Technical Pearls to Effectively Use 5-ALA in Fluorescence-Guided Tumor Resection—5 Lessons from the Operating Room

Background: Since its introduction in 2007 in Europe and in 2017 in the United States, 5-ALA has demonstrated an undisputed advantage in providing real-time tumor visualization. The aim of the present paper is to summarize our institutional experience over a decade of routine 5-ALA-guided procedures in order to provide five surgical tricks to ease surgical workflow. Methods: Data were collected from 822 patients diagnosed with histopathologically confirmed high-grade gliomas (HGG)—according to the WHO 2021 criteria—who underwent surgery at the Fondazione Policlinico Universitario Agostino Gemelli between January 2012 and January 2022. Results: From our large institutional experience, the learned technical pearls were grouped in five distinct domains: 1. Analysis of visualization, overall workflow, and technical recommendations to improve intraoperative set-up; 2. Techniques to reduce the risk of inadvertent residuals and failure to evocate fluorescence; 3. Analysis of specific surgical conditions favoring remnants; 4. Assessment of different degrees of fluorescence and their surgical meaning; 5. Analysis of false positive cases. Conclusions: With all the limitations of a qualitative and retrospective analysis, this paper was specifically conceived as a vademecum for educational purposes to promote and maximize 5-ALA employment.