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Irreversible Electroporation (IRE)

Irreversible  Electroporation (IRE)

Courtesy of AngioDynamics

IRE (Irreversible Electroporation) is a relatively new and innovative technique used for the treatment of  cancer, particularly in cases where surgery is not an option due to the tumor's location or the patient's overall health. IRE is a non-thermal, minimally invasive procedure that uses electrical pulses to destroy cancerous cells. IRE does not injure surrounding non-cancerous cells, blood vessels and other vital structures. It has been in patients since 2008 in the treatment of some types of cancers. One of the largest unmet needs in cancer that IRE has been used is in locally advanced (Stage III) pancreatic cancer.  Studies have demonstrated its safety with encouraging improvement in overall survival. There are limitations to the treatment and every patient does not qualify.

 

How IRE Works:

  • Electroporation: During IRE, thin needles or probes are inserted directly into the tumor through the skin or during surgery. These probes are carefully placed to encompass the tumor.

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  • Pulsed Electrical Fields: Short, high-voltage electrical pulses are applied through the probes. These electrical pulses create nanopores or small defects in the cell membranes of the cancer cells within the targeted area.

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  • Cell Death: The disruption of the cell membranes leads to the loss of cellular homeostasis, ultimately resulting in cell death. Importantly, this cell death occurs without significant heating of the tissue, which is in contrast to other thermal ablation techniques like radiofrequency ablation (RFA) or microwave ablation.

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  • Immune Response: The process of cell death induced by IRE can stimulate an immune response, potentially enhancing the body's ability to recognize and attack remaining cancer cells in the area.

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Advantages of IRE

  • Preservation of Surrounding Tissues: One of the significant advantages of IRE is that it can selectively target cancer cells while preserving nearby vessels and critical structures, such as major blood vessels and ducts, which are often difficult to spare during surgical resection.

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  • Minimally Invasive: IRE is a minimally invasive procedure, which means it is associated with shorter hospital stays and faster recovery times compared to traditional open surgery.

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  • Applicability to Locally Advanced Tumors: IRE is particularly useful for treating locally advanced pancreatic cancer that is unresectable by surgery. It can be used to reduce tumor size, alleviate symptoms, and potentially improve the patient's quality of life.

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Considerations:

  • Patient Selection: Not all patients with cancer are candidates for IRE. It is typically reserved for patients with advanced disease or those who are not candidates for surgery due to their overall health or the resection may have risk of incomplete resection.

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  • Effectiveness: The long-term effectiveness of IRE in terms of overall survival is still a subject of ongoing research and clinical trials.​

 

IRE of the Pancreas

IRE Margin Enhancement

The complexity of pancreatic cancer and the challenges associated with achieving clean surgical margins or R0 are key factors that make Irreversible Electroporation (IRE) an attractive treatment option in some cases. Pancreatic cancer presents unique challenges due to its location in close proximity to critical structures, making surgical resection challenging. Here's an explanation of these complexities and why IRE may be considered:

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Proximity to Critical Structures:

  • The pancreas is nestled deep within the abdomen, surrounded by vital structures, including blood vessels (such as the superior mesenteric artery and portal vein), bile ducts, and major nerves. These structures are crucial for digestion, blood supply, and overall bodily functions.

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Difficulty in Achieving Clean Margins:

  • Achieving clean surgical margins (removing all cancer cells with a margin of healthy tissue) is a fundamental goal in cancer surgery. However, in the case of pancreatic cancer, clean margins can be challenging due to the tumor's proximity to these critical structures.

  • Surgeons must balance the goal of removing all cancerous tissue with the need to preserve vital structures to maintain normal bodily functions.

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Tumor Involvement:

  • Pancreatic tumors often encase or invade nearby blood vessels, bile ducts, and nerves. This involvement makes it difficult to safely remove the tumor while preserving these structures, leading to incomplete resections.

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Inoperable Cases:

  • In cases where the tumor cannot be safely removed by surgery due to its involvement with critical structures, the tumor is deemed "unresectable." Inoperable pancreatic cancer poses a significant challenge for treatment and is associated with poorer prognosis.

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Role of IRE:

  • IRE offers a non-thermal, precise, and minimally invasive approach to treating pancreatic cancer that is difficult to resect. By applying electrical pulses, IRE can selectively destroy cancer cells while sparing critical nearby structures.

  • IRE can effectively treat the tumor and its margins without the need for extensive surgery, making it a valuable option in cases where achieving clean surgical margins is challenging.

