| The Surgical Technologist | MARCH 2021 112 show that this technique resulted in much higher rates of gross total resection when compared to the control group of patients. 5 5-ALA is a naturally occurring metabolite in the human body. It is produced within the metabolic pathway. The unique characteristic of this metabolite is that it eas- ily crosses the blood brain barrier and consequently easily passes through the surgical capsule or tumor interface. Nor- mal tissue can metabolize the drug to hemoglobin where cancer cells cannot, and therefore, the fluorescence accu- mulates within the tumor cells causing them to glow red under blue light. Once 5-ALA is taken up by malignant glioma cells, it is metabolized into the fluorescent metabolite, protoporphy- rin IX (PpIX). Elevated PpIX production within malignant brain tumor cells permits violet-red fluorescence visu- alization of malignant tumor tissue after excitation with 405 nm wavelength blue light. The preferential accumula- tion of 5-ALA within malignant glioma cells is felt to occur due to decreased levels of ferrochelatase (a heme produc- tion enzyme that produces heme with the addition of iron (Fe)) and selective uptake by an ATP-binding cassette trans- porter (ABCB6). Other factors that correlate with fluores- cence induced by 5-ALA are cellular density, tumor cell proliferative activity, neovascularity of the tumor, and BBB permeability. 2 5-ALA has offered tremendous advancement in the treatment of malignant gliomas. However, it is not without its draw- backs. There is a risk for false positive fluorescence. Some patients have expe- rienced fluorescence in viable tissue areas sur- rounding the resected tumor site. It is notewor- thy to state that the fluo- rescence usually will not be found in normal brain tissue distant from the original tumor site. Reactive astrocytes may be to blame in patients who do experience false posi- tive fluorescence. In rare cases, a patient might experience what is called autofluorescence of normal brain tissue. Moreover, research has shown that in 313 patients operated on for suspected recurrent glioblastomas, about 3% turned out to have pathology consistent with radiation necrosis in tissues demonstrating fluorescence. 2 Conversely, there are some occasions where 5-ALA does not properly mark the margins of the tumor. This usually occurs for specific reasons. Malignant gliomas are charac- terized by a disseminated in-growth pattern within normal brain tissue. To that end, cancer cells may be found cen- timeters away from the bulk of the tumor and will not be highlighted in the same way as more dense parts of the glio- ma would be. However, the success rate in identifying these less dense margins is increased with the use of spectrom- etry. Spectrometry is what aids in identifying fluorescence in regions of low-density cell infiltration too weak to be visualized directly with the microscope alone by causing the fluorescence to glow. Moreover, false negatives can occur due to structural barriers that interfere with the visualiza- tion of the fluorescence. This can occur due to photobleach- ing, blood and/or normal brain tissue obstructing the direct visualization of the resection cavity. Photobleaching occurs when the fluorescence breaks down due to prolonged light exposure. Thus, fluorescence cannot replace proper surgical technique and adequate visualization of the entire resection cavity. Additionally, timing is critically important when it comes to positive patient outcomes. Once 5-ALA is given it is rapidly absorbed into the bloodstream within one hour. However, protoporphyrin IX (PpIX) plasma levels peak four hours after oral administration of 5-ALA. Consequently, taking the patient to surgery too soon or too late will nega- tively impact the efficacy of the tumor fluorescence. Lastly, tumor necrosis may not demonstrate tumor fluorescence and could therefore be misidentified. 2 Fluorescence-guided surgery is a great and simple tool that allows for real-time intraoperative identification of residual glioma tissue. Despite its risks, research suggests this method will continue to be an important component to any neurosurgeon’s armamentarium when it comes to the definitive treatment of malignant gliomas. Tumor dissection often utilizes white light microscopy, unlike the blue light microscopy used with 5-ALA. To this end, 5-ALA FGS has aided in achieving a significantly high- er rate of complete resections in malignant gliomas cases.