RESUMEN
Glioblastoma, isocitrate dehydrogenase-wildtype (GB), is the most common and aggressive primary brain malignancy with poor outcome. Immune checkpoint inhibitors (ICIs) have been tested in GB and, despite disappointing results, the identification of a small subgroup of responders underlies the need to improve our understanding of the tumour microenvironment (TME) immunity. This study aimed to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumour samples were collected from 45 patients with histologically confirmed GB (WHO grade 4) and processed to obtain single-cell suspensions. Patients were assessed for the correlation of Trm phenotype with overall survival (OS) or progression-free survival (PFS) using multiparametric flow cytometry and uni/multivariate analyses. Levels of Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) were found to be linked to clinical outcome. Low frequency of Trm expressing PD1 or TIM3 or both markers defined subgroups as independent positive prognostic factors for patient survival. On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 were confirmed to be the most predictive independent factors associated with longer OS (hazard ratios-HR [95%CI]: 0.14 [0.04-0.52] p < 0.001, 0.39 [0.16-0.96] p = 0.04, respectively). The CD8+CD103+ Trm subgroups were also age-related predictors for survival in GB.
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Glioblastoma , Receptor 2 Celular del Virus de la Hepatitis A , Humanos , Receptor de Muerte Celular Programada 1/metabolismo , Pronóstico , Linfocitos T CD8-positivos , Microambiente TumoralRESUMEN
Surgery and endovascular therapy are the primary treatment options for spinal dural arteriovenous fistula (SDAVF). Due to the absence of a consensus regarding which therapy yields a superior outcome, we conducted a comparative analysis of the surgical and endovascular treatment of SDAVF through a multicenter case series and a systematic literature review. Patients with SDAVF, surgically or endovascularly treated at four neurosurgical centers from January 2001 to December 2021, were included in this study. Level of SDAVF, primary treatment modality, baseline and post-procedural neurological status were collected. The primary outcomes were failure, complication rates, and a newly introduced parameter named as therapeutic delay. A systematic review of the literature was performed according to PRISMA-P guidelines. The systematic review identified 511 papers, of which 18 were eligible for analysis, for a total of 814 patients, predominantly male (72%) with a median age of 61 and mainly thoracic SDAVFs (65%). The failure rate was significantly higher for endovascular therapy (20%) compared to surgery (4%) (p < 0.01). Neurological complications were generally rare, with similar rates among the two groups (endovascular 2.9%; surgery 2.6%). Endovascular treatment showed a statistically significantly higher rate of persistent neurological complications than surgical treatment (2.9% versus 0.2%; p < 0.01). Both treatments showed similar rates of clinical improvement based on Aminoff Logue scale score. The multicenter, retrospective study involved 131 patients. The thoracic region was the most frequent location (58%), followed by lumbar (37%). Paraparesis (45%) and back pain (41%) were the most common presenting symptoms, followed by bladder dysfunction (34%) and sensory disturbances (21%). The mean clinical follow-up was 21 months, with all patients followed for at least 12 months. No statistically significant differences were found in demographic and clinical data, lesion characteristics, or outcomes between the two treatment groups. Median pre-treatment Aminoff-Logue score was 2.6, decreasing to 1.4 post-treatment with both treatments. The mean therapeutic delay for surgery and endovascular treatment showed no statistically significant difference. Surgical treatment demonstrated significantly lower failure rates (5% vs. 46%, p < 0.01). In the surgical group, 2 transient neurological (1 epidural hematoma, 1 CSF leak) and 3 non-neurological (3 wound infections) complications were recorded; while 2 permanent neurological (spinal infarcts), and 5 non-neurological (inguinal hematomas) were reported in the endovascular group. According to the literature review and this multicenter clinical series, surgical treatment has a significantly lower failure rate than endovascular treatment. Although the two treatments have similar complication rates, endovascular treatment seems to have a higher rate of persistent neurological complications.
