Beyin Tümörlerinin Sodyum Floresan Kılavuzluğunda Rezeksiyonu: 237 Hastadan Oluşan Bir Serinin Retrospektif Analizi ve Histopatolojik Tanıya Göre Yararlılığının Değerlendirilmesi

Öz

Beyin tümörlü hastaların tedavisinde cerrahi rezeksiyon en önemli prognostik faktörlerden biridir. Sodyum floresan (NaFl), beyin tümörlerinde introperatif görselleştirme için kullanılan floresan bir maddedir. Özel filtre (FL 560 nm) ile donatılmış mikroskop ışığının altında tümöral dokuda yeşil floresan renk oluşmasını sağlar. Bununla birlikte intrakranial yerleşimli her tümörde aynı oranda floresan yoğunluğu sağlayamaz. Bu çalışmada farklı histopatolojik tanılardaki beyin tümörlerinin cerrahisinde NaFl’nin floresan etkisini ve güvenliğini araştırmak amaçlanmıştır.2020-2023 yılları arasında beyin tümörü nedeniyle NaFl rehberliğinde opere edilen toplam 237 hastanın verileri retrospektif olarak incelendi. Hastaların yaşı, cinsiyeti, preoperatif ve postoperatif nörolojik muayenesi, tümör rezeksiyon derecesi, histopatolojik tanısı ve intraoperatif NaFl ile boyanma derecesi analiz edildi. Histopatolojik olarak 73 (%30.8) metastatik tümör, 68 (%28.7) glioblastoma multiforme, 41 (%17.3) menengioma, 21 (%8.9) anaplastik astrositoma, 10 (%4.2) oligodendroglioma, 6 (%2.5) pilositik astrositoma, 6 (%2.5) epidermoid tümör, 5 (%2.1) schwannoma, 3 (%1.3) lenfoma, 2 (%0.8) disembriyoplastik nöroektodermal tümör ve 2 (%0.8) ependimoma tanılı hasta mevcuttu. İntraoperatif olarak 211 (%89) hastada NaFl ile boyanma izlendi. Glioblastoma multiforme ve menengiomaların tamamında, metastatik tümörlerin %90.4’ünde NaFl boyanması gözlendi. Oligodendrogliomaların ve epidermoid tümörlerin hiçbirisinde boyanma saptanmadı (p<0.001). NaFL kullanımı, özellikle yüksek dereceli glial tümörlerde ve metastatik lezyonlarda intraoperatif olarak tümör sınırlarının belirlenmesine etkilidir. Bununla birlikte tümör histopatolojisine, uygulama dozu ve zamanına göre kullanımında sınırlamalar mevcuttur.

Anahtar Kelimeler

• Sodyum floresan
• beyin tümörü
• floresan rehberliğinde cerrahi

Sodium Fluorescence-Guided Resection of Brain Tumors: Retrospective Analysis of a Series of 237 Patients and Evaluation of its Usefulness According to Histopathologic Diagnosis

Öz

Surgical resection is one of the most important prognostic factors in the treatment of patients with brain tumors. Sodium fluorescein (NaFl) is a fluorescent agent used for intraoperative imaging in brain tumors. It produces a green fluorescent color in tumoral tissue under microscope light equipped with a special filter (FL 560 nm). However, it cannot provide the same fluorescence intensity in all intracranial tumors. In this study, we aimed to investigate the fluorescence effect of NaFl in the surgery of brain tumors with different histopathological diagnoses. Data of a total of 237 patients who underwent NaFl-guided surgery for brain tumors between 2020 and 2023 were retrospectively analyzed. Age, gender, preoperative and postoperative neurological examination, degree of tumor resection, histopathological diagnosis, and degree of intraoperative NaFl staining were analyzed. Histopathologically, 73 (30.8%) metastatic tumors, 68 (28.7%) glioblastoma multiforme, 41 (17.3%) meningioma, 21 (8.9%) anaplastic astrocytoma, 10 (4.2%) oligodendroglioma, 6 (2.5%) pilocytic astrocytoma, 6 (2.5%) epidermoid tumor, 5 (2.1%) schwannoma, 3 (1.3%) lymphoma, 2 (0.8%) dysembryoplastic neuroectodermal tumor and 2 (0.8%) ependymoma. Intraoperative NaFl staining was observed in 211 (89%) patients. NaFl staining was observed in all glioblastoma multiforme and meningiomas and in 90.4% of metastatic tumors. None of the oligodendrogliomas and epidermoid tumors showed NaFl staining (p<0.001). The use of NaFL is effective in determining tumor margins intraoperatively, especially in high-grade glial tumors and metastatic lesions. However, there are limitations in its use according to tumor histopathology, dose and time of application.

