Combined Fluorescence Using 5-Aminolevulinic Acid and Fluorescein Sodium at Glioblastoma Border: Intraoperative Findings and Histopathologic Data About 3 Newly Diagnosed Consecutive Cases

World Neurosurg. 2019 Feb:122:e856-e863. doi: 10.1016/j.wneu.2018.10.163. Epub 2018 Nov 2.

Abstract

Objective: Fluorescence-guided glioblastoma surgery is an intraoperative technique developed in recent years. Two main compounds have been used so far: 5-amilovelulinic acid (5-ALA) and fluorescein sodium (Fl-Na). Despite a large amount of literature on both techniques, few data are available on the use of both compounds in the same patient.

Methods: Three consecutive patients affected by a newly diagnosed glioblastoma underwent surgical resection using both 5-ALA and Fl-Na. 5-ALA was orally administered 3 hours before induction of anesthesia at a dosage of 20 mg/kg, whereas fluorescein was intravenously administered at induction of anesthesia at a dosage of 4 mg/kg. Tumor resection was carried out combining these fluorophores. At tumor borders, multiple samples were collected, and fluorescent pattern of each sample was registered. Samples were then analyzed by a neuropathologist blinded for intraoperative fluorescence findings.

Results: Eighteen samples were analyzed. At tumor margin, bright pink fluorescence was highly indicative of residual tumor (positive predictive value [PPV], 94%), and it was superior to faint pink and fluorescein (PPVs, 89% and 87%, respectively). The gradual reduction of pink fluorescence warned of the risk of gradually entering healthy tissue (specificity of 67% compared with 33% with fluorescein). Using 5-ALA, detecting no fluorescence was highly suggestive of healthy tissue (negative predictive value of 100% compared with 50% with fluorescence).

Conclusions: In our experience with 3 patients, the 2 techniques presented different advantages and limitations in specific steps of tumor resection, showing complementary properties. Larger studies are mandatory to investigate the synergistic use of both techniques.

Keywords: 5-ALA; Fluorescein; Glioblastoma; Tumor border.

MeSH terms

  • Aminolevulinic Acid / administration & dosage*
  • Aminolevulinic Acid / metabolism
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / surgery
  • Female
  • Fluorescein / administration & dosage*
  • Fluorescein / metabolism
  • Fluorescent Dyes / administration & dosage
  • Fluorescent Dyes / metabolism
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / metabolism
  • Glioblastoma / surgery
  • Humans
  • Male
  • Monitoring, Intraoperative / methods*
  • Optical Imaging / methods*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / metabolism

Substances

  • Fluorescent Dyes
  • Photosensitizing Agents
  • Aminolevulinic Acid
  • Fluorescein