A THIRD of patients who undergo surgery to remove cancerous tumours end up with microscopic pieces left behind.
THESE overlooked remnants can lead to the recurrence of cancer after what was thought to be a successful surgery.
Two surgeons at the University of Pennsylvania have joined forces to try to solve this problem. Their solution: making tumours glow. Using a combination of injectable dyes and high-resolution cameras, the surgeons found a way to image tumours during surgery and more easily identify their margins. They published their findings in July in the journal PLoS One. “Once you get into surgery, you’ve only got your eyes and your hands to tell you where the margin of the cancer is,” said David Holt, lead author of the study and professor of surgery at the Penn School of Veterinary Medicine. Tumours could be studied before surgery with MRIs or CT scans, but these images were helpful only to a certain extent, he said. After an initial study in mice, Holt used the new imaging technology on eight dogs with naturally occurring lung tumours. Holt and his team injected the dogs with indocyanine green, a dye that accumulates in tumours, more so than other tissues, due to their leaky blood vessels. The dye cannot be seen directly because it emits light in wavelengths that cannot be seen by human eyes. But when the doctors shined a near-infrared light on the tumours during surgery, they glowed an “Incredible Hulk green” on computer screens hooked up to their cameras, Holt said. With the help of this real-time image, Holt could make decisions about where to make incisions during surgery on the dogs. The successful dog study led to approval for a human clinical trial run by another surgeon, Sunil Singhal, a co-author on the study and assistant professor of surgery at Penn’s Perelman School of Medicine. Using the same technology, which he compared to night-vision goggles, Singhal examined lung and chest tumours in five human patients. Just as in the dog study, the tumours strongly fluoresced under the near-infrared cameras. Singhal also used this imaging approach in another study published in August in the Annals of Thoracic Surgery. In two out of 18 patients with lung cancer, the imaging system helped surgeons identify cancer in areas that had previously gone undetected. Singhal is already exploring its applications in other cancers, including breast cancer. He has seven open clinical trials using dyes to image tumours during surgery. This type of imaging does not involve radiation, making it safe to use for most patients, even pregnant women. But the dye Holt and Singhal used can be detected at depths of only 10-15 millimetres in tissues, leaving deeper areas unexplored. Also, the dye does not specifically bind to tumour cells; thus, adjacent tissues can also collect dye, especially if they are inflamed. Singhal and Holt plan to use targeted dyes in future studies that are molecularly selective for tumour cells as well as continuing to improve their camera technology. Their work is not ready for mass use. But Singhal hopes it will ultimately lead to more sophisticated approaches, including three-dimensional holograms of tumours generated during surgery.