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Histology of high-grade glioma samples resected using 5-ALA fluorescent headlight and loupe combination

  • Original Article - Tumor - Glioma
  • Published:
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Abstract

Purpose

5-Aminolevulinic acid (5-ALA) fluorescence-guided resection of high-grade gliomas (HGG) increases the extent of resection (EOR) and progression-free survival. The headlamp/loupe combination has been introduced as a method of performing fluorescent-guided surgery. This study aims to understand the correlation between fluorescent intensity and histology and between residual fluorescence and radiographic EOR utilizing the headlamp/loupe device.

Methods

Intraoperative samples resected using the headlamp/loupe device from 14 patients were labeled as PINK, VAGUE, or NEGATIVE depending on the degree of fluorescence. Histological assessment of microvascular proliferation, necrosis, and cell density was performed, and samples were classified as histologically consistent with glioblastoma (GBM), high-grade infiltrating glioma (HGIG), IG, or non-diagnostic (NDX). The presence of intraoperative residual fluorescence was compared to EOR on post-operative MRI.

Results

There was a significant difference in cell density comparing PINK, VAGUE, and NEGATIVE specimens (ANOVA, p < 0.00001). The PPV of PINK for GBM or HGIG was 88.4% (38/43). The NPV of NEGATIVE for IG or NDX was 74.4% (29/39). The relationship between the degree of fluorescence determination and histological results was significant (X2 (6 degrees of freedom, N = 101) = 42.57, p < 0.00001). The PPV of intraoperative GTR for post-operative GTR on MRI was 100%, while the NPV of intraoperative STR for post-operative STR on MRI was 60%.

Conclusion

The headlamp/loupe device provides information about histology, cell density, and necrosis with similar PPV for tumor to the operative microscope. Safe complete resection of florescence has a PPV of 100% for radiographic GTR and should be the goal of surgery.

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Abbreviations

5ALA:

5-Aminolevuilnic acid

EOR:

Extent of resection

GBM:

Glioblastoma

GTR:

Gross total resection

HGG:

High-grade gliomas

HGIG:

High-grade infiltrating glioma

MRI:

Magnetic resonance imaging

NDX:

Non-diagnostic

NPV:

Negative predictive value

PFS:

Progression-free survival

PPV:

Positive predictive value

References

  1. Brown TJ, Brennan MC, Li M et al (2016) Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol 2(11):1460–1469

    Article  PubMed  PubMed Central  Google Scholar 

  2. Coburger J, Engelke J, Scheuerle A et al (2014) Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA-enhanced intraoperative MRI at the border of contrast-enhancing lesions: a prospective study based on histopathological assessment. Neurosurg Focus 36(2):E3

    Article  PubMed  Google Scholar 

  3. de Leeuw CN, Vogelbaum MA (2019) Supratotal resection in glioma: a systematic review. Neuro Oncol 21(2):179–188

    Article  PubMed  Google Scholar 

  4. Design for vision I. Reveal-FGS. https://www.designsforvision.com/REVEAL-FGS.htm. Published 2021. Accessed 20 Oct 2021

  5. Díez Valle R, Tejada Solis S, IdoateGastearena MA, García de Eulate R, Domínguez Echávarri P, AristuMendiroz J (2011) Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience. J Neurooncol. 102(1):105–113

    Article  PubMed  Google Scholar 

  6. Giantini-Larsen AM, Parker WE, Cho SS, Goldberg JL, Carnevale JA, Michael AP, Teng CW, De Ravin E, Brennan CW, Lee JYK, Schwartz TH (2022) The evolution of 5-aminolevulinic acid fluorescence visualization: time for a headlamp/loupe combination. World Neurosurg 159:136–143

    Article  PubMed  Google Scholar 

  7. Hadjipanayis CG, Widhalm G, Stummer W (2015) What is the surgical benefit of utilizing 5-aminolevulinic acid for fluorescence-guided surgery of malignant gliomas? Neurosurgery 77(5):663–673

    Article  PubMed  Google Scholar 

  8. Idoate MA, Díez Valle R, Echeveste J, Tejada S (2011) Pathological characterization of the glioblastoma border as shown during surgery using 5-aminolevulinic acid-induced fluorescence. Neuropathology 31(6):575–582

    Article  PubMed  Google Scholar 

  9. Molinaro AM, Hervey-Jumper S, Morshed RA et al (2020) Association of maximal extent of resection of contrast-enhanced and non–contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma. JAMA Oncol 6(4):495–503

