Irreversible electroporation (IRE)

Post by: Dr. Ali Asgar Sabir

IRE is a novel treatment approach that employs high-voltage pulses to induce cell membrane porosity, leading to slow cell death over time. It is a type of non thermal ablation and therefore does not demonstrate heat sink effect. During the procedure, a total of 70 high-voltage DC current pulses, ranging from 1,500 to 3,000 volts, are delivered between the probes to complete the treatment for one pair of probes. Depending on the number of probe pairs involved, the generator automatically switches to the next pair(s) to continue the treatment. Each treatment cycle between a pair of probes lasts for 70 seconds. Following the procedure, a post-procedure CT scan is performed to check for any immediate complications. Contrast is utilized in patients with intact renal function to evaluate vascular structures.


Method of Action of IRE	IRE induces permanent cell death via cell membrane perforation, leading to electrolyte instability and apoptosis.
Tissue Effects of IRE	1. IRE does not damage surrounding cartilaginous structures, including vital ones like superior mesenteric vein, portal vein complex, superior mesenteric artery, celiac artery, and bile duct. 2. This allows for ablation even in lesions abutting large vessels. 3. Protein denaturation is not present.
Heat Sink Effect	Not affected by the heat-sink effect, therefore lesions abutting vessels can also be treated.
Generator and Probes	1. Generator delivers low-voltage, high-energy DC current through monopolar probes. 2. Probes are 19-gauge needles with adjustable active exposed electrode surfaces (1 and 4 cm, depending on the desired size of the ablation zone and the depth of the lesion).
Treatment zones	1. At least two probes, up to six, with software-guided planning. 2. Better defined ablation zone, compared to thermal ablation techniques
Optimal Tumor Size	3-4 cm
Image-Guidance	USG, CT
Optimal Probe spacing	1. Optimal distance between two probes - 1.5 - 2.0 cm 2. Probes should be parallel to each other without convergence or divergence, for uniform ablation. 3. Variance of greater than 4.0 mm can lead to an ineffective irreversible electroporation. 4. Spacing more than the recommended distance increases the chances of high current errors. 5. Three-dimensional (3D) CT scan image is obtained to confirm the position of the probes and the distance between each pair.
Defibrillator pads	Placed prior to initiating the procedure to intervene in case of a ventricular arrhythmia
Anesthesia	General anesthesia mandatory
Patient	Intubated and closely monitored (ensure their vital signs remain stable) Probes can cause muscle contractions induced by the high voltage used, therefore complete neuromuscular blockade is administered.
Post Procedure Imaging	1. Triple-phase CT scan in the immediate postoperative period (less than 1 month postoperatively): -Assessing the patency of vital structures. -Establishing a baseline of the post-ablation bed (irregular, amorphous, and hazy without clear margins or boundaries) 2. Size of the ablation zone is considered secondary in the CT evaluation due to poorly defined margins, making objective size and attenuation assessment challenging.
Earliest pathologic confirmation	At least 2 to 4 hours after irreversible electroporation with electron microscopy
Current Clinical Use	Locally advanced stage III pancreatic adenocarcinoma of either the pancreatic head or body/neck without metastasis

TNM staging for Pancreatic Adenocarcinoma (8th edition):

Stage Groupings	Description
Stage 0	Tis N0 M0
Stage Ia	T1 N0 M0
Stage Ib	T2 N0 M0
Stage IIa	T3 N0 M0
Stage IIb	T1, T2, or T3 with N1 M0
Stage III	N2 M0 with any T or T4 with any N M0
Stage IV	M1 with any T and N

T1 = Tumor ≤ 2 cm in greatest dimension
T2 =Tumor >2 cm in greatest dimension but less than ≤ 4 cm
T3 =Tumor >4 cm in greatest dimension
T4 = Involvement of superior mesenteric artery or coeliac axis
Nx = Nodes cannot be assessed
N0 = No evidence of nodal involvement
N1 = 1-3 regional node metastases present
N2 = 4 or more regional node metastases present
Mx = Presence of metastases cannot be assessed
M0 = No evidence of metastases
M1 = Distant metastases present

As most of the diagnosis is made in advanced disease stages ~ 52% (III and IV), only a small percentage of pancreatic adenocarcinoma patients are eligible for surgical resection.
Locally advanced unresectable pancreatic cancer has a poor prognosis (median survival ~12 months) despite chemotherapy and conventional radiation therapy.
Palliative options for staged locally advanced pancreatic cancer include systemic chemotherapy, radiation therapy (IMRT, cyberknife, proton therapy), and surgical therapy (e.g., celiac axis alcohol ablation, thoracoscopic thoracic splanchnicectomy)
IRE is predominantly used in locally advanced stage III pancreatic adenocarcinoma without metastasis.
A single CT image at one time point is insufficient to confirm recurrence in patients with locally advanced pancreatic cancer, given the heterogeneity of the imaged tissue, the ongoing IRE effects, and the limitations of this modality

Contraindications:

Identification of varices on pretreatment imaging, which is particularly important due to the high incidence of portal vein and splenic vein thrombosis in patients with pancreatic adenocarcinoma. Not all patients with LAPC (locally advanced pancreatic cancer) may be suitable candidates for percutaneous IRE due to the absence of a safe treatment “window.”
The presence of a nearby metallic stent is another significant contraindication.
A history of cardiac arrhythmias represents a third important contraindication for this procedure.

Complications:

Major Complications:

Death
Severe pancreatitis
Biliary obstruction
Fistula formation
Portal vein thrombosis
Bile leak
GI perforation

Minor Complications:

Abscess formation
Post-procedural pneumonia

References