TO THE EDITOR: We read with great interest the article by Hansen et al.3 (Hansen RW, Pedersen CB, Halle B, et al: Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study. J Neurosurg [epub ahead of print October 4, 2019. DOI: 10.3171/2019.6.JNS191531]). Their retrospective study compares 5-aminolevulinic acid (5-ALA) with sodium fluorescein in the resection of high-grade gliomas (HGGs), showing a comparable extent of resection with the two agents. The authors concluded that fluorescein is a viable alternative to 5-ALA, a conclusion that harbors an important economic impact since fluorescein is inexpensive compared to 5-ALA. The authors admit that the patients were not randomly assigned; instead, there was a departmental shift from 5-ALA to fluorescein because of the cost-effectiveness of the latter. For the same reason, we have shifted from 5-ALA to fluorescein over the years in our department. We were glad to read the results of this study given our aim of always improving the quality of care of our patients; however, caution must be exercised in the data interpretation. One randomized controlled trial showed that 5-ALA in HGG increases the extent of resection and overall survival by optimizing visualization and thus the completeness of tumor resection through the agent’s accumulation in the tumor cells.4 The use of 5-ALA may be synergistic with other strategies.1 Several studies, but none with level I evidence, have indicated the utility of sodium fluorescein in HGG surgery. Fluorescein extravagates in the absence of the blood-brain barrier and accumulates in the tumor via a mechanism similar to gadolinium contrast on MRI. 5-ALA detects tumor cells outside the contrast-enhancing layer on MRI.2 In our experience, fluorescein is also present outside the contrast-enhancing lesion on MRI, but because of the edema, and thus is not entirely reliable.
The cost-effectiveness message about fluorescein is important; however, as the authors suggest, studies with level I evidence are needed.
Disclosures
The authors report no conflict of interest.
References
- 1↑
Della Puppa A, Lombardi G, Rossetto M, Rustemi O, Berti F, Cecchin D, : Outcome of patients affected by newly diagnosed glioblastoma undergoing surgery assisted by 5-aminolevulinic acid guided resection followed by BCNU wafers implantation: a 3-year follow-up. J Neurooncol 131:331–340, 2017
- 2↑
Della Puppa A, Rustemi O, Rampazzo E, Persano L: Combining 5-aminolevulinic acid fluorescence and intraoperative magnetic resonance imaging in glioblastoma surgery: a histology-based evaluation. Neurosurgery 80:E188–E190, 2017 (Letter)
- 3↑
Hansen RW, Pedersen CB, Halle B, Korshoej AR, Schulz MK, Kristensen BW, : Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study. J Neurosurg [epub ahead of print October 4, 2019. DOI: 10.3171/2019.6.JNS191531]
- 4↑
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401, 2006
