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CC BY-NC-ND 4.0 · Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery 2022; 41(01): e35-e42
DOI: 10.1055/s-0041-1739272
Original Article

Extending the Indications of 5-Aminolevulinic Acid for Fluorescence-Guided Surgery for Different Central Nervous System Tumors: A Series of 255 Cases in Latin America

Ampliando as indicações de ácido 5-aminolevulínico em cirugia guiada por fluorescência para diferentes tumores do sistema nervoso central: Uma série de 255 casos na América Latina
Erasmo Barros da Silva Jr 
1   Department of Neurosurgery, Section of Neuro-oncology, Instituto de Neurologia de Curitiba, Curitiba, Paraná, Brazil
,
Ricardo Ramina 
1   Department of Neurosurgery, Section of Neuro-oncology, Instituto de Neurologia de Curitiba, Curitiba, Paraná, Brazil
,
Maurício Coelho Neto
1   Department of Neurosurgery, Section of Neuro-oncology, Instituto de Neurologia de Curitiba, Curitiba, Paraná, Brazil
,
Guilherme Augusto de Souza Machado
1   Department of Neurosurgery, Section of Neuro-oncology, Instituto de Neurologia de Curitiba, Curitiba, Paraná, Brazil
,
Marcella Santos Cavalcanti 
2   Departament of Neuropathology, Instituto de Neurologia de Curitiba, Paraná, Brazil
,
Joseph Franklin Chenisz da Silva 
1   Department of Neurosurgery, Section of Neuro-oncology, Instituto de Neurologia de Curitiba, Curitiba, Paraná, Brazil
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Abstract

Introduction Fluorescence guidance with 5-aminolevulinic acid (5-ALA) is a safe and reliable tool in total gross resection of intracranial tumors, especially malignant gliomas and cases of metastasis. In the present retrospective study, we have analyzed 5-ALA-induced fluorescence findings in different central nervous system (CNS) lesions to expand the indications of its use in differential diagnoses.

Objectives To describe the indications and results of 5-ALA fluorescence in a series of 255 cases.

Methods In 255 consecutive cases, we recorded age, gender, intraoperative 5-ALA fluorescence tumor response, and 5-ALA postresection status, as well the complications related to the method. Postresection was classified as ‘5-ALA free’ or ‘5-ALA residual’. The diagnosis of histopathological tumor was established according to the current classification of the World Health Organization (WHO).

Results There were 195 (76.4%) 5-ALA positive cases, 124 (63.5%) of whom underwent the ‘5-ALA free’ resection. The findings in the positive cases were: 135 gliomas of all grades; 19 meningiomas; 4 hemangioblastomas; 1 solitary fibrous tumor; 27 metastases; 2 diffuse large B cell lymphomas; 2 cases of radionecrosis; 1 inflammatory disease; 2 cases of gliosis; 1 cysticercosis; and 1 immunoglobulin G4-related disease.

Conclusion Fluorescence with 5-ALA can be observed in lesions other than malignant gliomas or metastases, including meningiomas, hemangioblastomas, pilocytic astrocytomas, and lymphomas. Although there is need for further evidence for the use of 5-ALA beyond high-grade gliomas, it may be a safe and reliable tool to improve resection in positive tumors or to guide the histopathologic analysis in biopsies.

Resumo

Introdução A fluorescência com ácido 5-aminolevulínico (5-ALA) é uma ferramenta segura e confiável para a ressecção total de tumores intracranianos, especialmente gliomas malignos e casos de metástase. Neste estudo retrospectivo, analisamos os achados de fluorescência induzida por 5-ALA em diferentes lesões do sistema nervoso central (SNC), visando ampliar as indicações de seu uso no diagnóstico diferencial.

Objetivos Descrever as indicações e resultados da fluorescência com 5-ALA em uma série de 255 casos.

