More than 80 percent of people with pancreatic cancer are diagnosed after the cancer has metastasized, and by then the prognosis for long-term survival is dismal. However, surgeons and scientists at the University of California-San Diego (UCSD) are developing a laparoscopic technique that uses fluorescent light to improve pancreatic cancer staging and treatment. Their findings were presented today at the 2011 Clinical Congress of the American College of Surgeons.
The UCSD researchers compared a standard xenon laparoscope with a laparoscope using a light emitting diode (LED) source. Surgeons took two antibodies that are commonly expressed by pancreatic cancer and tagged them with a fluorescent marker, thus, making the cancerous tumors "light up" in colors of bright green or red, reported study leaders, Michael Bouvet, MD, FACS, and Robert M. Hoffman, Ph.D., both UCSD professors of surgery.
The surgeons and scientists then administered fluorescent antibodies into six-week old female mice. The researchers were able to see primary and metastatic tumors more vividly with the LED light, at a sensitivity rate of 96 percent, than with traditional laparoscopy, which had a sensitivity rate of 40 percent. Moreover, fluorescent laparoscopy rendered fewer false positives than traditional laparoscopy, and the researchers were able to clearly see the surrounding anatomy in the abdominal cavity of the mice. Fluorescent laparoscopy was also sensitive enough to illuminate metastatic lesions smaller than one millimeter, which are not visible with a standard laparoscope.
"Laparoscopy is used for staging in patients with cancer, often before we make a big incision," said Dr. Bouvet. "Now, we've made it even better with the LED light source. We modified it so you can see both the normal background of the anatomy plus the fluorescent tumor signal at the same time. We were able to perform LED fluorescence laparoscopy in mice with small, three millimeter laparoscopes."
The fluorescent marker did not show evidence of toxicity or side effects in the mice. The combination of LED light and fluorescent markers for malignant tumors could potentially sharpen how surgeons detect and treat pancreatic cancer in human patients. If patients have received the fluorescent antibodies prior to an operation, the surgeon can insert the LED laparoscope through a small incision and determine if the cancer has metastasized to other areas of the abdomen. "If it has spread, then we can biopsy those areas and better determine if the best initial treatment should be chemotherapy and save the patient the large incision," Dr. Bouvet said. "If there's no or limited metastases, then we can more completely remove the primary and metastatic tumors because we can see the edges better. We're hoping for a lower rate of local recurrence."
Once the cancerous tumors are illuminated, Dr. Bouvet explains, the surgeons are able to more precisely remove the tumor and any surrounding malignant tissue without injuring the aorta and other nearby blood vessels. Furthermore, another potential application for this technique could involve medically treating pancreatic cancer: "You could tag a specific drug or isotope to target tumor cells. Since the fluorescent antibodies bind specifically to cancer cells, you could deliver certain payloads of drugs that would kill the cancer cells more effectively," Dr. Bouvet said.
The technique could also be applied to staging and treating colon cancer, which often is expressed through the same antibodies as pancreatic cancer and treated with the same laparoscopic technology. Within the next four years, Dr. Bouvet plans to work with OncoFluor, Inc., a biotech company that develops fluorescent compounds for malignant tumors, on securing FDA approval for clinical trials of the fluorescent antibodies in humans.
Other members of the research team included Cristina Angela Metildi Raimo, MD; Sharmeela Kaushal, Ph.D.; Chanae Hardamon, BSc, Hop Tran Cao, MD; Cynthia S. Snyder, MD; George A. Luiken, MD; and Mark A. Talamini, MD, FACS, all from the University of California-San Diego, San Diego, CA; OncoFluor, Inc., San Diego, CA; and AntiCancer, Inc., San Diego, CA.
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