Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain tumors in children—a technical report

Beez, Thomas; Sarikaya-Seiwert, Sevgi; Steiger, Hans‐Jakob; Hänggi, Daniel

doi:10.1007/s00701-014-1997-9

Cited by 47 publications

(42 citation statements)

References 33 publications

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“…It was noted that some children displayed up to a 3-fold increase in transaminases [5]. This is a well-known phenomenon in adults receiving 5ALA, and it gradually decreases over the course of a few days.…”

Section: Discussionmentioning

confidence: 97%

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5ALA in pediatric brain tumors is not routinely beneficial

Roth

Constantini

2017

Childs Nerv Syst

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5ALA showed a low rate of fluorescence amongst this pediatric brain tumor cohort. These findings are consistent with the literature, where the role of 5ALA in guidance of pediatric brain tumor resection is limited mainly to glioblastoma multiforme. This stems not only from the low rate of significant fluorescence, but also from inherent structural properties of these lesions such as color, consistency, and invasion.

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Section: Discussionmentioning

confidence: 97%

“…To date, 120 cases applying 5ALA in pediatric brain tumors have been published (Table 1) [4][5][6][7][8][9][10][11][12]. Most publications have included only a handful of cases.…”

Section: Literature Reviewmentioning

confidence: 97%

5ALA in pediatric brain tumors is not routinely beneficial

Roth

Constantini

2017

Childs Nerv Syst

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“…1,7,10,11,13,15,17,20,29,30,34,35,41,47,49,52 However, the vast majority of clinical studies on fluorescence-guided neurosurgery have only considered the qualitative, visible PpIX emissions. In these investigations, a surgical microscope modified for fluorescence imaging is typically deployed and provides a violet-blue light excitation mode (λ = 405 nm) with fluorescence collection via a long-pass filter (λ = 450–720 nm).…”

mentioning

confidence: 99%

Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

Valdés

Jacobs

Harris

et al. 2015

JNS

147

137

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OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were detected quantitatively. CONCLUSIONS The authors’ initial experience with ALA-induced PpIX fluorescence in LGGs concurs with other literature reports that the resulting visual fluorescence has poor diagnostic accuracy. However, the authors also found that diagnostically significant levels of CPpIX do accumulate in LGGs, and the resulting fluorescence emissions are very often below the detection threshold of current visual fluorescence imaging methods. Indeed, at least in the authors’ initial experience reported here, if quantitative detection methods are deployed, the diagnostic performance of ALA-induced PpIX fluorescence in LGGs approaches the accuracy associated with visual fluorescence in HGGs.

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“…Recent studies have also begun extending the technique to the pediatric population for microsurgical resection of highly invasive tumors such as medulloblastoma (Beez et al, 2014;Preuß et al, 2013). Initial results suggest administration of 5-ALA generates fluorescence in anaplastic astrocytoma, glioblastoma, medulloblastoma, and anaplastic ependymoma comparable to the adult population (Beez et al, 2014). However, while fluorescence-guided intracranial surgery has become well established, research on its benefits to spinal pathologies has been limited.…”

Section: Figurementioning

confidence: 97%

“…As a result of these extensive preliminary findings, fluorescence-guided resection is increasingly practiced as a surgical adjunct for treatment of adult gliomas in Europe. Recent studies have also begun extending the technique to the pediatric population for microsurgical resection of highly invasive tumors such as medulloblastoma (Beez et al, 2014;Preuß et al, 2013). Initial results suggest administration of 5-ALA generates fluorescence in anaplastic astrocytoma, glioblastoma, medulloblastoma, and anaplastic ependymoma comparable to the adult population (Beez et al, 2014).…”

Section: Figurementioning

confidence: 98%