Métodos Em 255 casos consecutivos, registramos idade, sexo, resposta tumoral de fluorescência intraoperatória com 5-ALA, e status de 5-ALA pós-ressecção, bem como as complicações relacionadas ao método. A pós-ressecção foi graduada como “5-ALA livre” ou “5-ALA residual”. O diagnóstico histopatológico foi estabelecido de acordo com a classificação atual da Organização Mundial de Saúde (OMS).

Resultados Houve 195 (76.4%) casos 5-ALA positivos, 124 (63,5%) dos quais foram submetidos a ressecção “5-ALA livre”. Os achados nos casos positivos foram: 135 gliomas; 19 meningiomas; 4 hemangioblastomas; 1 tumor fibroso solitário; 27 metástases; 2 linfomas difusos de grandes células B; 2 radionecroses; 1 doença inflamatória; 2 glioses; 1 cisticercose; e 1 doença relacionada à imunoglobulina G4.

Conclusões Fluorescência com 5-ALA pode ser observada em outras lesões além de gliomas malignos ou metástases, incluindo meningiomas, hemangioblastomas, astrocitomas pilocíticos, e linfomas. Embora haja necessidade de mais evidências para o uso de 5-ALA que não em casos de gliomas de alto grau, sua aplicação pode ser segura e confiável para melhorar a ressecção de tumores positivos ou orientar a análise histopatológica em biópsias.

