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Ependymal fluorescence in fluorescence-guided resection of malignant glioma: a systematic review

  • Review Article - Tumor - Glioma
  • Published:
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Abstract

Background

Fluorescence in the ventricular wall or the ependyma during fluorescence-guided resection (FGR) of malignant glioma is commonly observed when malignant gliomas infiltrate the ventricles. However, the underlying pathophysiology and clinical importance are largely unknown but may play a role in deciding whether to continue resection into the ventricles or not. Here, we systematically review available data regarding ependymal fluorescence in FGR using five aminolevulinic acid (5-ALA) and sodium fluorescein (SF).

Methods

A literature search on MEDLINE, EMBASE, and WEB OF SCIENCE was performed using the following headings and search operators: ependy* fluorescence AND (5-ALA OR five aminolevulinic acid), ventric* wall fluorescence AND (5-ALA OR five aminolevulinic acid), ependy* fluorescence AND fluorescein, and ventric* wall fluorescence AND fluorescein. Both authors analyzed abstracts independently. Included articles were further reviewed for prevalence of ependymal fluorescence, patterns of fluorescence, and histopathological characteristics of sampled tissues as well as radiological signs of ependymal fluorescence. Results are reported according to the PRISMA statement.

Results

Of 202 records identified, 6 studies were included compiling a total number of 198 patients treated with FGR using 5-ALA. No study on ependymal fluorescence after administration of SF was found. Overall prevalence of ependymal fluorescence was 61.4%. A total of 54.5% of cases were found to be positive for tumor cells. A total of 25.5% of patients with ependymal fluorescence were related to contrast enhancement in ventricular walls.

Conclusions

The phenomenon of ventricular wall fluorescence in 5-ALA-derived fluorescence-guided resection of malignant glioma is poorly understood and not always may fluorescence represent tumor infiltration. A larger scale prospective sampling study with molecular analyses is currently ongoing and will hopefully provide further insight into pathophysiology and clinical implications of ependymal fluorescence.

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References

  1. Acerbi F, Broggi M, Eoli M, Anghileri E, Cuppini L, Pollo B, Schiariti M, Visintini S, Orsi 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 155:1277–1286. https://doi.org/10.1007/s00701-013-1734-9

    Article  PubMed  Google Scholar 

  2. Albert FK, Forsting M, Sartor K, Adams HP, Kunze S (1994) Early postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis. Neurosurgery 34:45–60 discussion 60-41

    CAS  PubMed  Google Scholar 

  3. Aldave G, Tejada S, Pay E, Marigil M, Bejarano B, Idoate MA, Diez-Valle R (2013) Prognostic value of residual fluorescent tissue in glioblastoma patients after gross total resection in 5-aminolevulinic Acid-guided surgery. Neurosurgery 72:915–920; discussion 920-911. https://doi.org/10.1227/NEU.0b013e31828c3974

    Article  PubMed  Google Scholar 

  4. Beez T, Sarikaya-Seiwert S, Steiger HJ, Hanggi D (2014) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain tumors in children--a technical report. Acta Neurochir 156:597–604. https://doi.org/10.1007/s00701-014-1997-9

    Article  PubMed  Google Scholar 

  5. Behling F, Kaltenstadler M, Noell S, Schittenhelm J, Bender B, Eckert F, Tabatabai G, Tatagiba M, Skardelly M (2017) The prognostic impact of ventricular opening in glioblastoma surgery: a retrospective single center analysis. World Neurosurg 106:615–624. https://doi.org/10.1016/j.wneu.2017.07.034

    Article  PubMed  Google Scholar 

  6. Cage TA, Pekmezci M, Prados M, Berger MS (2013) Subependymal spread of recurrent glioblastoma detected with the intraoperative use of 5-aminolevulinic acid: case report. J Neurosurg 118:1220–1223. https://doi.org/10.3171/2013.1.JNS121537

    Article  PubMed  Google Scholar 

  7. Hayashi Y, Nakada M, Tanaka S, Uchiyama N, Hayashi Y, Kita D, Hamada J (2010) Implication of 5-aminolevulinic acid fluorescence of the ventricular wall for postoperative communicating hydrocephalus associated with cerebrospinal fluid dissemination in patients with glioblastoma multiforme: a report of 7 cases. J Neurosurg 112:1015–1019. https://doi.org/10.3171/2009.8.JNS09516

    Article  PubMed  Google Scholar 

  8. Inamasu J, Nakamura Y, Saito R, Kuroshima Y, Mayanagi K, Orii M, Ichikizaki K (2003) Postoperative communicating hydrocephalus in patients with supratentorial malignant glioma. Clin Neurol Neurosurg 106:9–15

    Article  PubMed  Google Scholar 

  9. Jaber M, Ewelt C, Wolfer J, Brokinkel B, Thomas C, Hasselblatt M, Grauer O, Stummer W (2018) Is visible aminolevulinic acid-induced fluorescence an independent biomarker for prognosis in histologically confirmed (World Health Organization 2016) Low-Grade Gliomas? Neurosurgery. https://doi.org/10.1093/neuros/nyy365

