Smallest Clinically Meaningful Improvement in Amputation-Related Pain and Brief Pain Inventory Scores as Defined by Patient Reports of Global Improvement After Cryoneurolysis: a Retrospective Analysis of a Randomized, Controlled Clinical Trial.

BACKGROUND: The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both interpreting published data and designing a clinical trial. However, limited information is available for patients with chronic pain conditions, and what is published is derived from studies involving pharmacologic and psychological interventions. We here calculate these values based on data collected from 144 participants of a previously published multicenter clinical trial investigating the effects of a single treatment with percutaneous cryoneurolysis. METHODS: In the original trial, we enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. At both baseline and 4 months (primary end point), participants rated their phantom limb pain based on a numeric rating scale (NRS) and their interference of pain on physical and emotional functioning as measured with the Brief Pain Inventory's interference subscale. They subsequently qualitatively defined the change using the 7-point ordinal Patient Global Impression of Change (PGIC). The smallest clinically meaningful improvements in phantom limb pain and Brief Pain Inventory scores were calculated using an anchor-based method based on the PGIC. RESULTS: The median (interquartile range [IQR]) phantom pain NRS (0-10) improvements at 4 months considered small, medium, and large were 1 [1-1], 3 [3-4], and 4 [3-6], respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with a small, medium, and large analgesic changes were 16 [6-18], 24 [22-31], and 34 [22-46]. The proportions of patients that experienced PGIC ≥5 were 33% and 36% in the active and placebo groups, respectively. The relative risk of a patient experiencing PGIC ≥5 in the active group compared to the sham group with 95% confidence interval was 0.9 (0.6-1.4), P = .667. CONCLUSIONS: Amputees with phantom limb pain treated with percutaneous cryoneurolysis rate analgesic improvements as clinically meaningful similar to pharmacologic treatments, although their MCID for the Brief Pain Inventory was somewhat larger than previously published values. This information on patient-defined clinically meaningful improvements will facilitate interpretation of available studies and guide future trial design.

Safety and Effectiveness of Stellate Ganglion Cryoablation in Complex Regional Pain Syndrome.

This was a retrospective, observational, descriptive study to evaluate the safety and 6-month effectiveness of percutaneous cryoablation of the stellate ganglion for the treatment of complex regional pain syndrome (CRPS). Eight patients with CRPS diagnosed by Budapest criteria were treated with this procedure. CRPS symptom severity was assessed prior to the procedure and at 3-month intervals after the procedure using a novel CRPS scoring system-the Budapest score-created by the authors. The mean Budapest score prior to and 6 months (187 days, SD ± 43) after stellate ganglion cryoablation was 7.0 (SD ± 2.0) (n = 6) and 3.8 (SD ± 2.3) (n = 6), respectively, showing a decrease of 3.2 (SD ± 1.7) (n = 6; P = .006). There were no major adverse events due to the procedure, and there was only 1 minor adverse event. Stellate ganglion cryoablation is a feasible, safe, and minimally invasive procedure that may represent an efficacious adjunct treatment option for select patients with CRPS.

Relative Effects of Various Factors on Ice Ball Formation and Ablation Zone Size During Ultrasound-Guided Percutaneous Cryoneurolysis: A Laboratory Investigation to Inform Clinical Practice and Future Research.

INTRODUCTION: Ultrasound-guided percutaneous cryoneurolysis provides analgesia using cold temperatures to reversibly ablate peripheral nerves. Cryoneurolysis probes pass a gas through a small internal annulus, rapidly lowering the pressure and temperature, forming an ice ball to envelope the target nerve. Analgesia is compromised if a nerve is inadequately frozen, and laboratory studies suggest that pain may be paradoxically induced with a magnitude and duration in proportion with the incomplete ablation. We therefore investigated the relative effects of various factors that may contribute to the size of the ice ball and the effective cryoneurolysis zone. METHODS: A cryoprobe was inserted into a piece of meat, a gas was passed through for 2 min, and the resulting ice ball width (cross-section) and length (axis parallel to the probe) were measured using ultrasound, with the temperature evaluated in nine concentric locations concurrently. RESULTS: The factor with the greatest influence on ice ball size was probe gauge: in all probe types, a change from 18 to 14 increased ice ball width, length, and volume by up to 70%, 113%, and 512% respectively, with minimum internal temperature decreasing as much as from -5 to -32 °C. In contrast, alternating the type of meat (chicken, beef, pork) and the shape of the probe tip (straight, coudé) affected ice ball dimensions to a negligible degree. The ice ball dimensions and the zone of adequate temperature drop were not always correlated, and, even within a visualized ice ball, the temperature was often inadequate to induce Wallerian degeneration. CONCLUSIONS: Percutaneous probe design can significantly influence the effective cryoneurolysis zone; visualizing a nerve fully encompassed in an ice ball does not guarantee adequate treatment to induce the desired Wallerian degeneration because ice forms at temperatures between 0 and -20 °C, whereas only temperatures below -20 °C induce Wallerian degeneration. The correlation between temperatures in isolated pieces of meat and perfused human tissue remains unknown, and further research to evaluate these findings in situ appears highly warranted.

