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2.
Neurosurg Rev ; 46(1): 211, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37642794

ABSTRACT

This is a retrospective monocentric study. The aim of this study is to analyze the incidence of recurrent or junctional lumbar foraminal herniated disc, in patients treated with trans pars microsurgical approach. Foraminal lumbar disc herniation represents a challenging pathology for the spinal surgeon. The appropriate surgical approach still represents a matter of debate. Several open and minimally-invasive techniques have been developed, in order to allow a proper tissue exposure and preserving the vertebral stability. The trans pars approach has already been described as a possible alternative, allowing excellent exposure of the herniated fragment with minimum bone removal. While few studies have analyzed the very low rate of post-operative instability, no articles deal with the incidence of post-operative herniated disc recurrence or junctional disc herniation in patients treated with this technique. We enrolled 160 patients operated at our institution. A univariate and multivariate analysis of possible factors influencing outcome (age, sex, level and BMI) was performed. Outcome variables were recurrent or junctional herniated disc. At the end, 135 patients were analyzed. Of the 135 patients, six presented recurrent herniated disc (4.4%) and other three developed a junctional herniation (2.2%). The occurrence of junctional herniated disc or recurrent herniated disc was not influenced by the analyzed variables, both at univariate and at multivariate analyses. The trans pars approach presents a low rate of recurrence and junctional herniation. Age, sex, level, and BMI do not influence the recurrence rate, both at same level and at junctional level.


Subject(s)
Intervertebral Disc Displacement , Humans , Intervertebral Disc Displacement/surgery , Retrospective Studies , Multivariate Analysis , Postoperative Period , Spine
3.
Biomedicines ; 11(6)2023 May 24.
Article in English | MEDLINE | ID: mdl-37371615

ABSTRACT

Glioblastoma (GBM) is the most common and aggressive central nervous system tumor, requiring multimodal management. Due to its malignant behavior and infiltrative growth pattern, GBM is one of the most difficult tumors to treat and gross total resection is still considered to be the first crucial step. The deep understanding of GBM microenvironment and the possibility of manipulating the patient's innate and adaptive immune system to fight the neoplasm represent the base of immunotherapeutic strategies that currently express the future for the fight against GBM. Despite the immunotherapeutic approach having been successfully adopted in several solid and haematologic neoplasms, immune resistance and the immunosuppressive environment make the use of these strategies challenging in GBM treatment. We describe the most recent updates regarding new therapeutic strategies that target the immune system, immune checkpoint inhibitors, chimeric antigen receptor T cell therapy, peptide and oncolytic vaccines, and the relevant mechanism of immune resistance. However, no significant results have yet been obtained in studies targeting single molecules/pathways. The future direction of GBM therapy will include a combined approach that, in contrast to the inescapable current treatment modality of maximal resection followed by chemo- and radiotherapy, may combine a multifaceted immunotherapy treatment with the dual goals of directly killing tumor cells and activating the innate and adaptive immune response.

4.
Genes (Basel) ; 13(8)2022 08 12.
Article in English | MEDLINE | ID: mdl-36011350

ABSTRACT

The G105G SNP (rs11554137) in the IDH1 gene is observed in about 10-15% of patients with a diffuse glioma. Data regarding its impact on gliomas are poor and partially conflicting, possibly due to the evolving classification of CNS tumors. The aim of this study was to investigate the G105G SNP prognostic significance in a homogenous cohort of IDH-wildtype glioblastomas, in agreement with the 2021 WHO classification. The study analyzed 211 patients by collecting several clinico-pathological and molecular characteristics, including the age, lesion localization, number of involved lobes, type of surgical treatment, disease outcome and MGMT promoter methylation status. PFS and DSS curves were plotted according to the Kaplan-Meier method and statistical analyses were performed using parametric and non-parametric tests. A total of 32 patients out of 211 (15.2%) were found to be G105G SNP carriers. No significant impact of the IDH1 G105G SNP on patients' outcomes was observed in terms of PFS and DSS, while MGMT promoter methylation and gross total resection resulted as key prognostic factors in our cohort as expected. No prognostic impact of the IDH1 G105G SNP was detected in this strict cohort of IDH-wildtype glioblastomas. Analysis of larger cohorts is warranted to address the sample size limitations.


