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: Stereotactic needle biopsy is valuable for tissue diagnosis of suspected high-grade gliomas, but limited by a sampling error that can lead to inappropriate grading of the tumor or failure to provide diagnosis. Increasing the number of biopsy attempts can increase morbidity. The authors designed a protocol to increase safety and efficiency of the procedure. Six consecutive patients with suspected high-grade gliomas who were not candidates for cytoreductive surgery underwent fluorescein-guided stereotactic needle biopsy. All received an injection of 3 mg/kg fluorescein sodium during anesthesia induction. Samples were obtained and observed under a microscope-integrated fluorescent module. If the initial specimens were fluorescent, the procedure was complete if the pathologist confirmed diagnostic tissue. Additional specimens were obtained only at the pathologist's request. An independent neuropathologist later analyzed and graded samples for diagnostic value, tumor, and necrosis. This information was correlated to the degree of intraoperative fluorescent signal in biopsy samples. During six biopsy procedures, 26 specimens were obtained: 15 (58 %) fluorescent and 11 (42 %) nonfluorescent. All fluorescent specimens contained diagnostic tissue appropriate for tumor grading. Of 11 nonfluorescent specimens, four (36 %) did not contain tumor, three (27 %) contained minor hypercellularity or gliosis, and four (36 %) contained tumor with a high proportion of necrosis. All six tumors were diagnosed as glioblastoma multiforme. The sensitivity and specificity for fluorescein fluorescence was 79 % and 100 %, respectively. Fluorescein fluorescence may improve diagnostic accuracy and expedite stereotactic biopsy procedures.Acta Neurochirurgica 04/2014; · 1.55 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Object Subtotal resection (STR) of spinal tumors can result in tumor recurrence. Currently, no clinically reliable marker is available for intraoperative visualization of spinal tumor tissue. Protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) is capable of visualizing malignant gliomas. Fluorescence-guided resections of malignant cerebral gliomas using 5-ALA have resulted in an increased rate of complete tumor removal. Recently, the application of 5-ALA has also been described in the first cases of spinal tumors. Therefore, the aim of this observational study was to systematically investigate 5-ALA-induced fluorescence characteristics in different spinal tumor entities. Methods Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of PpIX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification. Results Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy. Conclusions In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci.Neurosurgical FOCUS 02/2014; 36(2):E11. · 2.49 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background Intraoperative blood vessel detection based on intraluminal indocyanin-green (ICG) would allow to minimize the risk of blood vessel perforation during stereotactic brain tumor biopsy. For a fiber-based approach compatible with clinical conditions, the maximum tolerable excitation light power was derived from simulations of the thermal heat load on the tissue. Methods Using the simulation software LITCIT, the temperature distribution in human brain tissue was calculated as a function of time for realistic single-fiber probes (0.72 mm active diameter, numerical aperture 0.35, optional focusing to 0.29 mm diameter) and for the optimum ICG excitation wavelength of 785 nm. The asymptotic maximum temperature in the simulated tissue region was derived for different radiant fluxes at the distal fiber end. Worst case values were assumed for all other parameters. In addition to homogeneous (normal and tumor) brain tissue with homogeneous blood perfusion, models with localized extra blood vessels incorporated ahead of the distal fiber end were investigated. Results If one demands that destruction of normal brain tissue must be excluded by limiting the tissue heating to 42 °C, then the radiant flux at the distal fiber end must be limited to 33 mW with and 43 mW without focusing. When considering extra blood vessels of 0.1 mm diameter incorporated into homogeneously perfused brain tissue, the tolerable radiant flux is reduced to 22 mW with and 32 mW without focusing. The threshold value according to legal laser safety regulations for human skin tissue is 28.5 mW. Conclusions For the envisaged modality of blood vessel detection, light power limits for an application-relevant fiber configuration were determined and found to be roughly consistent with present legal regulations for skin tissue.Photodiagnosis and photodynamic therapy 01/2014;