From the SIR Residents and Fellows Section
Teaching Topic: Percutaneous Image-Guided Irreversible Electroporation for the Treatment of Unresectable, Locally Advanced Pancreatic Adenocarcinoma
Narayanan G, Hosein PJ, Beulaygue IC, et al. Percutaneous image-guided irreversible electroporation for the treatment of unresectable, locally advanced pancreatic adenocarcinoma. J Vasc Interv Radiol. 2017; 28: 342-48.
Click here for abstract
Pancreatic adenocarcinoma is associated with five-year survival less than 5%. It is expected to surpass breast cancer to become the third leading cause of cancer-related deaths in the US. Narayanan et al. conducted a retrospective study of 50 patients with unresectable locally advanced pancreatic cancer (LAPC) to identify the treatment safety and efficacy of percutaneous irreversible electroporation (IRE). All patients received chemotherapy before IRE. Post-IRE, patients received follow-up contrast-enhanced CT at 1- and 3-month intervals. Repeat IRE was performed in 9 (18%) patients with unequivocal residual disease on follow-up CT. Three (6%) patients received surgical resection after IRE due to tumor downstaging. There were no treatment-related deaths or deaths within 30 days of treatment. Complications included abdominal pain, pancreatitis, sepsis, gastric leak, and non-fatal portal and splenic vein thrombosis. In univariate and multivariate analyses, tumor size <3 cm was the only factor associated with prolonged survival. The separation of survival curves between the small (<3 cm) and large (>3 cm) tumor groups near 12 months after diagnosis (correlating with the median time from diagnosis to IRE of 11.6 months) supported small tumor response to treatment. Study limitations include difficulty identifying residual disease due to the similar hypoattenuating appearances of tumor and ablation zone.
What is the mechanism of action of IRE?
IRE is a nonthermal ablative technique that utilizes targeted high-voltage electrical pulses to create holes in the cell membrane, thereby irreversibly damaging cell homeostasis and inducing apoptosis. Pulses can be delivered through a bipolar electrode or a pair of unipolar electrodes. The ablation zone size is influenced by the length of the active tip, pulse number, duration of pulses, distance between probes, and voltage.
What are the advantages and disadvantages of IRE?
Given the technique does not depend on heating or cooling tissue, IRE is well-suited for treating tumors close to critical organs and vascular structures with less risk of thermal injury. It is also helpful for preserving sensitive structures such as nerves and bile duct. The IRE ablation zone can be difficult to predict, because it varies by tissue composition and electrical characteristics of tumor and surrounding tissue. Zones are also altered by conductivity of the local environment (e.g. the presence of metal biliary stent).
What are common complications following pancreatectomy? What is the role of the interventional radiologist in the management of these complications?
· Delayed gastric emptying (19-23%)
· Anastomotic leak or leak of bile or pancreatic enzymes (29-34%): Percutaneous catheter drainage placement can be guided by CT, or a combination of ultrasound and fluoroscopy. Catheter drainage with or without endoscopic intervention can avoid re-exploration in 94.7% of patients with pancreatic leaks. Bile leakage is defined as fluid from catheter drainage or abdominal collection with elevated bilirubin level three times greater than the serum bilirubin value.
· Intra-abdominal abscesses (9-13%): While most leaks resolve without intervention, abscesses can form if fluid collections are colonized by bowel contents or superinfected. Large-bore (up to 24F) catheters may be needed to drain purulent or viscous contents.
· Post-pancreatectomy hemorrhage (PPH) (1-8%): PPH can occur when pancreatic enzymes and bile erode into vascular structures. This complication is associated with high mortality, causing up to 38% of all post-pancreatectomy deaths. PPH is often managed with arterial embolization with rates of definitive therapy of 77-88%. Bleeds can be treated by placing a stent over the origin of the GDA for GDA stump leaks or positioning a covered stent over the extravasating site.
How do the results by Narayanan et al. compare to previous reports of open pancreatic IRE?
The largest series was reported by Martin et al. and was composed of 150 patients in the unresectable group. This group showed a median OS of 23.2 months from time of diagnosis and 19 months from time of procedure. The present study shows a median OS of 27 months from time of diagnosis and 14.2 months from time of IRE. While they show seemingly different results, in the series by Martin et al. the median time from diagnosis to IRE was 6.2 months (compared to 11.6 months from Narayanan et al.). In addition, the group from Martin et al. has diagnostic laparoscopy to exclude occult peritoneal mets before proceeding. While there are limitations in the present study and it is difficult to establish if IRE improves survival, the results are promising and warrant a prospective, randomized clinical trial.
Additional references:
Silk M, Tahour D, Srimathveeravalli G. The state of irreversible electroporation in interventional oncology. Sem Interv Radiol. 2014; 31: 111-17.
