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Safely maximizing extent of resection has become the central goal in glioma surgery. Especially in eloquent cortex, the goal of maximal resection is balanced with neurological risk. As new technologies emerge in the field of neurosurgery, the standards for maximal safe resection have been elevated. Fluorescence-guided surgery, intraoperative magnetic resonance imaging, and microscopic imaging methods are among the most well-validated tools available to enhance the level of accuracy and safety in glioma surgery. Each technology uses a different characteristic of glioma tissue to identify and differentiate tumor tissue from normal brain and is most effective in the context of anatomic, connectomic, and neurophysiologic context. While each tool is able to enhance resection, multiple modalities are often used in conjunction to achieve maximal safe resection. This paper reviews the mechanism and utility of the major adjuncts available for use in glioma surgery, especially in tumors within eloquent areas, and puts forth the foundation for a unified approach to how leverage currently available technology to ensure maximal safe resection., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Introduction: Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells., Materials/methods: A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs)., Results: PDT has been approved by the United States Food and Drug Administration (FDA) for the treatment of premalignant and malignant diseases, such as actinic keratoses, Barrett's esophagus, esophageal cancers, and endobronchial non-small cell lung cancers, as well as for the treatment of choroidal neovascularization. In neuro-oncology, clinical trials are currently underway to demonstrate PDT efficacy against a number of malignancies that include HGGs and other brain tumors. Both photosensitizers and photosensitizing precursors have been used for PDT. 5-aminolevulinic acid (5-ALA), an intermediate in the heme synthesis pathway, is a photosensitizing precursor with FDA approval for PDT of actinic keratosis and as an intraoperative imaging agent for fluorescence-guided visualization of malignant tissue during glioma surgery. New trials are underway to utilize 5-ALA as a therapeutic agent for PDT of the intraoperative resection cavity and interstitial PDT for inoperable HGGs., Conclusion: PDT remains a promising therapeutic approach that requires further study in HGGs. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies.

5-aminolevulinic acid (5-ALA) is a prodrug that results in the fluorescence of high-grade gliomas relative to the surrounding brain parenchyma. 5-ALA has been increasingly utilized in fluorescence-guided surgery for these tumors, and its intraoperative use has been associated with a significantly improved extent of resection and progression-free survival. This review outlines the growing body of evidence that has culminated in the recent Food and Drug Administration approval of 5-ALA, as well as emerging applications for this agent., (© 2018 Wiley Periodicals, Inc.)

