5-Aminolevulinic acid–enhanced fluorescence-guided treatment of high-grade glioma using angled endoscopic blue light visualization: technical case series with preliminary follow-up
Open accessAbstract
OBJECTIVE: 5-Aminolevulinic acid (5-ALA)–enhanced fluorescence-guided resection of high-grade glioma (HGG) using microscopic blue light visualization offers the ability to improve extent of resection (EOR); however, few descriptions of HGG resection performed using endoscopic blue light visualization are currently available. In this report, the authors sought to describe their surgical experience and patient outcomes of 5-ALA–enhanced fluorescence-guided resection of HGG using primary or adjunctive endoscopic blue light visualization. METHODS: The authors performed a retrospective review of prospectively collected data from 30 consecutive patients who underwent 5-ALA–enhanced fluorescence-guided biopsy or resection of newly diagnosed HGG was performed. Patient demographic data, tumor characteristics, surgical technique, EOR, tumor fluorescence patterns, and progression-free survival were recorded. RESULTS: In total, 30 newly diagnosed HGG patients were included for analysis. The endoscope was utilized for direct 5-ALA–guided port-based biopsy (n = 9), microscopic to endoscopic (M2E; n = 18) resection, or exoscopic to endoscopic (E2E; n = 3) resection. All endoscopic biopsies of fluorescent tissue were diagnostic. 5-ALA–enhanced tumor fluorescence was visible in all glioblastoma cases, but only in 50% of anaplastic astrocytoma cases and no anaplastic oligodendroglioma cases. Gross-total resection (GTR) was achieved in 10 patients in whom complete resection was considered safe, with 11 patients undergoing subtotal resection. In all cases, endoscopic fluorescence was more avid than microscopic fluorescence. The endoscope offered the ability to diagnose and resect additional tumor not visualized by the microscope in 83.3% (n = 10/12) of glioblastoma cases, driven by angled lenses and increased fluorescence facilitated by light source delivery within the cavity. Mean volumetric EOR was 90.7% in all resection patients and 98.8% in patients undergoing planned GTR. No complications were attributable to 5-ALA or blue light endoscopy. CONCLUSIONS: The blue light endoscope is a viable primary or adjunctive visualization platform for optimization of 5-ALA–enhanced HGG fluorescence. Implementation of the blue light endoscope to guide resection of HGG glioma is feasible and ergonomically favorable, with a potential advantage of enabling increased detection of tumor fluorescence in deep surgical cavities compared to the microscope.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Endoscopes with angled lenses increase PpIX detection by providing focused light illumination within the cavity, resulting in the diagnosis and resection of glioblastomas that were not visible by the microscope in 10 out of 12 (83.3%) patients.
“Endoscopes with angled lenses are able to increase PpIX detection by providing focused light illumination within the cavity, resulting in the diagnosis and resection of glioblastomas that were not visible by the microscope in 10 out of 12 (83.3%) patients [77].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [77]
Cites
Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043330 · Cited by 21,807 · see citing works
Stummer, W., Pichlmeier, U., Meinel, T., Wiestler, O. D., Zanella, F., & Reulen, H.-J. (2006) · The Lancet Oncology · doi:10.1016/s1470-2045(06)70665-9 · Cited by 3,423 · see citing works
Lacroix, M., Abi-Said, D., Fourney, D. R., V, Gokaslan, Z. L., Shi, W., DeMonte, F., Lang, F. F., McCutcheon, I. E., Hassenbusch, S. J., Holland, E. C., et al. (2001) · Journal of neurosurgery · doi:10.3171/jns.2001.95.2.0190 · Cited by 3,095 · see citing works
