Fluorescence-Guided “Cure” for Pancreatic Cancer?

Fluorescence-guided surgery (FGS) entails the use of a light-sensitizing agent, or photosensitizer, to help reveal the precise location of cancer cells or malignant tissue during the operation. When surgeons attempt to remove a tumor, they cannot see how much of the margin (area surrounding the visible tumor) may contain cancer cells, and yet it is those cells that may later develop into a recurrence.

The fluorescence-guided approach may greatly increase the likelihood of removing cancer that otherwise would be invisible to the surgeon, thus lowering the chances of disease progression or recurrences following the operation.

In the past decade, a group of research scientists at the University of California in San Diego (USA) has been developing an approach to FGS for pancreatic cancer. Pancreatic cancer is an extremely deadly cancer, and the prognosis has not improved in recent years. Indeed, pancreatic cancer is the only cancer for which deaths are predicted to increase rather than decrease in European men and women this year and going forward. Using animal models, the San Diego study involved two treatment groups.

The first group received standard surgery under bright light and was termed bright light surgery, or the BLS group. The second group underwent fluorescence-buided surgery—the FGS group. After intravenous injection of the light-sensitizing agent (a fluorophore-conjugated antibody to CEA), the following results were achieved:

• Complete removal of the pancreatic tumor was achieved in 92% of the FGS group compared to only 46% in the BLS group.
• Cure rates with FGS compared to BLS improved from about 5% to 40%, respectively
• The one-year postoperative survival rates increased from 0% with BLS to 28% with FGS
• Disease-free survival increased from 5 weeks with BLS to 11 weeks with FGS, while overall survival increased from 13.5 weeks with BLS to 22 weeks with FGS.
• In the FGS group, 25% of the mice were free of cancer at the end of study, compared to less than 5% of the BLS group.

The San Diego research team concluded that fluorescence-guided laparoscopic surgery is more effective than standard surgery (i.e., without the advantage of a photosensitizer) and therefore has major potential for surgical oncology, as reported in the July 2014 Journal of the American College of Surgeons.  

Combining UV Light with Fluorescence-Guided Surgery

Another promising angle on pancreatic cancer treatment may involve the use of ultraviolet (UV) light, possibly in conjunction with fluorescence-guided surgery.  Even without administering a photosensitizer, UV light treatment has shown some anticancer efficacy in laboratory studies of various tumor types.  It appears that the expression of fluorescent proteins in cancer cells can enhance the natural photodynamic effect of UV light on those cancer cells.

For this study, researchers from Yokohama City University Graduate School of Medicine in Yokohama, Japan, teamed up with some of the aforementioned researchers from the University of California in San Diego.  The international team of scientists sought to determine whether UV light treatment in combination with FGS could eradicate metastatic human pancreatic cancer in mice.

Two weeks after implanting the pancreatic cancer cells that expressed the green fluorescent protein, bright-light surgery, or BLS, was performed on all tumor-bearing mice.  After BLS, the mice were randomly assigned to three treatment groups: (1) BLS-only, (2) FGS only, or (3) FG plus UVC.  What follows were the main findings from this study:

• The average residual tumor area after FGS was significantly smaller than after BLS only.
• The BLS treated mice had significantly lower survival rates (both relapse-free survival and overall survival) compared to FGS- and FGS-UVC-treated mice for.
• FGS-UVC-treated mice had significantly better survival rates compared to FGS-only treated mice
• The relapse-free survival for FGS-UVC-treated mice lasted at least 150 days, indicating the animals were “cured”.  (This would be the equivalent of over five years survival in humans.)

The researchers also concluded that UV light treatment was an effective way to sterilize the surgical resection bed of cancer cells following FGS. The findings from this study suggest that UV light treatment in combination with FGS has the clinical potential to bolster survival after a diagnosis of pancreatic cancer, as reported in the 12 June 2014 issue of PloS One.  

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Sources

Metildi CA, Kaushal S, Luiken GA, Hoffman RM, Bouvet M. Advantages of fluorescence-guided laparoscopic surgery of pancreatic cancer labeled with fluorescent anti-carcinoembryonic antigen antibodies in an orthotopic mouse model. J Am Coll Surg. 2014 Jul;219(1):132-41.

Hiroshima Y, Maawy A, Zhang Y, Sato S, Murakami T, Yamamoto M, et al. Fluorescence-guided surgery in combination with UVC irradiation cures metastatic human pancreatic cancer in orthotopic mouse models. PLoS One. 2014 Jun 12;9(6):e99977.

Metildi CA1, Kaushal S, Hardamon CR, Snyder CS, Pu M, Messer KS, Talamini MA, Hoffman RM, Bouvet M. Fluorescence-guided surgery allows for more complete resection of pancreatic cancer, resulting in longer disease-free survival compared with standard surgery in orthotopic mouse models. J Am Coll Surg. 2012;215(1):126-35