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Fluorescence-guided resection of intradural spinal tumors: a systematic review and meta-analysis

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Abstract

Intradural spinal tumors present significant challenges due to involvement of critical motor and sensory tracts. Achieving maximal resection while preserving functional tissue is therefore crucial. Fluorescence-guided surgery aims to improve resection accuracy and is well studied for brain tumors, but its efficacy has not been fully assessed for spinal tumors. This meta-analysis aims to delineate the efficacy of fluorescence guidance in intradural spinal tumor resection. The authors performed a systematic review in four databases. We included studies that have utilized fluorescence agents, 5-aminolevulinic acid (5-ALA) or sodium fluorescein, for the resection of intradural spinal tumors. A meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 12 studies involving 552 patients undergoing fluorescence-guided intradural spinal tumor resection were included. Meningiomas demonstrated a 98% fluorescence rate and were associated with a homogenous florescence pattern; however, astrocytomas had variable fluorescence rate with pooled proportion of 70%. There was no significant difference in gross total resection (GTR) rates between fluorescein and 5-ALA (94% vs 84%, p = .22). Pre-operative contrast enhancement was significantly associated with intraoperative fluorescence with fluorescein. Intramedullary tumors with positive intraoperative fluorescence were significantly associated with higher GTR rates (96% vs 73%, p = .03). Utilizing fluorescence guidance during intradural spinal tumor resection holds promise of improving intraoperative visualization for specific intradural spinal tumors. Meningiomas and ependymomas have the highest fluorescence rates especially with sodium fluorescein; on the other hand, astrocytomas have variable fluorescence rates with no superiority of either agent. Positive fluorescence of intramedullary tumors is associated with a higher degree of resection.

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Data and materials used in this systematic review are available upon request.

References

  1. Garcés-Ambrossi GL, McGirt MJ, Mehta VA et al (2009) Factors associated with progression-free survival and long-term neurological outcome after resection of intramedullary spinal cord tumors: analysis of 101 consecutive cases. J Neurosurg Spine 11:591–599. https://doi.org/10.3171/2009.4.SPINE08159

    Article  PubMed  Google Scholar 

  2. Wostrack M, Ringel F, Eicker SO et al (2018) Spinal ependymoma in adults: a multicenter investigation of surgical outcome and progression-free survival. J Neurosurg Spine 28:654–662. https://doi.org/10.3171/2017.9.SPINE17494

    Article  PubMed  Google Scholar 

  3. Tarapore PE, Modera P, Naujokas A et al (2013) Pathology of spinal ependymomas: an institutional experience over 25 years in 134 patients. Neurosurgery 73:247–255. https://doi.org/10.1227/01.neu.0000430764.02973.78

    Article  PubMed  Google Scholar 

  4. Acerbi F, Broggi M, Eoli M et al (2014) Is fluorescein-guided technique able to help in resection of high-grade gliomas? Neurosurg Focus 36:E5. https://doi.org/10.3171/2013.11.FOCUS13487

    Article  PubMed  Google Scholar 

  5. Acerbi F, Broggi M, Schebesch K-M et al (2018) Fluorescein-guided surgery for resection of high-grade gliomas: a multicentric prospective phase II study (FLUOGLIO). Clin Cancer Res Off J Am Assoc Cancer Res 24:52–61. https://doi.org/10.1158/1078-0432.CCR-17-1184

    Article  Google Scholar 

  6. Bowden SG, Neira JA, Gill BJA et al (2018) Sodium fluorescein facilitates guided sampling of diagnostic tumor tissue in nonenhancing gliomas. Neurosurgery 82:719. https://doi.org/10.1093/neuros/nyx271

    Article  PubMed  Google Scholar 

  7. Hadjipanayis CG, Widhalm G, Stummer W (2015) What is the surgical benefit of utilizing 5-ALA for fluorescence-guided surgery of malignant gliomas? Neurosurgery 77:663–673. https://doi.org/10.1227/NEU.0000000000000929

    Article  PubMed  Google Scholar 

  8. Nagaya T, Nakamura YA, Choyke PL, Kobayashi H (2017) Fluorescence-guided surgery. Front. Oncol 7:314. https://doi.org/10.3389/fonc.2017.00314

    Article  Google Scholar 

  9. Puppa AD, Ciccarino P, Lombardi G et al (2014) 5-Aminolevulinic acid fluorescence in high grade glioma surgery: surgical outcome, Intraoperative Findings, and Fluorescence Patterns. BioMed Res Int 2014:e232561. https://doi.org/10.1155/2014/232561