An extent of resection threshold for newly diagnosed glioblastomas
Sanai, N., Polley, M. C., McDermott, M. W., Parsa, A. T., & Berger, M. S. (2011) · Journal of neurosurgery · doi:10.3171/2011.2.jns10998 · Cited by 1,650 · see citing works
GLIOMA EXTENT OF RESECTION AND ITS IMPACT ON PATIENT OUTCOME
Sanai, N., & Berger, M. S. (2008) · Neurosurgery · doi:10.1227/01.neu.0000318159.21731.cf · Cited by 1,323 · see citing works
Association of the Extent of Resection With Survival in Glioblastoma
Brown, T. J., Brennan, M., Li, M. J., Church, E. W., Brandmeir, N. J., Rakszawski, K. L., Patel, A. S., Rizk, E., Suki, D., Sawaya, R. A., et al. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.1373 · Cited by 1,087 · see citing works
EXTENT OF RESECTION AND SURVIVAL IN GLIOBLASTOMA MULTIFORME
Stummer, W., Reulen, H. J., Meinel, T., Pichlmeier, U., Schumacher, W., Tonn, J., Rohde, V., Oppel, F., Turowski, B., Woiciechowsky, C., et al. (2008) · Neurosurgery · doi:10.1227/01.neu.0000317304.31579.17 · Cited by 1,033 · see citing works
Stummer, W., Novotny, A., Stepp, H., Goetz, C., Bise, K., & Reulen, H. J. (2000) · Journal of Neurosurgery · doi:10.3171/jns.2000.93.6.1003 · Cited by 881 · see citing works
Walter, S., Susanne, S., Simon, W., Herbert, S., Clemens, F., Claudia, G., Alwin, E. G., Rainer, K., & Hans, J. R. (1998) · Neurosurgery · doi:10.1097/00006123-199803000-00017 · Cited by 690 · see citing works
Hadjipanayis, C. G., Widhalm, G., & Stummer, W. (2015) · Neurosurgery · doi:10.1227/neu.0000000000000929 · Cited by 369 · see citing works
5-Aminolevulinic Acid-derived Tumor Fluorescence
Stummer, W., Tonn, J., Goetz, C., Ullrich, W., Stepp, H. G., Bink, A., Pietsch, T., & Pichlmeier, U. (2013) · Neurosurgery · doi:10.1227/neu.0000000000000267 · Cited by 278 · see citing works
Neuronavigation in the surgical management of brain tumors: current and future trends
Orringer, D. A., Golby, A. J., & Jolesz, F. A. (2012) · Expert Review of Medical Devices · doi:10.1586/erd.12.42 · Cited by 267 · see citing works
Widhalm, G., Wolfsberger, S., Minchev, G., Wöehrer, A., Krššák, M., Czech, T., Prayer, D., Asenbaum, S., Hainfellner, J. A., & Knosp, E. (2010) · Cancer · doi:10.1002/cncr.24903 · Cited by 214 · see citing works
Lau, D., Hervey‐Jumper, S. L., Chang, S. M., Molinaro, A. M., McDermott, M. W., Phillips, J. J., & Berger, M. S. (2015) · Journal of neurosurgery · doi:10.3171/2015.5.jns1577 · Cited by 172 · see citing works
Widhalm, G., Kiesel, B., Wöehrer, A., Traub‐Weidinger, T., Preusser, M., Marosi, C., Prayer, D., Hainfellner, J. A., Knosp, E., & Wolfsberger, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076988 · Cited by 168 · see citing works
Coburger, J., Engelke, J., Scheuerle, A., Thal, D. R., Hlaváč, M., Wirtz, C. R., & König, R. (2014) · Neurosurgical FOCUS · doi:10.3171/2013.11.focus13463 · Cited by 145 · see citing works
Little, A. S., Kelly, D. F., White, W. L., Gardner, P. A., Fernandez-Miranda, J. C., Chicoine, M. R., Barkhoudarian, G., Chandler, J. P., Prevedello, D. M., Liebelt, B. D., et al. (2019) · Journal of neurosurgery · doi:10.3171/2018.11.jns181238 · Cited by 131 · see citing works
Advances in Intraoperative Optics: A Brief Review of Current Exoscope Platforms
Langer, D. J., White, T. G., Schulder, M., Boockvar, J. A., Labib, M., & Lawton, M. T. (2019) · Operative Neurosurgery · doi:10.1093/ons/opz276 · Cited by 125 · see citing works
Chaichana, K. L., Jusué-Torres, I., Lemos, A. M., Gokaslan, A. K., Cabrera‐Aldana, E. E., Ashary, A., Olivi, A., & Quiñones‐Hinojosa, A. (2014) · Journal of Neuro-Oncology · doi:10.1007/s11060-014-1597-9 · Cited by 122 · see citing works
Newly Diagnosed Glioblastoma: A Review on Clinical Management.
