RESUMEN
Diffuse midline glioma (DMG) is a pediatric cancer that originates in the midline structures of the brain. Prognosis of DMG patients remains poor due to the infiltrative nature of these tumors and the protection they receive from systemically delivered therapeutics via an intact blood-brain barrier (BBB), making treatment difficult. While the cell of origin remains disputed, it is believed to reside in the ventral pons. Recent research has pointed toward epigenetic dysregulation inducing an OPC-like transcriptomic signature in DMG cells. This epigenetic dysregulation is typically caused by a mutation (K27M) in one of two histone genes-H3F3A or HIST1H3B -and can lead to a differentiation block that increases these cells oncogenic potential. Standard treatment with radiation is not sufficient at overcoming the aggressivity of this cancer and only confers a survival benefit of a few months, and thus, discovery of new therapeutics is of utmost importance. In this review, we discuss the cell of origin of DMGs, as well as the underlying molecular mechanisms that contribute to their aggressivity and resistance to treatment. Additionally, we outline the current standard of care for DMG patients and the potential future therapeutics for this cancer that are currently being tested in preclinical and clinical trials.
RESUMEN
Background: Surgery of parasagittal meningiomas (PSMs) is still technically challenging, for the balance between radical resection and preservation of venous circulation. In this article, we'd systemically introduce the technical nuances of a simplified strategy for radical resection of all types of PSMs. All the cases were operated by one single neurosurgeon from a single institution.Methods: Clinical charts of patients with PSMs between 2014 and 2020were retrospectively reviewed. A simplified classification method was adopted, which was based on the relationship between the tumor and superior sagittal sinus (SSS). Surgery aiming at radical resection and venous flow preservation was performed. Only in case of total occlusion of SSS, we performed tumor resection without reconstruction of the venous sinus.Results: Clinical data obtained in 55 consecutive patients (47 primary and 8 recurrent cases) were analyzed, among which 20 were with patent sinus, 27 were with partially occluded sinus and 8 were with completely occluded sinus. Forty-two (76.4%) and 13 patients (23.6%) had the same and improved functional status as compared to that of pre-operation, respectively. Four patients (7.3%) experienced transient neurological deterioration but improved to the normal level in the long-term follow-up. All patients achieved Simpson I/II radical resection. No patients suffered from post-operative recurrence in the follow-up duration of 27.05 ± 19.55 (2-91) months.Conclusion: Radical and safe resection of all types of PSMs is achievable and not difficult if the simplified surgical strategy mentioned in the article is adopted, no matter to which extent the sinus is invaded.