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Polymorphism, Single Nucleotide , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Glioblastoma/genetics , Glioma/genetics , Humans , Isocitrate Dehydrogenase/genetics , Mutation , Prognosis
5.
Brain Sci ; 12(5)2022 Apr 26.
Article in English | MEDLINE | ID: mdl-35624942

ABSTRACT

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor's borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are the most used. Only a few studies have directly compared these two fluorophores. METHODS: A single center retrospective analysis of patients treated for GBM in the period between January 2018 and January 2021 was built to find any differences in terms of EOR, Karnofsky Performance Status (KPS), and overall survival (OS) on the use of 5-ALA, SF, or both. RESULTS: Overall, 99 patients affected by isocitrate dehydrogenase (IDH) wild-type Glioblastoma were included. 5-ALA was administered to 40 patients, SF to 44, and both to 15. No statistically significant associations were identified between the fluorophore and EOR (p = 0.783) or postoperative KPS (p = 0.270). Survival analyses did not show a selective advantage for the use of a given fluorophore (p = 0.184), although there appears to be an advantageous trend associated with the concomitant use of both dyes, particularly after stratification by MGMT (p = 0.071). CONCLUSIONS: 5-Ala and SF are equally useful in achieving gross total resection of the enhancing tumor volume. The combination of both fluorophores could lead to an OS advantage.

6.
Front Neurol ; 12: 712532, 2021.
Article in English | MEDLINE | ID: mdl-34512525

ABSTRACT

When discussing "mentalization," we refer to a very special ability that only humans and few species of great apes possess: the ability to think about themselves and to represent in their mind their own mental state, attitudes, and beliefs and those of others. In this review, a summary of the main cortical areas involved in mentalization is presented. A thorough literature search using PubMed MEDLINE database was performed. The search terms "cognition," "metacognition," "mentalization," "direct electrical stimulation," "theory of mind," and their synonyms were combined with "prefrontal cortex," "temporo-parietal junction," "parietal cortex," "inferior frontal gyrus," "cingulate gyrus," and the names of other cortical areas to extract relevant published papers. Non-English publications were excluded. Data were extracted and analyzed in a qualitative manner. It is the authors' belief that knowledge of the neural substrate of metacognition is essential not only for the "neuroscientist" but also for the "practical neuroscientist" (i.e., the neurosurgeon), in order to better understand the pathophysiology of mentalizing dysfunctions in brain pathologies, especially those in which integrity of cortical areas or white matter connectivity is compromised. Furthermore, in the context of neuro-oncological surgery, understanding the anatomical structures involved in the theory of mind can help the neurosurgeon obtain a wider and safer resection. Though beyond of the scope of this paper, an important but unresolved issue concerns the long-range white matter connections that unify these cortical areas and that may be themselves involved in neural information processing.

7.
Brain Sci ; 11(6)2021 Jun 16.
Article in English | MEDLINE | ID: mdl-34208653

ABSTRACT

BACKGROUND: Despite the aggressiveness of multimodal treatment, glioblastoma (GBM) is still a challenge for neurosurgeons, neurooncologists, and radiotherapists. A surgical approach is still a cornerstone in GBM therapeutic management, as the extent of resection is strongly related both to overall survival and progression-free survival. From this perspective, the use of photodynamic molecules could represent an interesting tool to achieve maximal and safe resection. Being able to trace the lesion's edges, indeed, could allow to improve the extent of resection and to minimize residual tumor while sparing normal tissue. The use of 5-aminolevulinic acid (5-ALA) as a photodynamic tracer is well established due to its strict correlation both with cellularity and metabolic activity of the GBM cell clones. OBJECTIVE: Our study aims to define whether a different molecular asset of GBM (especially investigating IDH 1/2 mutation, proliferation index, and MGMT promoter methylation) results in different fluorescence expression, possibly because of differences in metabolic pathways due to different genotypes. METHODS: Patients undergoing surgery for GBM removal at our Institute (Dep. Of Neurosurgery, Ospedale Città della Salute e della Scienza, University of Turin, Italy) were retrospectively reviewed. Patients with histological diagnosis confirmation and to whom 5-ALA was given before surgery were included. The whole surgical procedure was recorded and then analyzed by three different people (a medical student, a resident, and a senior surgeon with an interest in neurooncology and experience in using 5-ALA) and a score was assigned to the different degrees of intraoperative fluorescence. The degree of fluorescence was then matched with the genotype. RESULTS: A trend of grade 2 fluorescence (i.e., "strong") was observed in the IDH 1/2 wild-type (WT) genotype, suggesting a more intense metabolic activity in this particular subgroup, while, no or weak fluorescence was observed more often in the IDH 1/2 mutated tumors, suggesting a lower metabolic activity. No relations were found between fluorescence grade and MGMT promoter methylation or, interestingly, cellularity. As a secondary analysis, more epileptogenicity of the IDH 1/2 mutated GBM was noticed, similarly to other recent literature. CONCLUSION: Our results do not support the use of 5-ALA as a diagnostic tool, or a way to substitute the molecular profiling, but confirm 5-ALA as a powerful metabolic tracer, able to easily detect the pathological cells, especially in the IDH WT genotype, and in this perspective, further studies will be necessary to better describe the metabolic activity of GBM cells.

