Maximal safe resection represents the gold standard for surgery of malignant brain tumors. As regards gross-total resection, accurate localization and precise delineation of the tumor margins are required. Intraoperative diagnostic imaging (Intra-Operative Magnetic Resonance-IOMR, Intra-Operative Computed Tomography-IOCT, Intra-Operative Ultrasound-IOUS) and dyes (fluorescence) have become relevant in brain tumor surgery, allowing for a more radical and safer tumor resection. IOUS guidance for brain tumor surgery is accurate in distinguishing tumor from normal parenchyma, and it allows a real-time intraoperative visualization. We aim to evaluate the role of IOUS in gliomas surgery and to outline specific strategies to maximize its efficacy. We performed a literature research through the Pubmed database by selecting each article which was focused on the use of IOUS in brain tumor surgery, and in particular in glioma surgery, published in the last 15 years (from 2003 to 2018). We selected 39 papers concerning the use of IOUS in brain tumor surgery, including gliomas. IOUS exerts a notable attraction due to its low cost, minimal interruption of the operational flow, and lack of radiation exposure. Our literature review shows that increasing the use of ultrasound in brain tumors allows more radical resections, thus giving rise to increases in survival.

Gliomas have poor prognosis no matter the treatment applied, remaining an unmet clinical need. As background for a substantial change in this situation, this review will focus on the following points: (i) the steady progress in establishing the role of molecular chaperones in carcinogenesis; (ii) the recent advances in the knowledge of miRNAs in regulating gene expression, including genes involved in carcinogenesis and genes encoding chaperones; and (iii) the findings about exosomes and their cargo released by tumor cells. We would like to trigger a discussion about the involvement of exosomal chaperones and miRNAs in gliomagenesis. Chaperones may be either targets for therapy, due to their tumor-promoting activity, or therapeutic agents, due to their antitumor growth activity. Thus, chaperones may well represent a Janus-faced approach against tumors. This review focuses on extracellular chaperones as part of exosomes’ cargo, because of their potential as a new tool for the diagnosis and management of gliomas. Moreover, since exosomes transport chaperones and miRNAs (the latter possibly related to chaperone gene expression in the recipient cell), and probably deliver their cargo in the recipient cells, a new area of investigation is now open, which is bound to generate significant advances in the understanding and treatment of gliomas.

High-grade gliomas (HGGs) are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first step of multimodal therapy is an accepted goal in malignant glioma surgery. Gross total resection has an important role in improving overall survival (OS) and progression-free survival (PFS), but identification of tumor borders is particularly difficult in HGGS. For this reason, imaging adjuncts, such as 5-aminolevulinic acid (5-ALA) or fluorescein sodium (FS) have been proposed as superior strategies for better defining the limits of surgical resection for HGG. 5-aminolevulinic acid (5-ALA) is implicated as precursor in the synthetic pathway of heme group. Protoporphyrin IX (PpIX) is an intermediate compound of heme metabolism, which produces fluorescence when excited by appropriate light wavelength. Malignant glioma cells have the capacity to selectively synthesize or accumulate 5-ALA-derived porphyrins after exogenous administration of 5-ALA. Fluorescein sodium (FS), on the other hand, is a fluorescent substance that is not specific to tumor cells but actually it is a marker for compromised blood-brain barrier (BBB) areas. Its effectiveness is confirmed by multicenter phase-II trial (FLUOGLIO) but lack of randomized phase III trial data. We conducted an analytic review of the literature with the objective of identifying the usefulness of 5-ALA and FS in HGG surgery in adult patients.

The European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada Phase III trial has validated as a current regimen for high-grade gliomas (HGG) a maximal safe surgical resection followed by radiotherapy with concurrent temozolamide. However, it is essential to balance maximal tumor resection with preservation of the patient’s neurological functions. Important developments in the fields of pre-operative and intra-operative neuro-imaging and neuro-monitoring have ameliorated the survival rate and the quality of life for patients affected by HGG. Moreover, even though the natural history remains extremely poor, advancement in the molecular and genetic fields have opened up new potential frontiers in the management of this devastating brain disease. In this review, we aim to present a comprehensive account of the main current pre-operative, intra-operative and molecular approaches to HGG with particular attention to specific chaperones, also called heat shock proteins (Hsps), which represent potential novel biomarkers to detect and follow up HGG, and could also be therapeutic agents.

Diffuse idiopathic skeletal hyperostosis (DISH), also known as Forestier's disease, is a rheumatologic condition characterized by ossification of the spinal ligaments and tendons. Large anterior osteophytes are typically present in the lower cervical levels, while upper cervical ossification resulting in dysphagia is very rare. Here, we presented a patient with Forestier's disease involving massive ossification of the anterior longitudinal ligament extending from C3 to C4 downward contributing to severe dysphagia. A 65-year-old male presented with cervical pain and dysphagia. The computed tomography of the cervical spine demonstrated massive anterior longitudinal ligament ossification (DISH) extending from C3 to C7. There was an additional large osteophyte at the C3-C4 level, and also a high-grade intracanalicular C6-C7 cervical stenosis due to ossification of the posterior longitudinal ligament. The patient was offered surgical intervention (e.g., resection of the C3-C7 anterior DISH and anterior cervical discectomy/fusion at the C6-C7 level), but he declined. When conservative management fails to resolve severe dysphagia for cervical DISH/Forestier's disease, anterior surgical resection is typically performed. In this case, the patient refused surgery and opted for conservative management strategies.