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Malformaciones Vasculares del Sistema Nervioso Central , Procedimientos Endovasculares , Humanos , Malformaciones Vasculares del Sistema Nervioso Central/cirugía , Procedimientos Endovasculares/métodos , Procedimientos Neuroquirúrgicos/métodos , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Anciano , Complicaciones Posoperatorias/epidemiología , Embolización Terapéutica/métodosRESUMEN
Intraoperative neurophysiological monitoring (IONM) represents one of the available technologies able to assess ischemia and aimed to improve surgical outcome reducing the treatment related morbidity in surgery for intracranial aneurysms. Many studies analyzing the impact of IONM are poised by the heterogeneity bias affecting the cohorts. We report our experience with IONM for surgery of unruptured middle cerebral artery (MCA) aneurysm in order to highlight its influence on functional and radiological outcome and surgical strategy. We retrospectively reviewed all MCA unruptured aneurysms treated between January 2013 and June 2021 by our institutional neurovascular team. Patients were divided into 2 groups according to the use of IONM. A total of 153 patients were included in the study, 52 operated on without IONM and 101 with IONM. The groups did not differ preoperatively regarding clinical status and aneurysm characteristics. Patients operated with IONM had better functional outcomes at discharge as well as at follow-up (p= 0.048, p=0.041) due to lower symptomatic ischemia and better radiological outcome due to lower rate of unexpected aneurysmal remnants (p= 0.0173). The introduction of IONM changed the use of temporary clipping (TeC), increasing its average duration (p= 0.01) improving the safety of dissecting and clipping the aneurysm. IONM in surgery for unruptured MCA aneurysm could improve the efficacy and safety of clipping strategy in the way it showed a role in changing the use of TeC and was associated to the reduction of unexpected aneurysmal remnants' rate and improvement in both short- and long-term patient's outcome.
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Aneurisma Intracraneal , Monitorización Neurofisiológica Intraoperatoria , Humanos , Estudios Retrospectivos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/etiología , Resultado del Tratamiento , Procedimientos Neuroquirúrgicos/efectos adversos , Arteria Cerebral Media/cirugíaRESUMEN
Spinal atypical meningiomas are rare, and those whose main extension is in the epidural space are anecdotal. Here, we report a case of a young woman presenting with sensory disturbances and a radiological diagnosis of a dorsal epidural sleeve-like mass. The surgical resection of the lesion allowed the decompression of the spinal cord and led to the histopathological diagnosis of atypical meningioma. At the 3-month follow-up, her neurological recovery was complete. Because of the gross total removal of the lesion, adjuvant radiotherapy was not performed: At the 2-year follow-up, no recurrence of disease was detected. A comprehensive literature review was performed, and just two more case reports on epidural atypical meningiomas were found in the English literature. Through this case report and literature review, we described a rare manifestation of spinal meningioma that entered into a differential diagnosis for extradural spinal lesions, such as secondary malignancies.
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Neoplasias Meníngeas , Meningioma , Neoplasias de la Columna Vertebral , Humanos , Femenino , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Médula Espinal , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugíaRESUMEN
Meningiomas are mostly benign tumors that, at times, can behave aggressively, displaying recurrence despite gross-total resection (GTR) and progression to overt malignancy. Such cases represent a clinical challenge, particularly because they are difficult to recognize at first diagnosis. SOX2 (Sex-determining region Y-box2) is a transcription factor with a key role in stem cell maintenance and has been associated with tumorigenesis in a variety of cancers. The purpose of the present work was to dissect the role of SOX2 in predicting the aggressiveness of meningioma. We analyzed progressive/recurrent WHO grade 1−2 meningiomas and WHO grade 3 meningiomas; as controls, non-recurring WHO grade 1 and grade 2 meningioma patients were enrolled. SOX2 expression was evaluated using both immunohistochemistry (IHC) and RT-PCR. The final analysis included 87 patients. IHC was able to reliably assess SOX2 expression, as shown by the good correlation with mRNA levels (Spearman R = 0.0398, p = 0.001, AUC 0.87). SOX2 expression was an intrinsic characteristic of any single tumor and did not change following recurrence or progression. Importantly, SOX2 expression at first surgery was strongly related to meningioma clinical behavior, histological grade and risk of recurrence. Finally, survival data suggest a prognostic role of SOX2 expression in the whole series, both for overall and for recurrence-free survival (p < 0.0001 and p = 0.0001, respectively). Thus, SOX2 assessment could be of great help to clinicians in informing adjuvant treatments during follow-up.
