Fluorescein sodium in brain tumor surgery – Response

Abstract

Dear Editor, We would like to thank Florian Stockhammer [10] and Ricardo Diez Valle [3] for their comments on our manuscript, "Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery – a feasibility study" [9]. Because of the similarity of Diez Valle’s and Stockhammer’s criticism of our scientific approach, we take the liberty of addressing their comments in one single response: Our study─ in terms of an off-label use (ethic vote 12-1010215) ─ exclusively dealt with the subject of the technical feasibility of intraoperative fluorescence due to the injection of fluorescein sodium and the application of the newly developed surgical microscope filter YELLOW 560 nm in malignant intracranial tumors. To illustrate the surgeon’s subjective assessment of the fluorescent effect, we deliberately chose the termini "helpful" and "not helpful", because we explicitly wanted to avoid the impression that the evaluation of the fluorescent effect in the tumor area was validated to a referencing scale─a method recommended by Diez Valle. We purposely did not present any detailed assessment protocol of, for instance, possible side effects of fluorescein sodium, because this dye has already been used in even higher doses in ophthalmic surgery for some 40 years [6]. Such analyses maybe the goal of phase-II trials, but not of a feasibility study. Furthermore, we believe that the side effects of 5aminolevulinic acid (5-ALA) is common knowledge to the addressed audience. In contrast to Stockhammer’s statement, the fact that fluorescein sodium can be intraoperatively injected "on the fly" should be seen as an advantage. This type of application schedule guarantees flexibility during a surgical procedure which is not the case when using 5-ALA. Stockhammer has questioned the resection of contrastenhanced mass in MRI in the surgical removal of high-grade gliomas. He indicated that metabolic depiction using amino acid positron emission tomography (PET) imaging is the more feasible approach. The papers cited in the article to support this statement indicate that O-(2-[18F]Fluoroethyl)-L-tyrosine (FET )PET can be useful for the detection of anaplastic foci within gliomas, and that 5-ALA uptake correlated to PET findings. To our best knowledge, resection of the contrast enhancing mass [T1-weighted, contrast enhanced magnetic resonance imaging (MRI)] still is the benchmark for the resection of glioblastomas (GBM) [2]. It has not been established yet that PET-guided surgery has added any clinical benefit to GBM patients. In contrast, a recent study has shown that ALA-uptake exceeded the area of tracer uptake in amino acid PET [7]. A recent review article by Orringer et al. [5] is still based on MRI imaging for the analysis of radiographically determined extent of resection (EOR). Whether amino acid PETcan be pronounced as new gold standard for the resection of malignant gliomas still remains an open question. The major critique byDiez Valle and Stockhammer referred to the EOR. We would like to address this issue in detail: