Simultaneous fluorescein sodium and 5-ALA in fluorescence-guided glioma surgery.
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ABSTRACT:
SUBMITTER: Schwake M
PROVIDER: S-EPMC4477944 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC4644203 | biostudies-literature
Project description:Targeted treatment of high-grade gliomas (HGGs) is challenging due to intra- and inter-tumoral heterogeneity. Prognosis of these tumors relies largely on the extent of resection. Fluorescence guided surgery using 5-ALA as adjunct has been on the rise in the recent years. However, 5-ALA has been ineffective in a small subset of population with similar histological phenotypes but varying metabolic/biochemical properties. Visualized fluorescence can sometimes be subjective and lead to variability in defining fluorescing regions with respect to their biological grade. Objective assessment of fluorescence is possible using spectroscopic techniques and with ex vivo PpIX assessment assays. The biometric study in our previous work revealed that even with objective assessment using PpIX assays, there exists a small subpopulation of tumor cells with similar histological phenotypes but discordant metabolic/biochemical properties w.r.t accumulation of PpIX. In the current study, we extended the investigation further and have carried out proteomic analysis of high-grade glioma tissue samples resected using 5-ALA fluorescence guided surgery to understand molecular differences leading to differential fluorescence in these complex and heterogenous tumors.
2023-07-20 | PXD039170 | Pride
Project description:5-Aminolevulinic acid (5-ALA) is widely employed to assist fluorescence-guided surgery for malignant brain tumors. Positron emission tomography with 11C-methionine (MET-PET) represents the activity of brain tumors with precise boundaries but is not readily available. We hypothesized that quantitative 5-ALA-induced fluorescence intensity might correlate with MET-PET uptake in gliomas. Adult patients with supratentorial astrocytic gliomas who underwent preoperative MET-PET and surgical tumor resection using 5-ALA were enrolled in this prospective study. The regional tumor uptake of MET-PET was expressed as the ratio of standardized uptake volume max to that of the normal contralateral frontal lobe. A spectrometric fluorescence detection system measured tumor specimens' ex vivo fluorescence intensity at 635 nm. Ki-67 index and IDH mutation status were assessed by histopathological analysis. Use of an antiepileptic drug (AED) and contrast enhancement pattern on MRI were also investigated. Thirty-two patients, mostly with Glioblastoma IDH wild type (46.9%) and anaplastic astrocytoma IDH mutant (21.9%), were analyzed. When the fluorescence intensity was ranked into four groups, the strongest fluorescence group exhibited the highest mean MET-PET uptake and Ki-67 index values. When rearranged into fluorescence Visible or Non-visible groups, the Visible group had significantly higher MET-PET uptake and Ki-67 index compared to the Non-visible group. Contrast enhancement on MRI and IDH wild type tumors were more frequent among the Visible group. AED use did not correlate with 5-ALA-induced fluorescence intensity. In astrocytic glioma surgery, visible 5-ALA-induced fluorescence correlated with high MET-PET uptake, along with a high Ki-67 index.
| S-EPMC8946621 | biostudies-literature
Project description:The US Food and Drug Administration (FDA) approved 5-aminolevulinic acid (5-ALA; Gleolan®; photonamic GmbH and Co. KG) for use as an intraoperative optical imaging agent in patients with suspected high-grade gliomas (HGGs) in 2017. This was the first ever optical imaging agent approved as an adjunct for the visualization of malignant tissue during surgery for brain tumors. The approval occurred a decade after European approval and a multicenter, phase III randomized trial which confirmed that surgeons using 5-ALA fluorescence-guided surgery as a surgical adjunct could achieve more complete resections of tumors in HGG patients and better patient outcomes than with conventional microsurgery. Much of the delay in the US FDA approval of 5-ALA stemmed from its conceptualization as a therapeutic and not as an intraoperative imaging tool. We chronicle the challenges encountered during the US FDA approval process to highlight a new standard for approval of intraoperative optical imaging agents in brain tumors.
| S-EPMC6445645 | biostudies-literature
Project description:Simple Summary Surgical resection still plays an important role in the treatment of lung cancer with brain metastases. Accurately identifying the border between normal brain tissue and tumor invasion under the microscope to maximize the extent of resection without causing neurological dysfunction is critical but still challenging. Here, we introduced the utilization of sodium fluorescein in the surgical resection compared with the previous studies, focusing on brain metastases from lung cancer, the most common secondary malignant brain tumors, and included the control group. This study will provide a valuable reference for the precise surgical treatment of brain metastases from lung cancer. Abstract (1) Introduction and objective: Surgical resection plays an important role in the multidisciplinary treatment of lung cancer patients with brain metastases (BMs). Precisely distinguishing the tumor border intraoperatively to improve and maximize the extent of resection (EOR) without causing permanent neurological defects is crucial but still challenging. Therefore, we introduced our experience of utilizing sodium fluorescein (SF) in microneurosurgery of BMs from lung cancer. This study aims to evaluate whether the use of SF-guided surgery has a positive impact on postoperative outcomes. (2) Materials and methods: A retrospective study was performed to collect data on a consecutive case series of patients with BMs from lung cancer who underwent surgical resection from January 2020 to December 2021 at the Department of Neuro-Oncology, Chongqing University Cancer Hospital. A total of 52 patients were enrolled, of which 23 received SF-guided surgery and 29 did not. EOR was assessed pre- and postoperatively on T1 contrast-enhanced MRI. Clinical and epidemiological data as well as follow-up were gathered and analyzed. (3) Results: Compared with the non-SF-guided group, the SF-guided group revealed a significantly better EOR (87.0% vs. 62.1%) and a lower incidence of local recurrence (8.7% vs. 34.5%). Survival benefits were seen in patients with NSCLC, patients who were undergoing SF-guided surgery, and patients receiving postoperative systemic therapy. (4) Conclusions: SF-guiding under the YELLOW 560 nm filter is a safe and feasible tool for improving the EOR in patients with BMs from lung cancer, leading to better local recurrence control and prolonged survival.
| S-EPMC9913632 | biostudies-literature
Project description:BackgroundIndocyanine green (ICG) imaging has been increasingly used for intraoperative guidance in colorectal surgery over the past decade. The aim of this study was to review and organize, according to different type of use, all available literature on ICG guided colorectal surgery and highlight areas in need of further research and discuss future perspectives.MethodsPubMed, Scopus, and Google Scholar databases were searched systematically through November 2022 for all available studies on fluorescence-guided surgery in colorectal surgery.ResultsAvailable studies described ICG use in colorectal surgery for perfusion assessment, ureteral and urethral assessment, lymphatic mapping, and hepatic and peritoneal metastases assessment. Although the level of evidence is low, results are promising, especially in the role of ICG in reducing anastomotic leaks.ConclusionsICG imaging is a safe and relatively cheap imaging modality in colorectal surgery, especially for perfusion assessment. Work is underway regarding its use in lymphatic mapping, ureter identification, and the assessment of intraperitoneal metastatic disease.
| S-EPMC9865296 | biostudies-literature
Project description:Simple Summary 5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence is used in neurosurgery for intraoperative identification of high-grade glioma tissue. In this paper, using a fluorescence microscopy analysis on human tumor specimens, we assessed the actual number of fluorescence-positive tumor cells both in low-grade and high-grade glioma, and the ability of 5-ALA to cross the blood–brain barrier (BBB). We found that in high-grade gliomas, 32.7–75.5 percent of cells display 5-ALA induced PpIX fluorescence, whereas in low-grade gliomas the tumor cells did not fluoresce following 5-ALA. Immunofluorescence for BBB components suggested that 5-ALA does not cross the un-breached BBB. These findings are of crucial importance in planning neurosurgical resection of gliomas. Abstract 5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence is used by neurosurgeons to identify the tumor cells of high-grade gliomas during operation. However, the issue of whether 5-ALA-induced PpIX fluorescence consistently stains all the tumor cells is still debated. Here, we assessed the cytoplasmatic signal of 5-ALA by fluorescence microscopy in a series of human gliomas. As tumor markers, we used antibodies against collapsin response-mediated protein 5 (CRMP5), alpha thalassemia/mental retardation syndrome X-linked (ATRX), and anti-isocitrate dehydrogenase 1 (IDH1). In grade III–IV gliomas, the signal induced by 5-ALA was detected in 32.7–75.5 percent of CRMP5-expressing tumor cells. In low-grade gliomas (WHO grade II), the CRMP5-expressing tumor cells did not fluoresce following 5-ALA. Immunofluorescence with antibodies that stain various components of the blood–brain barrier (BBB) suggested that 5-ALA does not cross the un-breached BBB, in spite of its small dimension. To conclude, 5-ALA-induced PpIX fluorescence has an established role in high-grade glioma surgery, but it has limited usefulness in surgery for low-grade glioma, especially when the BBB is preserved.
| S-EPMC9221265 | biostudies-literature
Project description:The use of indocyanine green (ICG) fluorescence near-infrared (NIR) imaging during gastrointestinal surgery has surged in recent years. Its use in esophageal surgery is actively being studied both in the clinical setting and in the lab. NIR imaging has several important applications in esophageal surgery including assessing perfusion of the gastrointestinal-esophageal anastomosis, lymphatic drainage and tracheal blood flow after mediastinal dissection. This is a review of the modern literature summarizing the current knowledge on fluorescence-guided surgery of the esophagus.
| S-EPMC8184486 | biostudies-literature
Project description:BackgroundThe BLUE 400 filter system (Carl Zeiss Meditec, Oberkochen, Germany) has provided visualization of 5-ALA-induced fluorescence-guided surgery for more than 20 years. Nevertheless, constraints, e.g., limited background discrimination during hemostasis, obstruct fluency of surgery. A novel filter with improved background visualization was developed, requiring validation regarding fluorescence discrimination. The aim of this article is to determine diagnostic accuracy and perception of protoporphyrin IX (PpIX) discrimination of a novel filter system with higher background illumination (BLUE 400 AR) compared with the gold standard, BLUE 400.MethodsA surgical microscope equipped with both BLUE 400 and BLUE 400 AR was used. Comparisons were performed on a biological basis and on the visual perception of margins. High-resolution images were compared during and after surgery by senior neurosurgeons. In a predefined biopsy algorithm, four biopsies per patient at tumor margins of PpIX fluorescence and adjacent brain were acquired using BLUE 400 AR only from regions intended for resection and assessed for cell count and density.ResultsThirty-two patients with malignant gliomas were included in this study. BLUE 400 AR markedly enhanced the brightness of the surgical field, allowing superior discrimination of brain anatomy. A total of 128 biopsies from fluorescence margins were collected. Positive predictive value (PPV) was 98.44% (95% CI, 90.06-99.77%) for malignant glioma. Residual median cell density in non-fluorescent tissue was 13% (IQR 13 to 31). Perception of the location of fluorescent margins on HD images was equivalent for both filter combinations.ConclusionsBLUE 400 AR demonstrated superior background compared with conventional BLUE 400 in malignant glioma surgery but comparable fluorescence margins and PPV. Therefore, BLUE 400 AR can be considered safe and effective in supporting malignant glioma surgery.
| S-EPMC7066295 | biostudies-literature
Project description:Gliomas are infiltrative brain tumors with a margin difficult to identify. 5-ALA induced PpIX fluorescence measurements are a clinical standard, but expert-based classification models still lack sensitivity and specificity. Here a fully automatic clustering method is proposed to discriminate glioma margin. This is obtained from spectroscopic fluorescent measurements acquired with a recently introduced intraoperative set up. We describe a data-driven selection of best spectral features and show how this improves results of margin prediction from healthy tissue by comparison with the standard biomarker-based prediction. This pilot study based on 10 patients and 50 samples shows promising results with a best performance of 77% of accuracy in healthy tissue prediction from margin tissue.
| S-EPMC6989497 | biostudies-literature