations to an applied electric field. We show that cell viability is significantly dependent on cell orientation, elongation, and spread. Further, these trends are dependent on the external buffer conductivity. Additionally, we see that cell survival for elongated cells is still supported by the standard pore model of electroporation. Lastly, we see that manipulating the cell orientation and shape can be leveraged for increased transfection efficiencies when compared to spherical cells. An improved understanding of cell shape and pulsation buffer conductivity may lead to improved methods for enhancing cell viability post-electroporation by engineering the cell morphology, cytoskeleton, and electroporation buffer conditions.
Acute ATP loss during irreversible electroporation mediates caspase independent cell death
2023, Bioelectrochemistry
Irreversible electroporation (IRE) has been reported to variably cause apoptosis, necrosis, oncosis or pyroptosis. Intracellular ATP is a key substrate for apoptosis which is rapidly depleted during IRE, we sought to understand whether intracellular ATP levels is a determinant of the mode of cell death following IRE. A mouse bladder cancer cell line (MB49) was treated with electric fields while increasing the number of pulses at a fixed electric field strength, and pulse width. Cell proliferation and viability and ATP levels were measured at different timepoints post-treatment. Cell death was quantified with Annexin-V/Propidium Iodide staining. Caspase activity was measure with a fluorometric kit and western blotting. A pan-caspase (Z-VAD-FMK) inhibitor was used to assess the impact of signal inhibition. We found cell death following IRE was insensitive to caspase inhibition and was correlated with ATP loss. These findings were confirmed by cell death assays and measurement of changes in caspase expression on immunoblotting. This effect could not be rescued by ATP supplementation. Rapid and acute ATP loss during IRE interferes with caspase signaling, promoting necrosis. Cell necrosis from IRE is expected to be immunostimulatory and may be effective in cancer cells that carry mutated or defective apoptosis genes.
The latest research progress on minimally invasive treatments for hepatocellular carcinoma
2023, Hepatobiliary and Pancreatic Diseases International
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail.
The data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using “minimally invasive” and “hepatocellular carcinoma” or “liver cancer” as the keywords.
Percutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC.
A variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis.
Optimal Irreversible Electroporation Combined with Nano-Enabled Immunomodulatory to Boost Systemic Antitumor Immunity
2024, Advanced Healthcare Materials

View all citing articles on Scopus

: None of the authors have identified a conflict of interest.

: Appendices A and B are available online at www.jvir.org.

View full text

Clinical StudyIrreversible Electroporation for Nonthermal Tumor Ablation in the Clinical Setting: A Systematic Review of Safety and Efficacy

Abstract

Purpose

Methods

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

HPB

Cancer Lett

HPB

Urology

J Clin Epidemiol

J Vasc Interv Radiol

J Am Coll Surg

J Vasc Interv Radiol

J Am Coll Surg

J Vasc Interv Radiol

J Vasc Interv Radiol

J Vasc Interv Radiol

HPB

J Vasc Interv Radiol

Biophys J

Principles of and advances in percutaneous ablation

Radiology

Irreversible electroporation: a novel image-guided cancer therapy

Gut Liver

Irreversible electroporation on the small intestine

Br J Cancer

Irreversible electroporation: implications for prostate ablation

Technol Cancer Res Treat

Irreversible electroporation adjacent to the rectum: evaluation of pathological effects in a pig model

Cardiovasc Intervent Radiol

Urinary tract effects after multifocal nonthermal irreversible electroporation of the kidney: acute and chronic monitoring by magnetic resonance imaging, intravenous urography and urinary cytology

Cardiovasc Intervent Radiol

Irreversible electroporation of the pancreas: definitive local therapy without systemic effects

J Surg Oncol

The effects of irreversible electroporation (IRE) on nerves

PloS One

The delayed effects of irreversible electroporation ablation on nerves

Eur Radiol

Advanced hepatic ablation technique for creating complete cell death: irreversible electroporation

Radiology

Irreversible electroporation therapy in the liver: longitudinal efficacy studies in a rat model of hepatocellular carcinoma

Cancer Res

Irreversible electroporation near the heart: ventricular arrhythmias can be prevented with ECG synchronization

AJR Am J Roentgenol

Clinical Study
Irreversible Electroporation for Nonthermal Tumor Ablation in the Clinical Setting: A Systematic Review of Safety and Efficacy