Quantitative and qualitative 5-aminolevulinic acid–induced protoporphyrin IX fluorescence in skull base meningiomas

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

doi:10.3171/2011.2.focus1112

Cited by 62 publications

(53 citation statements)

References 29 publications

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“…1,5,7,26,27 In our series, 77% (n = 85/110) of meningiomas were 5-ALA fluorescence positive. In our previous series, 94% of 33 consecutive cases of meningioma demonstrated visible fluorescence.…”

Section: -Ala Fluorescence In Meningiomasmentioning

confidence: 95%

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

Marbacher

Klinger

Schwyzer

et al. 2014

FOC

141

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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: 95%

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

Marbacher

Klinger

Schwyzer

et al. 2014

FOC

141

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“…Therefore, this method may be very useful for surgery in Table 2 Linear correlation between the video fluorescence visually perception and spectroscopic fluorescence recurrence meningioma [19], skull base meningiomas [8], and spinal meningiomas [11].…”

Section: Discussionmentioning

confidence: 99%

“…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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“…approach, particularly (but not exclusively) for low-grade tumors. 4,10,14,27,[39][40][41] Studies designed to identify mechanisms of false-positive and false-negative results have shown effects from differences in the levels of tumor cell metabolism, intraoperative microscope sensitivity, 5-ALA uptake, 5-ALA metabolism (resulting from intrinsic molecular characteristics of the tumor and/or interactions with other therapies), diffusion of protoporphyrin IX, and other factors. 4,8,16,23,27,29,36,[40][41][42] Despite these caveats, the improved patient outcomes reported after use of 5-ALA underscore the utility of tumor markers that can be used intraoperatively to improve tumor cell identification and facilitate more complete resections.…”

mentioning

confidence: 99%

In vivo visualization of GL261-luc2 mouse glioma cells by use of Alexa Fluor–labeled TRP-2 antibodies

Fenton¹,

Martirosyan²,

Abdelwahab³

et al. 2014

FOC

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Object For patients with glioblastoma multiforme, median survival time is approximately 14 months. Longer progression-free and overall survival times correlate with gross-total resection of tumor. The ability to identify tumor cells intraoperatively could result in an increased percentage of tumor resected and thus increased patient survival times. Available labeling methods rely on metabolic activity of tumor cells; thus, they are more robust in high-grade tumors, and their utility in low-grade tumors and metastatic tumors is not clear. The authors demonstrate intraoperative identification of tumor cells by using labeled tumor-specific antibodies. Methods GL261 mouse glioma cells exhibit high expression of a membrane-bound protein called second tyrosinase-related protein (TRP-2). The authors used these cells to establish an intracranial, immunocompetent model of malignant glioma. Antibodies to TRP-2 were labeled by using Alexa Fluor 488 fluorescent dye and injected into the tail vein of albino C57BL/6 mice. After 24 hours, a craniotomy was performed and the tissue was examined in vivo by using an Optiscan 5.1 handheld portable confocal fiber-optic microscope. Tissue was examined ex vivo by using a Pascal 5 scanning confocal microscope. Results Labeled tumor cells were visible in vivo and ex vivo under the respective microscopes. Conclusions Fluorescently labeled tumor-specific antibodies are capable of binding and identifying tumor cells in vivo, accurately and specifically. The development of labeled markers for the identification of brain tumors will facilitate the use of intraoperative fluorescence microscopy as a tool for increasing the extent of resection of a broad variety of intracranial tumors.

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Quantitative and qualitative 5-aminolevulinic acid–induced protoporphyrin IX fluorescence in skull base meningiomas

Cited by 62 publications

References 29 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

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

In vivo visualization of GL261-luc2 mouse glioma cells by use of Alexa Fluor–labeled TRP-2 antibodies

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