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Influence of dexamethasone on visible 5-ALA fluorescence and quantitative protoporphyrin IX accumulation measured by fluorescence lifetime imaging in glioblastomas: is pretreatment obligatory before fluorescence-guided surgery?

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TLDR
In this paper, the influence of dexamethasone on visible fluorescence and quantitative PpIX accumulation was investigated and no significant influence was found on either visible 5-aminolevulinic acid (5-ALA) fluorescence during GBM surgery or Ppix accumulation based on FLIM.
Abstract
Objective Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is nowadays widely applied for improved resection of glioblastomas (GBMs). Initially, pretreatment with dexamethasone was considered to be essential for optimal fluorescence effect. However, recent studies reported comparably high rates of visible fluorescence in GBMs despite absence of dexamethasone pretreatment. Recently, the authors proposed fluorescence lifetime imaging (FLIM) for the quantitative analysis of 5-ALA-induced protoporphyrin IX (PpIX) accumulation. The aim of this study was thus to investigate the influence of dexamethasone on visible fluorescence and quantitative PpIX accumulation. Methods The authors prospectively analyzed the presence of visible fluorescence during surgery in a cohort of patients with GBMs. In this study, patients received dexamethasone preoperatively only if clinically indicated. One representative tumor sample was collected from each GBM, and PpIX accumulation was analyzed ex vivo by FLIM. The visible fluorescence status and mean FLIM values were correlated with preoperative intake of dexamethasone. Results In total, two subgroups with (n = 27) and without (n = 20) pretreatment with dexamethasone were analyzed. All patients showed visible fluorescence independent from preoperative dexamethasone intake. Furthermore, the authors did not find a statistically significant difference in the mean FLIM values between patients with and without dexamethasone pretreatment (p = 0.097). Conclusions In this first study to date, the authors found no significant influence of dexamethasone pretreatment on either visible 5-ALA fluorescence during GBM surgery or PpIX accumulation based on FLIM. According to these preliminary data, the authors recommend administering dexamethasone prior to fluorescence-guided surgery of GBMs only when clinically indicated.

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Citations
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Raman Imaging and Fluorescence Lifetime Imaging Microscopy for Diagnosis of Cancer State and Metabolic Monitoring.

TL;DR: In this paper, a combination of non-invasive and molecular-sensitive in situ techniques and advanced 3D tumor models such as patient-derived organoids or microtumors allows the recapitulation of tumor physiology and metabolism and facilitates the screening for patient-individualized drug treatment options.
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Analysis of corticosteroid and antiepileptic drug treatment effects on heme biosynthesis mRNA expression in lower-grade gliomas: potential implications for 5-ALA metabolization.

TL;DR: In this article , the effect of preoperative corticosteroid/AED treatment on heme biosynthesis mRNA expression in a clinically relevant patient population was investigated and no significant differences in expression of any of the 11 investigated heme enzymes/transporters were found.
References
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Journal ArticleDOI

The 2007 WHO Classification of Tumours of the Central Nervous System

TL;DR: The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneurs tumour of the fourth ventricle, Papillary tumourof the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis.
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Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial.

TL;DR: Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.
Journal ArticleDOI

Fluorescence Lifetime Measurements and Biological Imaging

TL;DR: The lifetime of a photophysical process is the time required by a population of N electronically excited molecules to be reduced by a factor of e via the loss of energy through fluorescence and other non-radiative processes and the average length of time τ is called the mean lifetime, or simply lifetime.
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Glioma extent of resection and its impact on patient outcome.

TL;DR: Despite persistent limitations in the quality of data, mounting evidence suggests that more extensive surgical resection is associated with longer life expectancy for both low- and high-grade gliomas.
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Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias.

TL;DR: The present data provide Level 2b evidence (Oxford Centre for Evidence-based Medicine) that survival depends on complete resection of enhancing tumor in glioblastoma multiforme and treatment bias was demonstrated regarding resection and second-line therapies.
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