  10. Kreth FW, Thon N, Simon M, Westphal M, Schackert G, Nikkhah G, Hentschel B, Reifenberger G, Pietsch T, Weller M, Tonn JC (2013) Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy. Ann Oncol 24:3117–3123. https://doi.org/10.1093/annonc/mdt388

    Article  PubMed  Google Scholar 

  11. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198. https://doi.org/10.3171/jns.2001.95.2.0190

    Article  CAS  PubMed  Google Scholar 

  12. Li YM, Suki D, Hess K, Sawaya R (2016) The influence of maximum safe resection of glioblastoma on survival in 1229 patients: can we do better than gross-total resection? J Neurosurg 124:977–988. https://doi.org/10.3171/2015.5.JNS142087

    Article  PubMed  Google Scholar 

  13. McGirt MJ, Chaichana KL, Gathinji M, Attenello FJ, Than K, Olivi A, Weingart JD, Brem H, Quinones-Hinojosa AR (2009) Independent association of extent of resection with survival in patients with malignant brain astrocytoma. J Neurosurg 110:156–162. https://doi.org/10.3171/2008.4.17536

    Article  PubMed  Google Scholar 

  14. Moiyadi AV, Shetty P, Sridhar E (2017) Periventricular glioblastomas and ependymal involvement interrogated using intraoperative fluorescence - a pathological correlative study. Br J Neurosurg 31:107–112. https://doi.org/10.1080/02688697.2016.1229750

    Article  PubMed  Google Scholar 

  15. Moon JH, Kim SH, Shim JK, Roh TH, Sung KS, Lee JH, Park J, Choi J, Kim EH, Kim SH, Kang SG, Chang JH (2016) Histopathological implications of ventricle wall 5-aminolevulinic acid-induced fluorescence in the absence of tumor involvement on magnetic resonance images. Oncol Rep 36:837–844. https://doi.org/10.3892/or.2016.4881

    Article  CAS  PubMed  Google Scholar 

  16. Moore GE (1947) Fluorescein as an agent in the differentiation of normal and malignant Tissues. Science 106:130–131. https://doi.org/10.1126/science.106.2745.130-a

    Article  CAS  PubMed  Google Scholar 

  17. Piccirillo SG, Spiteri I, Sottoriva A, Touloumis A, Ber S, Price SJ, Heywood R, Francis NJ, Howarth KD, Collins VP, Venkitaraman AR, Curtis C, Marioni JC, Tavare S, Watts C (2015) Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone. Cancer Res 75:194–202. https://doi.org/10.1158/0008-5472.CAN-13-3131

    Article  CAS  PubMed  Google Scholar 

  18. Preuss M, Renner C, Krupp W, Christiansen H, Fischer L, Merkenschlager A, Kiess W, Muller W, Manzo N, Meixensberger J, Nestler U (2013) The use of 5-aminolevulinic acid fluorescence guidance in resection of pediatric brain tumors. Childs Nerv Syst 29:1263–1267. https://doi.org/10.1007/s00381-013-2159-8

    Article  CAS  PubMed  Google Scholar 

  19. Rey-Dios R, Cohen-Gadol AA (2013) Technical principles and neurosurgical applications of fluorescein fluorescence using a microscope-integrated fluorescence module. Acta Neurochir 155:701–706. https://doi.org/10.1007/s00701-013-1635-y

    Article  PubMed  Google Scholar 

  20. Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:3–8. https://doi.org/10.3171/2011.2.JNS10998

    Article  PubMed  Google Scholar 

  21. Schebesch KM, Proescholdt M, Hohne J, Hohenberger C, Hansen E, Riemenschneider MJ, Ullrich W, Doenitz C, Schlaier J, Lange M, Brawanski A (2013) Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery--a feasibility study. Acta Neurochir 155:693–699. https://doi.org/10.1007/s00701-013-1643-y

    Article  PubMed  Google Scholar 

  22. Schucht P, Beck J, Abu-Isa J, Andereggen L, Murek M, Seidel K, Stieglitz L, Raabe A (2012) Gross total resection rates in contemporary glioblastoma surgery: results of an institutional protocol combining 5-aminolevulinic acid intraoperative fluorescence imaging and brain mapping. Neurosurgery 71:927–935; discussion 935-926. https://doi.org/10.1227/NEU.0b013e31826d1e6b

    Article  PubMed  Google Scholar 

  23. Schucht P, Knittel S, Slotboom J, Seidel K, Murek M, Jilch A, Raabe A, Beck J (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 156:305–312; discussion 312. https://doi.org/10.1007/s00701-013-1906-7

    Article  PubMed  Google Scholar 

  24. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, Group P-P (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350:g7647. https://doi.org/10.1136/bmj.g7647

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. 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 93:1003–1013. https://doi.org/10.3171/jns.2000.93.6.1003

    Article  CAS  PubMed  Google Scholar 

  27. Stummer W, Reulen HJ, Novotny A, Stepp H, Tonn JC (2003) Fluorescence-guided resections of malignant gliomas--an overview. Acta Neurochir Suppl 88:9–12

    CAS  PubMed  Google Scholar 

  28. 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 7:392–401. https://doi.org/10.1016/S1470-2045(06)70665-9