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Neoplasias Meníngeas , Meningioma , Factores de Transcripción SOXB1 , Humanos , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Meningioma/diagnóstico , Meningioma/genética , Recurrencia Local de Neoplasia/genética , Pronóstico , ARN Mensajero , Estudios Retrospectivos , Factores de Transcripción SOXB1/genéticaRESUMEN
Treatment of intraosseous meningiomas is a two-staged procedure including tumor resection and cranial reconstruction. Several are the potential pitfall of this kind of surgery such as the conspicuous dimensions usually reached by the tumor and the peculiar involvement of irregular and deep bony structures. For these reasons, a surgical accurate virtual planning and a careful removal followed by tailored reconstruction are mandatory to achieve satisfactory results. We analyzed six patients operated on for intraosseous meningiomas between September 2014 and June 2018. Resection strategy was planned beforehand and shared with the manufacturer who provided the PEEK cranioplasty used in the reconstructive phase. Between September 2014 and April 2018, six patients affected by intraosseous meningioma were operated on. Female/male ratio was 5:1 and mean age was 54 ± 10.8 years. Mean FU was 20.3 ± 16.4 months. Mean dimension was 73.9 ± 24.8 mm × 69.2 ± 16.2 mm. Mean surgical time was 5.1 ± 1.1 h. The resection of intraosseous meningiomas requires the earliest and finest reconstructive phase. Custom-made implants should be considered the gold-standard for cranioplasty, especially in large skull and in frontal or hairless areas of the skull. The described technique is simple, accurate, and effective in achieving good results in disease control as well as cosmetic and functional restoration.
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Cetonas , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Procedimientos de Cirugía Plástica/instrumentación , Polietilenglicoles , Prótesis e Implantes , Neoplasias Craneales/cirugía , Adulto , Anciano , Benzofenonas , Femenino , Humanos , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Polímeros , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Neoplasias Craneales/patologíaRESUMEN
Spinal cord stimulation (SCS) is well known for its early role in the management of chronic pain, mainly failed back surgery syndrome (FBSS), spasticity, and bowel and bladder dysfunction. In more recent years, SCS has been proposed for patients suffering from refractory angina or peripheral vasculopathies in order to gain symptom relief, thus indicating some hemodynamic effect on the peripheral circulation. Taking into account this scientific observation, since the late1980s, researchers have started to investigate the potential effect of SCS on cerebral blood flow (CBF) regulation and its possible application in certain pathological settings dealing with vascular pattern dysfunction, such as ischemia, subarachnoid hemorrhage, head trauma, and brain tumors. The aim of this study was to review the scientific literature about SCS and its effect on CBF, evaluating the results both in "physiological" experimental models and clinical studies, as well as in the particular pathological conditions we have mentioned above.