8.
Technol Cancer Res Treat ; 20: 15330338211021605, 2021.
Article in English | MEDLINE | ID: mdl-34212784

ABSTRACT

High-grade gliomas are aggressive tumors that require multimodal management and gross total resection is considered to be the first crucial step of treatment. Because of their infiltrative nature, intraoperative differentiation of neoplastic tissue from normal parenchyma can be challenging. For these reasons, in the recent years, neurosurgeons have increasingly performed this surgery under the guidance of tissue fluorescence. Sodium fluoresceine and 5-aminolevulinic acid represent the 2 main compounds that allow real-time identification of residual malignant tissue and have been associated with improved gross total resection and radiological outcomes. Though presenting different profiles of sensitivity and specificity and further investigations concerning cost-effectiveness are need, Sodium fluoresceine, 5-aminolevulinic acid and new phluorophores, such as Indocyanine green, represent some of the most important tools in the neurosurgeon's hands to achieve gross total resection.


Subject(s)
Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Fluorescent Dyes , Glioma/diagnostic imaging , Glioma/surgery , Surgery, Computer-Assisted/methods , Aminolevulinic Acid , False Positive Reactions , Fluorescein , Fluorescence , Glioma/pathology , Humans , Indocyanine Green , Neoplasm Grading , Neoplasm, Residual , Optical Imaging/methods , Progression-Free Survival
9.
Childs Nerv Syst ; 37(8): 2713-2718, 2021 08.
Article in English | MEDLINE | ID: mdl-33491151

ABSTRACT

Lenz microphthalmia syndrome (LMS) is an allelic X-linked syndrome correlated to a null mutation of B cell lymphoma (BCL-6) corepressor (BCOR) gene, which is essential in the early embryonic development. Phenotypically, this rare hereditary syndrome is characterized by microphthalmia/anophthalmia and other eye disorders; mental disability; dental, ear, and digital abnormalities; and variable malformations affecting the heart, skeleton (limbs and/or spine), and genitourinary tract. In this paper, a case of a young adult with LMS affected additionally by immuno-hematological disturbances was treated with decompressive craniectomy after domestic accidental fall. Case description and a brief review of the current literature about this rare condition are presented here.


Subject(s)
Abnormalities, Multiple , Anophthalmos , Intellectual Disability , Microphthalmos , Anophthalmos/genetics , Female , Humans , Microphthalmos/genetics , Pregnancy , Young Adult
10.
Br J Neurosurg ; 35(2): 236-240, 2021 Apr.
Article in English | MEDLINE | ID: mdl-29557198

ABSTRACT

BACKGROUND: Brain metastases in pancreatic cancer are a rare condition and are usually seen in case of pancreatic adenocarcinoma. Only few cases of brain metastasis in patients affected by Intraductal papillary mucinous neoplasm (IPMN) are actually reported. CASE DESCRIPTION: We report a patient diagnosed with double cystic brain lesions that the histological examination reveal to be consistent, with pancreatic metastasis. Our patient had an history shown of stable pancreatic IPMN which has never made the oncologist suspicious about neoplastic progression or degeneration into pancreatic carcinoma. Considering the rarity of these metastasis we did a literature review on the topic. CONCLUSIONS: Despite rare, pancreatic origin of a cystic brain metastasis should considered in differential diagnosis in both patient with IPMN or patient with unknown primitive tumor.


