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Confocal laser technology has been recently suggested as a promising method to obtain near real-time intraoperative histological data. We recently demonstrated the accuracy of a newly designed confocal endomiscroscope (CONVIVO) in offering an intraoperative diagnosis during high-grade gliomas (HGGs) removal in an ex vivo study. With this work we aim to perform a standardized, prospective and blinded-to-histological section study for evaluating the potentiality of CONVIVO in offering in vivo data regarding histological diagnosis and presence of tumor at margins during resection of central nervous system (CNS) tumors.This prospective, observational, standardized, blinded-to-histological section, clinical trial was approved by the institutional review board in Fondazione IRCCS Istituto Neurologico Carlo Besta in Milan and is expected to last 24 months. 75 patients will be included, with at least 53 of them being HGGs based on the statistical sample size calculation. Main objectives will be the assessing of the concordance of tumor diagnoses between CONVIVO images and frozen section at the center of all tumor subtypes and the evaluation of the accuracy of CONVIVO in the identification of tumor tissue at the margins, compared to standard histology. For this purpose, "virtual biopsies" and physical biopsies will be performed directly on patient tumor tissue and surrounding brain parenchima during tumor resection, comparing the results of CONVIVO analysis and frozen and histological sections.Despite promising preliminary data on ex vivo usefulness of CLE machines are emerging in literature, still few studies are available when looking at in vivo potentiality of CONVIVO. At this regard, this study will be the first work where a standardized, prospective, and blinded-to-histological section CONVIVO analysis will be performed in an in vivo setting in neuro-oncological surgery.We hypothesize that this new technique may have a role in offering data regarding presence of tumor tissue, eventually giving an intraoperative diagnosis in neurooncological surgery, rendering more fluid the decision-making process in the operating room. Furthermore, the result of this study will provide a solid base for further expanding the clinical applications of confocal machines in neurosurgery.

Background Surgery has a fundamental role in central nervous system (CNS) tumors in the pediatric population, as aggressive resection correlates with prognosis. Due to its accumulation in areas with damaged blood brain barrier, sodium fluorescein (SF) could be a valid tool to improve the extent of resection in tumors enhancing at preoperative MRI. This study is aimed to systematically assess the utility of SF in a pediatric population. Methods Patient data were collected in two centers, one in Italy and the other in Germany. At the induction of anesthesia, SF was administered intravenously (5 mg/kg). Surgery was performed using a YELLOW560 filter. Fluorescence intensity was graduated as bright, moderate or absent based on surgeon's opinion; furthermore, SF use was judged as "helpful," "not helpful" or "not essential" in tumor removal. Results Twenty-four patients for 27 surgical procedures were identified. In 21 of 27 (77.8%) procedures fluorescence was reported as bright or moderate, in two of 27 (7.4%) absent and in four of 27 (14.8%) data were unavailable. Intraoperative fluorescence was reported in 21 of 25 (84%) surgeries whose corresponding preoperative MRI had shown contrast enhancement. In 14 of 27 (51.8%) surgical procedures SF was considered "helpful"; in two of 27 (7.4%) not "helpful"; in seven of 27 (25.9%) "not essential." In four of 27 (14.8%) data were unavailable. No adverse effect to SF was registered. Conclusions SF could be considered a valid and safe tool to improve visualization of tumors enhancing at preoperative MRI also in pediatric patients. Future prospective studies are needed to confirm these preliminary data.

Background In recent years several techniques have been proposed with the aim of improving tumors visualization and extent of resection and, among them, the use of photosensitive dyes is gaining great interest. Regarding the application of the two most used dyes, 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF), there is still a lack of shared and established protocols among different centers. The main objective of the present study was to evaluate the current practice of fluorescence-guided techniques in neuro-oncological surgery in Europe. Methods An online questionnaire consisting of 33 questions was completed by 136 European Association of Neurosurgical Societies neurosurgeons. Responses were entered into a database and subsequently analyzed. Results Data were analyzed from 136 out of 1476 active European neurosurgeons which had been contacted, with a 9,2% response rate. Based on the data from the questionnaire, Germany was the most responsive country (15% of the total respondents) and the main indication for 5-ALA and SF utilization were high-grade gliomas. 5-ALA was mainly used as defined in Gliolan® datasheet, while SF as off-label technique with a 5 mg/kg dose of injection at the end of patient intubation. Both the dyes were mainly used in adult population, more frequently by neurosurgeons with less-than 20 cases per year expertise. Mean price per patient were 817,6 € and 7,7 € for 5-ALA and SF, respectively. Conclusions 5-ALA acid is still the preferred and more established fluorescent dye used during high-grade gliomas resection, with SF as a gaining-attention, really cheaper and more ductile alternative.