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Circulación Cerebrovascular/fisiología , Hemodinámica , Estimulación de la Médula Espinal , Animales , Lesiones Encefálicas/fisiopatología , Isquemia Encefálica/fisiopatología , Neoplasias Encefálicas/irrigación sanguínea , Homeostasis , Humanos , Accidente Cerebrovascular/fisiopatología , Hemorragia Subaracnoidea/fisiopatología , Simpatectomía , Vasoespasmo Intracraneal/fisiopatologíaRESUMEN
Surgical treatment of traumatic nerve lesions is a matter of debate, mostly about the timing and technical aspects of the procedure. In deciding about and planning the operation, it is often necessary to repeat the electrophysiological and neuroradiological studies several times. Here we present our experience with ultrasonography taken before and after surgery: this simple and handy tool allowed clear visualization of the preoperative anatomy, thorough preparation and fast carrying out of surgery, and accurate postoperative monitoring of the graft's vitality at follow-up. Though this is a limited series, the importance of ultrasonographic evaluation in traumatic peripheral nerve lesions appears remarkable.
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Traumatismos de los Nervios Periféricos/diagnóstico por imagen , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismos de los Nervios Periféricos/cirugía , UltrasonografíaRESUMEN
BACKGROUND: Interruption of the fistulous point is the goal of treatment of spinal dural arteriovenous fistulas (dAVFs). Microsurgery remains a highly efficient treatment in terms of complete occlusion with the lowest risk of recurrence rate. It is reported that the hardest step involves finding the fistulous site itself, potentially extending surgical access and time and increasing potential postoperative surgical-related complications. The accurate preoperative detection of the shunt and spinal level together is crucial for guiding optimal, fast, and safe microsurgical treatment. METHODS: We describe a preoperative angiographic protocol for achieving a safe and simple resection of spinal dural arteriovenous fistulas based on a 6-year institutional experience of 42 patients who underwent minimally invasive procedures. Two illustrative cases are included to support the technical descriptions. RESULTS: The suspected artery associated with the vascular malformation of interest is studied in our angiographic protocol through nonsubtracted selective acquisitions in lateral projection. The resulting frames are reconstructed with three-dimensional rotational angiography. The implementation of the preoperative angiographic protocol allowed 100% of intraoperative identification of the fistulous point in all cases with the use of a minimally invasive approach. CONCLUSIONS: Nowadays, neurosurgeons advocate for minimally invasive procedures and procedures with low morbidity risk for treatment of spinal dural arteriovenous fistulas. Our preoperative approach for accurate angiographic localization of the fistulous point through nonsubtracted and three-dimensional reconstructed angiography allowed us to achieve safe and definitive occlusion of the shunt.
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Malformaciones Vasculares del Sistema Nervioso Central , Procedimientos Quirúrgicos Mínimamente Invasivos , Cuidados Preoperatorios , Humanos , Malformaciones Vasculares del Sistema Nervioso Central/cirugía , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Femenino , Anciano , Cuidados Preoperatorios/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Adulto , Procedimientos Neuroquirúrgicos/métodos , Angiografía/métodos , Microcirugia/métodos , Médula Espinal/diagnóstico por imagen , Médula Espinal/irrigación sanguínea , Médula Espinal/cirugíaRESUMEN
Background: The concept of aneurysm "complexity" has undergone significant changes in recent years, with advancements in endovascular treatments. However, surgical clipping remains a relevant option for middle cerebral artery (MCA) aneurysms. Hence, the classical criteria used to define surgically complex MCA aneurysms require updating. Our objective is to review our institutional series, considering the impacts of various complexity features, and provide a treatment strategy algorithm. Methods: We conducted a retrospective review of our institutional experience with "complex MCA" aneurysms and analyzed single aneurysmal-related factors influencing treatment decisions. Results: We identified 14 complex cases, each exhibiting at least two complexity criteria, including fusiform shape (57%), large size (35%), giant size (21%), vessel branching from the sac (50%), intrasaccular thrombi (35%), and previous clipping/coiling (14%). In 92% of cases, the aneurysm had a wide neck, and 28% exhibited tortuosity or stenosis of proximal vessels. Conclusions: The optimal management of complex MCA aneurysms depends on a decision-making algorithm that considers various complexity criteria. In a modern medical setting, this process helps clarify the choice of treatment strategy, which should be tailored to factors such as aneurysm morphology and patient characteristics, including a combination of endovascular and surgical techniques.
