Congratulations to Our Latest Grant RecipientsApr 9, 2018
ASRA has announced the 2018 recipients of three of its research grants including the inaugural recipients of ASRA's new Young Investigator and Graduate Student Awards.
Lidocaine Infusions in Pancreatic Cancer
Gina (Effrossyni) Votta-Velis, MD, PhD
Gina (Effrossyni) Votta-Velis, MD, PhD, of the University of Illinois at Chicago, has been awarded the 2018 Carl Koller Memorial Research Grant. She and her co-investigators will receive $198,760 to conduct a study of “Lidocaine Infusions in Pancreatic Cancer: Translational Studies in a Preclinical Model and Human Subjects."
According to her grant proposal, pancreatic cancer is the fourth most common cancer, and patients often face poor prognoses because of the disease's late diagnosis and aggressiveness. The majority of patients require surgery, which can introduce processes known to play a role in tumor metastasis such as surgical stress, immune suppression, and inflammation. One way that surgery can add additional risk is by releasing cancer cells into circulation. Changes in gene expression induced by surgery may also enhance tumor growth. The release of cytokines and growth factors stimulate Src Tyrosine kinase activity in endothelial and circulating tumor cells, contributing to solid tumor metastasis. Excess Src activity is present in pancreatic cancer and is able to influence its invasiveness and metastatic capability.
Studies have shown that perioperative use of regional anesthesia and local anesthetic agents (LAs) may improve outcomes. In this study the investigators hypothesize that lidocaine infusion might control metastasis or recurrence by inhibiting Src tyrosine kinase activity and by some yet to be identified new mechanism(s) in circulating tumor cells (CTCs) or tumors. This translational study will be conducted in a preclinical genetically engineered mouse model of pancreatic cancer, and in pancreatic cancer patients undergoing robotic pancreatectomy. This is a "Proof of Concept " study elucidating the effect of lidocaine infusions in the biology of the CTCs. It is expected that demonstrating the reduced Src Kinase activity in CTCs and preventing their survival will strengthen the evidence that lidocaine infusions may have a distinct clinical application in the perioperative period in pancreatic cancer patients, and would provide a sound rationale for conducting a prospective randomized control clinical trial evaluating the effect of perioperative lidocaine infusions in preventing pancreatic cancer metastasis.
Co-investigators on the project are Ajay Rana, PhD, from the University of Illinois College of Medicine, and Alain Borgeat, MD, professor at Orthopedic University Hospital Balgrist, Zurich, Switzerland.
Clinical Decision Support Tool for Prescribing Opioids
Delara Brandal, MD
Delara Brandal, MD, of the UCLA Department of Anesthesiology and Perioiperative Medicine, is the first-ever recipient of ASRA's Young Investigator Award, designed to support a project by a physician within 5 years of graduation from residency/fellowship. Dr. Brandal has been awarded $30,000 to support the project “Development and Implementation of a Clinical Decision Support (CDS) Tool for Prescribing Opioids at Discharge from the Hospital: Impact on Chronic Opioid Use After Surgery."
Investigators propose development of a tool built within a major vendor electronic medical record to help physicians prescribe discharge pain medications for patients undergoing colorectal surgery.
"Our study focuses on the transition point between the perioperative setting and hospital discharge and, therefore, addresses a crucial step in the control of the chronic use and misuse of opioid medications and has major implications for addressing the growing opioid epidemic," Dr. Brandal said.
The project will leverage models of care such as Enhanced Recovery After Surgery (ERAS) and the Perioperative Surgical Home (PSH), where anesthesiologists specialized in acute and chronic pain management play an essential role.
"This presents an opportunity for altering prescription practices, as physician behavior, rather than the condition of the patient, may be the primary determinant of opioid prescribing practices," Dr. Brandal noted.
Co-investigators are Maxime Cannesson, MD, PhD and Siamak Rahman, MD, both of the UCLA Department of Anesthesiology and Perioperative Medicine. Dr. Cannesson, the project mentor, is a professor of Clinical Anesthesiology and vice chair for Perioperative Medicine, and Dr. Rahman is a clinical professor and director of Regional Anesthesia and Acute Pain Anesthesiology.
Graduate Student Project Will Study Lidocaine Derivatives
Desmond H. Fung, BSc
Desmond H. Fung, BSc, an MSc student in Pharmacology at the University of British Columbia in Vancouver, is the first-ever recipient of ASRA's Graduate Student Award. He has been selected to receive a $10,000 award for his project "Evaluation of Local Anesthesia in Mice Produced by Quaternary Lidocaine Derivatives."
In his proposal, Fung noted that local anesthetics (LAs) are among the most effective treatment options for pain relief, but one that produces long-lasting nociceptive-specific blockade after a single administration and that possess a large therapeutic index is still, unfortunately, non-existent. Long-lasting sensory blockade using LAs can be accomplished through indwelling catheters, but they can lead to infection, malposition, or discomfort. Previous experiments have found longer-lasting local anesthesia with quaternary lidocaine derivative, QX-314. However, studies found that QX-314 had an inferior toxicity profile compared to lidocaine.
Fung's project would investigate a series of other quaternary local anesthetic molecules, in the hope of identifying agents that produce long-lasting blockade with reduced local and systemic toxicity compared to lidocaine. The proposed experiments will help identify agents with nociceptive-specific blockade and define their relative efficacy. In addition, they will allow to investigate promising local anesthetic candidate compounds that may in the future be used for improved postoperative pain relief and answer questions regarding toxicity.
Stephan K. W. Schwarz, MD, PhD, FRCPC, professor & Dr. Jean Templeton Hugill Chair in Anesthesia in the department of Anesthesiology, Pharmacology & Therapeutics at the University of British Columbia, will serve as Fung's mentor on the project.
Learn more about ASRA Research Grants here.