Lukas, R. V., Wainwright, D. A., Ladomersky, E., Sachdev, S., Sonabend, A. M., & Stupp, R. (2019) · PubMed · Cited by 117 · see citing works
Lessons learned in the evolution of endoscopic skull base surgery
Schwartz, T. H., Morgenstern, P. F., & Anand, V. K. (2019) · Journal of neurosurgery · doi:10.3171/2018.10.jns182154 · Cited by 109 · see citing works
Widhalm, G., Minchev, G., Wöehrer, A., Preusser, M., Kiesel, B., Furtner, J., Mert, A., Ieva, A. D., Tomanek, B., Prayer, D., et al. (2012) · Neurosurgical Review · doi:10.1007/s10143-012-0374-5 · Cited by 101 · see citing works
For the European ALA Pediatric Brain Tumor Study Group, Stummer, W., Rodrigues, F., Schucht, P., Preuß, M., Wiewrodt, D., Nestler, U., Stein, M., Artero, J. M. C., Platania, N., et al. (2014) · Acta Neurochirurgica · doi:10.1007/s00701-014-2234-2 · Cited by 101 · see citing works
Gandhi, S., Meybodi, A. T., Belykh, E. G., Cavallo, C., Zhao, X., Syed, M. P., Moreira, L. B., Lawton, M. T., Nakaji, P., & Preul, M. C. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00620 · Cited by 95 · see citing works
Widhalm, G., Olson, J. D., Weller, J., Bravo, J. J., Han, S. J., Phillips, J. J., Hervey‐Jumper, S. L., Chang, S. M., Roberts, D. W., & Berger, M. S. (2019) · Journal of neurosurgery · doi:10.3171/2019.1.jns182614 · Cited by 84 · see citing works
Yamada, S., Muragaki, Y., Maruyama, T., Komori, T., & Okada, Y. (2015) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2015.01.005 · Cited by 81 · see citing works
Gogos, A., Young, J. S., Morshed, R. A., Avalos, L. N., Noss, R. S., Villanueva-Meyer, J. E., Hervey‐Jumper, S. L., & Berger, M. S. (2020) · Journal of neurosurgery · doi:10.3171/2020.3.jns193434 · Cited by 71 · see citing works
von Campe, G., Moschopulos, M., & Hefti, M. (2012) · Acta Neurochirurgica · doi:10.1007/s00701-012-1290-8 · Cited by 58 · see citing works
Ferreira, M. P., Ferreira, N. P., Filho, A. A. P., Filho, G. A. P., & Franciscatto, A. C. (2006) · Surgical Neurology · doi:10.1016/j.surneu.2005.11.036 · Cited by 58 · see citing works
Rapp, M., Kamp, M. A., Steiger, H., & Sabel, M. (2013) · World Neurosurgery · doi:10.1016/j.wneu.2013.07.002 · Cited by 57 · see citing works
Somma, A. D., Langdon, C., de Notaris, M., Reyes, L. A., Ortiz-Pérez, S., Alobid, I., & Enseñat, J. (2020) · Journal of neurosurgery · doi:10.3171/2020.4.jns20707 · Cited by 56 · see citing works
Kabuto, M., Kubota, T., Kobayashi, H., Nakagawa, T., Ishii, H., Takeuchi, H., Kitai, R., & Kodera, T. (1997) · Neurological Research · doi:10.1080/01616412.1997.11740766 · Cited by 47 · see citing works
Akshulakov, S., Kerimbayev, T. T., Biryuchkov, M. Y., Urunbayev, Y. A., Farhadi, D. S., & Byvaltsev, V. A. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00947 · Cited by 46 · see citing works
Millesi, M., Kiesel, B., Wöehrer, A., Mercea, P. A., Bissolo, M., Roetzer-Pejrimovsky, T., Wolfsberger, S., Furtner, J., Knosp, E., & Widhalm, G. (2019) · Neurosurgery · doi:10.1093/neuros/nyz086 · Cited by 45 · see citing works
Erkkilä, M. T., Bauer, B., Hecker‐Denschlag, N., Madera Medina, M. J., Leitgeb, R. A., Unterhuber, A., Gesperger, J., Roetzer, T., Hauger, C., Drexler, W., et al. (2019) · Journal of Biophotonics · doi:10.1002/jbio.201800378 · Cited by 39 · see citing works