Subject(s)
Adenocarcinoma, Mucinous , Adenocarcinoma , Brain Neoplasms , Carcinoma, Pancreatic Ductal , Pancreatic Intraductal Neoplasms , Pancreatic Neoplasms , Adenocarcinoma, Mucinous/diagnostic imaging , Adenocarcinoma, Mucinous/surgery , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/surgery , Humans , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery
11.
Eur Neurol ; 83(6): 626-629, 2020.
Article in English | MEDLINE | ID: mdl-33296894

ABSTRACT

Cervical spondylogenic myelopathy (CSM) represents a common differential diagnosis for spinal onset Amyotrophic Lateral Sclerosis (ALS). Identifying occurrence of ALS in patients with CSM may be challenging. We evaluated the accuracy of Awaji criteria in the diagnosis of ALS in a cohort of patients with CSM. We screened all patients attending Turin ALS Center during the 2006-2018 period. We selected only patients for whom cervical cord MRI showed radiological signs of CSM. All patients underwent electromyography (EMG), and Awaji criteria were used for diagnosis of clinically probable ALS. All patients were followed up clinically for at least 6 months, and ALS diagnosis was eventually confirmed according to El-Escorial revised criteria, based on disease progression. Of 2,059 patients screened, in 42 cases, MRI showed signs of CSM; CSM incidence and prevalence risks were 0.16 and 2.04%, respectively. Based on clinical progression, 72.7% of patients were diagnosed as CSM and 27.3% as CSM + ALS. At EMG 6 (18.2%) patients fulfilled the criteria for ALS, 5 of them (83.3%) during clinical follow-up were diagnosed as clinical definite ALS + CSM. Accuracy of Awaji criteria in diagnosing ALS was good (AUC = 0.757, p = 0.03). Sensitivity and specificity of Awaji criteria were, respectively, 55.6 and 95.8%. Positive predictive value was 83.3%, while negative predictive value was 85.2%. CSM-ALS comorbidity is a relatively common problem in clinical practice. To better choose patients who could benefit from surgery, EMG should be performed in CSM patients, due to its good accuracy in recognizing ALS.


Subject(s)
Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/epidemiology , Spinal Cord Diseases/epidemiology , Adult , Aged , Cohort Studies , Comorbidity , Electromyography , Female , Humans , Male , Middle Aged
12.
Oper Neurosurg (Hagerstown) ; 19(6): E600-E601, 2020 Nov 16.
Article in English | MEDLINE | ID: mdl-32717072

ABSTRACT

Cortical bone trajectory (CBT) screw fixation is an attractive technique.1-4 However, the ideal insertion of those screws could be technically demanding.5,6 The use of 3-dimensional (3D) patient-matched guides increase safety for CBT screws implantation.7 In this video, the case of a 46 yr old male is presented. He complained low back pain with left sciatica. magnetic resonance imaging showed an L5/S1 degenerative disc disease with left herniation. The patient was positioned prone; the L5 spinous process was identified under fluoroscopic guidance than skin incision was performed. Preserving the cranial facet joints, spinous processes and laminae of L5 and S1 vertebrae were exposed. Guides were positioned on the corresponding vertebra and the contact areas checked to avoid any discrepancy. With a high-speed drill the cortical bone was violated through the guide tubes. The drill itself has a stop mechanism provided by the guides. With this mechanism the drilling can be safely performed up to the planned depth. Guidewires were than introduced into the pedicle and body of the vertebra; undertapping could be performed with cannulated instrument. Laminectomy and facetectomy were performed. Diskectomy was performed, then a titanium kidney-shaped pivoting cage was implanted. Four Screws were finally placed. Proper positioning of the implants were verified on fluoroscopy and on the postoperative computed tomography scan confirming the accuracy of the trajectory. All procedures performed for this study were in accordance with the ethical standards of our Institute and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from the patient who is operated in this video.