Ultrasound-guided Percutaneous Cryoneurolysis to Treat Chronic Postamputation Phantom Limb Pain: A Multicenter Randomized Controlled Trial.

BACKGROUND: Postamputation phantom pain is notoriously persistent with few validated treatments. Cryoneurolysis involves the application of low temperatures to reversibly ablate peripheral nerves. The authors tested the hypothesis that a single cryoneurolysis treatment would decrease phantom pain 4 months later. METHODS: The authors enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. The primary outcome was the change in average phantom pain intensity between baseline and 4 months as measured with a numeric rating scale (0 to 10), after which an optional crossover treatment was offered. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. RESULTS: Pretreatment phantom pain scores were similar in both groups, with a median [quartiles] of 5.0 [4.0, 6.0] for active treatment and 5.0 [4.0, 7.0] for sham. After 4 months, pain intensity decreased by 0.5 [-0.5, 3.0] in patients given cryoneurolysis (n = 71) versus 0 [0, 3] in patients given sham (n = 73), with an estimated difference (95% CI) of -0.1 (-1.0 to 0.7), P = 0.759. Following their statistical gatekeeping protocol, the authors did not make inferences or draw conclusions on secondary endpoints. One serious adverse event occurred after a protocol deviation in which a femoral nerve cryolesion was induced just below the inguinal ligament-instead of the sensory-only saphenous nerve-which resulted in quadriceps weakness, and possibly a fall and clavicle fracture. CONCLUSIONS: Percutaneous cryoneurolysis did not decrease chronic lower extremity phantom limb pain 4 months after treatment. However, these results were based upon the authors' specific study protocol, and since the optimal cryoneurolysis treatment parameters such as freeze duration and anatomic treatment location remain unknown, further research is warranted.

Percutaneous CT-Guided Cryoneurolysis of the Intercostobrachial Nerve for Management of Postmastectomy Pain Syndrome.

PURPOSE: To evaluate the feasibility, safety, and efficacy of intercostobrachial nerve (ICBN) cryoneurolysis for pain control in patients with postmastectomy pain syndrome (PMPS). MATERIALS AND METHODS: Fourteen patients with PMPS were prospectively enrolled into this clinical trial after a positive response to a diagnostic computed tomography (CT)-guided percutaneous block of the ICBN. Participants subsequently underwent CT-guided percutaneous cryoneurolysis of the same nerve and were observed on postprocedural Days 10, 90, and 180. Pain scores, quality-of-life measurements, and global impression of change values were recorded before the procedure and at each follow-up point using established validated outcome instruments. RESULTS: Cryoneurolysis of the ICBN was technically successful in all 14 patients. The mean pain decreased significantly by 2.1 points at 10 days (P = .0451), by 2.4 points at 90 days (P = .0084), and by 2.9 points at 180 days (P = .0028) after cryoneurolysis. Pain interference with daily activities decreased significantly by 14.4 points after 10 days (P = .0161), by 16.2 points after 90 days (P = .0071), and by 20.7 points after 180 days (P = .0007). There were no procedure-related adverse events. CONCLUSIONS: Cryoneurolysis of the ICBN in patients with PMPS was technically feasible and safe and resulted in a significant decrease in postmastectomy pain for up to 6 months in this small cohort.

Agents Used for Nerve Blocks and Neurolysis.

The recognition of pain and the treatments used for it are vital for all practitioners. Many types of pain can be treated in a locoregional fashion, which has significant implications not just for any individual patient but for society as a whole. These treatments are most effective when performed in a minimally invasive, image-guided fashion. Interventional radiologists should play a central role in providing these lifestyle-limiting treatments. This article describes the medications most typically used for spinal and extra-axial treatments in the management of patients in pain.