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BACKGROUND: In accordance with technique advancement and minimal invasiveness surgical approaches, the minipterional has progressively replaced the standard pterional approach for treatment of unruptured middle cerebral artery (MCA) aneurysms. Nowadays, multimodal intraoperative resources including microDoppler and microflow probes, indocyanine green videoangiography, and neurophysiologic monitoring constitute a fundamental prerequisite for increasing the safety of the clipping procedure. Our study investigated and compared in a single-center experience the effect of the evolution of a minimally invasive and multimodal approach in unruptured MCA aneurysm surgery by measuring postoperative complication rate, recovery time, and long-term neuropsychological and functional outcomes. METHODS: One hundred and thirty-one patients who underwent surgical treatment for unruptured MCA aneurysms at our institution were evaluated retrospectively. Patients' clinical, radiologic, and surgical reports were collected. Cognitive evaluation and quality of life were assessed through validated tests in telephone interviews. Patients who met the inclusion criteria were divided into 2 groups: "PT (pterional)" and "MPT (minipterional)." RESULTS: Ninety-two patients were included in the analysis. A significant reduction of postoperative complication rates and new-onset postoperative seizures was recorded in the MPT group (P value = 0.006). Severe cognitive deficits were lower in the MPT group, although without a clear statistical correlation. CONCLUSIONS: Decreased complication rates, faster recovery time, and a trend toward better cognitive and functional performances were documented for the MPT group of patients. In our experience, the minipterional approach with multimodality-assisted microsurgery reduced neurologic complications and recovery time and improved long-term cognitive outcome and quality of life.
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Aneurisma Intracraneal , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Aneurisma Intracraneal/cirugía , Resultado del Tratamiento , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Procedimientos Neuroquirúrgicos/métodos , Adulto , Pruebas Neuropsicológicas , Calidad de Vida , Microcirugia/métodosRESUMEN
BACKGROUND: Spontaneous non-traumatic subarachnoid hemorrhage (sSAH) is a severe brain vascular accident. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) can be theoretically assayed to predict a patient's progression, picturing different aspects of clinical failure after sSAH. The study aims to: a) explore the correlation between sSAH blood volume and biomarkers variation; b) evaluate if these can be predictive of the neurogenic response after sSAH and be prognostic of patient outcome; c) establish eventual threshold levels of biomarkers to define patients' clinical outcome. METHODS: Blood volumetry at CT scan upon admission, GFAP and UCH-L1 were collected at 24 h, at 72 h, and after 7 days from hemorrhage. Trends and cut-off serum sampling were determined. Clinical outcome was assessed with mRS scale at 14 days. RESULTS: A strong correlation between GFAP and UCH-L1 and blood diffusion volume in all explored serum intervals related to unfavorable outcome. GFAP and UCH-L1 were very early predictors of unfavorable outcomes at 24 h from sSAH (p = 0.002 and 0.011 respectively). Threshold levels of UCH-L1 apparently revealed a very early, early and late predictor of unfavorable outcomes. CONCLUSION: GFAP and UCH-L1 represent a potential tool for prompt monitoring and customization of therapies in neurosurgical patients.
