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.

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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

Radiation Exposure of Patients and Interventional Radiologists during Prostatic Artery Embolization: A Prospective Single-Operator Study

Summary

Prostatic artery embolization (PAE) is a technically challenging, often lengthy procedure due to the complex, variable anatomy of the prostatic arteries, which may require multiple views, magnification, and cone-beam computed tomography (CT), all of which contribute to elevated radiation doses to the patient and interventional radiologist. Existing studies on PAE have reported indirect measures of radiation exposure including fluoroscopy times and dose area product (DAP), but none have evaluated direct radiation measures, which are a more accurate assessment of radiation dose. Andrade et al conducted a prospective evaluation of radiation exposure to the patient and practitioner during 25 PAE procedures. Patient peak skin dose (PSD) was measured with radiochromic film, placed under the patient’s hip. Operator radiation dose were attained from 9 pairs of thermoluminescent dosimeters, positioned at various body positions on both sides. All procedures were performed by a single interventional radiologist, whose experience with PAE included completion of a PAE course, assisting with 5 cases, and independent performance of 5 cases. Procedures were performed using an Artis Zee ceiling-mounted angiography system equipped with a flat-panel detector. Ceiling-suspended screen and table curtain were always employed. Fluoroscopy was performed at 15 images/second, digital subtraction angiography performed at 2 images per second. Cone-beam CT was performed only if deemed necessary. Mean patient weight was 71.4 kg (range: 54-88 kg), and prostate volume was 79 cm3 (range: 36-157 cm3). Embolization was performed with 100-200 um polyvinyl alcohol particles or 400-um microspheres to complete prostate artery occlusion. Average fluoroscopy time was 30.9 minutes (range: 15.5-48.3 minutes), with mean total DAP of 451 Gy-cm2 (range: 248-792 Gy-cm2), 75% of which was from fluoroscopy. Mean patient PSD was 2420 mGy (range: 1390-3616 mGy), which is in the range of other complex interventional radiology procedures like transjugular intrahepatic portosystemic shunt, transarterial chemoembolization, and neural embolization. Average effective dose to the practitioner was 17 uSv (range : 4-47 uSv), with higher doses to the left side of the body, including average 0.378 mSv to the left eye. Post-PAE clinical evaluation of patients, including skin check to the lower back and hip, at 15 days, 1 month, and 3 months demonstrated no sequelae of radiation exposure. 

Commentary
PAE is known to be a challenging procedure that may require lengthy fluoroscopy times and high radiation exposure, even in the hands of experienced practitioners. As more interventional radiologists undertake this complex procedure, it is essential to elucidate the degree of associated radiation exposure to patients and operators. In prior PAE series, the degree of radiation exposure has been reported through indirect measures, which may be inaccurate surrogates for direct measures of radiation dose. The direct measures of radiation dose assessed by Andrade et al therefore provide a unique and important addition to the PAE evidence base. For operators, the PAE exposure levels of average 17 uSv were similar to other complex interventional radiology procedures, highlighting the importance of optimizing radiation protection techniques and equipment when performing PAE. Although no patients developed skin radiation injury in this series, the mean patient PSD of >2 Gy with range up to 3.6 Gy, in combination with prior case reports of radiation dermatitis following PAE, suggest that vigilant clinical follow-up is merited. These high radiation doses are particularly relevant considerations for patients who undergo repeat PAE for whom attempts should be made to distribute the dose to a different skin region. Although this study was subject to biases of being a small, single center series with all cases performed by a single interventional radiologist, these results provide an important foundation to our understanding of radiation exposure during PAE. Reduction of these radiation exposure levels will be important aims for further refinement and maturation of PAE for the treatment of benign prostatic hyperplasia.

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Andrade G, Khoury HJ, Garzón WJ, Dubourcq F, Bredow MF, Monsignore LM, Abud DG. Radiation Exposure of Patients and Interventional Radiologists during Prostatic Artery Embolization: A Prospective Single-Operator Study. J Vasc Interv Radiol 2017; 28:517-21.

Post Authors:
Jeffrey Forris Beecham Chick, MD, MPH, DABR
Assistant Professor of Vascular and Interventional Radiology
Vice Quality Assurance and Safety Officer
University of Michigan Health Systems
Michigan Medicine

James X. Chen, MD
Resident in Radiology
Hospital of the University of Pennsylvania

From the SIR Residents and Fellows Section

Teaching Topic: Determining efficacy of RF ablation for primary or metastatic lung cancer based on tumor characteristics and environment.

Qiuxia Yang, MD, Han Qi, MD, Rong Zhang, MD, Chao Wan, MD, Ze Song, MD, Liang Zhang, MD, and Weijun Fan, MD. Risk Factors for Local Progression after Percutaneous Radiofrequency Ablation of Lung Tumors: Evaluation Based on a Review of 147 Tumors. 2017. 28 (4): 481-9.

Click here for abstract

Tumor-related factors that influence local tumor progression (LTP) include, size, site, orientation, organ, histology, and biology. The decision to treat primary or metastatic lung cancer with surgery or minimally invasive RF ablation is generally based on size. Larger tumors > 3 cm are considered to be more amenable to surgery. For smaller tumors or those close to 3 cm, the authors retrospectively reviewed factors influencing the complete ablative rate (CAR) and LTP. 147 tumors with an average maximum diameter of 1.8 cm +/- 1.2 receiving a single ablation and followed > 6 months were evaluated in 93 patients. 26% of patients had primary lung cancer and 74% had metastatic disease.