    Article  CAS  Google Scholar 

  10. Muto J, Mine Y, Nagai S et al (2022) Utility of intraoperative real-time near-infrared fluorescence surgery for spinal schwannoma. Neurosurg Focus Video 6:V12. https://doi.org/10.3171/2021.10.FOCVID21158

    Article  PubMed  PubMed Central  Google Scholar 

  11. Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71

    Article  PubMed  PubMed Central  Google Scholar 

  12. McCormack T, Karaikovic E, Gaines RW (1994) The load sharing classification of spine fractures. Spine 19:1741–1744. https://doi.org/10.1097/00007632-199408000-00014

    Article  PubMed  CAS  Google Scholar 

  13. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. https://doi.org/10.1007/s10654-010-9491-z

  14. Sterne JA, Egger M (2001) Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol 54:1046–1055. https://doi.org/10.1016/s0895-4356(01)00377-8

    Article  PubMed  CAS  Google Scholar 

  15. Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634. https://doi.org/10.1136/bmj.315.7109.629

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Viechtbauer W (2010) Conducting meta-analyses in R with the metafor Package. J Stat Softw 36:1–48. https://doi.org/10.18637/jss.v036.i03

    Article  Google Scholar 

  17. Viechtbauer W (2010) Conducting Meta-Analyses in R with themetafor Package. J Stat Softw 36:1–48. https://doi.org/10.18637/jss.v036.i03

  18. Lipsey MW, Wilson DB (2001) Practical meta-analysis. Sage Publications, Inc, Thousand Oaks, CA, US

    Google Scholar 

  19. McHugh ML (2013) The Chi-square test of independence. Biochem Medica 23:143–149. https://doi.org/10.11613/BM.2013.018

    Article  CAS  Google Scholar 

  20. Millesi M, Kiesel B, Mazanec V et al (2020) 5-ALA fluorescence for intraoperative visualization of spinal ependymal tumors and identification of unexpected residual tumor tissue: experience in 31 patients. J Neurosurg Spine 34:374–382. https://doi.org/10.3171/2020.6.SPINE20506

    Article  PubMed  Google Scholar 

  21. Inoue T, Endo T, Nagamatsu K et al (2013) 5-aminolevulinic acid fluorescence-guided resection of intramedullary ependymoma: report of 9 cases. Neurosurgery 72:159–168. https://doi.org/10.1227/NEU.0b013e31827bc7a3

    Article  Google Scholar 

  22. Millesi M, Kiesel B, Woehrer A et al (2014) Analysis of 5-aminolevulinic acid-induced fluorescence in 55 different spinal tumors. Neurosurg Focus 36:E11. https://doi.org/10.3171/2013.12.FOCUS13485

    Article  PubMed  Google Scholar 

  23. Ung TH, Serva S, Chatain GP et al (2022) Application of sodium fluorescein for spinal cord lesions: intraoperative localization for tissue biopsy and surgical resection. Neurosurg Rev 45:1563–1569. https://doi.org/10.1007/s10143-021-01676-1

    Article  PubMed  Google Scholar 

  24. Acerbi F, Cavallo C, Schebesch K-M et al (2017) Fluorescein-guided resection of intramedullary spinal cord tumors: results from a preliminary, multicentric, retrospective study. World Neurosurg 108:603–609. https://doi.org/10.1016/j.wneu.2017.09.061

    Article  Google Scholar 

  25. Cardali SM, Ricciardo G, Garufi G et al (2022) Fluorescein-guided surgery for intradural spinal tumors: a single-center experience. Brain Spine 2:100908. https://doi.org/10.1016/j.bas.2022.100908

    Article  PubMed Central  Google Scholar 

  26. Sun Z, Jing L, Fan Y et al (2020) Fluorescein-guided surgery for spinal gliomas: analysis of 220 consecutive cases. Int Rev Neurobiol 151:139–154. https://doi.org/10.1016/bs.irn.2020.03.004

    Article  PubMed  Google Scholar 

  27. Goryaynov SA, Okhlopkov VA, Golbin DA et al (2019) Fluorescence diagnosis in neurooncology: retrospective analysis of 653 cases. Front Oncol 9:830. https://doi.org/10.3389/fonc.2019.00830

