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Tuesday, April 18, 2017

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.

Click here for abstract

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

Thursday, April 13, 2017

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





Thursday, March 23, 2017

Outcome Results on Ablation versus Surgery for HCC: A Report from the SEER Registry


Summary

The comparative efficacy of percutaneous ablation versus surgical resection for hepatocellular carcinoma (HCC) remains a controversial topic, with conflicting literature reporting equivalent outcomes between modalities or superior outcomes with surgery. This study by Mironov et al used the Surveillance, Epidemiology, and End Results (SEER) database to compare survival outcomes for small solitary HCCs treated with thermal ablation versus surgical resection. Only cases with available Ishak fibrosis score were included in the analysis to account for the effect of cirrhosis. To reduce confounding, patients with metastatic disease, treatment other than ablation or surgery, both surgery and ablation, and liver transplantation were excluded. There were baseline differences in the ablation and surgery patients including a higher prevalence of fibrosis in the ablation group (higher Ishak scores) and smaller tumors in the ablation group (mean 2.6 cm versus 3.0 cm, p<0.001). For tumors ≤2 cm (ablation = 264; resection = 79) and tumors between 2.1 and 4 cm (ablation = 335; resection = 209), there was no significant difference in observed or disease-specific survival between ablation and surgical resection. For tumors between 4.1 and 5 cm (ablation = 46; resection = 66), there was a significantly longer observed and disease-specific survival for surgical resection when stratified by presence of fibrosis (observed survival p=0.009, disease specific survival p=0.046). The 5-year observed survival was 72% (surgery) versus 29% (ablation) and disease-specific survival was 80% (surgery) versus 40% (ablation). Notably, the difference in disease-specific survival was not clinically significant by Cox regression with fibrosis covariate (p=0.145). When all tumors ≤4 cm were pooled, there was again no difference in survival outcomes between ablation and surgical resection. Significant predictive factors for observed and disease-specific survival by Cox model included tumor size and degree of fibrosis.





Commentary

Percutaneous ablation is maturing as an important part of the treatment armamentarium for HCC. The relative efficacy of ablation techniques compared to surgery remains controversial and current guidelines from the Barcelona Clinic Liver Cancer (BCLC) recommend ablation only for patients who are not surgical candidates. These recommendations are derived from a very limited evidence base, with only one prospective study demonstrating superior outcomes after surgery. The SEER registry offers a powerful resource to answer these questions, affording a large patient sample from diverse medical institutions and detailed survival outcome data. The authors of this paper effectively identified potential confounders including patients who had received both treatments or went on to receive a liver transplant. The results of their study demonstrate equivalent survival outcomes in tumors <4 cm, which suggests that it would be reasonable to consider ablation as an alternative to surgery in this patient population. The results in the 4-5 cm tumor group demonstrated superiority of surgery, reflecting limitations of ablation in larger tumor sizes. The SEER population included both patients who had been treated with radiofrequency and microwave ablation (and does not differentiate the two modalities), so it could not be determined in this study whether outcomes in these larger tumors may be superior with microwave. It is important to recognize limitations to the SEER data including lack of BCLC or Child-Pugh scores, performance status, or comorbidities, which may all be important contributors to survival. Nonetheless, this study serves as additional evidence that percutaneous ablation affords equivalent survival outcomes to surgery in HCC ≤4 cm and may help to further define the evolving role of ablation in the treatment of HCC patients.

Click here for abstract

Mironov O, Jaberi A, Kachura JR. Thermal Ablation versus Surgical Resection for the Treatment of Stage T1 Hepatocellular Carcinoma in the Surveillance, Epidemiology, and End Results Database Population. J Vasc Interv Radiol 2017; 28:325-33.

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

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

Wednesday, March 22, 2017


From the SIR residents and fellows section


Topic: Gastric Artery Embolization Trial for the Lessening of Appetite Nonsurgically (GET LEAN): Six Month Preliminary Data 


Syed, M I, Morar K, Shaikh A, Craig P, Khan O, Patel S, Khabiri, H. Gastric Artery Embolization Trial for the Lessening of Appetite Nonsurgically (GET LEAN): Six Month Preliminary Data. J Vasc Interv Radiol. 2016. 27 (10): 1502-8.

