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.

Percutaneous Image-Guided Cryoneurolysis.

OBJECTIVE: The aim of this article is to review the available evidence regarding image-guided percutaneous cryoneurolysis, with a focus on indications, technique, efficacy, and potential complications. CONCLUSION: Percutaneous image-guided cryoneurolysis is safe and effective for the management of several well-described syndromes involving neuropathic pain. Additional rigorous prospective study is warranted to further define the efficacy and specific role of these interventions.

p120 Catenin is required for normal tubulogenesis but not epithelial integrity in developing mouse pancreas.

The intracellular protein p120 catenin aids in maintenance of cell-cell adhesion by regulating E-cadherin stability in epithelial cells. In an effort to understand the biology of p120 catenin in pancreas development, we ablated p120 catenin in mouse pancreatic progenitor cells, which resulted in deletion of p120 catenin in all epithelial lineages of the developing mouse pancreas: islet, acinar, centroacinar, and ductal. Loss of p120 catenin resulted in formation of dilated epithelial tubules, expansion of ductal epithelia, loss of acinar cells, and the induction of pancreatic inflammation. Aberrant branching morphogenesis and tubulogenesis were also observed. Throughout development, the phenotype became more severe, ultimately resulting in an abnormal pancreas comprised primarily of duct-like epithelium expressing early progenitor markers. In pancreatic tissue lacking p120 catenin, overall epithelial architecture remained intact; however, actin cytoskeleton organization was disrupted, an observation associated with increased cytoplasmic PKCζ. Although we observed reduced expression of adherens junction proteins E-cadherin, ß-catenin, and α-catenin, p120 catenin family members p0071, ARVCF, and δ-catenin remained present at cell membranes in homozygous p120(f/f) pancreases, potentially providing stability for maintenance of epithelial integrity during development. Adult mice homozygous for deletion of p120 catenin displayed dilated main pancreatic ducts, chronic pancreatitis, acinar to ductal metaplasia (ADM), and mucinous metaplasia that resembles PanIN1a. Taken together, our data demonstrate an essential role for p120 catenin in pancreas development.

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.

Probes for narcotic receptor mediated phenomena. 41. Unusual inverse µ-agonists and potent µ-opioid antagonists by modification of the N-substituent in enantiomeric 5-(3-hydroxyphenyl)morphans.

Conformational restraint in the N-substituent of enantiomeric 5-(3-hydroxyphenyl)morphans was conferred by the addition of a cyclopropane ring or a double bond. All of the possible enantiomers and isomers of the N-substituted compounds were synthesized. Opioid receptor binding assays indicated that some of them had about 20-fold higher µ-affinity than the compound with an N-phenylpropyl substituent (K(i) = 2-450 nM for the examined compounds with various N-substituents). Most of the compounds acted unusually as inverse agonists in the [(35)S]GTP-γ-S functional binding assay using nondependent cells that stably express the cloned human µ-opioid receptor. Two of the N-substituted compounds with a cyclopropane ring were very potent µ-opioid antagonists ((+)-29, K(e) = 0.17 and (-)-30, K(e) =0.3) in the [(35)S]GTP-γ-S functional binding assay. By comparison of the geometry-optimized structures of the newly synthesized compounds, an attempt was made to rationalize their µ-opioid receptor affinity in terms of the spatial position of N-substituents.