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

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

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