Percutaneous Image-guided Cryoneurolysis: Applications and Techniques.

The expansion and dissemination of interventional cryoneurolysis in recent years has been fueled by the integration of advanced imaging guidance, the evolution of our understanding of neuropathologic processes after exposure of nerves to cold, and opportunities for its use beyond pain management. The clinical translation of cryoneurolysis through interventional radiology requires consideration of many factors, including (a) the supply and composition of target nerves, (b) the value of diagnostic injection with imaging guidance for confirmation, (c) the integration of advanced imaging guidance that allows safe ablation, (d) the difference between neoplastic and nonneoplastic causes of pain, (e) the phenomenon of percutaneously induced neuroregeneration, (f) the potential to manage conditions other than pain, (g) the consideration of protocols, (h) the limitations of current technology, and (i) the potential complications and adverse effects. Cryoneurolysis has societal and legislative endorsement as an effective nonopioid option for pain palliation. The Centers for Medicare and Medicaid Services (CMS) approved three new category III Current Procedural Terminology (CPT) codes specifically for the cryoablation of nerves with advanced imaging guidance. Interventional radiologists who are aware of nerve-directed strategies see eligible patients in their daily practice and have opportunities to bundle procedures (eg, celiac plexus block at the time of a biliary drain for pancreatic cancer with low bile duct obstruction), offering an avenue to serve the patient, reduce opioid dependence, allow faster discharge, and establish name recognition of interventional radiologists. Also, the ability to use CT to target deep structures accurately and swiftly, often with only local anesthesia, compared with the usual monitored anesthesia care in a surgical setting, may provide another avenue to build a cryoneurolysis practice. ©RSNA, 2022.

Review of Extraosseous Applications of Thermal Ablation in the Treatment of Moderate to Severe Large Joint Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease worldwide, leading to significant pain, restricted range of motion, and disability. A gap exists between short- and long-term symptom-relieving therapies. Although arthroplasty is an effective treatment for symptomatic end-stage disease, most patients ultimately do not receive a joint replacement due to suboptimal surgical qualifications, comorbidities, or an aversion to surgery. The lack of additional treatment options in this setting makes opioid agonists a commonly used pharmacologic agent, contributing to the addiction epidemic that greatly afflicts our communities. Cooled radiofrequency ablation (CRFA) has arisen as a treatment modality in the setting of moderate to severe OA among patients refractory to conservative management, generally showing greater efficacy compared with other existing strategies. This review focuses on the benefits of CRFA and its technical feasibility as a management option among patients experiencing debilitating large joint OA with limited clinical options.

Interventional Radiology Obesity Therapeutics: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The Society of Interventional Radiology Foundation commissioned a Research Consensus Panel to establish a research agenda on "Obesity Therapeutics" in interventional radiology (IR). The meeting convened a multidisciplinary group of physicians and scientists with expertise in obesity therapeutics. The meeting was intended to review current evidence on obesity therapies, familiarize attendees with the regulatory evaluation process, and identify research deficiencies in IR bariatric interventions, with the goal of prioritizing future high-quality research that would move the field forward. The panelists agreed that a weight loss of >8%-10% from baseline at 6-12 months is a desirable therapeutic endpoint for future IR weight loss therapies. The final consensus on the highest priority research was to design a blinded randomized controlled trial of IR weight loss interventions versus sham control arms, with patients receiving behavioral therapy.

Cryoablation for Palliation of Painful Bone Metastases: The MOTION Multicenter Study.

