Locally advanced pancreatic cancer (Stage 3) is defined by encasement or abutment of vital venous and arterial structures. Irreversible electroporation (IRE) represents an effective local non-thermal ablation modality for treatment of solid tumors involving critical vascular and biliary structures. Electroporation creates pores in the cell membrane and disrupts the ionic gradients while sparing the extracellular matrix, resulting in preservation of blood vessel and biliary scaffolding.
Editor Recruited by: Jeffrey B. Matthews
For an open technique, after induction of general endotracheal anesthesia with full muscle relaxation, an upper midline incision should be made from 4-6 cm inferior to the xiphoid to the umbilicus. After thorough exploration, a Thompson retractor should be placed with one blade at the apex of the upper midline incision and two bladder blades retracting laterally. Intraoperative ultrasound (IOUS) should be performed of the liver to assess for metastases as well as of the pancreatic tumor to examine its three dimensional size. Additionally, a transgastric ultrasound should be used to ensure unresectability of the tumor.3 The lesser sac should then be opened and target sites chosen for needle placement. Needles should then be inserted parallel to each other under continuous ultrasound monitoring. This ensures needles are placed so as to 1) avoid injury to vital structures and 2) result in maximal tumor killing and adequate ablation margins. After ensuring muscle paralysis and pain control, a test pulse at 10% planned energy should be delivered to asses that adequate current is achieved. 90 direct current, high-voltage (pulses of 100 microseconds each should then be delivered in groups of 10 with a pulse interval of 250 milliseconds. Subsequently, electroporation current should be passed between electrodes to assess for a change in tissue resistivity. This validates that sufficient electroporation has occurred. Finally, ultrasound should be used to confirm ablation and to assess vascular flow and patency.
IRE is indicated for locally advanced pancreatic cancer, defined as encasement of the celiac axis, superior mesenteric artery, or both.1 IRE is indicated for treatment of tumors occluding the superior mesenteric vein (SMV)-portal vein confluence.
Absolute contraindications include tumor size >5 cm, metastatic disease, increase in tumor diameter by >30% while undergoing pre-operative chemotherapy and/or radiation, and uncontrolled angina or inducible ischemia on cardiac stress test. Relative contraindications include atrial fibrillation, tumor diameter >3.5 cm, poor functional status (Karnofsky Performance Status <80%), inability to tolerate general endotracheal anesthesia.2,3
IRE can be performed via an open, laparoscopic, or percutaneous approach. All cases require general endotracheal anesthesia with complete muscle relaxation/chemical paralysis. Patients must undergo continuous EKG monitoring, as the IRE device delivers pulses in synchronization with cardiac electrical impulses.4 Intraoperative ultrasound is required for tumor dimensional analysis as well as for probe placement. Monopolar electrode probes consist of a 19 gauge needle with an adjustable active length and an echogenic surface. NanoKnifeâ„¢ (AngioDynamicsÂ®), Queensbury, USA Energy output -- 3 kV, 50-amp maximum energy output) represents the most commonly used IRE generator.2,3
In addition to routine laboratory analyses for patients diagnosed with pancreatic cancer, (e.g. CBC, CMP, PT/INR, PTT, CA 19-9), recommended pre-operative workup includes complete staging of pancreatic adenocarcinoma including three phase thin cut pancreatic protocol computed tomography (CT) or dynamic MRI with diagnostic laparoscopy to rule out radiologically undetectable occult metastases. Patients being considered for IRE usually undergo 3-4 months of pre-operative chemotherapy with or without external beam radiation therapy (XRT) and are precluded from IRE if they demonstrate significant tumor growth during this period (see above).2
Advantages to IRE compared with thermal ablative modalities include high tissue selectivity, sharply defined irreversible ablation zone margins with decreased thermal spread and resultant collateral tissue damage, and preservation of critical vascular structures.1,2 Disadvantages include requirement for multi-probe arrays, increased technical difficulty, and decreased efficacy in treating tumors >3.5 cm in anterior-posterior dimension, inability to utilize in patients with metallic pancreaticobiliary stents, and requirement for complete intra-operative paralysis.1
Procedure related complications include, but are not limited to, fever, bleeding, cardiac dysrhythmia and/or arrest, portal vein thrombosis, deep venous thrombosis, and post-procedural ileus.2,3,5,6
1. Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Annals of surgical oncology. Aug 2006;13(8):1035-1046.
2. Martin RC, 2nd. Irreversible electroporation of locally advanced pancreatic neck/body adenocarcinoma. Journal of gastrointestinal oncology. Jun 2015;6(3):329-335.
3. Martin RC, 2nd, McFarland K, Ellis S, Velanovich V. Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma. Journal of the American College of Surgeons. Sep 2012;215(3):361-369.
4. Nielsen K, Scheffer HJ, Vieveen JM, et al. Anaesthetic management during open and percutaneous irreversible electroporation. British journal of anaesthesia. Dec 2014;113(6):985-992.
5. Cannon R, Ellis S, Hayes D, Narayanan G, Martin RC. Safety and early efficacy of irreversible electroporation for hepatic tumors in proximity to vital structures. J Surg Oncol. Apr 2013;107(5):544-549.
6. Martin RC, 2nd, McFarland K, Ellis S, Velanovich V. Irreversible electroporation in locally advanced pancreatic cancer: potential improved overall survival. Annals of surgical oncology. Dec 2013;20 Suppl 3:S443-449.