Dear Sir,
I appreciate the opportunity for commenting on a Letter by Acerbi and coworkers concerning our past submission (http://link.springer.com/article/10.1007%2Fs00701-015-2471-z).
Fluorescein is being investigated for fluorescence-guided resections of brain metastasis and gliomas [1–3].
Eager to exploit the new potential of this application, our group is also exploring fluorescein, and has been exploring it for a while. However, in our hands we are having continuing problems using this method and are simply not observing the selectivity that we would desire.
In our experience with metastases (Fig. 1) and malignant gliomas (Supplementary Video), significant fluorescein fluorescence is found after resection at the margins in obviously normal and perifocal edematous brain tissue despite all efforts to follow the guidance of Dr. Acerbi and coworkers using low doses (4 mg/kg) given with induction of anesthesia and performing surgery with the Zeiss Yellow 560 filter system. This confounds applicability.
We find this worrisome. Our differing vantage points have obviously now generated a very lively discussion. Dr. Acerbi et al. feel (wrongly) accused, with accusations certainly not having been my intention. I highly respect their efforts to improve the surgical management of brain tumor patients. Nevertheless, I do critically reiterate that I believe the use of fluorescein outside of studies to be premature and requiring further investigation in a complex field in which histology, timing, dose, illumination, tissue perfusion, and edema play a role, with a marker of blood–brain barrier integrity that offers a tissue signal that is not simply binary. Others are critical as well [4, 5]. Dr. Acerbi et al. are thankfully involved in such studies and others and I are awaiting their results.
Sincerely,
Walter Stummer
References
Acerbi F, Broggi M, Eoli M, Anghileri E, Cavallo C, Boffano C, Cordella R, Cuppini L, Pollo B, Schiariti M, Visintini S, Orsi C, La Corte E, Broggi G, Ferroli P (2014) Is fluorescein-guided technique able to help in resection of high-grade gliomas? Neurosurg Focus 36:E5
Acerbi F, Broggi M, Eoli M, Anghileri E, Cuppini L, Pollo B, Schiariti M, Visintini S, Ori C, Franzini A, Broggi G, Ferroli P (2013) Fluorescein-guided surgery for grade IV gliomas with a dedicated filter on the surgical microscope: preliminary results in 12 cases. Acta Neurochir (Wien) 155:1277–1286
Schebesch KM, Hoehne J, Hohenberger C, Proescholdt M, Riemenschneider MJ, Wendl C, Brawanski A (2015) Fluorescein sodium-guided resection of cerebral metastases—experience with the first 30 patients. Acta Neurochir (Wien) 157:899–904
Diez Valle R, Tejada Solis S (2013) Answer to: sodium fluorescein-guided resection under the YELLOW 560-nm surgical microscope filter in malignant brain tumor surgery—a feasibility study. Acta Neurochir (Wien) 155:1319–1320
Stockhammer F (2013) What does fluorescence depict in glioma surgery? Acta Neurochir (Wien) 155:1479–1480
Conflict of interest
Walter Stummer has received consultant fees from medac, Wedel, and speaker’s fees from Carl Zeiss Meditech, Oberkochen, Germany.
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Video
Glioblastoma surgery using fluorescein (4 mg/kg, given with induction of anesthesia, Zeiss Yellow 560 filter) after tumor debulking. Again, there is unclear fluorescence at the resection margins and in the cortex which is outside the region defined as tumor on the MRI. (M4V 57600 kb)
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Stummer, W. Fluorescein in brain metastasis and glioma surgery. Acta Neurochir 157, 2199–2200 (2015). https://doi.org/10.1007/s00701-015-2576-4
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DOI: https://doi.org/10.1007/s00701-015-2576-4