Molina, E. S., Stögbauer, L., Jeibmann, A., Warneke, N., & Stummer, W. (2020) · Acta Neurochirurgica · doi:10.1007/s00701-020-04227-7 · Cited by 33 · see citing works
Kim, K.-R., & Park, J. Y. (2020) · Neurospine · doi:10.14245/ns.2040174.087 · Cited by 30 · see citing works
Valdebenito, S., Damico, D. C. S., & Eugenín, E. A. (2019) · Cancer Reports · doi:10.1002/cnr2.1220 · Cited by 29 · see citing works
Minimally Invasive Endoscopic Resection of Intraparenchymal Brain Tumors
Plaha, P., Livermore, L. J., Voets, N., Pereira, E. A. C., & Cudlip, S. (2014) · World Neurosurgery · doi:10.1016/j.wneu.2014.07.034 · Cited by 29 · see citing works
Transnasal endoscopic approach for pediatric skull base lesions: a case series
Quon, J. L., Kim, L. H., Hwang, P. H., Patel, Z. M., Grant, G. A., Cheshier, S. H., & Edwards, M. S. B. (2019) · Journal of Neurosurgery Pediatrics · doi:10.3171/2019.4.peds18693 · Cited by 28 · see citing works
Erkkilä, M. T., Reichert, D., Hecker‐Denschlag, N., Wilzbach, M., Hauger, C. G., Leitgeb, R. A., Gesperger, J., Kiesel, B., Roetzer-Pejrimovsky, T., Widhalm, G., et al. (2020) · Journal of Biomedical Optics · doi:10.1117/1.jbo.25.7.071202 · Cited by 22 · see citing works
Current clinical management of patients with glioblastoma
Lowe, S. R., Bhat, K., & Olar, A. (2019) · Cancer Reports · doi:10.1002/cnr2.1216 · Cited by 20 · see citing works
Endoscopic Fluorescence-Guided Resection Increases Radicality in Glioblastoma Surgery
Bettag, C., Hussein, A., Behme, D., Maragkou, T., Rohde, V., & Mielke, D. (2019) · Operative Neurosurgery · doi:10.1093/ons/opz082 · Cited by 17 · see citing works
Ohara, Y., Nakajima, Y., Kimura, T., Kikuchi, N., & Sagiuchi, T. (2020) · Neurospine · doi:10.14245/ns.2040172.086 · Cited by 16 · see citing works
Morshed, R. A., Han, S. J., Lau, D., & Berger, M. S. (2017) · Journal of neurosurgery · doi:10.3171/2017.1.jns161949 · Cited by 14 · see citing works
Achieving Higher Diagnostic Results in Stereotactic Brain Biopsy by Simple and Novel Technique
Gülşen, S. (2015) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2015.016 · Cited by 10 · see citing works
Illumination in Spinal Surgery Depending on Different Approaches and Light Sources
Wilbers, E., Ewelt, C., Schipmann, S., Stummer, W., & Klingenhöfer, M. (2017) · World Neurosurgery · doi:10.1016/j.wneu.2017.06.013 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy
Howley, R., Chandratre, S., & Chen, B. (2023) · Bioengineering · doi:10.3390/bioengineering10040496 · Cited by 33 · see citing works
Shah, S., Ivey, N. A., Matur, A. V., & Andaluz, N. O. (2023) · Tomography · doi:10.3390/tomography9050124 · Cited by 16 · see citing works
Gomes, F. C., Ferreira, M. Y., Larcipretti, A. L. L., Freitas, B. C. B., Andreão, F. F., Turpin, J., Bertani, R., Singha, S., Polverini, A. D., Ferreira, C. C., et al. (2024) · Journal of Neuro-Oncology · doi:10.1007/s11060-024-04779-z · Cited by 9 · see citing works
Ma, R., Livermore, L. J., Taylor, L., Laycock, J., Williams, S., Ansorge, O., Vallance, C., & Plaha, P. (2024) · World Neurosurgery · doi:10.1016/j.wneu.2024.03.067 · Cited by 6 · see citing works