    Article  PubMed  PubMed Central  Google Scholar 

  28. Moreno RG, García LMB, Bastidas HI et al (2019) Fluorescence guided surgery with 5-aminolevulinic acid for resection of spinal cord ependymomas. Asian Spine J 13:119–125. https://doi.org/10.31616/asj.2018.0165

    Article  PubMed  Google Scholar 

  29. Sun Z, Yuan D, Sun Y et al (2022) Intraoperative application of yellow fluorescence in resection of intramedullary spinal canal ependymoma. J Int Med Res 50:3000605221082889. https://doi.org/10.1177/03000605221082889

    Article  CAS  Google Scholar 

  30. Olguner SK, Arslan A, Açık V et al (2020) Sodium fluorescein for spinal intradural tumors. Front Oncol 10:618579. https://doi.org/10.3389/fonc.2020.618579

    Article  PubMed  Google Scholar 

  31. Eicker SO, Floeth FW, Kamp M et al (2013) The impact of fluorescence guidance on spinal intradural tumour surgery. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc 22:1394–1401. https://doi.org/10.1007/s00586-013-2657-0

    Article  Google Scholar 

  32. Stummer W, Pichlmeier U, Meinel T et al (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401. https://doi.org/10.1016/S1470-2045(06)70665-9

    Article  PubMed  CAS  Google Scholar 

  33. Chen B, Wang H, Ge P et al (2012) Gross total resection of glioma with the intraoperative fluorescence-guidance of fluorescein Sodium. Int J Med Sci 9:708–714. https://doi.org/10.7150/ijms.4843

    Article  PubMed  CAS  Google Scholar 

  34. Dilek O, Ihsan A, Tulay H (2011) Anaphylactic reaction after fluorescein sodium administration during intracranial surgery. J Clin Neurosci 18:430–431. https://doi.org/10.1016/j.jocn.2010.06.012

    Article  PubMed  Google Scholar 

  35. Tanahashi S, Lida H, Dohi S (2006) An anaphylactoid reaction after administration of fluorescein sodium during neurosurgery. Anesth Analg 103:503. https://doi.org/10.1213/01.ANE.0000227205.37935.10

    Article  PubMed  Google Scholar 

  36. Chung IWH, Eljamel S (2013) Risk factors for developing oral 5-aminolevulinic acid-induced side effects in patients undergoing fluorescence guided resection. Photodiagnosis Photodyn Ther 10:362–367. https://doi.org/10.1016/j.pdpdt.2013.03.007

    Article  PubMed  CAS  Google Scholar 

  37. Raco A, Esposito V, Lenzi J et al (2005) Long-term follow-up of intramedullary spinal cord tumors: a series of 202 cases. Neurosurgery 56:972. https://doi.org/10.1227/01.NEU.0000158318.66568.CC

    Article  PubMed  Google Scholar 

  38. Hongo H, Takai K, Komori T, Taniguchi M (2018) Intramedullary spinal cord ependymoma and astrocytoma: intraoperative frozen-section diagnosis, extent of resection, and outcomes. J Neurosurg Spine 30:133–139. https://doi.org/10.3171/2018.7.SPINE18230

    Article  PubMed  Google Scholar 

  39. Bakhshi SK, Waqas M, Shakaib B, Enam SA (2016) Management and outcomes of intramedullary spinal cord tumors: a single center experience from a developing country. Surg Neurol Int 7:S617–S622. https://doi.org/10.4103/2152-7806.189733

    Article  PubMed  PubMed Central  Google Scholar 

  40. Rashad S, Elwany A, Farhoud A (2018) Surgery for spinal intramedullary tumors: technique, outcome and factors affecting resectability. Neurosurg Rev 41:503–511. https://doi.org/10.1007/s10143-017-0879-z

    Article  PubMed  Google Scholar 

  41. Li T-Y, Chu J-S, Xu Y-L et al (2014) Surgical strategies and outcomes of spinal ependymomas of different lengths: analysis of 210 patients: clinical article. J Neurosurg Spine 21:249–259. https://doi.org/10.3171/2014.3.SPINE13481

    Article  PubMed  Google Scholar 

  42. Azad TD, Pendharkar AV, Pan J et al (2018) Surgical outcomes of pediatric spinal cord astrocytomas: systematic review and meta-analysis. J Neurosurg Pediatr 22:404–410. https://doi.org/10.3171/2018.4.PEDS17587