Keywords

5-aminolevulinic acid - brain cancer - extent of resection

Palavras-chave

ácido 5-aminolevulínico - câncer no cérebro - extensão de ressecção


Publication History

Received: 25 March 2021

Accepted: 16 June 2021

Article published online:
04 January 2022

© 2022. Sociedade Brasileira de Neurocirurgia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Stummer W, Stepp H, Möller G, Ehrhardt A, Leonhard M, Reulen HJ. Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue. Acta Neurochir (Wien) 1998; 140 (10) 995-1000
    CrossrefPubMedGoogle Scholar
  • 2 Stummer W, Stocker S, Wagner S. et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 1998; 42 (03) 518-525 , discussion 525–526
    CrossrefPubMedGoogle Scholar
  • 3 Ewelt C, Nemes A, Senner V. et al. Fluorescence in neurosurgery: Its diagnostic and therapeutic use. Review of the literature. J Photochem Photobiol B 2015; 148: 302-309
    CrossrefPubMedGoogle Scholar
  • 4 Ferraro N, Barbarite E, Albert TR. et al. The role of 5-aminolevulinic acid in brain tumor surgery: a systematic review. Neurosurg Rev 2016; 39 (04) 545-555
    CrossrefPubMedGoogle Scholar
  • 5 Senders JT, Muskens IS, Schnoor R. et al. Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results. Acta Neurochir (Wien) 2017; 159 (01) 151-167
    CrossrefPubMedGoogle Scholar
  • 6 Kamp MA, Grosser P, Felsberg J. et al. 5-aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: a retrospective study. Acta Neurochir (Wien) 2012; 154 (02) 223-228 , discussion 228
    CrossrefPubMedGoogle Scholar
  • 7 Kamp MA, Munoz-Bendix C, Mijderwijk HJ. et al. Is 5-ALA fluorescence of cerebral metastases a prognostic factor for local recurrence and overall survival?. J Neurooncol 2019; 141 (03) 547-553
    CrossrefPubMedGoogle Scholar
  • 8 Knipps J, Fischer I, Neumann LM. et al. Quantification of PpIX-fluorescence of cerebral metastases: a pilot study. Clin Exp Metastasis 2019; 36 (05) 467-475
    CrossrefPubMedGoogle Scholar
  • 9 Millesi M, Kiesel B, Mischkulnig M. et al. Analysis of the surgical benefits of 5-ALA-induced fluorescence in intracranial meningiomas: experience in 204 meningiomas. J Neurosurg 2016; 125 (06) 1408-1419
    CrossrefPubMedGoogle Scholar
  • 10 Rustemi O, Della Puppa A. Hyperostosis and osteolysis in skull base meningiomas: are different nuances of 5-ALA fluorescence related to different invasion patterns?. J Neurosurg Sci 2019; 63 (04) 484-485
    CrossrefPubMedGoogle Scholar
  • 11 Valdes PA, Millesi M, Widhalm G, Roberts DW. 5-aminolevulinic acid induced protoporphyrin IX (ALA-PpIX) fluorescence guidance in meningioma surgery. J Neurooncol 2019; 141 (03) 555-565
    CrossrefPubMedGoogle Scholar
  • 12 Hadjipanayis CG, Stummer W. 5-ALA and FDA approval for glioma surgery. J Neurooncol 2019; 141 (03) 479-486
    CrossrefPubMedGoogle Scholar
  • 13 Haider SA, Lim S, Kalkanis SN, Lee IY. The impact of 5-aminolevulinic acid on extent of resection in newly diagnosed high grade gliomas: a systematic review and single institutional experience. J Neurooncol 2019; 141 (03) 507-515
    CrossrefPubMedGoogle Scholar
  • 14 Lakomkin N, Hadjipanayis CG. Fluorescence-guided surgery for high-grade gliomas. J Surg Oncol 2018; 118 (02) 356-361
    CrossrefPubMedGoogle Scholar
  • 15 Chohan MO, Berger MS. 5-Aminolevulinic acid fluorescence guided surgery for recurrent high-grade gliomas. J Neurooncol 2019; 141 (03) 517-522
    CrossrefPubMedGoogle Scholar
  • 16 Halani SH, Adamson DC. Clinical utility of 5-aminolevulinic acid HCl to better visualize and more completely remove gliomas. OncoTargets Ther 2016; 9: 5629-5642
    CrossrefPubMedGoogle Scholar
  • 17 Agência Nacional de Vigilância Sanitária. Retificação de Publicação em Produtos para Saúde. Brasília, DF: Diário oficial da União. ; June 10, 2014. Suppl 109. 8419
    PubMedGoogle Scholar
  • 18 Ramina R, Silva Júnior EB, Constanzo F, Coelho Neto M. Indications of 5-Aminolevulinic Acid and Intraoperative MRI in Glioma Surgery: First Cases in Latin America in a Single Reference Center. Braz Neurosurg 2018; 37 (02) 88-94
    PubMedGoogle Scholar
