5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma

Valdés, Pablo; Bekelis, Kimon; Harris, Brent T.; Wilson, Brian C.; Leblond, Frédéric; Kim, Anthony; Simmons, Nathan E.; Erkmen, Kadir; Paulsen, Keith D.; Roberts, David W.

doi:10.1227/neu.0000000000000117

Cited by 65 publications

(92 citation statements)

References 58 publications

(95 reference statements)

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“…A recent study of 15 patients reported 5-ALA positivity for 80% of meningioma cases. 43 The overall high rate of 5-ALA positivity suggests that 5-ALA could be a useful surgical adjunct, especially in the presence of ill-defined tumor margins (bone, dura, and brain parenchyma invasion), which is seen with some high-grade meningiomas. 26 …”

Section: -Ala Fluorescence In Meningiomasmentioning

confidence: 99%

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Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Marbacher

Klinger

Schwyzer

et al. 2014

FOC

137

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Object The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

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Section: -Ala Fluorescence In Meningiomasmentioning

confidence: 99%

“…5,43,45 More recently, a retrospective study of 52 patients demonstrated that 62% of brain metastases were positive for intraoperative 5-ALA fluorescence. 20 Preliminary reports indicate that 5-ALA fluorescence increases the safety and accuracy of stereotactic and endoscopic brain biopsy procedures.…”

mentioning

confidence: 99%

Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Marbacher

Klinger

Schwyzer

et al. 2014

FOC

137

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“…Therefore, spectroscopic probes for quantitative assessment of PpIX fluorescence were introduced for neurosurgical procedures. 8,40,41 With the use of such spectroscopic probes, small residual fluorescing foci can be more objectively identified. Furthermore, small amounts of PpIX accumulation were detected even in macroscopically nonfluorescing tumors.…”

Section: Future Directionsmentioning

confidence: 99%

Analysis of 5-aminolevulinic acid–induced fluorescence in 55 different spinal tumors

Millesi

Kiesel

Wöehrer

et al. 2014

FOC

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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.

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“…At the same time, no statistically significant effect on the overall survival rate was identified. Nevertheless, this technology has attracted an increased attention of neurosurgeons resulting in more reports on FN, as well as the application of this method for other central nervous system tumors [4,[7][8][9][10][11][12][13][14][15][16] including intracranial meningiomas [16][17][18][19][20]. However, the assessment of FN's sensitivity and specificity was not demonstrated clearly and in particular, no comparison was made between the data obtained from visible fluorescence, and the data obtained from laser biospectroscopy in meningiomas of different World Health Organization (WHO) grades.…”

Section: Introductionmentioning

confidence: 99%

Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection

et al. 2016

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5-aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PP IX), which possesses fluorescent properties and is more intensively accumulated in tumor cells than in normal tissue. Therefore, the use of 5-ALA in the surgical treatment of intracranial tumors, particularly gliomas, has gained popularity in the last years, whereas its use in other intracranial pathological entities including meningiomas has been reported occasionally. This study describes a series of 28 patients with intracranial meningiomas, who were administered 5-ALA for a better visualization of tumor boundaries. Twelve patients underwent also laser spectroscopic analysis in order to confirm the visual impression of tumor tissue visualization. Bone infiltration was readily demonstrated. In one case, the tumor recurrence could have been prevented by removal of a tumor remnant, which would possibly have been better recognized if spectroscopic analysis had been used. Fluorescent navigation (FN) is a useful method for maximizing the radicality of meningioma surgery, particularly if the tumor infiltrates the bone, the skull base, and/or the surrounding structures

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5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma

Cited by 65 publications

References 58 publications

Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Analysis of 5-aminolevulinic acid–induced fluorescence in 55 different spinal tumors

Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection

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