    Article  PubMed  PubMed Central  Google Scholar 

  10. Nabavi A, Thurm H, Zountsas B et al (2009) Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: a phase ii study. Neurosurgery 65(6):1070–1076 (discussion 1076-1077)

    Article  PubMed  Google Scholar 

  11. Panciani PP, Fontanella M, Schatlo B et al (2012) Fluorescence and image guided resection in high grade glioma. Clin Neurol Neurosurg 114(1):37–41

    Article  PubMed  Google Scholar 

  12. Panciani PP, Fontanella M, Garbossa D, Agnoletti A, Ducati A, Lanotte M (2012) 5-Aminolevulinic acid and neuronavigation in high-grade glioma surgery: results of a combined approach. Neurocirugia (Astur) 23(1):23–28

    Article  PubMed  Google Scholar 

  13. Roberts DW, Valdés PA, Harris BT et al (2011) Coregistered fluorescence-enhanced tumor resection of malignant glioma: relationships between δ-aminolevulinic acid-induced protoporphyrin IX fluorescence, magnetic resonance imaging enhancement, and neuropathological parameters. Clinical article. J Neurosurg 114(3):595–603

    Article  PubMed  Google Scholar 

  14. Schucht P, Knittel S, Slotboom J et al (2014) 5-ALA complete resections go beyond MR contrast enhancement: shift corrected volumetric analysis of the extent of resection in surgery for glioblastoma. Acta Neurochir 156(2):305–312

    Article  PubMed  Google Scholar 

  15. Stummer W, Stocker S, Novotny A et al (1998) In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid. J Photochem Photobiol B 45(2–3):160–169

    Article  CAS  PubMed  Google Scholar 

  16. Stummer W, Stepp H, Möller G, Ehrhardt A, Leonhard M, Reulen HJ (1998) Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue. Acta Neurochir (Wien) 140(10):995–1000

    Article  CAS  PubMed  Google Scholar 

  17. Stummer W, Stocker S, Wagner S et al (1998) Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 42(3):518–525 (discussion 525-516)

    Article  CAS  PubMed  Google Scholar 

  18. Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ (2000) Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J Neurosurg 93(6):1003–1013

    Article  CAS  PubMed  Google Scholar 

  19. Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7(5):392–401

    Article  CAS  PubMed  Google Scholar 

  20. 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(12):2315–2324

    Article  PubMed  Google Scholar 

  21. Stummer W, Tonn JC, Goetz C et al (2014) 5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging. Neurosurgery 74(3):310–319 (discussion 319-320)

    Article  PubMed  Google Scholar 

  22. Suero Molina E, Hellwig SJ, Walke A, Jeibmann A, Stepp H, Stummer W (2021) Development and validation of a triple-LED surgical loupe device for fluorescence-guided resections with 5-ALA. J Neurosurg 31:1–9

    Google Scholar 

  23. Widhalm G, Kiesel B, Woehrer A et al (2013) 5-Aminolevulinic acid induced fluorescence is a powerful intraoperative marker for precise histopathological grading of gliomas with non-significant contrast-enhancement. PLoS ONE 8(10):e76988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yamada S, Muragaki Y, Maruyama T, Komori T, Okada Y (2015) Role of neurochemical navigation with 5-aminolevulinic acid during intraoperative MRI-guided resection of intracranial malignant gliomas. Clin Neurol Neurosurg 130:134–139

    Article  PubMed  Google Scholar 

  25. Zhang X, Jaman E, Habib A et al (2022) A novel 5-aminolevulinic acid-enabled surgical loupe system-a consecutive brain tumor series of 11 cases. Oper Neurosurg (Hagerstown) 22(5):298–304

    Article  PubMed  Google Scholar 

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Authors

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Correspondence to Theodore H. Schwartz.

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Ethical approval

The study was approved by the Institutional Review Board (IRB) at our institution.

Consent to participate

All patients gave their informed consent to receive 5-ALA prior to resection.

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The authors declare no competing interests.

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This article is part of the Topical Collection on Tumor—Glioma

This work has not been previously published. An abstract has been accepted for presentation to the Congress of Neurological Surgeons 2022 meeting.

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Giantini-Larsen, A.M., Kharas, N., Pisapia, D. et al. Histology of high-grade glioma samples resected using 5-ALA fluorescent headlight and loupe combination. Acta Neurochir 165, 567–575 (2023). https://doi.org/10.1007/s00701-023-05496-8

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