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Background. Glioblastoma (GBM) represents the most aggressive malignant brain tumor in adults, with a risible median life expectancy despite gold standard treatment. Novel drug-delivery methods have been explored. Here we evaluated the possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic lineage as drug-carrier. Methods. MCs were obtained from 10 patients harboring a GBM, and from healthy volunteers, considered as controls. GBM tissue was also obtained from patients. MCs were cultured and the adherent population on fibronectin (FN-MCs), after immunocytochemistry and flow cytometry characterization, was loaded with Paclitaxel (FN-MCs-PTX). Antiproliferative and migration activity of FN-MCs-PTX was evaluated in two-dimensional (2D) and three-dimensional (3D) co-culture assays with red fluorescent U87 Malignant Glioma cells and primary GBM cells. Antiangiogenic properties of FN-MCs-PTX were tested on cultures with endothelial cells. Results. Phenotypical characterization showed a high expression of monocytic-dendritic markers in GBM cells and FN-MCs. FN-MCs demonstrated to effectively uptake PTX and to strongly inhibit GBM growth in vitro (P < 0.01). Moreover, tumor-induced migration of MCs, although partially affected by the PTX cargo, remained statistically significant when compared with unprimed cells and this was confirmed in a 3D Matrigel model (P < 0.01) and in aTrans-well assay (P < 0.01). FN-MCs-PTX also disclosed considerable antiangiogenic properties. Discussion. Our results suggest that the fibronectin-adherent population of MCs isolated from peripheral blood can be an effective tool to inhibit GBM growth. Given the relative facility to obtain such cells and the short time needed for their culture and drug loading this approach may have potential as an adjuvant therapy for GBM. [ABSTRACT FROM AUTHOR]

Maximizing surgical resection of medulloblastoma (MB) affects overall survival; nevertheless, surgical resection remains a because of the infiltrative behavior of this tumor. Several dyes have been tested for improving tumor visualization; however, few reports with different protocols of fluorophores use are available and the results are inconsistent. Hence, we report our experience with sodium fluorescein in MB surgery, aiming to assess the role of this technique on the extent of resection. Furthermore, we performed a literature review of this topic. Fluorescence characteristics, extent of resection, and clinical outcome were analyzed in 9 consecutively operated patients with MB. A comprehensive literature search and review for English-language articles concerning fluorescein application in MB was conducted. In our cohort, no side effect related to fluorescein occurred; all tumors presented with an intense or moderate yellow-green enhancement, and fluorescein was judged fundamental in distinguishing tumors from viable tissue in 7 of 9 cases. Gross total resection or near-total resection (i.e., a residual tumor volume <1.5 cm3) was achieved in 8 patients. The review explored the different techniques and surgical interpretations as well as surgical radicality; we did not find a homogenous protocol for fluorescein injection in the published articles. Fluorescence appeared moderate or intense in almost all cases, with a high percentage of usefulness and consensual achievement of a high rate of gross total resection. Based on these results, we can infer that fluorescein-guided surgical resection is a safe and valuable method for patients with MB. [ABSTRACT FROM AUTHOR]

Purpose A very promising technique for radio-guided surgery (RGS) based on β -radiation is being developed. The lower background, with respect to the established approach with high penetrant γ radiation, can allow for a large diffusion of such a technique and extending the RGS to cases with a large uptake of surrounding healthy organs, such as abdominal and brain neoplastic disease or tumor of infancy. Methods To validate the β -RGS feasibility study, tests on ex-vivo specimens of brain meningioma and gastro-entero-pancreatic neuroendocrine tumors have been performed. These clinical cases were selected between the tumors known to express receptors to a β -emitting radio-tracer already in use in the clinical routine: 90 Y-labelled DOTATOC. Voluntary patients were enrolled according to the standard uptake value (SUV) and the expected tumor-to-non-tumor ratios (TNR) estimated from PET/CT images after administration of 68 Ga-DOTATOC. All of them gave written informed consent to participate in the clinical trial, already approved by the Ethics Committee. After administration of a low activity (about 2.5 mCi) of 90 Y-DOTATOC, the extracted ex-vivo specimens and the healthy tissue around the lesions were examined to assess the correlation between the counting rates measured by the developed β -detecting probe and the expected 90Y activity. Results All the neoplastic samples were correctly identified. A dependence of the counting rate both on the volume V and on the total activity of the sample were observed. Even injecting as low as 1.4 MBq/kg of radio-tracer, tumor remnants of 0.1 ml would be detectable in few seconds. Conclusions The results of the clinical tests showed the validity of the underlying assumptions and strengthening the feasibility studies already published. Small radiopharmaceutical activity is required to detect a tumor remnant as expected due to the low background rates. The negligible medical staff exposure was also confirmed. [ABSTRACT FROM AUTHOR]

