What is the Surgical Benefit of Utilizing 5-Aminolevulinic Acid for Fluorescence-Guided Surgery of Malignant Gliomas?

Abstract

The current neurosurgical goal for patients with malignant gliomas is maximal safe resection of the contrast-enhancing tumor. However, a complete resection of the contrast-enhancing tumor is achieved only in a minority of patients. One reason for this limitation is the difficulty in distinguishing viable tumor from normal adjacent brain during surgery at the tumor margin using conventional white-light microscopy. To overcome this limitation, fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) has been introduced in the treatment of malignant gliomas. FGS permits the intraoperative visualization of malignant glioma tissue and supports the neurosurgeon with real-time guidance for differentiating tumor from normal brain that is independent of neuronavigation and brain shift. Tissue fluorescence after oral administration of 5-ALA is associated with unprecedented high sensitivity, specificity, and positive predictive values for identifying malignant glioma tumor tissue. 5-ALA-induced tumor fluorescence in diffusely infiltrating gliomas with non-significant MRI contrast-enhancement permits intraoperative identification of anaplastic foci and establishment of an accurate histopathological diagnosis for proper adjuvant treatment. 5-ALA FGS has enabled surgeons to achieve a significantly higher rate of complete resections of malignant gliomas as compared to conventional white-light resections. Consequently, 5-ALA FGS has become an indispensable surgical technique and standard of care at many neurosurgical departments around the world. We conducted an extensive literature review concerning the surgical benefit of utilizing 5-ALA for FGS of malignant gliomas. According to the literature, there are a number of reasons for the neurosurgeon to perform 5-ALA FGS, which will be discussed in detail in the current review.

Fluorescein sodium-guided surgery of malignant brain tumors: history, current concepts, and future projects

“…The surrogate for complete resection is the contrast-enhanced tumor in the T1-weighted MR-sequence, as recently outlined again by Hadjipanayis et al In a review on the use of 5-ALA in HGG (17), the rates of complete resection by means of 5-ALA ranged from 63% to 89%. However, due to its high purchase costs and its limited availability, the use of 5-ALA is restricted to a few countries only.…”

Fluorescence-guided resection of brain tumor: review of the significance of intraoperative quantification of protoporphyrin IX fluorescence

“…One successful example is the use of δ-or 5-aminolevulinic acid (5-ALA or ALA)-mediated exgogenous fluorescence to facilitate a complete or aggressive resection of brain tumor. 3,4,7,8 Available clinical data suggest that the ALA-based approach is comparable if not superior to fluorescein fluorescence examination in terms of tumor demarcation and high-degree resection. A total of 89 fluorescing and nonfluorescing biopsies taken from the tumor perimeters were examined histologically, which demonstrated 85% sensitivity and 100% specificity for the detection of malignant tissue.…”

“…Consequently, ALA/PpIX FGR has become an indispensable surgical technique and standard of care at many neurosurgical departments around the world. 7,8 Although not yet standardized universally, the optical components in ALA/PpIX FGR systems used by neurosurgical departments of different countries are similar. The commonly applied excitation wavelength for diagnostic purposes is blue light (e.g., 405 nm) which can be delivered from a coherent light source (e.g., laser) or noncoherent light source (e.g., narrow band LED).…”

Epithelial Growth Factor Receptor Expression influences 5-ALA Induced Glioblastoma Fluorescence

“…A significant difference in 5-ALA induced fluorescence was obtained in U87MG (low EGFR expression) and LN229EGFR cells (EGFR glioma and GBM can primarily impact overall survival, but it has to be carefully balanced with preserving the functional and neurological status of the patient in eloquent areas [3]. Over the last several years, 5-aminolevulinic acid (5-ALA) has been established as an intra-operative tool to augment the extent of resection in high-grade glioma and GBM surgery [4]. Clinically, the exogenous, oral administration of 5-ALA is usually performed 4h prior to surgery.…”

“…5-ALA is resorbed through the upper intestine into the blood, where it diffuses through the blood-brain barrier, which has been typically disrupted by infiltrative tumor cells [5][6][7][8][9]. During fluorescence assisted tumor resection a variance of the fluorescence intensity within GBM can be observed, especially at the infiltrating zone [4,8,10]. 5-ALA induced fluorescence may vary upon many factors such as cell density, proliferation index, mitochondrial mass and index and furthermore exogenous factors such as application or fading during surgery [5][6][7][8].…”