Anahtar Kelimeler

• Sodium fluorescein
• brain tumor
• fluorescence-guided surgery

Kaynakça

1. 1. Ostrom QT, Price M, Neff C et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015-2019. Neuro Oncol 2022;24:1-95. doi: 10.1093/NEUONC/NOAC202
2. 2. Byun J, Kim JH. Revisiting the role of surgical resection for brain metastasis. Brain Tumor Res Treat 2023;11:1-7 doi: 10.14791/BTRT.2022.0028
3. 3. Duffau H. Long-term outcomes after supratotal resection of diffuse low-grade gliomas: a consecutive series with 11-year follow-up. Acta Neurochir (Wien) 2016;158:51-8. doi: 10.1007/S00701-015-2621-3
4. 4. Weller M, Van den Bent M, Tonn JC et al. European association for neuro-oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 2017;18:e315-e329. doi: 10.1016/S1470-2045(17)30194-8
5. 5. Falco J, Cavallo C, Vetrano IG et al. Fluorescein application in cranial and spinal tumors enhancing at preoperative MRI and operated with a dedicated filter on the surgical microscope: Preliminary results in 279 patients enrolled in the FLUOCERTUM prospective study. Front Surg 2019;6:49. doi: 10.3389/FSURG.2019.00049
6. 6. Lacroix M, Abi-Said D, Fourney DR et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 2001;95:190-8. doi: 10.3171/JNS.2001.95.2.0190
7. 7. Li YM, Suki D, Hess K, Sawaya R. The influence of maximum safe resection of glioblastoma on survival in 1229 patients: Can we do better than gross-total resection? J Neurosurg 2016;124:977-88. doi: 10.3171/2015.5.JNS142087
8. 8. Grabowski MM, Recinos PF, Nowacki AS et al. Residual tumor volume versus extent of resection: Predictors of survival after surgery for glioblastoma. J Neurosurg 2014;121:1115-23. doi: 10.3171/2014.7.JNS132449

