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.

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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

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

From the SIR residents and fellows section (RFS)

Teaching Topic: Whether or Not to Use Free Hepatic Vein Pressure to Calculate the Portal Pressure Gradient in Cirrhosis.

Martin Rössle, MD, Philipp Blanke, MD, Benjamin Fritz, MD, Michael Schultheiss, MD, and Dominik Bettinger, MD. Free Hepatic Vein Pressure Is Not Useful to Calculate the Portal Pressure Gradient in Cirrhosis: A Morphologic and Hemodynamic Study. J Vasc Interv Radiol 2016; 27: 1130-1137

Click here for abstract

In a recent study published in JVIR, researchers from the University Hospital Freiburg investigated the role of using free hepatic vein pressure in calculating the hepatic venous pressure gradient. Diameter and pressure measurement were obtained in multiple locations within the hepatic vein, IVC, and right atrium on 30 hepatic venograms in 29 consecutive patients with planned TIPS creation. The authors found a wide range of pressure measurements and diameters across the length of the hepatic vein creating a significant amount of variability in measured pressure gradients that were not reflective of the hemodynamic changes occurring within the portal system. This challenges the current guideline recommendations of measurement in the hepatic vein or the IVC, disregarding the right atrium as an internal reference. The manuscript concludes that using the free hepatic vein pressure (FHVP) to calculate the hepatic vein pressure gradient (HVPG) is not recommended given changes with catheter tip position and vein morphology. However, the high agreement between the wedged hepatic vein/IVC pressure gradient (HCPG) and hepatic atrial pressure gradient (HAPG) suggest that both may be used.

Clinical Pearls

What is the significance of the hepatic venous pressure gradient (HVPG)?

The HVPG is the calculated difference of the wedged hepatic vein pressure (WHVP) from the free hepatic vein pressure (FHVP). A value of more than 10 mm Hg is considered clinically significant portal hypertension. A reduction to less than 12 mm Hg or a reduction of more than 10% from the baseline value is associated with decreased risk of variceal hemorrhage and improved survival. Traditionally, FHVP should be measured close to the hepatic vein orifice within a distance of 4-5 cm of the IVC. When pressure measurement differences of more than 1-2 mm Hg exist between the hepatic vein and the IVC, the pressure measured at the IVC at the level of the entrance of the hepatic veins should be used in place of the FHVP.

This study sought to reevaluate the use of HVPG for several reasons. First, in patients with advanced cirrhosis, hepatic veins may be narrowed, irregular, or compressed. This may result in erroneous measurements with an apparently high FHVP and a low HVPG. Second, postprocedural measurement of the FHVP is difficult or impossible. Therefore, measurements are commonly performed in the IVC or right atrium, which is considered the “sea level” of the vascular system and therefore the natural reference for hemodynamic measurements.

What are the recommendations of the Baveno Consensus Workshop?

The most recent expanded Baveno VI Consensus recommends TIPS within 72 hours (ideally < 24 hours) in patients bleeding from esophageal or gastric varices at high risk of treatment failure (Child class C < 14 points or Child class B with active bleeding) after initial pharmacologic and endoscopic therapy (Class 1b; Level A). Persistent bleeding despite combined pharmacologic and endoscopic therapy is best managed by PTFE-covered TIPS (Class 2b; Level B). Rebleeding during the first five days may be managed by a second attempt at endoscopic therapy. If rebleeding is severe, PTFE-covered TIPS is likely the best option (Class 2b; Level B). New guidelines in this workshop now recommend TIPS for patients with refractory ascites who are intolerant to non-selective beta blockers (NSBB) (Class 5, Level D). TIPS can be considered in patients with transfusion-dependent portal hypertensive gastropathy in whom NSBB and/or endoscopic therapies fail (Class 4; Level C). The stepwise approach to management of Budd-Chiari syndrome/hepatic venous outflow tract obstruction is: anticoagulation, angioplasty/thrombolysis, TIPS, and orthotopic liver transplantation (Class 3b; Level B).

Morning Report Questions

What factors may contribute to the inaccuracy of FHVP measurement?