Purpose: To assess the clinical effectiveness of cryoablation for palliation of painful bone metastases. Materials and Methods: MOTION (Multicenter Study of Cryoablation for Palliation of Painful Bone Metastases) (ClinicalTrials.gov NCT02511678) was a multicenter, prospective, single-arm study of adults with metastatic bone disease who were not candidates for or had not benefited from standard therapy, that took place from February 2016 to March 2018. At baseline, participants rated their pain using the Brief Pain Inventory-Short Form (reference range from 0 to 10 points); those with moderate to severe pain, who had at least one metastatic candidate tumor for ablation, were included. The primary effectiveness endpoint was change in pain score from baseline to week 8. Participants were followed for 24 weeks after treatment. Statistical analyses included descriptive statistics and logistic regression to evaluate changes in pain score over the postprocedure follow-up period. Results: A total of 66 participants (mean age, 60.8 years ± 14.3 [standard deviation]; 35 [53.0%] men) were enrolled and received cryoablation; 65 completed follow-up. Mean change in pain score from baseline to week 8 was -2.61 points (95% CI: -3.45, -1.78). Mean pain scores improved by 2 points at week 1 and reached clinically meaningful levels (more than a 2-point decrease) after week 8; scores continued to improve throughout follow-up. Quality of life improved, opioid doses were stabilized, and functional status was maintained over 6 months. Serious adverse events occurred in three participants. Conclusion: Cryoablation of metastatic bone tumors provided rapid and durable pain palliation, improved quality of life, and offered an alternative to opioids for pain control.Keywords: Ablation Techniques, Metastases, Pain Management, Radiation Therapy/OncologySupplemental material is available for this article.© RSNA, 2021.

Interventional Cryoneurolysis: An Illustrative Approach.

The application of advanced imaging guidance and the interventional radiology skill set has expanded the breadth of nerve and nerve plexus targets in the body for potential cryoneurolysis. Advancement of the basic science supporting cryoneurolysis has further solidified proceduralists' confidence and ability to select and manage patients clinically. As these procedures continue to evolve, a structured approach to the wide variety of indications is necessary.

Percutaneous CT-Guided Cryoablation of the Celiac Plexus: A Retrospective Cohort Comparison with Ethanol.

PURPOSE: To retrospectively analyze and compare the incidence of diarrhea in patients who underwent cryoablation of the celiac plexus for intractable abdominal pain versus ethanol therapy over a 5-year period. MATERIALS AND METHODS: From June 2014 to August 2019, 83 patients were identified who underwent neurolysis of the celiac plexus for management of intractable abdominal pain by using either cryoablation (n = 39 [59% female; age range, 36-79 years old [average, 60 ± 11 years old]) or alcohol (n = 44 [48% female; age range, 29-76 years old [average, 60 ± 12 years old]). Pain scores and reports of procedure-related complications or side effects, with special attention to diarrhea and/or other gastrointestinal symptoms, were collected from follow-up visits at 1 week, 1 month, and 3 months post-intervention and were compared between groups. RESULTS: The mean time of follow-up was 17.7 days. Four patients who underwent cryoablation developed gastrointestinal symptoms consisting of 2 cases of nausea and vomiting and 2 cases of diarrhea (5.1%). Twelve patients who underwent ethanol ablation developed gastrointestinal symptoms, including 1 case of nausea, 3 cases of vomiting, and 9 cases of diarrhea (20.5%). There was a significantly higher incidence of both diarrhea (chi-squared likelihood ratio, P = .03) and overall gastrointestinal symptoms (chi-squared likelihood ratio, P = .04) in the ethanol group than in the cryoablation group. CONCLUSIONS: Cryoablation of the celiac plexus may provide a new treatment option for intractable abdominal pain, and it appears to have a lower incidence of diarrhea and fewer gastrointestinal side effects than ablation using ethanol.

Natural History of Mixed and Motor Nerve Cryoablation in Humans-A Cohort Analysis.

Eight patients who underwent percutaneous cryoablation of mixed and/or motor nerves over a period of 5 years were identified. Distances from the ablation sites to origins of distal musculature were measured, and times to initial clinical recovery were collected. Strength progression over time following muscle activation was also collected and analyzed. All patients demonstrated activation of all muscles distal to the ablation, and the calculated mean rate of nerve regeneration based on distance to the origin of the assessed musculature and time to muscle activation for the group was 1.5 mm/day ± 1.1.

Interventional Cryoneurolysis: What Is the Same, What Is Different, What Is New?

Cryoneurolysis is the deliberate application of cold temperatures to nerves for therapeutic purposes. The idea of treating pain with this technique is thousands of years old and has evolved over time through the application of surgical techniques, nerve stimulation and/or landmark guidance, and through device development. Recent integration of the interventional radiology skill set to this space has unlocked a myriad of opportunities-primarily through a unique ability to percutaneously access deep structures in the body with accuracy and precision, and the capacity to monitor ablation zones. Understanding of the specific neurohistological process that follows targeted cryoneurolysis leads to new options for treating patients in pain without drugs and opens doors for the potential modification of a wide array of disease states.

Percutaneous CT-Guided Cryovagotomy in Patients with Class I or Class II Obesity: A Pilot Trial.