    Article  CAS  PubMed  Google Scholar 

  29. Stummer W, Reulen HJ, Meinel T, Pichlmeier U, Schumacher W, Tonn JC, Rohde V, Oppel F, Turowski B, Woiciechowsky C, Franz K, Pietsch T (2008) Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 62:564–576; discussion 564-576. https://doi.org/10.1227/01.neu.0000317304.31579.17

    Article  PubMed  Google Scholar 

  30. Stummer W, Tonn JC, Mehdorn HM, Nestler U, Franz K, Goetz C, Bink A, Pichlmeier U (2011) 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 114:613–623. https://doi.org/10.3171/2010.3.JNS097

    Article  PubMed  Google Scholar 

  31. Stummer W, Meinel T, Ewelt C, Martus P, Jakobs O, Felsberg J, Reifenberger G (2012) Prospective cohort study of radiotherapy with concomitant and adjuvant temozolomide chemotherapy for glioblastoma patients with no or minimal residual enhancing tumor load after surgery. J Neuro-Oncol 108:89–97. https://doi.org/10.1007/s11060-012-0798-3

    Article  CAS  Google Scholar 

  32. Stummer W, Rodrigues F, Schucht P, Preuss M, Wiewrodt D, Nestler U, Stein M, Artero JM, Platania N, Skjoth-Rasmussen J, Della Puppa A, Caird J, Cortnum S, Eljamel S, Ewald C, Gonzalez-Garcia L, Martin AJ, Melada A, Peraud A, Brentrup A, Santarius T, Steiner HH, European ALAPBTSG (2014) Predicting the “usefulness” of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey. Acta Neurochir 156:2315–2324. https://doi.org/10.1007/s00701-014-2234-2

    Article  PubMed  Google Scholar 

  33. Stummer W, Tonn JC, Goetz C, Ullrich W, Stepp H, Bink A, Pietsch T, Pichlmeier U (2014) 5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging. Neurosurgery 74:310–319; discussion 319-320. https://doi.org/10.1227/NEU.0000000000000267

    Article  PubMed  Google Scholar 

  34. Suero Molina E, Ewelt C, Warneke N, Schwake M, Muther M, Schipmann S, Stummer W (2019) Dual labeling with 5-aminolevulinic acid and fluorescein in high-grade glioma surgery with a prototype filter system built into a neurosurgical microscope: technical note. J Neurosurg:1–7. https://doi.org/10.3171/2018.12.JNS182422

  35. Tejada-Solis S, Aldave-Orzaiz G, Pay-Valverde E, Marigil-Sanchez M, Idoate-Gastearena MA, Diez-Valle R (2012) Prognostic value of ventricular wall fluorescence during 5-aminolevulinic-guided surgery for glioblastoma. Acta Neurochir 154:1997–2002; discussion 2002. https://doi.org/10.1007/s00701-012-1475-1

    Article  PubMed  Google Scholar 

  36. The Oxford 2011 Levels of Evidence (2011) http://www.cebm.net/index.aspx?o = 5653. Accessed 20/08/2019

  37. Tykocki T, Michalik R, Bonicki W, Nauman P (2012) Fluorescence-guided resection of primary and recurrent malignant gliomas with 5-aminolevulinic acid. Preliminary results. Neurol Neurochir Pol 46:47–51

    Article  CAS  PubMed  Google Scholar 

  38. Valdes PA, Leblond F, Kim A, Harris BT, Wilson BC, Fan X, Tosteson TD, Hartov A, Ji S, Erkmen K, Simmons NE, Paulsen KD, Roberts DW (2011) Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker. J Neurosurg 115:11–17. https://doi.org/10.3171/2011.2.JNS101451

    Article  PubMed  PubMed Central  Google Scholar 

  39. Yamamoto J, Takahashi M, Idei M, Nakano Y, Soejima Y, Saito T, Akiba D, Kitagawa T, Ueta K, Miyaoka R, Nishizawa S (2012) A pitfall of fluorescence- guided surgery with 5-aminolevluinic acid for the treatment of malignant brain tumor – case report. ALA-Porphyrin Science 1

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  1. Department of Neurosurgery, University Hospital Münster, Albert-Schweitzer-Campus 1, 48147, Münster, Germany

    Michael Müther & Walter Stummer

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  1. Michael Müther
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Correspondence to Michael Müther.

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Conflict of interest

Walter Stummer reports consultant and lecture activities activity for medac (Wedel, Germany), Carl Zeiss Meditech (Oberkochen, Germany), and NxDc (Lexington, KY, USA). Michael Müther reports no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Ethics Committee University of Münster) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Comments

Important review with a very relevant focus on the everyday challenges working with the patients.

Jane Skjoth-Rasmussen

Copenhagen, Denmark

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Müther, M., Stummer, W. Ependymal fluorescence in fluorescence-guided resection of malignant glioma: a systematic review. Acta Neurochir 162, 365–372 (2020). https://doi.org/10.1007/s00701-019-04144-4

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  • DOI: https://doi.org/10.1007/s00701-019-04144-4

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