Click here for abstract

In the October 2016 edition of JVIR, a report on the 6 month safety and efficacy results of a pilot study of left gastric artery (LGA) embolization for the treatment of morbid obesity was discussed. Four patients, three women, one man, with an average age of 41 y (range 30-54), with a mean weight of 259.3lbs, and mean BMI of 42.4 kg/m2 had their LGA embolized with 300-500-um Bead Block particles for the treatment of morbid obesity.



Weight loss was calculated as a percentage versus baseline, as well as b percentage excess body weight loss as follows, where IBW represents “Ideal Body Weight”, using the Devine formula.



Treatment with a PPI was started one week prior to embolization, and continued one month after the procedure. The procedure was performed via a femoral artery access or a left radial artery access.



No immediate complication other than nausea and mild vomiting was reported. Average body weight loss among the four patients at 6 months was 20.3 lbs. Average body weight loss as a percentage was 8.5%. Average excess body weight loss at 6 months was 17.2%. Patient 4, a diabetic patient taking only oral medications, showed improvement in hemoglobin A1c levels (7.4% to 6.3%) at 3 months, which remained at 6 months. QOL measures showed that the average physical component score improved by 9.5 (on an absolute scale of 0–100), and the average mental component score improved by 9.6 (on an absolute scale of 0–100), at 6 months.



In conclusion, preliminary data supports LGA embolization as a potentially safe procedure that warrants further investigation for weight loss in morbidly obese patients.

Clinical Pearls


What were some patient selection and clinical management steps considered for this procedure?

Patients with morbid obesity, (BMI ≥ 40 kg/m2) whose previous attempts at weight loss through diet, exercise, and behavior modification had failed were recruited for this study. These patients also declined to participate in bariatric surgery, as part of the consent process. A complete history and physical exam was performed prior to the procedure.

All patients had dietary consultations for preoperative evaluation and were followed the procedure by a dietician. Any patient with type II diabetes (n = 1) was evaluated by an endocrinologist before participation in the study. Blood glucose levels were monitored with adjustments of diabetic drugs as needed by the endocrinologist throughout the study. Any female patient of childbearing potential (n = 2) was required to use two forms of contraception during the study (oral and barrier), which was monitored by their primary care provider or gynecologist. An upper endoscopy study was performed at baseline and 3 days after the procedure in all patients.

If any patient had any abnormality on 3-day endoscopy (n = 3), upper endoscopy was repeated at 30 days. Fasting morning, plasma ghrelin, leptin, and CCK measurements, in addition to BMI and other baseline and follow-up tests or procedures, were performed at regular intervals.

What were the confounding factors and limitations of this study?

The presence of superficial symptomatic gastric ulcerations (n = 3) was a confounding variable regarding mechanism of weight loss. One known mechanism of weight loss caused by gastric ulcerations is the postprandial pain that creates a fear of food. This postprandial pain was absent in the patients who had superficial gastric ulcerations after the initial few days. 

One other mechanism of weight loss caused by gastric ulceration is appetite suppression. In the present study, all patients except for patient 2 subjectively reported appetite reduction that persisted beyond 30 days (after documented ulcer healing by endoscopy).

Another potential confounding variable was the medications used (PPI and sucralfate). There is no evidence that the short-term use of a PPI or sucralfate has any effect on weight loss. In fact, according to literature, long-term PPI use may result in weight gain. Notably, no dietary restrictions (to promote healing) were given to patients who had superficial gastric ulcerations.

Another confounding variable is that diet modification and nutritional supervision may have occurred that could have accounted for weight loss.

Limitations of this study included the small sample size and relatively short follow up period. Another limitation of the study was that diet and caloric intake records were not obtained.

Questions to Consider


What physiologic pathway is altered when LGA is embolized?


Left gastric artery (LGA) embolization may fulfill a role as a minimally invasive alternative to the current surgical treatment of gastric bypass or reduction surgery for morbidly obese patients. The LGA supplies the fundus of the stomach, where it is known that the hormone ghrelin (one of the hormones responsible for appetite) is produced. Ghrelin is a 28-amino acid hunger-stimulating peptide and hormone that is produced mainly by P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas. Ghrelin is the only known circulating orexigenic, or appetite-enhancing, hormone

What are the risks / complications of Bariatric Surgery to manage obesity?