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Biomarcadores , Proteína Ácida Fibrilar de la Glía , Hemorragia Subaracnoidea , Ubiquitina Tiolesterasa , Humanos , Ubiquitina Tiolesterasa/sangre , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/complicaciones , Proteína Ácida Fibrilar de la Glía/sangre , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Pronóstico , Anciano , Adulto , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Acute hydrocephalus is a frequent complication of aneurysmal subarachnoid hemorrhage, and it is generally treated by external ventricular drainage. In the last decades, antibiotic-impregnated ventricular catheters have been introduced in the neurosurgical practice in order to reduce secondary cerebrospinal fluid infections which increase morbidity, mortality, and health care costs. METHODS: Data of 100 patients treated at Fondazione Policlinico Universitario Agostino Gemelli IRCCS between January 2012 and December 2019 were retrospectively reviewed in order to determine the cost-effectiveness and budget impact of antibiotic impregnated versus non-impregnated catheters in the management of patients with aneurysmal subarachnoid hemorrhage related hydrocephalus. A budget impact model was built depending on the use of antibiotic impregnated versus non-impregnated catheters. The model was populated with data extrapolated from existing literature concerning the Italian healthcare setting and national tariffs. RESULTS: A 25% reduction in the number of cerebrospinal fluid infections was achieved by using antibiotic impregnated catheters, resulting in an overall saving equal to 5730.52/patient. Expanding results to a 100-patient sample, the possible savings would amount to 573,052.40 for the National Health Service. CONCLUSIONS: Antibiotic impregnated catheters use was associated to a reduction in cerebrospinal fluid infections rate as well as in costs related to hospital care when compared to nonimpregnated catheters. Thus these catheters represent, besides lifesaving, cost-saving devices that reduce the economic burden and ensure a safe clinical outcome in patients with aneurysmal subarachnoid hemorrhage related hydrocephalus. The present study provides concrete evidence of the benefit of Antibiotic impregnated catheters to decision-makers responsible of defining health policies.
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Hidrocefalia , Hemorragia Subaracnoidea , Humanos , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/cirugía , Hemorragia Subaracnoidea/tratamiento farmacológico , Medicina Estatal , Catéteres/efectos adversos , Derivaciones del Líquido Cefalorraquídeo , Drenaje , Hidrocefalia/etiología , Hidrocefalia/cirugíaRESUMEN
BACKGROUND: Failure of clinical trials with targeted therapies in glioblastoma (GBM) is probably related to the enrollment of molecularly unselected patients. In this study we report the results of a precision medicine protocol in recurrent GBM. METHODS: We prospectively evaluated 34 patients with recurrent GBM. We determined the expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor variant III (EGFRvIII), and phosphatase and tensin homolog (PTEN). According to the molecular pattern we administered bevacizumab alone in patients with VEGF overexpression, absence of EGFRvIII, and normal PTEN (group A; N.=16); bevacizumab + erlotinib in patients with VEGF overexpression, expression of EGFRvIII, and normal PTEN (group B; N.=14); and bevacizumab + sirolimus in patients with VEGF overexpression and loss of PTEN, irrespective of the EGFRvIII status (group C; N.=4). We evaluated the response rate, the clinical benefit rate, the 6-month progression-free survival (PFS-6), the 12-month PFS (PFS-12) and the safety profile of the treatment. Moreover, we compared our results with the ones of EORTC 26101 trial. RESULTS: Response rate was 50% in the whole cohort with the highest rate in group C (75%). Clinical benefit rate was 71% with the highest rate in group C (75%). PFS-6 was 56% in the whole cohort with the highest rate in group B (64%). PFS-12 was 21% in the whole cohort with the highest rate in group B (29%). When comparing our results with those from the combination arm of the EORTC 26101 trial we found a significantly higher PFS-6 and PFS-12 in our cohort. CONCLUSIONS: The precision medicine protocol for recurrent GBM is feasible and leads to improved results if compared with studies lacking molecular selection.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Bevacizumab/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Clorhidrato de Erlotinib/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
Grade 3 meningiomas are rare malignant tumors that can originate de novo or from the progression of lower grade meningiomas. The molecular bases of anaplasia and progression are poorly known. We aimed to report an institutional series of grade 3 anaplastic meningiomas and to investigate the evolution of molecular profile in progressive cases. Clinical data and pathologic samples were retrospectively collected. VEGF, EGFR, EGFRvIII, PD-L1; and Sox2 expression; MGMT methylation status; and TERT promoter mutation were assessed in paired meningioma samples collected from the same patient before and after progression using immunohistochemistry and PCR. Young age, de novo cases, origin from grade 2 in progressive cases, good clinical status, and unilateral side, were associated with more favorable outcomes. In ten progressive meningiomas, by comparing molecular profile before and after progression, we identified two subgroups of patients, one defined by Sox2 increase, suggesting a stem-like, mesenchymal phenotype, and another defined by EGFRvIII gain, suggesting a committed progenitor, epithelial phenotype. Interestingly, cases with Sox2 increase had a significantly shortened survival compared to those with EGFRvIII gain. PD-L1 increase at progression was also associated with worse prognosis, portending immune escape. We thus identified the key drivers of meningioma progression, which can be exploited for personalized treatments.
