Pinned between the stomach and spine, the pancreas plays a crucial role in both digestion and blood sugar regulation. However, it is also the site of a particularly aggressive cancer known as pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer and the third-leading cause of cancer-related deaths in the United States. This type of cancer is notoriously difficult to detect and has a recurrence rate of about 70% post-treatment. Alarmingly, only 13% of those diagnosed with PDAC survive beyond five years.
A groundbreaking study by a multidisciplinary team from the University of Illinois Chicago is shedding light on new ways to combat this deadly disease. The team, comprising surgeons, anesthesiologists, and engineers, is investigating how lidocaine—a widely used local anesthetic—affects pancreatic cancer cells that enter the bloodstream during surgical procedures. Their latest findings, published in the journal Lab on a Chip, explore a novel method for capturing these rogue cells.
Exploring Lidocaine’s Potential
“I really expect that the results of this study may help our patients,” said Dr. Gina Votta-Velis, a UIC professor of anesthesiology and a lead investigator in the study. “The notion that lidocaine, which has been used to relieve pain for more than 65 years, may mitigate metastasis and favorably affect patient outcomes is highly innovative.”
Dr. Votta-Velis received a grant from the American Society of Regional Anesthesia and Pain Medicine in 2018 to support this research. The study focuses on circulating tumor cells (CTCs), which are cancerous cells that detach from the primary tumor—often during surgical removal—and enter the bloodstream. Patients with a higher presence of these aggressive CTCs generally face poorer prognoses and increased recurrence rates.
According to Dr. Votta-Velis, patients must recover from surgery before beginning chemotherapy, creating a window during which CTCs can travel throughout the body and potentially form new tumors. Preliminary in-vitro studies suggest that lidocaine may prevent these cells from re-entering the bloodstream, instead allowing them to be naturally eliminated by the immune system.
“CTCs are the seeds of metastasis,” she explained. “If we can detect them and decrease their aggressiveness with lidocaine infusion, we may lower the risk of the metastatic process.”
The Challenge of Isolating Tumor Cells
Isolating circulating tumor cells is akin to finding a needle in a haystack, as it involves extracting 30 to 40 cells from billions present in the bloodstream. To tackle this challenge, Dr. Votta-Velis collaborated with Ian Papautsky, a UIC Richard and Loan Hill Professor of Biomedical Engineering, who specializes in microfluidics—the study of how small volumes of fluids move through tiny channels.
Papautsky’s contribution to the project is a microfluidic device, a small apparatus made from glass and plastic, just a couple of inches long. This device isolates cancer cells from a patient’s blood sample based on size, a process known as a liquid biopsy.
“CTCs are typically larger than white blood cells, which are larger than red blood cells. Cancer cells also tend to be softer and more moldable,” Papautsky said. “When we put the blood into this device, we can filter out the CTCs without modifying or damaging the cells.”
In 2019, Papautsky’s team demonstrated that this method could identify cancer cells with 93% accuracy. The current study compares this method with a commercially available tool called EasySep, which uses magnetic separation. Papautsky noted that magnetic methods can be harsh and may damage the cells they aim to isolate.
Advancements in Cancer Detection
The researchers tested both systems using blood samples from pancreatic cancer patients. They discovered that Papautsky’s method recovered eight times as many cancer cells and processed samples faster, sometimes in as little as 20 minutes.
“The method’s success is so important for asymptomatic cancers like pancreatic cancer, where a blood draw may be the only way to diagnose early,” Papautsky emphasized.
Dr. Pier Giulianotti, a co-investigator and division chief of general, minimally invasive, and robotic surgery at the College of Medicine, highlighted the significance of this discovery in advancing personalized medical treatments.
“Science is based on little steps,” said Giulianotti, a world-renowned expert in the surgical treatment of hepatobiliary pancreatic cancer malignancies. “And this is a very good step. Most malignant cancers in humans spread through the bloodstream. Understanding how cancer cells are released into the bloodstream and being able to control this process is very, very important.”
Additional contributors to this research from UIC include Celine Macaraniag, Ifra Khan, Alexandra Barabanova, Valentina Valle, and Alain Borgeat, with Jian Zhou of Rush University Medical Center as a coauthor.
This innovative study not only opens new avenues for understanding and potentially controlling the spread of pancreatic cancer but also sets the stage for future research that could significantly improve patient outcomes.