Anastomotic leaks, bowel obstruction, deep vein thrombosis, pulmonary embolism, GI bleed, dumping syndrome, and anesthesia risks. Also reported, the 30 day mortality rate associated with BS is 0.31%, as of 2014, lower than previously reported in 2004. However, it is reported that repeat operation rate is 7%, and the overall complication rate is 17%. It is estimated that only 1% of eligible patients elect to undergo bariatric surgery.

Post author:

Ali Alikhani, MD
Diagnostic Radiology Resident, PGY-4
University of Tennessee Methodist Healthcare

Wednesday, February 22, 2017

Y-90 with Resin Microspheres without Routine Embolization of the Gastroduodenal Artery


Summary

Ward et al present a retrospective analysis of gastrointestinal complications in patients following radioembolization with resin microspheres without routine embolization of the gastroduodenal artery. In this study, 62 consecutive patients underwent Yttrium-90 (Y90) radioembolization with resin microspheres for cholangiocarcinoma or metastatic liver disease. Prior to treatment, preparatory angiography was performed with embolization of high-risk hepaticoenteric anastomoses and administration of technetium-99m macroaggregated albumin. On the day of treatment, repeat digital subtraction angiography and cone-beam computed tomography (CT) was utilized to identify and embolize additional hepaticoenteric anastomoses prior to resin microsphere administration. In addition, if the treatment vessel was less than ~2 cm distal to a hepaticoenteric anastomotic vessel that could not receive coil embolization, administration of RE was done via an antireflux microcatheter (ARMC) (Surefire Infusion System). Patients were discharged with a 1-month prescription for a proton pump inhibitor and a 10-day steroid taper. Follow-up was scheduled for 1 and 3 months post-treatment with an examination focused to detect symptoms of gastrointestinal complications. During planning angiography, 68% of patients had one or more hepaticoenteric vessels embolized, with the right gastric artery being the most commonly embolized. The gastroduodenal artery was embolized in only three patients, two during planning angiography and one immediately prior to radioembolization. ARMC was used in 14% (10 of 69) treatments. Stasis of flow was identified in three patients and administration of resin microspheres was terminated in these patients prior to complete administration of the prescribed dose. Clinical follow-up was available in 60 out of 62 patients and no patients experienced Grade 3 or 4 gastrointestinal symptoms (hematemesis, melena, severe nausea, vomiting, or abdominal pain). No patients required upper endoscopy or extension of prophylactic proton pump inhibitor.



Figure 2. (a) Celiac arteriography in a 48-year-old woman with metastatic neuroendocrine tumor who required embolization of the GDA demonstrated an accessory left hepatic artery (black arrow) from the left gastric artery, a right hepatic artery (white arrow), and a middle hepatic artery supplying segment 4 (dashed white arrow). The GDA (dashed black arrow) originated from the right hepatic artery distal to the origin of the middle hepatic artery. The middle hepatic artery demonstrated a tight kink at its origin, precluding use of an antireflux microcatheter, but supplied approximately 400 mL of diffuse tumor in segment 4. Redistribution of the middle hepatic artery territory by coil embolization was rejected because of irregular intrahepatic vessels occluded by tumors that may have jeopardized successful redistribution. (b) Plug embolization of the GDA (black arrow) and coil embolization of the right gastric artery (white arrow) were performed before microsphere administration in 3 separate doses, administered via the replaced left hepatic artery, the middle hepatic artery, and the right hepatic artery.