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BACKGROUND AND AIM: While many components of the ECM have been isolated and characterized, its modifications in the specific setting of GBMs have only been recently explored in the literature. The aim of this paper is to provide a systematic review on the topic and to assess the ECM's role in shaping tumoral development. METHODS: An online literature search was launched on PubMed/Medline and Scopus using the research string "((Extracellular matrix OR ECM OR matrix receptor OR matrix proteome) AND (glioblastoma OR GBM) AND (tumor invasion OR tumor infiltration))", and a systematic review was conducted in accordance with the PRISMA-P guidelines. RESULTS: The search of the literature yielded a total of 693 results. The duplicate records were then removed (n = 13), and the records were excluded via a title and abstract screening; 137 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 59 articles were finally included and were summarized as follows based on their focus: (1) proteoglycans; (2) fibrillary proteins, which were further subdivided into the three subcategories of collagen, fibronectin, and laminins; (3) glycoproteins; (4) degradative enzymes; (5) physical forces; (6) and glioma cell and microglia migratory and infiltrative patterns. CONCLUSIONS: Our systematic review demonstrates that the ECM should not be regarded anymore as a passive scaffold statically contributing to mechanical support in normal and pathological brain tissue but as an active player in tumor-related activity.
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(1) Background: Innovation and continuous demand in the field of visual enhancing technologies and video streaming have led to the discovery of new systems capable of improving visualization and illumination of the surgical field. The exoscope was brought into neurosurgical routine, and nearly ten years later, modern 3D systems have been introduced and tested, giving encouraging results. (2) Methods: In order to evaluate the surgeon's confidence with the exoscope and their increasing ability in terms of time spent and quality of the final achievement since their first encounter with the technique, an experimental trial on 18 neurosurgeons from a single Institution was performed to evaluate the learning curve for the use of the VITOM-3D exoscope in neurosurgical practice on a model of brain and dura mater. (3) Results: A significant improvement in the quality of the performance, number of errors made, and reduction in the time was found after the third iteration of the task, by when almost all the participants felt more comfortable and confident. No significant differences between senior neurosurgeons and resident neurosurgeons were reported. (4) Conclusions: Our results show that three iterations are enough to gain confidence with the exoscope from its first use, regardless of previous experience and training with an operating microscope.
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BACKGROUND/AIM: The Mediterranean diet may be deemed as the best combination of nutrients to play a protective role against cancer. Previous studies have demonstrated how a healthy lifestyle, and the adherence to the Mediterranean diet might affect the onset of most common cancers, focusing less on their relationship with central nervous system (CNS) tumoral pathologies, especially benign ones, such as meningiomas. PATIENTS AND METHODS: This was a retrospective multicenter study, involving 52 patients who underwent meningioma resection and a group of 100 subjects not affected by brain tumors. This preliminary study aimed to investigate whether the non-adherence to a dietary pattern, such as the Mediterranean diet, and pre-existing cardiovascular risk factors can affect the onset of cranial meningiomas. RESULTS: Patients affected by meningioma had a significantly lower mean Mediterranean Diet Score (MDS), and a similar distribution of the main cardiovascular risk factors. CONCLUSION: A larger patient cohort is required to corroborate our findings. However, these promising results open up a new avenue for further exploration of the role of the Mediterranean diet in the development of meningiomas.