  • 19 Ramina R, Da Silva Júnior EB, Coelho Neto M, Ruschel L, Navarrette F. 5-Aminolevulinic Acid–Protoporphyrin IX Fluorescence-Guided Surgery for CNS Tumors. J Bras Neurocir 2018; 27 (01) 13-19
    PubMedGoogle Scholar
  • 20 Ruschel LG, Ramina R, da Silva Jr EB, Cavalcanti MS, Duarte JFS. 5-Aminolevulinic acid fluorescence-guided surgery for spinal cord melanoma metastasis: a technical note. Acta Neurochir (Wien) 2018; 160 (10) 1905-1908
    CrossrefPubMedGoogle Scholar
  • 21 Stummer W, Stepp H, Wiestler OD, Pichlmeier U. Randomized, Prospective Double-Blinded Study Comparing 3 Different Doses of 5-Aminolevulinic Acid for Fluorescence-Guided Resections of Malignant Gliomas. Neurosurgery 2017; 81 (02) 230-239
    CrossrefPubMedGoogle Scholar
  • 22 Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ. ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 2006; 7 (05) 392-401
    CrossrefPubMedGoogle Scholar
  • 23 Stummer W, Tonn JC, Mehdorn HM. et al; ALA-Glioma Study Group. Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Clinical article. J Neurosurg 2011; 114 (03) 613-623
    CrossrefPubMedGoogle Scholar
  • 24 Ramina R, Coelho Neto M, Giacomelli A. et al. Optimizing costs of intraoperative magnetic resonance imaging. A series of 29 glioma cases. Acta Neurochir (Wien) 2010; 152 (01) 27-33
    CrossrefPubMedGoogle Scholar
  • 25 Jaber M, Ewelt C, Wölfer J. et al. Is Visible Aminolevulinic Acid-Induced Fluorescence an Independent Biomarker for Prognosis in Histologically Confirmed (World Health Organization 2016) Low-Grade Gliomas?. Neurosurgery 2019; 84 (06) 1214-1224
    CrossrefPubMedGoogle Scholar
  • 26 Al-Tamimi YZ, Palin MS, Patankar T. et al. Low-Grade Glioma with Foci of Early Transformation Does Not Necessarily Require Adjuvant Therapy After Radical Surgical Resection. World Neurosurg 2018; 110: e346-e354
    CrossrefPubMedGoogle Scholar
  • 27 Mansouri A, Mansouri S, Hachem LD. et al. The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review. Cancer 2016; 122 (16) 2469-2478
    CrossrefPubMedGoogle Scholar
  • 28 Roth J, Constantini S. 5ALA in pediatric brain tumors is not routinely beneficial. Childs Nerv Syst 2017; 33 (05) 787-792
    CrossrefPubMedGoogle Scholar
  • 29 Schwake M, Schipmann S, Müther M, Köchling M, Brentrup A, Stummer W. 5-ALA fluorescence-guided surgery in pediatric brain tumors-a systematic review. Acta Neurochir (Wien) 2019; 161 (06) 1099-1108
    CrossrefPubMedGoogle Scholar
  • 30 Eicker SO, Floeth FW, Kamp M, Steiger HJ, Hänggi D. The impact of fluorescence guidance on spinal intradural tumour surgery. Eur Spine J 2013; 22 (06) 1394-1401
    CrossrefPubMedGoogle Scholar
  • 31 Millesi M, Kiesel B, Woehrer A. et al. Analysis of 5-aminolevulinic acid-induced fluorescence in 55 different spinal tumors. Neurosurg Focus 2014; 36 (02) 1-11
    CrossrefPubMedGoogle Scholar
  • 32 Wainwright JV, Endo T, Cooper JB, Tominaga T, Schmidt MH. The role of 5-aminolevulinic acid in spinal tumor surgery: a review. J Neurooncol 2019; 141 (03) 575-584
    CrossrefPubMedGoogle Scholar
  • 33 Utsuki S, Oka H, Sato K, Shimizu S, Suzuki S, Fujii K. Fluorescence diagnosis of tumor cells in hemangioblastoma cysts with 5-aminolevulinic acid. J Neurosurg 2010; 112 (01) 130-132
    CrossrefPubMedGoogle Scholar
  • 34 Widhalm G, Minchev G, Woehrer A. et al. Strong 5-aminolevulinic acid-induced fluorescence is a novel intraoperative marker for representative tissue samples in stereotactic brain tumor biopsies. Neurosurg Rev 2012; 35 (03) 381-391 , discussion 391
    CrossrefPubMedGoogle Scholar
  • 35 Shooman D, Belli A, Grundy PL. Image-guided frameless stereotactic biopsy without intraoperative neuropathological examination. J Neurosurg 2010; 113 (02) 170-178
    CrossrefPubMedGoogle Scholar
  • 36 Yamamoto T, Ishikawa E, Miki S. et al. Photodynamic Diagnosis Using 5-Aminolevulinic Acid in 41 Biopsies for Primary Central Nervous System Lymphoma. Photochem Photobiol 2015; 91 (06) 1452-1457
    CrossrefPubMedGoogle Scholar
  • 37 Evers G, Kamp M, Warneke N. et al. 5-Aminolaevulinic Acid-Induced Fluorescence in Primary Central Nervous System Lymphoma. World Neurosurg 2017; 98: 375-380
    CrossrefPubMedGoogle Scholar