Feng, J. J., Cheok, S. K., Shiroishi, M. S., & Zada, G. (2023) · Journal of Neurosurgery Case Lessons · doi:10.3171/case23558 · Cited by 5 · see citing works
Self-citationFluorescence navigation and endoscopic assistance in surgery for brain glioblastomas
Rynda, A. Y., Олюшин, В. Е., Михайлович, Р. Д., Zabrodskaya, Y. M., Ulitin, A., & Papayan, G. V. (2025) · Burdenko s Journal of Neurosurgery · doi:10.17116/neiro20258906128 · Cited by 3 · see citing works
Kazemi, F., Liu, J., Parker, M., Jimenez, A. E., Ahmed, A. K., Salvatori, R., Hamrahian, A. H., Rowan, N. R., Ramanathan, M., London, N. R., et al. (2025) · Pituitary · doi:10.1007/s11102-024-01496-8 · Cited by 3 · see citing works
Yoshida, M., Yamaguchi, S., Iwasaki, K., & Iwanaga, M. (2023) · Surgical Neurology International · doi:10.25259/sni_204_2023 · Cited by 1 · see citing works
Özdemir, Z., Molina, E. S., Hellwig, S. J., Stepp, H. G., & Stummer, W. (2023) · Neurosurgery Open · doi:10.1227/neuprac.0000000000000059 · Cited by 1 · see citing works
Ikeda, N., Furuse, M., Nonoguchi, N., Kawabata, S., Kameda, M., Yokoyama, K., Takami, T., Kawanishi, M., Kajimoto, Y., Kuroiwa, T., et al. (2023) · Nippon Laser Igakkaishi · doi:10.2530/jslsm.jslsm-44_0017
Jacobo, J. A., Aristizabal, J., & Cardona-Zorrilla, A. F. (2025) · Cureus · doi:10.7759/cureus.79083
Yang, M., Shah, I., Renn, A., Satish, V., Guerra, G. A., Gómez, D., Coté, D. J., Cheok, S. K., Peterson, R., Cardinal, T. M., et al. (2025) · Operative Neurosurgery · doi:10.1227/ons.0000000000001682
Self-citationHuq, S., Kallos, J. A., Boggs, K., Diamond, K., Scanlon, S. E., Bin-Alamer, O., Rivera, D., Pearce, T. M., & Hadjipanayis, C. G. (2025) · Operative Neurosurgery · doi:10.1227/ons.0000000000001798
Navigare necesse est: The transorbital route to intraparenchymal temporal lesions
Agosti, E., Gelmini, L., Corrivetti, F., İaconetta, G., Lavergne, P., Fontanella, M. M., Champagne, P., Kong, D., & de Notaris, M. (2026) · Neurosurgical Review · doi:10.1007/s10143-026-04402-x
Toyota, P. R., Liu, E., Gould, L., Norton, J., Slough, K., Appendino, J. P., Persad, A. R. L., & Hnenny, L. P. (2026) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2026.112368
- Authors
- Strickland, B. A., Wedemeyer, M., Ruzevick, J., Micko, A., Shahrestani, S., Daneshmand, S., Shiroishi, M. S., Hwang, D. H., Attenello, F., Chen, T., & Zada, G.
- Affiliations
- Neurological Surgery (US)
- Urology, and
- University of Southern California (US)
- Venue
- Journal of Neurosurgery
- Published
- 2022-11-01
- Volume
- 137
- Issue
- 5
- Pages
- 1378-1386
- ISSN
- 0022-3085 (ISSN-L)
- 1933-0693
- OpenAlex
- W4220681458
- Cited by
- 15
- References
- 47
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 6
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Journal of neurosurgery (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Health Sciences › Medicine › Neurology › Neurosurgical Procedures and Complications
- Keywords
- 5-aminolevulinic acid, fluorescence-guided surgery, high-grade glioma, glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, extent of resection, gross total resection, progression-free survival
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