Clinical Pearls

What is the mechanism of action of radiofrequency ablation?

The Bovie knife is the first well-known medical device to incorporate RF ablation, which functions as cautery (pulsed current) and cutting (continuous current). Radiofrequency refers to the 3 Hz – 300 GHz range of the electromagnetic spectrum, which can cause thermal ablation of tissue. As with the Bovie knife, RF ablation devices operate in a closed electrical circuit, with the cathode (RF electrode or probe) transmitting energy through the patient’s tissue toward an anode (dispersing pads). Coagulative necrosis is achieved as dipole molecules (mostly water) next to the electrode remain aligned to the direction of the current and are forced to vibrate as rapidly as the applied current. Frictional energy released by adjacent molecules is deposited in surrounding tissue, resulting in local temperature increase. As the energy is dispersed by the pads, tissue damage is limited to the area surrounding the electrode tip. Application of too high of a generator power too quickly can cause tissue to desiccate or “char,” which acts as insulation and limits further extension of ablation.

What is meant by the “heat sink” effect?

Induced coagulation necrosis = (energy deposited x local tissue interactions) – heat loss. “Heat sink” is a cooling effect, which limits the effect of all thermal ablation methods. Flowing blood in vessels 3 mm or larger adjacent to a target lesion limit temperature variation in that area. This is potential cause for residual, unablated tissue and local tumor progression. Other studies have also postulated that tumors with proximal vascular or bronchial extension might lead to larger microscopic extension beyond the edge of the tumor. In this study, contact between tumor and blood vessels was determined as an independent risk factor for incomplete ablation in this study, and the CAR was significantly reduced.

What is considered effective tumor ablation?

A slow method of energy deposition, as to avoid desiccation with quick temperature rises, is used to heat tissue to 50-100 degrees Celsius for 4-6 minutes. Data extrapolation from surgery has established a general guideline to achieve an ablation margin 0.5 – 1.0 cm of ablated normal tissue, which is thought to account for microscopic tumor extension beyond the visualized confines of the lesion. The authors determined a complete ablative margin in this study to correspond to ground-glass opacities completely encircling the ablated lesion. In practice, it is difficult to distinguish inner necrosis areas from outer peripheral hemorrhage and inflammatory reaction on CT images and as a result, the shortest distance of overall ablative margin was measured and recorded in this study. Tumors can be monitored for local progression by determining contrast enhancement at the ablation margins on follow-up CT studies, as was done in this retrospective review. In the first three months following ablation, an enhancement zone that is peripheral, concentric, symmetric, and uniform and has smooth inner margins can be considered to correspond to reactive hyperemia, inflammation, or granulation at the marginal parenchyma. For tumors that are PET-avid prior to ablation, follow up PET studies may also be used. 

Questions to Consider

Which factors related to the efficacy of complete tumor ablation in this study?

The authors retrospectively investigated variables of tumor related factors before ablation including, tumor type, tumor size, morphology (smooth margins, lobulated and/or spiculated), and contact with blood vessels. For tumors < 3 cm, the CAR was 68.55%. For tumors > 3 cm, the CAR was 17.39%. CAR of tumors with a smooth margin was significantly greater than CAR of tumors with lobulated and/or spiculated edges. CAR of tumors with no surrounding blood vessels was 75%, which was remarkably higher than CAR of tumors with blood vessel contact. In tumors with complete ablative margin, the CAR was 74.77%, whereas it was 16.67% for tumors with incomplete ablative margin. Further, in tumors with complete ablative margins, completely ablated tumors had significantly larger ablative margin than incompletely ablated tumors (5.04 mm +/- 2.29 vs 3.71 mm +/- 2.51). Multivariate analysis showed that incomplete ablative margin and an ablative margin of 1–4 mm were independent risk factors for incomplete RF ablation of lung tumor.

Which factors related to local tumor progression (LTP)?

LTP after RF ablation is not rare, and progression at the RF ablation site is associated with poor overall survival in published reports. In this study, the LTP rate was 52% for primary lung cancers and 36.9% for lung metastases. This was higher than rates reported in the previous studies mentioned in the article, which were calculated for a period of several years and included the condition that patients received repeated lung tumor RF ablations. Of the 58 tumors with incomplete ablation, 56 tumors developed local progression at the edge of ablated lesions. 52 tumors locally recurred at the site of incomplete or shortest ablative margin. The site of shortest ablative margin was usually located at the tumor edge of contact with the blood vessels, in front of the ablation electrode, with the maximum radius perpendicular to the ablation electrode, and with protrusion of lobulated and/ or spiculated area of tumors.

Additional Citations:
Hong K, Georgiades C. Radiofrequency Ablation: Mechanism of Action and Devices. J Vasc Interv Radiol. 2010. 21(8): S179-S186

Post Author:
Rajat Chand, MD
Diagnostic Radiology Resident, PGY-2
John H. Stroger Hospital of Cook County