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Multidisciplinary Approach:

  • The management of pancreatic cancer often involves a multidisciplinary team of healthcare professionals, including surgeons, interventional radiologists, oncologists, and radiation oncologists. These experts work together to tailor the treatment approach to the patient's specific situation.

In-Situ Pancreas Ablation

In-situ Irreversible Electroporation (IRE) ablation for pancreatic cancer involves the application of electrical pulses directly to the tumor within the pancreas, sparing surrounding healthy tissue and critical structures. This technique is used when the tumor is considered unresectable (cannot be surgically removed) due to its location, involvement of blood vessels, or other factors. In situ IRE for pancreatic cancer has several specific considerations:

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Patient Evaluation:

  • Patients with locally advanced pancreatic cancer who are not surgical candidates are typically considered for in situ IRE ablation.

  • A multidisciplinary team of healthcare professionals, including interventional radiologists and oncologists, evaluates the patient's overall health and the tumor's characteristics to determine if IRE is a suitable option.

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Preoperative Imaging:

  • Detailed imaging, such as CT scans or MRI, is crucial for accurate planning. It helps identify the size, location, and extent of the tumor within the pancreas.

 

Electrode Placement:

  • Thin needle-like electrodes or probes are precisely positioned within and around the tumor under imaging guidance. The placement of electrodes is crucial to ensure comprehensive coverage of the tumor.

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Electrical Pulse Application:

  • Short, high-voltage electrical pulses are delivered through the electrodes. These pulses create nanopores or defects in the cell membranes of the cancer cells within the treated area, leading to cell death.

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Tumor Ablation:

  • The electrical pulses are carefully controlled to target the tumor while minimizing damage to healthy pancreatic tissue and nearby structures. This selective destruction of cancer cells is a hallmark of IRE.

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Monitoring and Follow-Up:

  • After the procedure, patients are closely monitored to assess the response to treatment and manage potential complications.

  • Regular follow-up imaging helps evaluate the effectiveness of the ablation and monitor for any signs of tumor recurrence.

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Potential Benefits:

  • In situ IRE ablation for pancreatic cancer aims to achieve local tumor control, alleviate symptoms, and potentially improve the patient's quality of life. It may also provide a bridge to other treatments or clinical trials.

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Considerations:

  • In situ IRE for pancreatic cancer is a specialized procedure that requires expertise in interventional radiology.

  • Its effectiveness in terms of overall survival and long-term outcomes is still being studied, and it may be combined with other treatments such as chemotherapy or radiation therapy.

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Immune Response:

  • The cell death induced by IRE may stimulate an immune response, which can potentially enhance the body's ability to recognize and attack any remaining cancer cells, whether in the treated area or elsewhere in the body.

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It's essential to consult with a medical team experienced in performing IRE for pancreatic cancer to determine if this technique is appropriate for the individual patient. Patient-specific factors, tumor characteristics, and overall health play a significant role in treatment decisions. 

UofL Indications for IRE in Pancreas

Indications:

  1. Appropriately staged Pancreatic Adenocarcinoma, including either 3 Phase Thin Cut CT Scan with Pancreatic Protocol or Dynamic MRI, with Diagnostic laparoscopy to rule out sub-radiologic occult metastasis

  2. Completion of 3-4 months of Induction Chemotherapy with or without radiation therapy based on patients symptoms

  3. Maximum Axial and Anterior to Posterior Tumor Dimension of ≤3.5cm (The Caudal to Cranial dimension can be longer since this is the plane the needles are pulled back on after initial insertion)

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Relative Contraindications:

  1. Axial or Ant-Post Tumor Size >3.5cm

  2. Inability to undergo general endotracheal anesthesia

  3. Atrial Fibrillation

  4. Karnofsky Performance Status

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Absolute Contraindications:

  1. Tumor Size >5cm

  2. Metastatic Disease

  3. Progression of local tumor >30% diameter while undergoing induction therapy

  4. Inducible ischemia on cardiac stress test or uncontrolled angina

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Expectations for IRE:

  1. Operation is performed through a small 6-10 inch incision (based on the patients size) midline incision.

  2. Operation takes 2-4 hours based on the size of tumor and the complexity of the IRE and/or resection that takes place

  3. Hospital Length of stay is 5-8 days based on how quickly the patient has return of bowel function.

  4. Overall time in Louisville is usually 2-3 weeks based on the patients recovery.

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