Commentary

Routine embolization of the gastroduodenal artery has previously been recommended in the context of Y90 radioembolization with resin microspheres to prevent gastrointestinal ulceration. This action has potential risks; however, including coil migration, recanalization, increased procedure costs, and development of hepaticoenteric collateral vessels prior to treatment. In addition, the overall risk of gastrointestinal ulceration following radioembolization is relatively low, with only 3.7% of patients demonstrating symptoms in the randomized multi-center SIRFLOX trial. Ward et al demonstrate that routine embolization of the gastroduodenal artery may not be necessary given developments that increase the safety of resin microsphere administration (eg. cone-beam CT and ARMC). In addition, 5% dextrose was utilized instead of sterile water for suspension and flushing of resin microspheres during treatment in order to decrease vasospasm and vascular stasis. Microspheres were also administered a day before official calibration so the activity per sphere was 65 Gy/sphere instead of 50 Gy/sphere. This allowed for administration of approximately 23% fewer microspheres and decreased the risk of vascular stasis. With these precautions, there were no observed gastrointestinal complications at follow-up for any of the patients in the study. This study was limited as a retrospective single center study with all procedures performed by two operators with significant experience in resin microsphere radioembolization, potentially limiting the generalizability of the results. In addition, patients did not undergo routine upper endoscopy and biopsy, so the authors were unable to rule out subclinical gastrointestinal ulceration. The results; however, suggest that leaving the gastroduodenal artery intact prior to radioembolization with resin microspheres is safe and has the potential to save procedural time and costs.

Click here for abstract

Ward TJ, Louie JD, Sze DY. Yttrium-90 Radioembolization with Resin Microspheres without Routine Embolization of the Gastroduodenal Artery. J Vasc Interv Radiol. 2017 Feb;28(2):246-253.

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

Thomas J. An, BA
Vanderbilt University School of Medicine

Thursday, January 26, 2017

From the SIR Residents and Fellows Section (RFS)


Teaching Topic: Cryoneurolysis in Patients with Refractory Chronic Peripheral Neuropathic Pain


Yoon JH, Grechushkin V, Chaudhry A, Bhattacharji P, Durkin B, Moore W. J Vasc Interv Radiol. 2016 Feb;27(2):239-43. doi: 10.1016/j.jvir.2015.11.027.

Click Here for Abstract

Approximately, 15 million people in the United States and Europe experience chronic neuropathic pain. In the current climate, non-opiate based pain control is a topic of discussion among doctors and patients as well as at the national level among politicians. Therefore, studies showing efficacy of percutaneous interventions for the purpose of pain alleviation are paramount. In this study, the authors performed ultrasound guided cryoneurolysis on 22 patients with refractory peripheral neuropathic pain. Mean pain levels were 8.3 +/- 1.9 prior to intervention with a statistically significant decrease in mean pain scores at 1, 3, 6, and 12 months post procedure with repeat intervention required in 50%. This suggests this method may be efficacious for moderate term pain relief. Limitations of the study included small sample size and non-uniform concurrent pain regimens. However, the results are quite promising given the positive response to therapy and the superior safety profile of cryoneurolysis compared to alternative invasive therapies for the treatment of neuropathic pain.

Clinical Pearls


What is the basic pathophysiology of pain generation?


Nociceptors in the tissue convert a noxious stimuli to an electric impulse signaling an efferent nerve. This signal travels to the dorsal root ganglion and ascend centrally via the spinothalamic tract. Glutamate is thought to be involved in signaling at this level. The electrical signaling continues to the thalamus where it then relays the stimulus to various centers in the brain including the primary sensory cortex, periaqueductal grey, amygdala, pons and reticular formation in the brainstem among others. Under normal circumstances, inhibitory pathways in the periaqueductal grey and Lissauer tract release endogenous opioids, norepinephrine (NE), and serotonin mediated by GABA inhibitory neurons to mediate the perceived pain.

What is the pathophysiology of Cryoneurolysis on the peripheral nerve?

Temperatures of at least -30°C causes axonotmesis (disruption of the axon) and results in Wallerian degeneration of the nerve distal and slightly proximal to the induced thermal injury. There is preservation of the perineurium and epineurium and, therefore, regeneration of the nerve may occur over time. According to the authors, some studies show that the time for nerve regeneration is proportional to length of cryoablation.

Questions to Consider


What are other common percutaneous interventions available for neuropathic pain and what are their drawbacks?

Percutaneous nerve blocks are among the most common types of anesthesia for neuropathic pain. This technique typically employs a steroid/analgesic concoction to chemically decrease inflammation and axonal conduction, respectively. Drawbacks include: relatively short term relief, adverse systemic effects of corticosteroids, and possible nerve damage with subsequent neuritis.