Aside from narrowed, irregular, or compressed veins in patients with cirrhosis, relative obstruction of a hepatic vein by a catheter may erroneously increase the measured FHVP. In this study, the percentage of vessel obstruction by the 8-F catheter (diameter, 2.4 mm) was 40% in the peripheral position and decreased to 10% in the central (proximal) position. Small hepatic veins with a diameter of < 6 mm have a considerable obstruction of 20% or more irrespective of the location of the tip of the catheter. This study found excellent correlation between the wedged hepatic vein/IVC pressure gradient (HCPG) and the hepatic atrial pressure gradient (HAPG), which justifies using either the IVC or right atrium as internal references to calculate the portosystemic pressure gradient, not the free hepatic venous pressure. If using the HAPG, the systemic difference of 2 mm Hg should be regarded by resetting the threshold for symptomatic portal hypertension at an HAPG of 14 mm Hg.

What concerns exist about the use of the right atrium as an internal reference when calculating the portosystemic pressure gradient?

The authors mention previous studies in which pressure measurement in the right atrium is neglected because changes in intraabdominal pressure may affect the portoatrial pressure gradient but not the portohepatic pressure gradient. Therefore, it can be argued that the portosystemic pressure gradient will be significantly higher when using right atrial pressure as an internal reference as compared to using the hepatic veins or IVC. These studies placed sandbags over the abdomen to mimic high intraabdominal pressure, which led to uniform increase in pressure downstream of the obstruction in the hepatic and portal veins but left the right atrium unaffected or even reduced. The authors argue that increased intraabdominal pressure in patients with true ascites reflects an “open” system and that such increased pressures result in a change in their respective blood pools but may have only a short and limited effect on the intravascular pressure.

Additional Citations:
De Franchis, Roberto. “Report of the Baveno VI Consensus Workshop: Stratifying Risk and Individualizing Care for Portal Hypertension.” Journal of Hepatology. 2015 September; 63(3): 743-752.

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

Management of May–Thurner Syndrome in Adolescents 

Although there is a mature body of evidence supporting the safety and efficacy of endovascular intervention for May-Thurner syndrome (MTS) in adults, few studies have described results of intervention in the pediatric population. Goldman et al present a retrospective, single institution study of 10 adolescent patients, ages 12-18 years, who underwent endovascular therapy for MTS between 1998 and 2015. Six patients had pro-thrombotic risk factors including heritable conditions like factor V Leiden and/or oral contraceptive use. Acute deep venous thrombosis (DVT) was the presentation of 6/10 patients, who were treated with catheter-directed thrombolysis (CDT) alone or in combination with pharmacomechanical thrombolysis. The remaining 4/10 presented with symptoms of chronic venous outflow obstruction. All patients (thrombotic and non-thrombotic) were treated with venoplasty and stenting. Stent models included S.M.A.R.T, Wallstent, and Protégé stents, varying between 12-mm-16-mm diameters. Thrombolysis was technically successful in 4/5 patients and stenting was technically successful in 9/10 patients (the last patient did not have available imaging for review). No periprocedural complications were observed. All patients were treated with systemic anticoagulation for at least 3-months following intervention and were followed for median 32-months (range: 6-109 months). The rates of post-thrombotic syndrome (PTS) following intervention was 0% by Villalta score and 60% by modified Villalta score (designed for use in the pediatric population), and all cases with positive PTS were mild in symptom severity. Iliofemoral patency rates at 12-months were 79% (primary) and 100% (secondary), and at 36-months were 79% (primary) and 89% (secondary). One patient with antiphospholipid syndrome and homozygous MTHFR gene mutation, as well as non-adherence to medical anticoagulation presented with occlusive thrombus 14-months after initial intervention, but no invasive therapy was pursued given relatively mild symptoms.

Commentary

Venothromboembolism (VTE) is rare in the pediatric population, and pediatric MTS therefore remains a nascent area of study, for which optimal therapeutic approach is not fully elucidated. The risks for recurrent DVTs, and long-term debility from PTS in the adult MTS population has been well described, and pediatric patients may suffer similar outcomes without treatment. The experience described by Goldman et al suggests that CDT and stenting techniques may be applied with similar efficacy and safety in the adolescent population as the adult population, suggesting that these techniques should be considered in these patients. In particular, the high primary and secondary patency rates at 12 and 36-months compare favorably to those reported in adults. The authors highlighted the challenges to stenting MTS patients with underlying thrombophilic syndromes, which overall had poorer patency outcomes than those without thrombophilic syndromes and included a case of re-occlusion associated with prothromobotic syndrome and non-compliance with anticoagulation regimen. The study was subject to biases of a small patient population, retrospective imaging and clinical assessment, and non-standardized anticoagulation regimens as well as follow-up times. Furthermore, the majority of patients were of adult body habitus so the endovascular techniques and venous patency outcomes cannot be generalized to younger pediatric patients, who still have significant growth potential. Nonetheless, this study bolsters the limited evidence base for endovascular management of MTS in the pediatric population by demonstrating excellent long-term patency rates and safety profile, concordant with results seen in adults and further follow-up studies would be beneficial.

