ReviewSystematic review of irreversible electroporation in the treatment of advanced pancreatic cancer
Introduction
Pancreatic cancer remains one of the most challenging malignancies to treat due to its late presentation, aggressive nature and resistance to most currently available treatments. As a result prognosis is dismal, with 1 and 5 year survival rates being 18% and 3.5% respectively. It represents the fifth most common cause of cancer death in the UK, with approximately 8000 cases per year.1 The location of the pancreas means patients are often asymptomatic until the disease presents at an advanced stage, at which point curative resection is not possible due to either distant metastases or involvement of local vascular structures, such as the portal vein, coeliac trunk and superior mesenteric vessels.2 At presentation only 20% of patients are suitable for surgery.3
In the palliative setting combination chemotherapy regimens have been developed to improve survival. This includes the FOLFIRINOX/gemcitabine combination which demonstrated marginally improved survival,4 and more recently the promising phase 3 study of Abraxane (nab-pcalitaxel) plus gemcitabine demonstrating significantly improved OS, PFS and response rate.5 Patients can also receive adjuvant chemotherapy post-resection to combat the risk of recurrence. However despite many well-designed RCT's describing aggressive chemotherapy (ESPAC)6 and/or radiotherapy7 combined with surgical resection, survival rates have remained relatively unchanged with postoperative 5 year survival of 10–20%. Neoadjuvant chemotherapy for borderline resectable locally advanced tumours also has a role, with evidence suggesting this can offer the potential for cure by inducing resectability in 30–40%.8
An alternative method of providing symptomatic relief, survival benefit, and potentially downsizing tumours to facilitate resection involves a number of ablative techniques. This includes radiofrequency ablation (RFA) and microwave ablation (MWA). These modalities demonstrate promising results, however due to the highly vascular nature of the pancreas, inadvertent thermal injury to adjacent vessels can result in significant bleeding. Furthermore thermal injury to the pancreatic and bile duct can result in fistulae or bile leaks respectively.
Irreversible electroporation (IRE) is a relatively novel procedure which represents a potentially ideal solution for the ablative treatment of pancreatic tumours as no thermal tissue damage occurs, thus avoiding vessel or duct injury.9 This technique involves the delivery of a high voltage current through electrodes placed into the tumour, either under radiological guidance, via laparoscopy or by an open surgical approach. This method results in the creation of pores in the phospholipid bilayer, and the cell membrane damage disrupts intra-cellular homeostasis, ultimately causing apoptotic cell death, whilst sparing surrounding structures such as vessels, ducts (biliary and pancreatic) and connective tissue.9, 10, 11 This review concentrates on current evidence regarding the clinical applicability of IRE in the management of pancreatic tumours, examining efficacy, safety and survival.
Section snippets
Search strategy
Multiple databases were searched up to January 27th 2014, including Medline, Embase, Pubmed, Cochrane library and Google Scholar. Search terms based on MeSH key words included pancreatic cancer/carcinoma/neoplasm and irreversible electroporation. The literature was searched and data extracted independently by the first author (JM), and any inconsistencies discussed with a second author (SW).
Criteria for inclusion/exclusion
Studies included were any retrospective or prospective case series or reports. The main aim of this
Results
The search strategy initially yielded 33 citations. After review of titles and abstracts 27 studies were excluded with reasons as documented in Fig. 1. Two studies were excluded after full text review, leaving a total of 4 included studies.
Discussion
Pancreatic cancer remains one of the most difficult malignancies to manage and survival remains poor due to late presentation with either locally advanced or metastatic disease. Typical management currently consists of chemotherapy, with or without radiotherapy, in an attempt to reduce tumour growth and dissemination, and control symptoms such as pain from neural invasion.
A multi-modal approach to treatment offers the greatest promise for improved outcomes, and the use of localised targeted
Conclusion
Initial evidence suggests IRE has a role in the management of locally advanced pancreatic cancer, with studies thus far suggesting a potential survival benefit, symptomatic improvement with limited morbidity, and a potential role as a bridge to surgery. Further studies are still required to determine if any significant survival benefit is achieved and to further define its place in the armamentarium of treatments against pancreatic cancer. Various questions are still to be answered, such as
Conflict of interest statement
All authors confirm there is no financial or personal conflict of interest with regards to this article.
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Combination therapy of irreversible electroporation and cytokine-induced killer cells for treating mice bearing panc02 pancreatic-cancer xenografts
2023, Biochemistry and Biophysics ReportsEffect of interphase and interpulse delay in high-frequency irreversible electroporation pulses on cell survival, membrane permeabilization and electrode material release
2020, BioelectrochemistryCitation Excerpt :In the past decade, irreversible electroporation (IRE) emerged as a new non-thermal ablation modality [10]. IRE is showing promising results in early clinical research of ablation of intra-abdominal tumors [11–13] and cardiac ablation [9,14–16]. During IRE treatment, electric pulses temporarily increase the semi-selective permeability of the cell membrane, thus allowing non-selective transport of molecules in and out of the targeted cells (through the compromised cell membrane).
Is irreversible electroporation safe and effective in the treatment of hepatobiliary and pancreatic cancers?
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