Abstract
Background
Microsurgical, circumferential stripping of intracerebral metastases often proves to be insufficient to prevent local tumor recurrence.
Objective
We were interested in the potential impact of 5-aminolevulinic acid (5-ALA)-induced-fluorescence (5-AIF) as a diagnostic tool for the resection of intracerebral metastases.
Methods
A retrospective analysis was performed for 52 patients who underwent 5-AIF-guided resection for intracerebral mass lesions that histologically corresponded to metastases from tumors outside the central nervous system. The presence of ALA fluorescence in the tumor was determined in each patient. In 42 patients, fluorescence of the resection cavity after tumor removal was additionally recorded. Data were correlated with neuropathological findings in tissue specimens.
Results
A total of 32 of the 52 metastases (62%) exhibited 5-AIF in tumor parts. All 5-AIF-positive metastases exhibited an inhomogeneous fluorescence pattern. 5-AIF was neither associated with the histological type nor with the site of origin of the metastases. Residual fluorescence of the resection cavity was detected after macroscopically complete white light resection in 24 patients with 5-AIF positive metastases. Residual tumor tissue was histologically confirmed in 6 of 18 patients with available tissue specimens from such 5-AIF positive areas (33%).
Conclusions
The majority of metastases (62%) were 5-AIF positive, suggesting a potential impact of 5-AIF for improved visualization of metastatic tumor tissue within the brain. However, residual 5-AIF after macroscopically complete resection of a metastasis needs to be interpreted with caution because of the limited specificity for detection of residual tumor tissue.
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References
Baas P, Triesscheijn M, Burgers S, van Pel R, Stewart F, Aalders M (2006) Fluorescence detection of pleural malignancies using 5-aminolaevulinic acid. Chest 129(3):718–724
Baumert BG, Rutten I, Dehing-Oberije C, Twijnstra A, Dirx MJ, Debougnoux-Huppertz RM, Lambin P, Kubat B (2006) A pathology-based substrate for target definition in radiosurgery of brain metastases. Int J Radiat Oncol Biol Phys 66(1):187–194
Brahimi-Horn MC, Chiche J, Pouyssegur J (2007) Hypoxia and cancer. J Mol Med 85(12):1301–1307
Brahimi-Horn MC, Chiche J, Pouyssegur J (2007) Hypoxia signalling controls metabolic demand. Curr Opin Cell Biol 19(2):223–229
DeAngelis LM (2001) Brain tumors. N Engl J Med 344(2):114–123
Felsberg J, Thon N, Eigenbrod S, Hentschel B, Sabel MC, Westphal M, Schackert G, Wilhelm, Kreth F, Pietsch T, Loeffler M, Weller M, Reifenberger G and Tonn JC (2011) Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6, and PMS2 in paired primary and recurrent glioblastomas. Int J Cancer
Gamarra F, Lingk P, Marmarova A, Edelmann M, Hautmann H, Stepp H, Baumgartner R, Huber RM (2004) 5-Aminolevulinic acid-induced fluorescence in bronchial tumours: dependency on the patterns of tumour invasion. J Photochem Photobiol B 73(1–2):35–42
Grimbergen MC, van Swol CF, van Moorselaar RJ, Uff J, Mahadevan-Jansen A, Stone N (2009) Raman spectroscopy of bladder tissue in the presence of 5-aminolevulinic acid. J Photochem Photobiol B 95(3):170–176
Huber RM, Gamarra F, Hautmann H, Häußinger R, Wagner S, Castro M, Baumgartner R (1999) 5-Aminolaevulinic Acid (ALA) for the fluorescence detection of bronchial tumors. Diagn Ther Endosc 5:113–118
Jenkinson MD, Haylock B, Shenoy A, Husband D, Javadpour M (2011) Management of cerebral metastasis: Evidence-based approach for surgery, stereotactic radiosurgery and radiotherapy. Eur J Cancer 47(5):649–655
Kemmner W, Wan K, Ruttinger S, Ebert B, Macdonald R, Klamm U, Moesta KT (2008) Silencing of human ferrochelatase causes abundant protoporphyrin-IX accumulation in colon cancer. FASEB J 22(2):500–509
Krammer B, Plaetzer K (2008) ALA and its clinical impact, from bench to bedside. Photochem Photobiol Sci 7(3):283–289
Leonhard M (1999) New incoherent autofluorescence/fluorescence system for early detection of lung cancer. Diagn Ther Endosc 5:71–75
Liu YL, Ang SO, Weigent DA, Prchal JT, Bloomer JR (2004) Regulation of ferrochelatase gene expression by hypoxia. Life Sci 75(17):2035–2043
Neves S, Mazal PR, Wanschitz J, Rudnay AC, Drlicek M, Czech T, Wustinger C, Budka H (2001) Pseudogliomatous growth pattern of anaplastic small cell carcinomas metastatic to the brain. Clin Neuropathol 20(1):38–42
Pichlmeier U, Bink A, Schackert G, Stummer W (2008) Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients. Neuro Oncol 10(6):1025–1034
Stummer W, Hassan A, Kempski O, Goetz C (1996) Photodynamic therapy within edematous brain tissue: considerations on sensitizer dose and time point of laser irradiation. J Photochem Photobiol B 36(2):179–181
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
Teng L, Nakada M, Zhao SG, Endo Y, Furuyama N, Nambu E, Pyko IV, Hayashi Y, Hamada JI (2011) Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy. Br J Cancer 104(5):798–807
Utsuki S, Miyoshi N, Oka H, Miyajima Y, Shimizu S, Suzuki S, Fujii K (2007) Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic acid-induced protoporphyrin IX: pathological study. Brain Tumor Pathol 24(2):53–55
Yoo H, Kim YZ, Nam BH, Shin SH, Yang HS, Lee JS, Zo JI, Lee SH (2009) Reduced local recurrence of a single brain metastasis through microscopic total resection. J Neurosurg 110(4):730–736
Zaak D, Sroka R, Khoder W, Adam C, Tritschler S, Karl A, Reich O, Knuechel R, Baumgartner R, Tilki D, Popken G, Hofstetter A, Stief CG (2008) Photodynamic diagnosis of prostate cancer using 5-aminolevulinic acid–first clinical experiences. Urology 72(2):345–348
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Comment
5-Aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: a retrospective study
At the authors’ institute, a total of 471 patients underwent open 5-ALA-guided resection for intracerebral lesions preoperatively considered as high-grade gliomas. It turned out that 52 lesions were actually intracerebral metastases, an unexpected research window. Of the 52 metastases, 32 (62%) exhibited 5-ALA-fluorescence, not associated with the histological type or site of origin of the metastases. Furthermore, in 24 (75%) of the 32 fluorescent metastases, there was recidual fluorescence in the cavity wall after seemingly complete removal under white light, confirmed histologically in 6 of the 18 patients with tissue specimens from fluorescent areas in the cavity wall.
This is an important pilot study, awaiting verification by others. Most importantly, these data support the view that many metastases infiltrate the edematous/gliotic brain around them and therefore require more drastic measures than microsurgical removal in white light only.
Juha E Jääskeläinen
Kuopio, Finland
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Kamp, M.A., Grosser, P., Felsberg, J. et al. 5-Aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: a retrospective study. Acta Neurochir 154, 223–228 (2012). https://doi.org/10.1007/s00701-011-1200-5
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DOI: https://doi.org/10.1007/s00701-011-1200-5