Microvessel density (MVD) represents a measure of angiogenesis and may be used as an indicator of neoplastic aggressiveness. Vascular endothelial growth factor (VEGF) plays a pivotal role as angiogenic promoter by stimulating endothelial cell proliferation and migration and enhancing vascular permeability. The aim of this study was to investigate MVD and VEGF expression in human pituitary adenomas and normal pituitary gland tissues by immunohistochemistry, and to correlate data with clinical characteristics. Fragments from 46 pituitary adenomas (18 non-functioning, 12 ACTH-secreting, 12 GH-secreting, 4 PRL-secreting) and 19 specimens of normal anterior pituitary gland obtained at surgery were evaluated. MVD in normal anterior pituitary was significantly higher than in tumors (69.2 +/- 28.5 vs 29.3 +/- 19.7; p < 0.0001). Within adenomas, no difference was found in MVD when different histotype, size, sex, age, rate of recurrence or medical pre-surgical treatment were considered. The degree of vascularity was somewhat related only to clinical invasiveness, as evaluated by pre-surgical MRI grading (grade 0 p < 0.05 vs grade 1 and vs grade 2). No statistically significant difference in VEGF expression was found between normal tissue and adenomas and among tumors of different histotype (p = 0.3978). Size, sex, age, rate of recurrence and medical pre-surgical treatment did not influence VEGF expression. No correlation was found between MVD and VEGF expression. In conclusion, MVD was reduced in pituitary adenomas with respect to normal gland. VEGF expression is however well preserved in adenomas and this might contribute to adequate tumoral vascular supply with complex mechanisms other than endothelial cells proliferation.

The European Stroke Organisation (ESO) guidelines on Moyamoya Angiopathy (MMA), developed according to ESO standard operating procedure and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, were compiled to assist clinicians in managing patients with MMA in their decision making. A working group involving neurologists, neurosurgeons, a geneticist and methodologists identified nine relevant clinical questions, performed systematic literature reviews and, whenever possible, meta-analyses. Quality assessment of the available evidence was made with specific recommendations. In the absence of sufficient evidence to provide recommendations, Expert Consensus Statements were formulated. Based on low quality evidence from one RCT, we recommend direct bypass surgery in adult patients with haemorrhagic presentation. For ischaemic adult patients and children, we suggest revascularization surgery using direct or combined technique rather than indirect, in the presence of haemodynamic impairment and with an interval of 6–12 weeks between the last cerebrovascular event and surgery. In the absence of robust trial, an Expert Consensus was reached recommending long-term antiplatelet therapy in non-haemorrhagic MMA, as it may reduce risk of embolic stroke. We also agreed on the utility of performing pre- and post- operative haemodynamic and posterior cerebral artery assessment. There were insufficient data to recommend systematic variant screening of RNF213 p.R4810K. Additionally, we suggest that long-term MMA neuroimaging follow up may guide therapeutic decision making by assessing the disease progression. We believe that this guideline, which is the first comprehensive European guideline on MMA management using GRADE methods will assist clinicians to choose the most effective management strategy for MMA.

Given the established direct correlation that exists among extent of resection and postoperative survival in brain tumors, obtaining complete resections is of primary importance. Apart from the various technological advancements that have been introduced in current clinical practice, histopathological study still remains the gold-standard for definitive diagnosis. Frozen section analysis still represents the most rapid and used intraoperative histopathological method that allows for an intraoperative differential diagnosis. Nevertheless, such technique owes some intrinsic limitations that limit its overall potential in obtaining real-time diagnosis during surgery. In this context, confocal laser technology has been suggested as a promising method to have near real-time intraoperative histological images in neurosurgery, thanks to the results of various studies performed in other non-neurosurgical fields. Still far to be routinely implemented in current neurosurgical practice, pertinent literature is growing quickly, and various reports have recently demonstrated the utility of this technology in both preclinical and clinical settings in identifying brain tumors, microvasculature, and tumor margins, when coupled to the intravenous administration of sodium fluorescein. Specifically in neurosurgery, among different available devices, the ZEISS CONVIVO system probably boasts the most recent and largest number of experimental studies assessing its usefulness, which has been confirmed for identifying brain tumors, offering a diagnosis and distinguishing between healthy and pathologic tissue, and studying brain vessels. The main objective of this systematic review is to present a state-of-the-art summary on sodium fluorescein-based preclinical and clinical applications of the ZEISS CONVIVO in neurosurgery.

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