13.
Neurosurgery ; 87(6): E672-E679, 2020 11 16.
Article in English | MEDLINE | ID: mdl-32629469

ABSTRACT

BACKGROUND: Gliomas are the most common malignant primary brain tumors. Assessment of the tumor volume represents a crucial point in preoperative and postoperative evaluation. OBJECTIVE: To compare pre- and postoperative tumor volumes obtained with an automated, semi-automatic, and manual segmentation tool. Mean processing time of each segmentation techniques was measured. METHODS: Manual segmentation was performed on preoperative and postoperative magnetic resonance images with the open-source software Horos (Horos Project). "SmartBrush," a tool of the IPlan Cranial software (Brainlab, Feldkirchen, Germany), was used to carry out the semi-automatic segmentation. The open-source BraTumIA software (NeuroImaging Tools and Resources Collaboratory) was employed for the automated segmentation. Pearson correlation coefficient was used to assess volumetric comparison. Subsequently deviation/range and average discrepancy were determined. The Wilcoxon signed-rank test was used to assess statistical significance. RESULTS: A total of 58 patients with a newly diagnosed high-grade glioma were enrolled. The comparison of the volumes calculated with Horos and IPlan showed a strong agreement both on preoperative and postoperative images (respectively: "enhancing" ρ = 0.99-0.78, "fluid-attenuated inversion recovery" ρ = 0.97-0.92, and "total tumor volume" ρ = 0.98-0.95). Agreement between BraTumIA and the other 2 techniques appeared to be strong for preoperative images, but showed a higher disagreement on postoperative images. Mean time expenditure for tumor segmentation was 27 min with manual segmentation, 17 min with semi-automated, and 8 min with automated software. CONCLUSION: The considered segmentation tools showed high agreement in preoperative volumetric assessment. Both manual and semi-automated software appear adequate for the postoperative quantification of residual volume. The evaluated automated software is not yet reliable. Automated software considerably reduces the time expenditure.


Subject(s)
Brain Neoplasms , Glioma , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Glioma/diagnostic imaging , Glioma/surgery , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Neuroimaging , Tumor Burden
14.
J Clin Neurosci ; 77: 41-48, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32409219

ABSTRACT

Hypnosis could extend the time of Intraoperative Neuropsychological Testing and Brain Mapping in Awake Surgery. A clinical validation for the Hypnosis aided AS (HAs) is still ongoing and further evidences are required. The objective of the present study is to compare two homogeneous cohorts of patients undergoing AS, the first with the aid of the hypnosis and the second according to a standard AS (SAs) protocols. The clinical, radiological and surgical data of two comparable procedures cohorts were retrospectively examined for the present study. All surgeries in Group A were performed with a HAs protocol. Procedures belonging to Group B were performed with a SAs protocol. Endpoints: to compare 1. Incidence of complications in the immediate postoperative period, 2. Clinical and neurological status in the immediate postoperative period and 30 days after surgery, 3. Duration of surgical interventions, 4. Extent of Resection (EOR). The final cohort is composed of 15 procedures; 6 belonging to Group A and 9 to Group B. The different methods outline statistically comparable results from the clinical (Neurological outcomes) both in the postoperative period and one month after surgery and from the surgical point of view (comparable EOR). The incidence of complications is comparable either. The duration of the procedures was significantly longer in HAs group. Hypnosis is a promising approach to increasing the duration of intraoperative "testability" of patients at the price of a longer operative time. A specific professional is needed to induce hypnosis in the difficult intraoperative setting.


Subject(s)
Brain Neoplasms/surgery , Disease Management , Glioma/surgery , Hypnosis/methods , Monitoring, Intraoperative/methods , Wakefulness , Adult , Brain Mapping/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/psychology , Cohort Studies , Craniotomy/methods , Female , Glioma/diagnostic imaging , Glioma/psychology , Humans , Male , Middle Aged , Neoplasm Grading/methods , Neuropsychological Tests , Operative Time , Retrospective Studies
15.
J Clin Neurosci ; 75: 106-111, 2020 May.
Article in English | MEDLINE | ID: mdl-32173153

ABSTRACT

In spinal oncology traditional titanium implants could significantly impair evaluation of postoperative imaging because of artifacts, potentially affecting proper planning and execution of radiotherapy and adequate radiological follow-up to rule out progression of the disease. This is why carbon fiber reinforced (CFR)-PEEK implants have been developed for spinal fixation. The advantages of this system include fewer artifacts on imaging, potentially improving the execution and quality of radiotherapy, with also a reduced scattering effect to neighboring tissues. A comparative clinical and radiological study between new CFR-PEEK and standard titanium implants is described. Data recorded for each case included patient demographics, clinical, radiological and surgical data, intra- and postoperative complications, follow-up information. The goal of this study was to verify the safety and effectiveness of CFR-PEEK devices compared to standard titanium implants. A total number of 78 patients were reviewed. 36 patients underwent CFR-PEEK fixation, while titanium implants were used for 42 patients. Functional recovery was obtained in both groups and registered at last follow-up in terms of axial pain and neurological status. No significative differences were found between the two groups in terms of post-operative clinical complications and hardware-related complications. CFR-PEEK implants constitute a feasible and effective way to restore stability in metastatic spine tumors. This study found a non inferior favorable profile in terms of intraoperative and postoperative complications and functional recovery, compared to titanium. Further prospective studies are needed to clarify the potential oncological advantage of their radiolucency.


