Irreversible electroporation enhances delivery of gemcitabine to pancreatic adenocarcinoma

Bhutiani, Neal; Agle, Steven C.; Li, Yan; Li, Suping; Martin, Robert C.G.

doi:10.1002/jso.24288

Cited by 51 publications

(36 citation statements)

References 39 publications

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“…The ablate-and-resect study performed by Scheffer et al showed the existence of a reversibly electroporated tissue zone between the irreversibly damaged ablation zone and the normal liver parenchyma. Combining IRE with systemic or electrochemotherapy could eradicate the infiltrative cells just outside the margin of the ablation zone, thereby decreasing the occurrence of LTP [36, 37]. …”

Section: Discussionmentioning

confidence: 99%

Conductivity Rise During Irreversible Electroporation: True Permeabilization or Heat?

Ruarus

Vroomen

Puijk

et al. 2018

Cardiovasc Intervent Radiol

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PurposeIrreversible electroporation (IRE) induces apoptosis with high-voltage electric pulses. Although the working mechanism is non-thermal, development of secondary Joule heating occurs. This study investigated whether the observed conductivity rise during IRE is caused by increased cellular permeabilization or heat development.MethodsIRE was performed in a gelatin tissue phantom, in potato tubers, and in 30 patients with unresectable colorectal liver metastases (CRLM). Continuous versus sequential pulsing protocols (10-90 vs. 10-30-30-30) were assessed. Temperature was measured using fiber-optic probes. After temperature had returned to baseline, 100 additional pulses were delivered. The primary technique efficacy of the treated CRLM was compared to the periprocedural current rise. Seven patients received ten additional pulses after a 10-min cool-down period.ResultsTemperature and current rise was higher for the continuous pulsing protocol (medians, gel: 13.05 vs. 9.55 °C and 9 amperes (A) vs. 7A; potato: 12.70 vs. 10.53 °C and 6.0A vs. 6.5A). After cooling-down, current returned to baseline in the gel phantom and near baseline values (Δ2A with continuous- and Δ5A with sequential pulsing) in the potato tubers. The current declined after cooling-down in all seven patients with CRLM, although baseline values were not reached. There was a positive correlation between current rise and primary technique efficacy (p = 0.02); however, the previously reported current increase threshold of 12–15A was reached in 13%.ConclusionThe observed conductivity rise during IRE is caused by both cellular permeabilization and heat development. Although a correlation between current rise and efficacy exists, the current increase threshold seems unfeasible for CRLM.Electronic supplementary materialThe online version of this article (10.1007/s00270-018-1971-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Conductivity Rise During Irreversible Electroporation: True Permeabilization or Heat?

Ruarus

Vroomen

Puijk

et al. 2018

Cardiovasc Intervent Radiol

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“…We posit that IRE efficacy would be dramatically reinforced if combined with gemcitabine-based regional intra-arterial infusion chemotherapy (RIAC), where chemotherapeutics would be delivered to the target area through a selective interventional indwelling catheter. Although it was demonstrated that IRE could enhance the delivery of gemcitabine to pancreatic tumors in nude mice,[26] the application of this novel combined therapy in LAPC requires further clinical validation.…”

Section: Discussionmentioning

confidence: 99%

A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma

Chen

et al. 2016

Chinese Medical Journal

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Background:Locally advanced pancreatic carcinoma (LAPC) is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation (IRE) has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC.Methods:Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE.Results:All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed (16%): two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge.Conclusions:IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy.

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“…Future studies of IRE, will go beyond just the use of IRE as an electroporation device. Recent data from Martin et al have confirmed the enhanced drug delivery that occurs in the surrounding reversible electroporation zone during concurrent IRE and Gemcitabine delivery . This has lead to a pending Pilot (FDA approved IDE) study with the use of concurrent IRE with either Gemcitabine or FOLFIRINOX in combination to enhance this drug delivery.…”

Section: Role Of Surgery—resection and Electroporationmentioning

confidence: 91%

“…Recent data from Martin et al have confirmed the enhanced drug delivery that occurs in the surrounding reversible electroporation zone during concurrent IRE and Gemcitabine delivery. 79 This has lead to a pending Pilot (FDA approved IDE) study with the use of concurrent IRE with either Gemcitabine or FOLFIRINOX in combination to enhance this drug delivery. Similar studies have also been initiated to demonstrate the changes in the systemic inflammatory response that a patient undergoes after IRE.…”

Section: Irreversible Electroporationmentioning

confidence: 99%

Multi‐disciplinary management of locally advanced pancreatic cancer with irreversible electroporation

Martin

2017

Journal of Surgical Oncology

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The essential diagnosis for LAPC is based on high-quality cross-sectional imaging, which demonstrates tumor invasion into the celiac/superior mesenteric arteries and/or superior mesenteric/portal venous system that is not reconstructable. The optimal management of these patients is evolving quickly with the advent of newer chemotherapeutics, radiation, and non-thermal ablation modalities. This review will present the current status of initial chemotherapy, surgical therapy, ablative therapy, and radiation therapy for patients with nonmetastatic locally advanced unresectable pancreatic cancer.

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Irreversible electroporation enhances delivery of gemcitabine to pancreatic adenocarcinoma

Cited by 51 publications

References 39 publications

Conductivity Rise During Irreversible Electroporation: True Permeabilization or Heat?

Conductivity Rise During Irreversible Electroporation: True Permeabilization or Heat?

A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma

Multi‐disciplinary management of locally advanced pancreatic cancer with irreversible electroporation

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