9. 9. Shinoda J, Yano H, Yoshimura SI et al. Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note. J Neurosurg 2003;99:597-603. doi: 10.3171/JNS.2003.99.3.0597
10. 10. Katsevman GA, Turner RC, Urhie O, Voelker JL, Bhatia S. Utility of sodium fluorescein for achieving resection targets in glioblastoma: İncreased gross- or near-total resections and prolonged survival. J Neurosurg 2019;132:914-20. doi: 10.3171/2018.10.JNS181174
11. 11. Schebesch KM, Brawanski A, Hohenberger C, Höhne J. Fluorescein sodium-guided surgery of malignant brain tumors: History, current concepts, and future projects. Turk Neurosurg 2016;26:185-94. doi: 10.5137/1019-5149.JTN.16952-16.0
12. 12. Belykh E, Bardonova L, Abramov I et al. 5-aminolevulinic acid, fluorescein sodium, and indocyanine green for glioma margin detection: Analysis of operating wide-field and confocal microscopy in glioma models of various grades. Front Oncol 2023;13:1156812. doi: 10.3389/fonc.2023.1156812
13. 13. Xue Z, Kong L, Hao S et al. Combined application of sodium fluorescein and neuronavigation techniques in the resection of brain gliomas. Front Neurol 2021;12:747072. doi: 10.3389/FNEUR.2021.747072
14. 14. Kurimoto M, Hayashi N, Kamiyama H et al. Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: A single-institution retrospective study. Minim Invasive Neurosurg 2004;47:278-83. doi: 10.1055/S-2004-830093
15. 15. Schebesch KM, Höhne J, Rosengarth K et al. Fluorescein-guided resection of newly diagnosed high-grade glioma: Impact on extent of resection and outcome. Brain & spine 2022;2:101690. doi: 10.1016/J.BAS.2022.101690
16. 16. Mazurek M, Kulesza B, Stoma F et al. Characteristics of fluorescent ıntraoperative dyes helpful in gross total resection of high-grade gliomas-a systematic review. Diagnostics (Basel) 2020;10:1100. doi: 10.3390/DIAGNOSTICS10121100
17. 17. Li Y, Rey-Dios R, Roberts DW, Valdés PA, Cohen-Gadol AA. Intraoperative fluorescence-guided resection of high-grade gliomas: a comparison of the present techniques and evolution of future strategies. World Neurosurg 2014;82:175-85. doi: 10.1016/j.wneu.2013.06.014.
18. 18. Zhang DY, Singhal S, Lee JYK. Optical principles of fluorescence-guided brain tumor surgery: a practical primer for the neurosurgeon. Neurosurgery 2019;85:312-24. doi: 10.1093/NEUROS/NYY31
19. 19. Barone DG, Lawrie TA, Hart MG. Image guided surgery for the resection of brain tumours. Cochrane Database of Systematic Reviews 2014;2014:CD009685 doi: 10.1002/14651858.CD009685.pub2
20. 20. Rey-Dios R, Cohen-Gadol AA. Technical principles and neurosurgical applications of fluorescein fluorescence using a microscope-integrated fluorescence module. Acta Neurochir (Wien) 2013;155:701-6. doi: 10.1007/S00701-013-1635-Y
21. 21. Xue Z, Kong L, Hao S et al. Combined application of sodium fluorescein and neuronavigation techniques in the resection of brain gliomas. Front Neurol 2021;12:747072 doi: 10.3389/FNEUR.2021.747072
22. 22. Schebesch KM, Brawanski A, Hohenberger C, Höhne J. Fluorescein sodium-guided surgery of malignant brain tumors: History, current concepts, and future projects. Turk Neurosurg 2016;26:185-94. doi: 10.5137/1019-5149.JTN.16952-16.0
23. 23. Xiang Y, Zhu XP, Zhao JN et al. Blood-brain barrier disruption, sodium fluorescein, and fluorescence-guided surgery of gliomas. Br J Neurosurg 2018;32:141-8. doi: 10.1080/02688697.2018.1428731
24. 24. Zhang DY, Singhal S, Lee JYK. Optical principles of fluorescence-guided brain tumor surgery: a practical primer for the neurosurgeon. Neurosurgery 2019;85:312-24. doi: 10.1093/NEUROS/NYY315
25. 25. Manoharan R, Parkinson J. Sodium fluorescein in brain tumor surgery: Assessing relative fluorescence ıntensity at tumor margins. Asian J Neurosurg 2020;15:88-93. doi: 10.4103/AJNS.AJNS_221_19
26. 26. Acerbi F, Broggi M, Schebesch KM et al. Fluorescein-guided surgery for resection of high-grade gliomas: A multicentric prospective phase ıı study (FLUOGLIO). Clin Cancer Res 2018;24:52-61. doi: 10.1158/1078-0432.CCR-17-1184
27. 27. Bowden SG, Neira JA, Gill BJA et al. Sodium fluorescein facilitates guided sampling of diagnostic tumor tissue in nonenhancing gliomas. Neurosurgery 2018;82:719-27. doi: 10.1093/NEUROS/NYX27
28. 28. Moore GE, Peyton WT. The clinical use of fluorescein in neurosurgery; The localization of brain tumors. J Neurosurg 1948;5:392-8. doi: 10.3171/JNS.1948.5.4.0392
29. 29. Acerbi F, Cavallo C, Broggi M et al. Fluorescein-guided surgery for malignant gliomas: a review. Neurosurg Rev 2014;37:547-57. doi: 10.1007/S10143-014-0546-6
30. 30. Hong J, Chen B, Yao X, Yang Y. Outcome comparisons of high-grade glioma resection with or without fluorescein sodium-guidance. Curr Probl Cancer 2019;43:236-44. doi: 10.1016/J.CURRPROBLCANCER.2018.07.007
31. 31. Bloch O, Han SJ, Cha S et al. Impact of extent of resection for recurrent glioblastoma on overall survival: Clinical article. J Neurosurg. 2012;117:1032-8. doi: 10.3171/2012.9.JNS12504
32. 32. Cramer AL, Green KM, Würgler HR et al. Effect of 5-aminolevulinic acid and sodium fluorescein on the extent of resection in high-grade gliomas and brain metastasis. Cancers (Basel) 2022;14:617. doi: 10.3390/CANCERS14030617
33. 33. Schebesch KM, Hoehne J, Hohenberger C et al. Fluorescein sodium-guided surgery in cerebral lymphoma. Clin Neurol Neurosurg 2015;139:125-8. doi: 10.1016/J.CLINEURO.2015.09.015
34. 34.Da Silv CE, Da Silva VD, Da Silva JLB. Convexitymeningiomas enhanced by sodium fluorescein. Surg Neurol Int2014;5:3. doi: 10.4103/2152-7806.124978
35. 35.Cheng X, Chen J, Tang R, et al. Sodium fluorescein-guided surgery for resection of brain metastases from lung cancer: A consecutive case series study and literature review. Cancers (Basel) 2023;15:882. doi: 10.3390/cancers15030882
36. 36.Belykh E, Onaka NR, Zhao X et al. High-dose fluorescein reveals unusual confocal endomicroscope ımaging of low-grade glioma. Front Neurol 2021;12:668656. doi: 10.3389/FNEUR.2021.668656
37. 37.Schupper AJ, Rao M, Mohammadi N et al. Fluorescence-guided surgery: A review on timing and use in brain tumor surgery. Front Neurol 2021;12: 682151. doi: 10.3389/FNEUR.2021.682151
38. 38.Molina ES, Stummer W. Where and when to cut? Fluoresceinguidance for brain stem and spinal cord tumor surgery-technical note. Operative Neurosurgery. 2018;15:325-31. doi: 10.1093/ons/opx269
39. 39.Xu K, Tzankova V, Li C, Sharma S. Intravenous fluorescein angiography-associated adverse reactions. Can J Ophthalmol 2016;51:321-5. doi: 10.1016/J.JCJO.2016.03.015
40. 40.Dilek O, Ihsan A, Tulay H. Anaphylactic reaction afterfluorescein sodium administration during intracranial surgery. JClin Neurosci 2011;18:430-1. doi: 10.1016/J.JOCN.2010.06.012