Subject(s)
Carbon Fiber/therapeutic use , Ketones , Polyethylene Glycols , Prostheses and Implants , Spinal Fusion/instrumentation , Titanium , Adult , Aged , Benzophenones , Female , Humans , Male , Middle Aged , Polymers , Prospective Studies , Spinal Neoplasms/secondary , Spinal Neoplasms/surgery
16.
J Clin Neurosci ; 73: 219-223, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32001111

ABSTRACT

Positive motor responses have been used in neurosurgery for the identification of motor structures. With the term "negative motor responses" (NMRs) a complete inhibition of movement without loss of muscle tone or consciousness is meant. Papers already exist in the literature regarding cortical areas in which such NMRs are evoked, the so-called "negative motor areas" (NMAs), but their location and functional meaning are still poorly understood. This paper discusses the anatomy of the NMAs of the human brain, in light of our brain mapping experience. 21 patients underwent awake surgery and direct electrical stimulation (DES) was performed using bipolar electrodes. Excision was interrupted when functional responses were intraoperatively identified through DES. The labeled mapping sites were recorded by photography prior to and following tumor resection. Results depicting a probabilistic map of negative motor network anatomy were retrospectively analyzed. Our findings strongly support the fact that the precentral gyrus, classical site of the of the Primary Motor Areas, is also strongly involved in generating NMRs. The distribution of NMAs was noted not to be as rigid as previously described, ranging in different brain areas with a somatotopic arrangement. Presented anatomical results are consistent with the literature, but the exact functional meaning of NMAs and their subcortical connectivity is still far from being completely understood.


Subject(s)
Brain Mapping , Brain/anatomy & histology , Adolescent , Adult , Aged , Aged, 80 and over , Brain Mapping/methods , Brain Neoplasms/surgery , Female , Humans , Male , Middle Aged , Movement/physiology , Neurosurgical Procedures/methods , Retrospective Studies , Wakefulness/physiology
17.
Int J Mol Sci ; 21(3)2020 Jan 23.
Article in English | MEDLINE | ID: mdl-31979374

ABSTRACT

The neurotrophic tropomyosin receptor kinase (NTRK) genes (NTRK1, NTRK2, and NTRK3) code for three transmembrane high-affinity tyrosine-kinase receptors for nerve growth factors (TRK-A, TRK-B, and TRK-C) which are mainly involved in nervous system development. Loss of function alterations in these genes can lead to nervous system development problems; conversely, activating alterations harbor oncogenic potential, promoting cell proliferation/survival and tumorigenesis. Chromosomal rearrangements are the most clinically relevant alterations of pathological NTRK activation, leading to constitutionally active chimeric receptors. NTRK fusions have been detected with extremely variable frequencies in many pediatric and adult cancer types, including central nervous system (CNS) tumors. These alterations can be detected by different laboratory assays (e.g., immunohistochemistry, FISH, sequencing), but each of these approaches has specific advantages and limitations which must be taken into account for an appropriate use in diagnostics or research. Moreover, therapeutic targeting of this molecular marker recently showed extreme efficacy. Considering the overall lack of effective treatments for brain neoplasms, it is expected that detection of NTRK fusions will soon become a mainstay in the diagnostic assessment of CNS tumors, and thus in-depth knowledge regarding this topic is warranted.


Subject(s)
Central Nervous System Neoplasms/genetics , Central Nervous System Neoplasms/metabolism , Gene Fusion , Membrane Glycoproteins/genetics , Protein Kinase Inhibitors/therapeutic use , Receptor, trkA/genetics , Receptor, trkB/genetics , Receptor, trkC/genetics , Animals , Biomarkers, Tumor/genetics , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/drug therapy , Humans , Membrane Glycoproteins/metabolism , Precision Medicine , Receptor, trkA/metabolism , Receptor, trkB/metabolism , Receptor, trkC/metabolism , Signal Transduction/genetics
18.
Front Neurol ; 11: 598619, 2020.
Article in English | MEDLINE | ID: mdl-33391161

