Glowing Dye Improves Cancer Removal in Kidney

June 05, 2007

A  new way to provide clear images of cancerous tumors in the kidney during surgery promises to help physicians preserve as much kidney function as possible while still removing all the malignant tissue – a significant advance as doctors discover that saving as much healthy kidney tissue as possible is crucial for the future health of cancer patients.

Results from a small pilot study were presented at the recent American Urological Association’s annual meeting, giving surgeons a sneak peek at a new imaging process that gives healthy kidney tissue a fluorescent glow, clearly differentiating it from cancerous tissue. This glow assists surgeons in the accurate removal of cancerous tissue during a partial nephrectomy, or the removal of a portion of the kidney.

According to the National Cancer Institute, in 2007, it’s estimated that there will be 51,190 new cases of kidney cancer, and almost 13,000 deaths from the disease.

“In general, surgery is the most effective treatment for kidney cancer.  Improving surgeons’ ability to see all of the malignant tumor is a significant step forward,” said Edward Messing, M.D., chair of the Department of Urology at the University of Rochester Medical Center.

Indocyanine Green or ICG, a dye that has been widely used for more than 50 years to help diagnose and treat various diseases of the eye, liver and heart, is the source of the guiding fluorescence. The compound, which binds to proteins in the blood, fluoresces and becomes visible once exposed to a laser beam, demonstrating patterns of blood and lymphatic circulation. It’s also very safe when injected into patients, and in fact is approved for use in pregnant women.

Doctors at the University of Rochester Medical Center’s James P. Wilmot Cancer Center recently discovered that when ICG is injected into the kidney during surgery, it clearly shows the boundaries of the cancerous tumor in just seconds, giving surgeons a quick and safe way to definitively mark the margins of cancerous tissue.  This allows them to spare as much healthy kidney tissue – and kidney function – as possible.

The study, presented by urologist Dragan Golijanin, M.D., included an analysis of images from 10 surgeries on people with cancer of the kidney. The technique outlined each of the tumors with a clarity not often seen in the operating room.

The discovery comes at a time when the number of partial nephrectomies is on the rise. In 2002, 12.3 percent of all kidney cancer operations were partial nephrectomies, compared with almost 20 percent today. Physicians are discovering that maintaining maximum kidney function is crucial, especially for older people on medications, who make up most kidney cancer patients. This is a sharp contrast with the traditional approach, which has been to remove the entire kidney – even if it contains only a small, localized tumor – so long as the patient has a second, functioning kidney.

“Sparing even a little bit of kidney tissue, that I might have otherwise taken out, is a very good thing,” said Messing, who performs over 50 full and partial nephrectomies each year and helped author the study. “Now, with the ICG dye process, I clearly see the tumor’s outline and know that I am eliminating as much cancer as possible. I also can see tiny satellite tumors that we never were able to see before. This technique couldn’t come at a better time, as more and more surgeons are opting for partial nephrectomies whenever possible.”

The extensions of many kidney tumors are extremely difficult to spot with the naked eye, so surgeons currently rely on pre-operative imaging, ultrasound and pathology to guide their excisions. Each approach has limitations. Ultrasound images greatly depend on the expertise of the technician, and it adds a step that can be cumbersome during delicate surgery. Preoperative imaging often misses small lesions, can be imprecise with complex tumors, and ineffective in guiding cancer removal when tumors are embedded deep within the kidney. Pathology tests, while very accurate, take time, and cannot point to all cancerous areas, because it's practical to only test a few samples from excised tissues during the operation (when the surgeon could still remove more kidney needed to get out the entire cancer). So in the end, most surgeons err on the side of caution, removing large chunks of healthy tissue surrounding the tumor to ensure maximum cancer control.

The idea of using a dye that had been floating around in the medical landscape since the 1950s was the brainchild of Golijanin, a resident training under Messing who was searching for a way to illuminate nerves that surround the prostate during prostatectomy surgery. His research led him to articles written by Robert W. Flower, M.D., the physician who first introduced ICG to the medical world some 40 years ago to help diagnose and treat blood circulation problems in the eye. Golijanin noticed a consistent theme in Flower’s writings: Not only did ICG seem to have amazing “glowing” properties inside the blood vessels, but it appeared to attach to other types of tissue as well.

“And so we began to look at ways we could use ICG in prostate surgery, and that has in turn led to a lot of additional discoveries, such as how well it illuminates normal kidney tissue, but not tumors,” Golijanin said.  For his development of ICG as an imaging tool, Golijanin and colleagues received the top prize for best scientific manuscript at the World Congress of Endourology in 2006.

“The basic technology has been around for decades, but it’s only recently that we are discovering its potential to differentiate tumors from healthy tissue in a variety of cancers where imaging is not as precise as we’d like it to be,” Golijanin added.

Next on the horizon in the kidney research is to develop a way to illuminate ICG laparoscopically, which will open the door for future use of this technique in other kidney procedures.

In addition, the research team will continue to work with Novadaq Technologies Inc., a Canadian medical devices company, to further explore ways to use ICG to accurately excise a tumor with minimal removal of healthy tissues in prostate, bladder and penile cancers, and in the treatment for a condition known as testicular torsion.

Other authors of the study, which was funded by Novadaq, include Ronald Wood, Ph.D.; Jay Reeder, Ph.D.; Vikram Dogra, M.D.; Jorge Yao, M.D.; Ralph Madeb, M.D.; Eric Singer, M.D., Ganesh Palapattu, M.D.; Erdal Erturk, M.D.; Jean Joseph, M.D.; and Guan Wu, M.D., Ph.D.

Editor’s Note:  Before and after photos are available.

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