Adjuncts for maximizing resection: 5-aminolevuinic acid.

The rationale for maximizing resection in surgery for malignant glioma has become broadly accepted in the neuro-oncology community, and technological adjuncts to facilitate achievement of this goal have incrementally assisted the neurosurgeon. One such adjunct of considerable interest today is 5-aminolevuinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence. Preoperative oral administration of 5-ALA leads to preferential accumulation of the fluorophore PpIX within tumor cells, and under the violet-blue light illumination of the surgical field with an adapted operating microscope, tumor tissue exhibits visible red and near-infrared fluorescence. A German multi-institutional trial in 2006 demonstrated the potential utility of this technique,1 and although Food and Drug Administration approval in the United States is still pending, Investigational New Drug (IND)-supported experience in this country has furthered our understanding of this technology. This article presents the background for this methodology, the early clinical experience, its practical utility in intraoperative tumor boundary appreciation, its role near the end of resection, the development of quantitative fluorescence techniques, the experience in low-grade gliomas, and the implications of using this technique with respect to the objectives of surgery.

[1]  A. Ehrhardt,et al.  Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor. , 2011, Journal of neurosurgery.

[2]  Xiaoyao Fan,et al.  Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker. , 2011, Journal of neurosurgery.

[3]  Keith D. Paulsen,et al.  Estimation of Brain Deformation for Volumetric Image Updating in Protoporphyrin IX Fluorescence-Guided Resection , 2009, Stereotactic and Functional Neurosurgery.

[4]  Y. Kajimoto,et al.  Endoscopic identification and biopsy sampling of an intraventricular malignant glioma using a 5-aminolevulinic acid-induced protoporphyrin IX fluorescence imaging system. Technical note. , 2007, Journal of neurosurgery.

[5]  Walter Stummer,et al.  Favorable outcome in the elderly cohort treated by concomitant temozolomide radiochemotherapy in a multicentric phase II safety study of 5-ALA , 2011, Journal of Neuro-Oncology.

[6]  Keith D. Paulsen,et al.  δ-aminolevulinic acid-induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy. , 2011, Neuro-oncology.

[7]  Frederic Leblond,et al.  Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery. , 2011, Journal of biomedical optics.

[8]  Y. Hayashi,et al.  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. , 2010, Journal of Neurosurgery.

[9]  G von Campe,et al.  5-aminolevulinic acid induced protoporphyrin IX fluorescence in high-grade glioma surgery: a one-year experience at a single institutuion. , 2008, Swiss medical weekly.

[10]  I. Yang 5-Aminolevulinic Acid Is a Promising Marker for Detection of Anaplastic Foci in Diffusely Infiltrating Gliomas With Nonsignificant Contrast Enhancement , 2011 .

[11]  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.

[12]  Xiaoyao Fan,et al.  Coregistered fluorescence-enhanced tumor resection of malignant glioma: relationships between δ-aminolevulinic acid-induced protoporphyrin IX fluorescence, magnetic resonance imaging enhancement, and neuropathological parameters. Clinical article. , 2011, Journal of neurosurgery.

[13]  Gabriele Schackert,et al.  Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients. , 2008, Neuro-oncology.

[14]  D. Prayer,et al.  5‐Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement , 2010, Cancer.

[15]  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.