Local Anesthetic Lidocaine May Mitigate Pancreatic Cancer Metastasis

Fastened between the stomach and the spine, the pancreas oversees both digestion and blood sugar in the body. It is also the site of an aggressive cancer called pancreatic ductal adenocarcinoma or PDAC.

PDAC is the most common type of pancreatic cancer, the third leading cause of cancer death in the U.S. It is difficult to detect and recurs about 70% of the time after treatment. Only 13% of those diagnosed survive more than five years.

A team of surgeons, anesthesiologists and engineers at the University of Illinois at Chicago is studying how lidocaine, a common local anesthetic, affects pancreatic cancer cells released into the bloodstream during surgery. Their latest advance evaluates a method to capture these rogue cells and is published in the journal Lab on a Chip.

I really hope that the results of this study can help our patients. “The notion that lidocaine, which has been used for pain relief for more than 65 years, can mitigate metastasis and favorably affect patient outcomes is very innovative.”

Dr. Gina Votta-Velis, professor of anesthesiology at UIC School of Medicine and principal investigator

In 2018, Votta-Velis received a grant from the American Society of Regional Anesthesia and Pain Medicine for this project. Circulating tumor cells are cancer cells that break away from the tumor (often during tumor removal surgery) and escape into the bloodstream. Patients with more aggressive circulating tumor cells in the blood have worse prognoses and higher recurrence rates.

Votta-Velis said patients should recover from surgery before starting chemotherapy. In that time, circulating tumor cells, or CTCs, can travel throughout the body and generate new tumors. But preliminary in vitro studies have shown that lidocaine can prevent cells from leaving the bloodstream again, rather than trapping them for our immune system to eliminate naturally.

“CTCs are the seeds of metastasis,” he said. “If we can detect them and reduce their aggressiveness with the infusion of lidocaine, we can reduce the risk of the metastatic process.”

Because circulating tumor cells are rare, isolating them could mean removing 30 to 40 cells from the billions in our bloodstream, like pulling a needle from a haystack. That’s why Votta-Velis partnered with University of Illinois Cancer Center affiliate Ian Papautsky, UIC’s Richard Professor and Loan Hill of Biomedical Engineering in the College of Engineering. He specializes in microfluidics: how small amounts of fluids, such as blood, flow through tiny channels.

Their contribution to the project is a small microfluidic device, made of glass and plastic, that measures just a couple of inches long and contains channels a little wider than a strand of hair. The device isolates cancer cells from a patient’s blood sample based on their size, a process known as liquid biopsy.

“CTCs tend to be 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 blood into this device, we can filter out CTCs without modifying or damaging the cells.”

In 2019, Papautsky’s team showed that this method detects cancer cells with 93% accuracy. This time, the researchers compared Papautsky’s method with a commercially available tool called EasySep, which separates cells magnetically. Papautsky said magnetic separation can be harsh and sometimes destroy the cells it is trying to catch.

The researchers tested both systems (EasySep and their original method) with blood samples from pancreatic cancer patients. They found that Papautsky’s method recovered eight times more cancer cells and processed blood samples faster, in just 20 minutes.

“The success of the method is very important for asymptomatic cancers like pancreatic cancer, where a blood draw may be the only way to diagnose early,” Papautsky said.

Dr. Pier Giulianotti, co-investigator and division chief of general, minimally invasive and robotic surgery at the School of Medicine, said this discovery opens the door to the next generation of personalized medical treatments.

“Science is all about small steps,” said Giulianotti, a world-renowned expert in the surgical treatment of hepatobiliary pancreatic cancer. “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.”

Other UIC researchers include Celine Macaraniag, Ifra Khan, Alexandra Barabanova, Valentina Valle and Alain Borgeat. Jian Zhou of Rush University Medical Center is a co-author.