Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies.
ABSTRACT Stereotactic biopsies represent a routine neurosurgical procedure for the diagnosis of intracranial lymphomas and selected diffusely infiltrating gliomas. Acquisition of tissue samples that do not allow correct tumor typing and grading is, however, not uncommon. Five-aminolevulinic acid (5-ALA) has been shown to accumulate in malignant tumor tissue. The aim of this study was to prospectively investigate the clinical usability of 5-ALA for intraoperative detection of representative tissue in stereotactic tumor biopsies. Fifty consecutive patients underwent frameless stereotactic biopsy for a suspected brain tumor. 5-ALA was administered 4 h before anesthesia. Serial biopsy samples were obtained and intraoperatively checked for 5-ALA fluorescence (strong, vague, or none) using a modified neurosurgical microscope. All samples were examined for the presence of representative tumor tissue according to neuroimaging (MRI, positron emission tomography, and/or chemical shift imaging) and histopathological parameters. Visible 5-ALA fluorescence was observed in 43/50 patients (strong in 39 and vague fluorescence in four cases). At biopsy target, 52/53 samples of glioblastomas, 9/10 samples of gliomas grade III, and 14/16 samples of lymphomas revealed strong 5-ALA fluorescence. Samples with strong 5-ALA fluorescence were only observed at, but not outside the biopsy target. All tissue samples with strong 5-ALA fluorescence were representative according to our neuroimaging and histopathological criteria (positive predictive value of 100%). Our data indicate that strong 5-ALA fluorescence is a reliable and immediately available intraoperative marker of representative tumor tissue of malignant gliomas and intracranial lymphomas in stereotactic biopsies. Thereby, the application of 5-ALA in stereotactic brain tumor biopsies may in future reduce costs for operating room and neuropathology and may decrease procedure-related morbidity.
- [Show abstract] [Hide abstract]
ABSTRACT: Object: Glioblastoma is a highly malignant brain tumor, for which standard treatment consists of surgery, radiotherapy, and chemotherapy. Increasing extent of tumor resection (EOTR) is associated with prolonged survival. Intraoperative magnetic resonance imaging (iMRI) is used to increase EOTR, based on contrast enhanced MR images. The correlation between intraoperative contrast enhancement and tumor has not been studied systematically. Methods: For this prospective cohort study, we recruited 10 patients with a supratentorial brain tumor suspect for a glioblastoma. After initial resection, a 0.15 Tesla iMRI scan was made and neuronavigation-guided biopsies were taken from the border of the resection cavity. Scores for gadolinium-based contrast enhancement on iMRI and for tissue characteristics in histological slides of the biopsies were used to calculate correlations (expressed in Kendall's tau). Results: A total of 39 biopsy samples was available for further analysis. Contrast enhancement was significantly correlated with World Health Organization (WHO) grade (tau 0.50), vascular changes (tau 0.53), necrosis (tau 0.49), and increased cellularity (tau 0.26). Specificity of enhancement patterns scored as “thick linear” and “tumor-like” for detection of (high grade) tumor was 1, but decreased to circa 0.75 if “thin linear” enhancement was included. Sensitivity for both enhancement patterns varied around 0.39-0.48 and 0.61-0.70, respectively. Conclusions: Presence of intraoperative contrast enhancement is a good predictor for presence of tumor, but absence of contrast enhancement is a bad predictor for absence of tumor. The use of gadolinium-based contrast enhancement on iMRI to maximize glioblastoma resection should be evaluated against other methods to increase resection, like new contrast agents, other imaging modalities, and “functional neurooncology” – an approach to achieve surgical resection guided by functional rather than oncological-anatomical boundaries.Surgical Neurology International 12/2012; 3:158. DOI:10.4103/2152-7806.105097 · 1.18 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Introduction: Malignant gliomas remain one of medicine's most daunting unsolved clinical problems. The development of new technologies is urgently needed to improve the poor prognosis of patients suffering from these brain tumors. Magnetic nanomaterials are appealing due to unique properties that allow for noninvasive brain tumor diagnostics and therapeutics in one multifunctional platform. Areas covered: We report on the recent advances of magnetic nanomaterials for brain tumor imaging and therapy, with an emphasis on novel approaches and clinical progress. We detail their biomedical applications including brain tumor targeting, MRI contrast enhancement, optical imaging, magnetic hyperthermia, magnetomechanical destruction, drug delivery, gene therapy, as well as tracking of cell-based and viral-based therapies. The clinical cases and obstacles encountered in the use of magnetic nanomaterials for malignant glioma are also examined. Expert opinion: To accelerate the effective translation of these materials to the clinic as theranostics for brain tumors, limitations such as poor intratumoral distribution, targeting efficiency and nonspecific systemic side effects must be addressed. Future innovations should focus on optimizing and combining the unique therapeutic applications of these magnetic nanomaterials as well as improving the selectivity of the system based on the molecular profiling of tumors.Expert Opinion on Drug Delivery 06/2014; 11(6). DOI:10.1517/17425247.2014.912629 · 4.12 Impact Factor