5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to "5-ALA" and "high-grade gliomas." Included studies were based on adults aged ≥18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469-78. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Objective: With the use of fluorescence-guided resection with 5-aminolevulinic acid (5-ALA), the rate of complete resection of the contrast-enhancing part of malignant gliomas could be increased from 36% to 65%. Because the visualization of 5-ALA-induced fluorescence depends on a sufficient exposure to fluorescent light, residual tumor tissue in deep-seated resection cavities might not be detected. In addition, subcortical parts of a large spherical tumor might not be visualized, owing to a tangential position at the periphery of the microscopic field. With the availability of a specially designed endoscope with the capability to visualize 5-ALA fluorescence, we investigated the impact of this new technique on the visualization of residual glioma tissue., Methods: A standard dose of 5-ALA 20 mg/kg was administered to 9 patients with deep-seated contrast-enhancing brain tumors 3 hours before surgery. A standard surgical exposure was performed and supplemented by the use of a specially designed endoscope with an option of 5-ALA fluorescence guidance. After microscopic visualization of the surgical cavity, endoscopic visualization was employed. If additional fluorescence tissue was detected, microscopic visualization was performed. Detected remnants of the tumor were removed and evaluated by histologic examination., Results: In all cases, fluorescence-guided endoscopic visualization identified 5-ALA-positive tissue not sufficiently exposed by conventional microscopic visualization. In 8 patients, histopathologic examination confirmed residual tumor tissue; in 1 patient, the endoscopic visualized tissue was classified as radiation necrosis. In this patient, the tumor was completely ALA negative microscopically., Conclusions: As an additional instrument, fluorescence-guided endoscopic visualization might help to overcome technical limitations of the conventional microscopic exposure of 5-ALA-positive tumor tissue. The false-positive 5-ALA tissue indicates that endoscopic visualization may overestimate the amount of tumor, so further analyses to ascertain the sensitivity and specificity of this technique are required., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Stereotactic photodynamic therapy (sPDT) using 5-aminolaevulinic acid (5-ALA) as a cytotoxic photosensitizer may be a potentially prospective treatment option for malignant gliomas. Material and Methods: We analyzed data from 10 patients with recurrent malignant gliomas of the brain who were treated with sPDT at the Department of Neurosurgery of the Military-Medical Academy S. M. Kirov, from 2020 to November 2021. Three patients were treated with sPDT again after 3, 7, and 15 months due to relapse. Results: The median age of the patients was 55.5 years, range was 30--60 years, there were six men and four women. At the time of sPDT, 7 (70%) patients with recurrent tumors were diagnosed with glioblastomas (WHO grade IV), and 3 (30%) with anaplastic astrocytomas (WHO grade III). Tumors were without IDH mutation in 7 (70%) patients; MGMT gene expression status was evaluated in tumors in 9 (90%) patients. A 1p/19q co-deletion was not detected in any of the patients. The median tumor volume was 5.85 cm3 (min. 3.2 cm3, max. 22.5 cm3). We have found that the median recurrence-free period after sPDT in patients with anaplastic astrocytomas and glioblastomas was 435 and 195 days, respectively. Conclusion: This result allows to consider sPDT as one of the perspective methods of treatment of patients with recurrent gliomas of high malignancy in cases when repeated open surgical intervention has high risks of new neurological deficit. [ABSTRACT FROM AUTHOR]

In patients operated for malignant glioma, 5-aminolevulinic acid (5-ALA)-induced fluorescence guidance is useful. However, we occasionally experience instances of non-visible fluorescence despite a histopathological diagnosis of high-grade glioma. We sought to identify factors that influence the intraoperative visualization of gliomas by their 5-ALA-induced fluorescence.

Background. In patients operated for malignant glioma, 5-aminolevulinic acid (5-ALA)-induced fluorescence guidance is useful. However, we occasionally experience instances of non-visible fluorescence despite a histopathological diagnosis of high-grade glioma. We sought to identify factors that influence the intraoperative visualization of gliomas by their 5-ALA-induced fluorescence. Patients and methods. We reviewed data from 60 patients with astrocytic or oligodendroglial tumors who underwent tumor removal under 5-ALA-induced fluorescence guidance between January 2014 and December 2015. Their characteristics, preoperative magnetic resonance imaging (MRI) findings, histological diagnosis, and genetic profile were analyzed and univariate and multivariate statistical analyses were performed. Results. In 42 patients (70%) we intraoperatively observed tumor 5-ALA fluorescence. They were 2 of 8 (25%) patients with World Health Organization (WHO) grade II, 9 of 17 (53%) with grade III, and 31 of 35 (89%) patients with grade IV gliomas. Univariate analysis revealed a statistically significant association between 5-ALA fluorescence and the isocitrate dehydrogenase 1 (IDH1) status, 1p19q loss of heterozygosity (LOH), the MIB-1 labeling index, and the tumor margin, -heterogeneity, and -contrast enhancement on MRI scans (p < 0.001, p = 0.003, p = 0.007, p = 0.046, p = 0.021, and p = 0.002, respectively). Multivariate analysis showed that the IDH1 status was the only independent, statistically significant factor related to 5-ALA fluorescence (p = 0.009). Conclusions. This study identified the IDH1 status as the factor with the most influence on the 5-ALA fluorescence of diffuse gliomas. [ABSTRACT FROM AUTHOR]