Click here for abstract

Goldman RE, Arendt VA, Kothary N, Kuo WT, Sze DY, Hofmann LV, Lungren MP. Endovascular Management of May-Thurner Syndrome in Adolescents: A Single-Center Experience. J Vasc Interv Radiol. 2017 Jan;28(1):71-77.

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

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

From the SIR Residents and Fellows Section (RFS)

Teaching Topic: Clinical Outcomes following Percutaneous Radiofrequency Ablation of Unilateral Aldosterone-Producing Adenoma: Comparison with Adrenalectomy

Sarwar A, Brook OR, Vaidya A, Sacks AC, Sacks BA, Goldberg SN, Ahmed M, Faintuch S. Clinical outcomes following percutaneous radiofrequency ablation of unilateral aldosterone-producing adenoma: comparison with adrenalectomy. J Vasc Interv Radiol. 2016. 27: 961-7.

Click here for abstract

In this recent manuscript in JVIR, researchers at Beth Israel Deaconess Medical Center compared adrenal RFA with adrenalectomy in treating unilateral aldosterone-producing adenoma (APA). The study included 44 patients with confirmed unilateral APA. Twelve of 44 underwent RFA and 32/44 underwent adrenalectomy. Both RFA and adrenalectomy resulted in normokalemia and normotension in all patients. However, RFA patients had a shorter lenth of stay (0.6 +/- 0.8 d vs. 1.7 +/- 1.4 d) less intraoperative blood loss. In addition, the adrenalectomy patients had procedural complication in 5/32 (15%) versus 0/12 in the RFA group. The authors concluded that RFA has similar effectiveness to adrenalectomy in treating patients with APA with less complications and a shorter hospital stay.

Clinical Pearls

Primary Aldosteronism (PA) is the most common cause of secondary hypertension, with a reported prevalence of 4.3% in the general population with hypertension and >11% in patients referred to specialized centers. Clinical practice guidelines from the Endocrine Society recommend unilateral laparoscopic adrenalectomy for patients with documented unilateral PA.

What patient factors/characteristics have studies shown to be associated with surgical cure of hypertension secondary to PA?

Demographic factors show that a younger age population, females and those with a BMI < 25 kg/m2 have been associated with surgical cure of hypertensin secondary to PA. Other factors that studies have shown to be associated with surgical cure are fewer antihypertensive medications before the procedure and a higher preoperative blood pressure.

Morning Report Questions

What constitutes a cure of hypertension and what constitutes improvement in hypertension from adrenalectomy?

A cure of hypertension is defined as normotension without the use of antihypertensive medications. An improvement in hypertension is normotension on the same regimen of medications that the patient was on prior to the procedure or normotension on a reduced number of antihypertensive medications.

What does The Endocrine Society recommend as the gold standard for laterization of excess hormone production?

The Endocrine Society recommends adrenal venous sampling (AVS) as the gold standard for laterization of excess hormone production. Unilateral production of excess aldosterone is most commonly due to an aldosterone-producing adenoma (APA) or unilateral adrenal hyperplasia.

What were some of the key findings observed in adrenalectomy vs RF ablation of unilateral aldosterone-producing adenoma?

This study demonstrated that RF ablation can achieve clinical outcomes similar to adrenalectomy with lower procedural morbidity in treating patients with AVS-proven unilateral APA. It showed that the efficacy in treating APA was similar with both treatments reducing blood pressure, number of anti-hypertensive medications and both treatments also increasing the serum potassium levels without the need for potassium replacement.

Another important finding in this study was that patients undergoing RF ablation had a significantly higher incidence of intraprocedural hypertensive urgency compared with patients undergoing adrenalectomy. These episodes of hypertensive urgency in the RF group were short in duration (<15 minutes) and were easily reversed by intraprocedural medications without any reported clinical sequelae. This raises an important consideration for future RF ablation procedures such as possibly adding alpha-adrenergic antagonist before the procedure to minimize the catecholamine surges that may occur secondary to incidental ablation of normal adrenal medullary tissue.

Post Author:
Andrew Niekamp, MD
Diagnostic Radiology Resident, PGY-3
UT Houston