OBJECTIVE: This study evaluated the safety of percutaneous CT-guided cryoablation of the vagus nerve (percutaneous cryovagotomy) in participants with class I or class II obesity. METHODS: The study was an open-label, single-group, prospective pilot investigation designed around safety-related stopping criteria. Twenty participants with 30 > BMI > 37 underwent percutaneous cryovagotomy with follow-up visits at day 7, 45, 90, and 180. Data related to adverse events, technical success, weight loss, quality of life, dietary intake, global impressions of hunger change, activity, and body composition were analyzed. RESULTS: The procedural technical success rate was 100%. There were no adverse events in 19 participants who completed the trial. Ninety-five percent of patients reported decreased appetite following the procedure, and reductions in mean absolute weight and BMI were observed at all time points. The mean quality of life and activity scores improved from baseline to 6 months post procedure, and mean caloric intake and overall body fat decreased over the same period. CONCLUSIONS: Percutaneous CT-guided cryovagotomy is feasible and was tolerated without complications or adverse events in this cohort. Quantitative preliminary data from this pilot investigation inform the design of a larger prospective randomized clinical trial.

Image-Guided Transarterial Directed Delivery of Human Mesenchymal Stem Cells for Targeted Gastrointestinal Therapies in a Swine Model.

PURPOSE: To evaluate the feasibility of catheter-directed intra-arterial stem cell delivery of human mesenchymal stem cells (MSCs) to the small bowel in a porcine model. MATERIALS AND METHODS: The cranial mesenteric artery of 6 Yucatan minipigs was selectively catheterized under fluoroscopic guidance following cut-down and carotid artery access. A proximal jejunal branch artery was selectively catheterized for directed delivery of embolic microspheres (100-300 µm) or MSCs (0.1-10 million cells). The pigs were euthanized after 4 hours and specimens collected from the proximal duodenum and the targeted segment of the jejunum. The Chiu/Park system for scoring intestinal ischemia was used to compare hematoxylin and eosin-stained sections of jejunum and duodenum. RESULTS: Successful delivery of microspheres or MSCs in a proximal jejunal branch artery of the cranial mesenteric artery was achieved in all subjects. Radiopaque microspheres and post-delivery angiographic evidence of stasis in the targeted vessels were observed on fluoroscopy after delivery of embolics. Preserved blood flow was observed after MSC delivery in the targeted vessel. The Chiu/Park score for intestinal ischemia in the targeted proximal jejunal segments were similar for microspheres (4, 4; n = 2) and MSCs (4, 4, 4, 3; n = 4), indicating moderate ischemic effects that were greater than for control duodenal tissue (3, 1; 0, 0, 3, 3). CONCLUSIONS: Selective arteriographic deployment of MSCs in swine is feasible for study of directed intestinal stem cell delivery. In this study, directed therapy resulted in intestinal ischemia.

Access to Interventional Radiology Services in Small Hospitals and Rural Communities: An ACR Membership Intercommission Survey.

PURPOSE: To evaluate the status of interventional radiology (IR) staffing, recruitment, and retention in the United States, specifically as they apply to small hospitals and rural communities. MATERIALS AND METHODS: A 22-question survey was created by an ACR intercommission workgroup and circulated via e-mail to ACR members who self-identified as a "group practice leader," "general radiologist," "interventional radiologist," or "abdominal radiologist." Contingency tables were constructed, and bivariate analyses were performed to assess overall responses and the distribution of responses among specific groups of respondents. RESULTS: A total of 1,005 e-mail recipients completed the survey. A statistically significant greater proportion of responders from rural hospitals (versus nonrural hospitals) answered that (1) their group falls short or far short of meeting demand for IR services (29.1% versus 14.3%), (2) they had difficulty recruiting IR physicians to their practice (67% versus 40.6%), and (3) they had difficulty retaining IR physicians (40% versus 29%). The most frequently reported reasons for difficulty recruiting were that IR-trained physicians "do not want to do diagnostic work" (56.2%) and "do not want to practice in a small or rural setting" (48.8%). A greater proportion of respondents from rural hospitals perceived that they had difficulty retaining IR physicians because of perceived inadequate "complexity of case mix" (67.5%) or "number of cases" (66.1%). CONCLUSION: Small hospitals and rural communities experience greater difficulty recruiting and retaining IR physicians and meeting IR service demands compared with their nonrural counterparts.