    Article  PubMed  Google Scholar 

  43. Hersh AM, Patel J, Pennington Z et al (2022) Perioperative outcomes and survival after surgery for intramedullary spinal cord tumors: a single-institution series of 302 patients. J Neurosurg Spine 37:252–262. https://doi.org/10.3171/2022.1.SPINE211235

    Article  Google Scholar 

  44. Schupper AJ, Rao M, Mohammadi N et al (2021) Fluorescence-Guided Surgery: A Review on Timing and Use in Brain Tumor Surgery. Front Neurol 12:682151. https://doi.org/10.3389/fneur.2021.682151

  45. Schebesch K-M, Proescholdt M, Höhne J et al (2013) Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study. Acta Neurochir (Wien) 155:693–699. https://doi.org/10.1007/s00701-013-1643-y

    Article  PubMed  Google Scholar 

  46. Shinoda J, Yano H, Yoshimura S-I et al (2003) Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note. J Neurosurg 99:597–603. https://doi.org/10.3171/jns.2003.99.3.0597

    Article  PubMed  Google Scholar 

  47. Palasuberniam P, Kraus D, Mansi M et al (2019) Ferrochelatase deficiency abrogated the enhancement of aminolevulinic acid-mediated protoporphyrin IX by iron chelator deferoxamine. Photochem Photobiol 95:1052–1059. https://doi.org/10.1111/php.13091

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Fontana AO, Piffaretti D, Marchi F et al (2017) Epithelial growth factor receptor expression influences 5-ALA induced glioblastoma fluorescence. J Neurooncol 133:497–507. https://doi.org/10.1007/s11060-017-2474-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Lau D, Hervey-Jumper SL, Chang S et al (2016) A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas. J Neurosurg 124:1300–1309. https://doi.org/10.3171/2015.5.JNS1577

    Article  PubMed  CAS  Google Scholar 

  50. Stummer W, Rodrigues F, Schucht P et al (2014) Predicting the “usefulness” of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey. Acta Neurochir (Wien) 156:2315. https://doi.org/10.1007/s00701-014-2234-2

    Article  PubMed  Google Scholar 

  51. Elliott JT, Dsouza AV, Davis SC et al (2015) Review of fluorescence guided surgery visualization and overlay techniques. Biomed Opt Express 6:3765–3782. https://doi.org/10.1364/BOE.6.003765

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Mischkulnig M, Traxler D, Wadiura LI et al (2023) Comparison of minimal detectable protoporphyrin IX concentrations with a loupe device and conventional 5-ALA fluorescence microscopy: an experimental study. J Biomed Opt 28:106004. https://doi.org/10.1117/1.JBO.28.10.106004

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

    Ibrahem Albalkhi & Areez Shafqat

  2. Department of Neuroradiology, Great Ormond Street Hospital NHS Foundation Trust, London, UK

    Ibrahem Albalkhi

  3. Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Othman Bin-Alamer, Arka N. Mallela, Ricardo J. Fernández-de Thomas, Pascal O. Zinn, Peter C. Gerszten, Constantinos G. Hadjipanayis & Hussam Abou-Al-Shaar

  4. College of Medicine, AlMaarefa University, Dariyah, Saudi Arabia

    Abdul Rahman Abou Al-Shaar

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  1. Ibrahem Albalkhi
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Contributions

HA, CH, PG, PZ, RF, IA: conception and design, provision of study patient, data analysis and interpretation, manuscript writing, final approval of the manuscript. AA, OB, IA, AS: collection and assembly of data, data analysis and interpretation, manuscript writing. All authors: writing the manuscript.

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Correspondence to Hussam Abou-Al-Shaar.

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Supplementary information

Supplementary Figure 1

Newcastle-Ottawa scale for non-randomized studies to determine the quality of the studies

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Supplementary Figure 2

Funnel plots for determining the risk of publication bias.

High resolution image

Supplementary Figure 3

Forest plots showing pooled proportions of fluorescence with subgroup analysis based on the administered agent for ependymomas.

Supplementary Figure 4

Forest plots showing pooled proportions of fluorescence with subgroup analysis based on the administered agent for astrocytomas.

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Albalkhi, I., Shafqat, A., Bin-Alamer, O. et al. Fluorescence-guided resection of intradural spinal tumors: a systematic review and meta-analysis. Neurosurg Rev 47, 10 (2024). https://doi.org/10.1007/s10143-023-02230-x

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