Irreversible Inhibition of Epidermal Growth Factor Receptor Activity by 3-Aminopropanamides
Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with a conserved cysteine residue in the kinase domain. The acrylamide fragment, a commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions with off-targets. We describe here a new series of irreversible inhibitors containing a 3-aminopropanamide linked in position 6 to 4-anilinoquinazoline or 4-anilinoquinoline-3- carbonitrile driving portions. Some of these compounds proved to be as efficient as their acrylamide analogues in inhibiting EGFR-TK (TK = tyrosine kinase) autophosphorylati…
With a Little Help from My Friends: The Role of Intraoperative Fluorescent Dyes in the Surgical Management of High-Grade 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 i…
Preliminary Experience with a Novel System of Facet Fixation to Treat Patients with Lumbar Degenerative Disease. A New Perspective in Minimally Invasive Spine Surgery?
Purpose We report our experience with a novel surgical device for the treatment of lumbar degenerative microinstability. Facet Wedge (DePuy Synthes, Raynham, Massachusetts, United States) is a novel technique of intra-articular lumbar facet fixation that provides a minimally invasive alternative to standard posterior fixation. Materials and Methods From November 2014 to July 2015, 38 patients underwent single-level Facet Wedge implantation. The main surgical indications included herniated disk (18 patients), spinal canal and foraminal stenosis (14 patients), and Meyerding grade I degenerative spondylolisthesis (6 patients). All the patients showed radiologic signs of microinstability: hype…
Fluorescein for resection of high-grade gliomas: A safety study control in a single center and review of the literature
Background: The importance of a complete resection of high-grade gliomas (HGGs) has been highlighted in scientific literature, in order to limit tumor recurrence and above all to improve disease-free survival rates. Several fluorescent biomarkers have been tested to improve intraoperative identification of residual tumor; 5-aminolevulinic acid (5-ALA) and fluorescein sodium (FS) are now starting to play a central role in glioma surgery. We performed a retrospective analysis on 47 patients operated for HGGs. Here we report our preliminary data. Methods: Data of 47 consecutive patients with HGG have been collected in our study (25 males, 22 females; mean age: 60.3 years, range: 27-86 years). …
Unusual recurrence of trigeminal neuralgia after microvascular decompression by muscle interposal.
Summary Background Patients with trigeminal neuralgia (TN) and persistent or recurrent facial pain after microvascular decompression (MVD) typically undergo less invasive procedures in the hope of providing pain relief. However, re-operation should be considered in selected patients. Case Report A 48-year-old woman presented with recurrent trigeminal neuralgia (TN) 3 years following microvascular decompression (MVD). The patient underwent brain magnetic resonance angiography (MRA), which did not reveal neurovascular compression; therefore surgical re-exploration was carried out. During the operation, the fifth cranial nerve was seen without impingement from any blood vessels; however, a ver…
New Hope in Brain Glioma Surgery: The Role of Intraoperative Ultrasound. A Review
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 ou…
Skull Bone Defects Reconstruction with Custom-Made Titanium Graft shaped with Electron Beam Melting Technology: Preliminary Experience in a Series of Ten Patients
Background: Cranioplasty represents a challenge in neurosurgery. Its goal is not only plastic reconstruction of the skull but also to restore and preserve cranial function, to improve cerebral hemodynamics, and to provide mechanical protection of the neural structures. The ideal material for the reconstructive procedures and the surgical timing are still controversial. Many alloplastic materials are available for performing cranioplasty and among these, titanium still represents a widely proven and accepted choice. Methods: The aim of our study was to present our preliminary experience with a “custom-made” cranioplasty, using electron beam melting (EBM) technology, in a series of ten patien…
Reconstruction of vertebral body in thoracolumbar AO type A post-traumatic fractures by balloon kyphoplasty: a series of 85 patients with a long follow-up and review of the literature.
Background Traumatic fractures of the thoracolumbar spine are common injuries, accounting for approximately 90% of all spinal traumas. Optimal management of these fractures still gives rises to much debate in the literature. Currently, one of the treatment options in young patients with stable traumatic vertebral fractures is conservative treatment using braces. Kyphoplasty as a minimally invasive procedure has been shown to be effective in stabilizing vertebral body fractures, resulting in immediate pain relief and improved physical function with early return to work activity. The aim of the study is to report VAS, ODI scores, and kyphosis correction following treatment. Methods This is a …