Martin RC, Kwon D, Chalikonda S, et al. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg 2015; 262:486–494.
Post Author:
Maggie Chung, BA
SIR RFS Communications Co-Chair
Warren Alpert Medical School
Click here for abstract
Pancreatic adenocarcinoma is associated with five-year survival less than 5%. It is expected to surpass breast cancer to become the third leading cause of cancer-related deaths in the US. Narayanan et al. conducted a retrospective study of 50 patients with unresectable locally advanced pancreatic cancer (LAPC) to identify the treatment safety and efficacy of percutaneous irreversible electroporation (IRE). All patients received chemotherapy before IRE. Post-IRE, patients received follow-up contrast-enhanced CT at 1- and 3-month intervals. Repeat IRE was performed in 9 (18%) patients with unequivocal residual disease on follow-up CT. Three (6%) patients received surgical resection after IRE due to tumor downstaging. There were no treatment-related deaths or deaths within 30 days of treatment. Complications included abdominal pain, pancreatitis, sepsis, gastric leak, and non-fatal portal and splenic vein thrombosis. In univariate and multivariate analyses, tumor size <3 cm was the only factor associated with prolonged survival. The separation of survival curves between the small (<3 cm) and large (>3 cm) tumor groups near 12 months after diagnosis (correlating with the median time from diagnosis to IRE of 11.6 months) supported small tumor response to treatment. Study limitations include difficulty identifying residual disease due to the similar hypoattenuating appearances of tumor and ablation zone.
Clinical Pearls
What is the mechanism of action of IRE?
IRE is a nonthermal ablative technique that utilizes targeted high-voltage electrical pulses to create holes in the cell membrane, thereby irreversibly damaging cell homeostasis and inducing apoptosis. Pulses can be delivered through a bipolar electrode or a pair of unipolar electrodes. The ablation zone size is influenced by the length of the active tip, pulse number, duration of pulses, distance between probes, and voltage.
What are the advantages and disadvantages of IRE?
Given the technique does not depend on heating or cooling tissue, IRE is well-suited for treating tumors close to critical organs and vascular structures with less risk of thermal injury. It is also helpful for preserving sensitive structures such as nerves and bile duct. The IRE ablation zone can be difficult to predict, because it varies by tissue composition and electrical characteristics of tumor and surrounding tissue. Zones are also altered by conductivity of the local environment (e.g. the presence of metal biliary stent).
Questions to Consider
What are common complications following pancreatectomy? What is the role of the interventional radiologist in the management of these complications?
· Delayed gastric emptying (19-23%)
· Anastomotic leak or leak of bile or pancreatic enzymes (29-34%): Percutaneous catheter drainage placement can be guided by CT, or a combination of ultrasound and fluoroscopy. Catheter drainage with or without endoscopic intervention can avoid re-exploration in 94.7% of patients with pancreatic leaks. Bile leakage is defined as fluid from catheter drainage or abdominal collection with elevated bilirubin level three times greater than the serum bilirubin value.
· Intra-abdominal abscesses (9-13%): While most leaks resolve without intervention, abscesses can form if fluid collections are colonized by bowel contents or superinfected. Large-bore (up to 24F) catheters may be needed to drain purulent or viscous contents.
· Post-pancreatectomy hemorrhage (PPH) (1-8%): PPH can occur when pancreatic enzymes and bile erode into vascular structures. This complication is associated with high mortality, causing up to 38% of all post-pancreatectomy deaths. PPH is often managed with arterial embolization with rates of definitive therapy of 77-88%. Bleeds can be treated by placing a stent over the origin of the GDA for GDA stump leaks or positioning a covered stent over the extravasating site.
How do the results by Narayanan et al. compare to previous reports of open pancreatic IRE?
The largest series was reported by Martin et al. and was composed of 150 patients in the unresectable group. This group showed a median OS of 23.2 months from time of diagnosis and 19 months from time of procedure. The present study shows a median OS of 27 months from time of diagnosis and 14.2 months from time of IRE. While they show seemingly different results, in the series by Martin et al. the median time from diagnosis to IRE was 6.2 months (compared to 11.6 months from Narayanan et al.). In addition, the group from Martin et al. has diagnostic laparoscopy to exclude occult peritoneal mets before proceeding. While there are limitations in the present study and it is difficult to establish if IRE improves survival, the results are promising and warrant a prospective, randomized clinical trial.
Additional references:
Silk M, Tahour D, Srimathveeravalli G. The state of irreversible electroporation in interventional oncology. Sem Interv Radiol. 2014; 31: 111-17.
Martin RC, Kwon D, Chalikonda S, et al. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg 2015; 262:486–494.
Post Author:
Maggie Chung, BA
SIR RFS Communications Co-Chair
Warren Alpert Medical School
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