Thermal ablation including microwave ablation and radiofrequency ablation/pulsed radiofrequency ablation cause tissue/nerve necrosis at predictable temperatures. Arguably, there is increased risk of thermal injury to potentially sensitive adjacent structures with thermal ablation.

Currently, what are the recommended first, second, and third line options for patients with neuropathic pain?

First line therapies: Tricyclic antidepressants, dual NE and serotonin reuptake inhibitors, calcium channel α2-δ ligands (gabapentin and pregabalin), and topical lidocaine.

Second line therapies: Opioid analgesics and Tramadol

Third line: Bupropion, Citalopram, Paroxetine, Antiepileptic medications, other topical ointments (i.e. capsaicin).

Additional references:
Chen H, Lamer TJ, Rho RH, Marshall KA, Sitzman BT, Ghazi SM, Brewer RP. Contemporary management of neuropathic pain for the primary care physician. Mayo Clin Proc. 2004 Dec;79(12):1533-45.

O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. 2009 Oct;122(10 Suppl):S22-32.

Post Author:
Lindsay Karr Thornton, MD
SIR RFS Clinical Education Chair
University of Florida

Monday, January 23, 2017

Image-Guided Cryoablation for the Treatment of Phantom Limb Pain in Amputees: A Pilot Study


Phantom limb pain (PLP) affects up to 50-80% of patients with limb loss amputations. This condition is defined by unpleasant, often painful, sensations that are perceived to originate from the amputated limb. Prologo et al present the results of a single-arm pilot study with 21 patients investigating the efficacy of percutaneous cryoneurolysis for treatment of PLP refractory to conventional treatments. The study patients underwent a two-step protocol consisting of initial computed tomography-guided perineural injection with 0.25% bupivacaine and betamethasone. If initial injection improved PLP symptoms, the patients underwent cryoneurolysis at a later date. Study endpoints included changes in pain intensity and functional impairment as measured by a visual analog scale and the Roland Morris Disability Questionnaire, respectively. At 7-days post-cryoablation, pain intensity scores decreased by 0.8 (5.4 versus 6.2) and functional impairment decreased by 1.9 (9.4 versus 11.3) compared to baseline; however, these changes were not statistically significant. At 45-days post-cryoablation, pain intensity scores decreased by 3.9 (2.3 versus 6.2) and functional impairment decreased by 8.0 (3.3 versus 11.3) compared to baseline, and these changes were statistically significant (p<0.0001). There were no statistically significant differences in pain intensity and functional impairment scores between the 45-day post-procedure visit and long-term follow-up visits (194 days +/- 99 days). Four patients volunteered to undergo repeat cryoablation and demonstrated consistent response to the second treatment with respect to both functional impairment and pain intensity score improvement. There was 100% technical success in the study with no reported adverse events related to treatment or participation in the study. Six patients (29%) required additional nonsteroidal anti-inflammatory drugs during the initial days following cryoneurolysis due to procedure related pain.




Commentary

This pilot study by Prologo et al provides preliminary data demonstrating safety and efficacy of cryoneurolysis for reducing refractory phantom limb pain. At 45-days post-treatment, patients demonstrated significant decreases in both pain intensity and functional impairment. The study had 100% technical success and no reported adverse events related to treatment or inclusion in the study. Interestingly, pain in the residual limb was a significant covariate for both baseline pain intensity and response to cryotherapy. Patients with residual limb pain had lower baseline pain and less overall change in pain intensity compared to patients without residual limb pain. This study was limited as a pilot study without a control arm or randomization. In addition, the authors did not collect or evaluate medication logs to determine how treatment affected use of pain control medication. The reported exploratory data; however, supports the design of a larger, parallel-arm randomized controlled trial in the future with more comprehensive outcome measurements. Overall, percutaneous cryoneurolysis has the potential be a safe and effective treatment option for refractory PLP.

Click here for abstract

Prologo JD, Gilliland CA, Miller M, Harkey P, Knight J, Kies D, Hawkins CM, Corn D, Monson DK, Edalat F, Dariushnia S, Brewster L. Percutaneous Image-Guided Cryoablation for the Treatment of Phantom Limb Pain in Amputees: A Pilot Study. J Vasc Interv Radiol. 2017 Jan;28(1):24-34.

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

Thomas J. An, BA
Vanderbilt University School of Medicine