Page 51 - Fluorescence-guided cancer surgery
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Detection of breast cancer using methylene blue 49
In the patients with negative resection margins, median minimal distance of tumor tissue to resection margin was 3 (range 1-20).
Histological validation of MB positive tumors with  uorescence microscopy showed a clear overlay between  uorescent signal and tumor tissue (Figure 2B). Three patients in the early administration group experienced transient mild pain of the lower arm during administration of MB, which disappeared after  ushing the intravenous cannula with saline. No other adverse reactions associated with the use of MB or the Mini-FLARETM image-guided surgery
system were observed.
DISCUSSION
The current study demonstrated feasibility of real-time identi cation of breast cancer using NIR  uorescence imaging and MB. In 83% of patients, tumor demarcation as identi ed by NIR  uorescence imaging corresponded to histological presence of tumor. In addition, in one case surgical management was changed based on intraoperative NIR  uorescence  ndings, which avoided the need for re-resection.
During breast cancer surgery, the distinction between healthy and malignant tissue is often not evident, resulting in positive resection margins in up to 40% of patients undergoing breast conserving surgery12;13. Despite major improvements in preoperative imaging, real-time intraoperative imaging modalities are lacking2. Therefore, breast cancer surgeons often still have to rely on palpation and previously obtained mammography or MRI to determine the extent of resection. Optical imaging using exogenous contrast agents could usher in a new era in surgical oncology. However, to successfully use this modality both a clinical-grade intraoperative  uorescence imaging system and a tumor-speci c NIR probe are obligatory. To date multiple camera systems have become clinically available, however FDA/EMA approved tumor-speci c probes are still lacking. Therefore, it is important to exploit clinically available contrast agents, such as indocyanine green and MB14 whenever possible.
Several papers have reported the intraoperative use of MB for identi cation of various tumors. As early as 1971, MB was used at high concentration as a visible blue dye to stain parathyroid adenomas after systemic administration15. Thereafter, it was shown that there was a high uptake of the tracer in various kinds of neuroendocrine tumors16-18. One of the disadvantages of using MB is


































































































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