ABSTRACT

Objective: Intradural Extramedullary (IDEM) tumors are usually treated with surgical excision. The aim of this study was to investigate the impact on clinical outcomes of pre-surgical clinical conditions, intraoperative neurophysiological monitoring (IONM), surgical access to the spinal canal, histology, degree of resection and intra/postoperative complications. Methods: This is a retrospective observational study analyzing data of patients suffering from IDEM tumors who underwent surgical treatment over a 12 year period in a double-center experience. Data were extracted from a prospectively maintained database and included: sex, age at diagnosis, clinical status according to the modified McCormick Scale (Grades I-V) at admission, discharge, and follow-up, tumor histology, type of surgical access to the spinal canal (bilateral laminectomy vs. monolateral laminectomy vs. laminoplasty), degree of surgical removal, use and type of IONM, occurrence and type of intraoperative complications, use of Ultrasonic Aspirator (CUSA), radiological follow-up. Results: A total number of 249 patients was included with a mean follow-up of 48.3 months. Gross total resection was achieved in 210 patients (84.3%) mostly in Schwannomas (45.2%) and Meningiomas (40.4%). IONM was performed in 162 procedures (65%) and D-wave was recorded in 64.2% of all cervical and thoracic locations (99 patients). The linear regression diagram for McCormick grades before and after surgery (follow-up) showed a correlation between preoperative and postoperative clinical status. A statistically significant correlation was found between absence of worsening of clinical condition at follow-up and use of IONM at follow-up (p = 0.01) but not at discharge. No associations were found between the choice of surgical approach and the extent of resection (p = 0.79), the presence of recurrence or residual tumor (p = 0.14) or CSF leakage (p = 0.25). The extent of resection was not associated with the use of IONM (p = 0.91) or CUSA (p = 0.19). Conclusion: A reliable prediction of clinical improvement could be made based on pre-operative clinical status. The use of IONM resulted in better clinical outcomes at follow-up (not at discharge), but no associations were found with the extent of resection. The use of minimally invasive approaches such as monolateral laminectomy showed to be effective and not associated with worse outcomes or increased complications.

19.
Cancer Control ; 26(1): 1073274819870549, 2019.
Article in English | MEDLINE | ID: mdl-31865766

ABSTRACT

In the last few years, the treatment of spinal metastases has significantly changed. This is due to the advancements in surgical technique, radiotherapy, and chemotherapy which have enriched the multidisciplinary management. Above all, the field of molecular biology of tumors is in continuous and prosperous evolution. In this review, the molecular markers and new approaches that have radically modified the chemotherapeutic strategy of the most common metastatic neoplasms will be examined together with clinical and surgical implications. The experience and skills of several different medical professionals are mandatory: an interdisciplinary oncology team represents the winning strategy in the treatment of patients with spinal metastases.


Subject(s)
Spinal Neoplasms/complications , Spinal Neoplasms/surgery , Surgeons/standards , Humans , Neoplasm Metastasis
20.
J Clin Neurosci ; 70: 55-60, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31537460

ABSTRACT

The first step of glioma treatment is surgery. Extent of resection (EOR) improves patient survival if surgery does not negatively impair a patient's neurological status. However, how surgery affects the patient's quality of life (QOL) has been less studied, especially as regards cognitive aspects. In our study, we retrospectively analyzed our cases with awake surgery. In all patients, surgical excision was stopped when active functions were intraoperatively identified. A neuropsychological assessment was performed both before and after surgery (5 days and 1 month after). Writing, motor speech, comprehension, expression, reading, pragmatics, attention, memory, problem solving and visuoperceptive functions were evaluated and scored with the NOMS scale. We found no differences in the median values of writing and motor speech, while there was a difference in the following variables: comprehension, expression, reading, pragmatics, attention, memory, problem solving and visuoperceptive functions. Moreover, the Dunn test did not show any difference between preoperative evaluation and evaluation performed 30 days after surgery regarding comprehension, expression, reading, pragmatics, attention, problem solving and visuoperceptive functions. However, there was a difference between preoperative and postoperative evaluation for memory. This retrospective study shows that awake surgery could be a reasonable possibility to preserve a patient's QOL achieving an EOR >82% of the Total Tumor Volume (Fluid-attenuated inversion recovery (FLAIR) hyperintense region in low-grade gliomas and enhancing nodules plus FLAIR hyperintense region in high-grade gliomas). In this series memory was the only aspect that had an impairment after surgery without a complete recovery at one month after surgery.


Subject(s)
Brain Neoplasms/surgery , Glioma/surgery , Neurosurgical Procedures/adverse effects , Neurosurgical Procedures/methods , Postoperative Complications/prevention & control , Adult , Cognition , Female , Humans , Male , Middle Aged , Motor Skills , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies
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