Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD.

[1]  S. Kaneko A Current Overview : Photodynamic Diagnosis and Photodynamic Therapy using 5-Aminolevulinic Acid in Neurosurgery , 2008 .

[2]  M. Irie Brain Tumor Registry of Japan (2001–2004) , 2014, Neurologia medico-chirurgica.

[3]  日本脳神経外科学会 Report of brain tumor registry of Japan , 1969 .

[4]  H. Fukuda,et al.  Tumour-localizing properties of porphyrins. In vivo studies using free and liposome encapsulated aminolevulinic acid. , 1992, Comparative biochemistry and physiology. B, Comparative biochemistry.

[5]  M. Berger,et al.  The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere. , 1999, Surgical neurology.

[6]  F. Zanella,et al.  Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. , 2006, The Lancet. Oncology.

[7]  Jörg-Christian Tonn,et al.  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. , 2011, Journal of neurosurgery.

[8]  W. Stummer,et al.  In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid. , 1998, Journal of photochemistry and photobiology. B, Biology.

[9]  S. Kaneko [Intraoperative photodynamic diagnosis of human glioma using ALA induced protoporphyrin IX]. , 2001, No shinkei geka. Neurological surgery.

[10]  Z L Gokaslan,et al.  A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. , 2001, Journal of neurosurgery.

[11]  H Stepp,et al.  Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. , 2000, Journal of neurosurgery.