This study aims to present a practical method to accurately diagnose ventriculoperitoneal shunt (VPS) malfunction and to detect the exact level at which the system has failed to tailor VPS revision at that level only. A tertiary referral single-center algorithm for diagnosis of VPS malfunction is proposed. Based on clinical symptoms and confirmed ventricular dilatation on computed tomography, the VPS reservoir is punctured; if no cerebrospinal fluid is obtained, ventricular catheter replacement is recommended. Conversely, if cerebrospinal fluid is obtained, a sample is sent for cultural examination and the macroscopic integrity of the whole system is checked via plain radiography in the angiographic suite. Then, through the injection of iodate contrast medium into the reservoir and selective exclusion of the proximal and distal catheters, the patency and correct VPS functioning are investigated. A total of 102 (56 males) patients (mean age, 41.5 years; range, 1–86 years) underwent a VPS function test from 2012 to 2018: 59 cases of VPS malfunction (57.8%) were diagnosed. Ventricular catheter obstruction/damage/displacement occurred in 12/59 patients (20.3%), valve damage in 11/59 patients (18.6%), distal catheter obstruction/damage/displacement in 17/59 patients (28.8%) and 2-level (valve/proximal catheter or valve/distal catheter) obstruction/damage/displacement in 16/59 patients (27.1%). Subclinical infection was diagnosed in 3 patients (5.1%). VPS revision was performed selectively at the level of failure. The proposed algorithm is a practical, simple and minimally invasive technique to accurately diagnose VPS malfunction, identifying the exact level of system failure and allowing surgical VPS revision to be tailored, avoiding unnecessary complete system replacement. [ABSTRACT FROM AUTHOR]

The optimal management of dural closure is unclear; therefore, we aimed to survey current common practices among Italian practitioners. The Delphi method was used to achieve a consensus on dura mater closing techniques in Italy. A steering committee decided 3 major topics to be investigated: pre- and postoperative conditions associated with cerebrospinal fluid (CSF) leak, indications to perform watertight dural closure, and dural closure technique. A questionnaire containing 12 statements was then submitted to Italian neurosurgeons. The response rate was 60%. Among 60 items, 36 reached a positive consensus, 5 reached a negative consensus, and 19 did not reach consensus. Intrathecal hypertension, arachnoid opening, previous treatments, spinal incidental durotomy, wide size of osteo-dural defect, and lack of nasoseptal flap were considered major risk factors for CSF leak. Early mobilization, avoidance of stress maneuvers, and use of CSF external drainage were considered to reduce CSF leak rate. Italian neurosurgeons always attempt watertight dural closure, ideally with monofilament nonabsorbable sutures. Both autologous and heterologous dural grafts are used. Among dural sealants, fibrin glues are preferred, which are used most commonly in transsphenoidal surgery. This study elucidates the areas of consensus and uncertainty on dural closure management among a group of Italian neurosurgeons. It provides reliable and comparable data for the investigation of the departments' daily practice in dural closure. Given the lack of solid evidence, there is a need for further comparative studies of dural repair strategies. [ABSTRACT FROM AUTHOR]

The supracerebellar transtentorial approach for the resection of brain lesion at the level of the mesial temporooccipital region is underused in the field of epilepsy surgery, despite the theoretical advantage of sparing normal brain structures, in particular in the dominant hemisphere for language. Hereby we present the case of a patient with a low-grade epilepsy associated tumor, presenting with weekly drug-resistant focal seizures, treated by a supracerebellar transtentorial lesionectomy. Surgery was uneventful and the histopathology revealed a pleomorphic low-grade neuroepithelial tumor of the young patient. At the 6-month follow-up, the patient did not present neurologic deficits and she never presented with seizures after surgery, so antiepileptic drug tapering started. The integration of supracerebellar transtentorial approach in the "armory" of the epilepsy neurosurgeon requires a dedicated expertise and an anesthesiologic setting used to manage the semisitting position; on the other hand, it could provide a relevant option to provide safe and complete lesionectomy in the mesial temporooccipital region, together with the more classical sublobar and transcerebral approaches (Video 1). [ABSTRACT FROM AUTHOR]

Accurate midline myelotomy through the posterior median sulcus (PMS) is the key step to minimize surgical morbidity during intramedullary tumor removal. 1,2 When an intramedullary mass is present, the cord is usually rotated and it may be difficult to distinguish its sulci. 2-4 Inadvertent dissection through the dorsal columns exposes the patient to disabling postoperative deficits. 5 In recent years, together with the well-established neurophysiologic phase-reversal method, newer intraoperative angiographic techniques have been developed to identify the PMS. 1-4 In order to illustrate the combination of the 2, we present the case of a 31-year-old man with a right claw hand syndrome who underwent surgical excision of a C6-D1 ependymoma (Video 1). 6 , 7 After localizing the tumor with ultrasound, somatosensory evoked potentials (obtained by stimulating the dorsal columns with the use of a bipolar handheld neurostimulator) were employed to identify the PMS by means of the phase reversal technique, which uncovered the silent central line corresponding to the PMS. Use of indocyanine green fluorescence (ICG) later confirmed with certainty the location of the spinal cord's midline by enabling identification of the dorsal medullary veins exiting the PMS. As expected, the midline was significantly laterally displaced by the tumor. After penetrating the PMS, gentle dissection between the 2 posterior chordae enabled the surgeon to reach and enucleate the tumor in a minimally traumatic fashion. No postoperative deficits were reported. This method represents a direct and effective way to reduce morbidity resulting from this type of surgery. [ABSTRACT FROM AUTHOR]

Objective The aim of this article is to investigate the frequency of neurosurgical complications according to Landriel-Ibañez Classification and their impact on patients' health status. Methods Patients undergoing neurosurgical procedures were enrolled in an observational longitudinal study at Neurological Institute Carlo Besta from January 2012 to September 2013. We evaluated patients' health status before surgery, at discharge, and follow-up with the Karnofsky Performance Status Scale (KPS), whereas the Landriel-Ibañez Classification was used to record complications. Descriptive statistics were performed to illustrate the distribution of sociodemographic and clinical data. We used nonparametric tests to compare KPS scores of patients with different grades of complication and to evaluate the differences between preoperative KPS scores, KPS scores at discharge and follow-up. The effect sizes were also calculated. Results We enrolled 1008 patients. We registered 228 complications (139 grade 1 complications, 63 grade 2 complications, 20 grade 3 complications, and 6 grade 4 complications). All patients with a complication showed KPS scores at discharge that were lower than preoperative scores and KPS scores at follow-up greater than scores at discharge. After patients with grade 4 complications, who had the worst outcomes, those with grade 3 complications were the most compromised after surgery whereas patients with grade 2 complications seemed to have a better health status than patients with grade 1 complication. Conclusions Our study highlights the impact of neurosurgical complications on patients' life and contributes to the debate on how define and classify adverse events because a classification only based on treatment seems to be not adequate. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the role of intraoperative neurophysiological monitoring in image-guided mini-invasive neurosurgery. Methods: Twenty-one patients were operated under general anaesthesia with the aid of multimodal intraoperative neurophysiological monitoring to remove supratentorials tumors closely related to the cortico-spinal tract. Pre-operative assessment included fMRI scans and tractography that were uploaded into the intraoperative neuro-navigation system. Monitoring consisted in simultaneously recording EEG, electrocorticography, transcranial and direct motor evoked potentials (tMEP and dMEP), somatosensory evoked potentials and subcortical stimulation during the whole procedures. Results: The recording of all the electrophysiological signals was possible in all procedures. SSEP guided the positioning of the strip electrode over the motor cortex (N20 phase inversion) that was used to evoke dMEP and monitor the lower limb motor responses; subcortical stimulation to unveil the spatial relationship between the tumors and motor fibers. Four patients had transient worsening of the symptoms, but only two had a long-term worsening, although not severe, of the pre-op clinical status. Conclusions: Intraoperative neurophysiology has a great value in mini-invasive neurosurgery, especially because the motor cortex is not exposed, consequently it cannot be directly mapped. This report describes a valuable scheme making use of as many electrophysiological signals as possible to constantly monitor the motor functions. Significance: A useful method to monitor motor functions in mini-invasive neurosurgery was described. [Copyright &y& Elsevier]

Objective: Postoperative cerebrospinal fluid (CSF) leak in neurosurgery remains a significant source of morbidity. TissuePatchDural (TPD), a novel impermeable adhesive membrane, can be used to reinforce dural closure in cases considered at high risk to develop postoperative CSF leak. Methods: A retrospective, single-center, clinical investigation was conducted on 119 patients who underwent elective neurosurgical procedures between January and June 2010. Inclusion criteria included adult patients undergoing clean elective surgeries where a primary watertight closure was not possible. Three groups of patients were considered: 1) infratentorial, 67 cases; 2) supratentorial, 34 cases; and 3) spinal, 18 cases. All these patients received TPD to reinforce dural closure. Preoperative (long-term corticosteroid therapy, previous surgery and radiotherapy), intraoperative (site of procedures and size of dural gap), and postoperative (early and late hydrocephalus) conditions were analyzed as possible risk factors associated with CSF leakage. Results: The mean follow-up was 7.14 months (range 6–12 months). CSF leak was detected in 11 of 119 cases (9.2%). The presence of pre- and postoperative risk factors was associated with a higher percentage of CSF leakage: 8 of 22 cases (36.3%) vs. 3 of 97 cases (3.1%) (P < 0.0001). All leaks could be conservatively treated and no patient required readmission or second surgery. No TPD-related adverse or allergic effects were observed. Conclusions: TPD seems to be a safe tool to be used to reinforce dural closure in patients with a high risk of developing CSF leaks. [Copyright &y& Elsevier]