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1.
Nat Commun ; 14(1): 4572, 2023 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516762

RESUMO

Accurate determination of the extent and grade of adult-type diffuse gliomas is critical to patient management. In clinical practice, contrast-enhancing areas of diffuse gliomas in magnetic resonance imaging (MRI) sequences are usually used to target biopsy, surgery, and radiation therapy, but there can be discrepancies between these areas and the actual tumor extent. Here we show that adding 18F-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) to MRI sequences accurately locates the most malignant areas of contrast-enhancing gliomas, potentially impacting subsequent management and outcomes. We present a prospective analysis of over 300 serial biopsy specimens from 23 patients with contrast-enhancing adult-type diffuse gliomas using a hybrid PET-MRI scanner to compare T2-weighted and contrast-enhancing MRI images with FET-PET. In all cases, we observe and confirm high FET uptake in early PET acquisitions (5-15 min after 18F-FET administration) outside areas of contrast enhancement on MRI, indicative of high-grade glioma. In 30% cases, inclusion of FET-positive sites changes the biopsy result to a higher tumor grade.


Assuntos
Aminoácidos , Glioma , Humanos , Adulto , Glioma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Transporte Biológico
2.
Curr Oncol ; 30(5): 5182-5194, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37232851

RESUMO

The aim of this study was to compare the pre- and postoperative function of patients qualifying for resection of malignant and nonmalignant primary brain tumors to determine the relationship among tumor type, function, and the course of rehabilitation after surgery. This single-center, prospective, observational study recruited 92 patients requiring prolonged postoperative rehabilitation during their inpatient stay, who were divided into a nonmalignant tumor group (n = 66) and a malignant tumor group (n = 26). Functional status and gait efficiency were assessed using a battery of instruments. Motor skills, postoperative complications, and length of hospital stay (LoS) were recorded and compared between groups. The frequency and severity of postoperative complications, the time needed to attain individual motor skills, and the proportion of patients losing independent gait (~30%) were similar between groups. However, paralysis and paresis were more frequent in the malignant tumor group before surgery (p < 0.001). While nonmalignant tumor patients deteriorated more according to all scales after surgery, patients with malignant tumors were still characterized by worse ADL, independence, and performance at discharge. Worse functional outcomes in the malignant tumor group did not affect LoS or rehabilitation. Patients with malignant and nonmalignant tumors have similar rehabilitation needs, and patient expectation-especially those with nonmalignant tumors-should be appropriately managed.


Assuntos
Neoplasias Encefálicas , Pacientes Internados , Humanos , Estudos Prospectivos , Resultado do Tratamento , Complicações Pós-Operatórias , Neoplasias Encefálicas/cirurgia
3.
Acta Neurochir (Wien) ; 165(7): 1739-1748, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37067618

RESUMO

BACKGROUND: The current literature on meningioma reveals a gap in knowledge regarding the impact of genetic factors on patient survival. Furthermore, there is a lack of data on the relationship between the perioperative use of corticosteroids and patient survival in meningioma patients. Our study aims to overcome these gaps by investigating the correlation between genetic factors and overall survival and the effect of postoperative corticosteroids and other clinical characteristics on patient outcomes in meningioma patients. METHODS: A retrospective analysis of the medical records of 85 newly diagnosed meningioma patients treated from 2016 to 2017 with follow-up until December 2022 was performed. RESULTS: NF2 mutations occurred in 60% of tumors, AKT1 mutations in 8.2%, and TRAF7 mutations in 3.6%. Most tumors in the parasagittal region had the NF2 mutation. On the other hand, almost all tumors in the sphenoid ridge area did not have the NF2 mutation. AKT-1-mutated meningiomas had more frequent peritumoral edema. Patients who received steroids perioperatively had worse overall survival (OS) than those without steroids (p = 0.034). Moreover, preoperative peri-meningioma edema also was associated with worse OS (p < 0.003). Contrarily, NF2 mutations did not influence survival. CONCLUSIONS: The combination of clinical, pathomorphological, and genetic data allows us to characterize the tumor better and assess its prognosis. Corticosteroids perioperatively and peri-meningioma edema were associated with shorter OS, according to our study. Glucocorticoids should be used judiciously for the shortest time required to achieve symptomatic relief.


Assuntos
Neoplasias Meníngeas , Meningioma , Esteroides , Humanos , Corticosteroides , Fator 4 Semelhante a Kruppel , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Meningioma/tratamento farmacológico , Meningioma/genética , Meningioma/cirurgia , Mutação , Estudos Retrospectivos , Esteroides/uso terapêutico
4.
Rev Neurosci ; 34(5): 483-516, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-36062548

RESUMO

Gliomas are the most common primary central nervous system tumors; despite recent advances in diagnosis and treatment, glioma patients generally have a poor prognosis. Hence there is a clear need for improved therapeutic options. In recent years, significant effort has been made to investigate immunotherapy and precision oncology approaches. The review covers well-established strategies such as surgery, temozolomide, PCV, and mTOR inhibitors. Furthermore, it summarizes promising therapies: tumor treating fields, immune therapies, tyrosine kinases inhibitors, IDH(Isocitrate dehydrogenase)-targeted approaches, and others. While there are many promising treatment strategies, none fundamentally changed the management of glioma patients. However, we are still awaiting the outcome of ongoing trials, which have the potential to revolutionize the treatment of glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/diagnóstico , Medicina de Precisão , Glioma/tratamento farmacológico , Temozolomida/uso terapêutico , Imunoterapia , Mutação
5.
J Clin Med ; 11(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36498658

RESUMO

AIM: Postoperative head computed tomography (POCT) is routinely performed in numerous medical institutions, mainly to identify possible postsurgical complications. This study sought to assess the clinical appropriateness of POCT in asymptomatic and symptomatic patients after ruptured or unruptured aneurysm clipping. METHODS: This is a retrospective multicenter study involving microsurgical procedures of ruptured (RA) and unruptured intracranial aneurysm (UA) surgeries performed in the Centers associated with the Pomeranian Department of the Polish Society of Neurosurgeons. A database of surgical procedures of intracranial aneurysms from 2017 to 2020 was created. Only patients after a CT scan within 24 h were included. RESULTS: A total of 423 cases met the inclusion criteria for the analysis. Age was the only significant factor associated with postoperative blood occurrence on POCT. A total of 37 (8.75%) cases of deterioration within 24 h with urgent POCT were noted, 3 (8.1%) required recraniotomy. The highest number necessary to predict (NNP) one recraniotomy based on patient deterioration was 50 in the RA group. CONCLUSION: We do not recommend POCTs in asymptomatic patients after planned clipping. New symptom onset requires radiological evaluation. Simultaneous practice of POCT after ruptured aneurysm treatment within 24 h is recommended.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36078585

RESUMO

Repeat surgery is often required to treat brain tumor recurrences. Here, we compared the functional state and rehabilitation of patients undergoing initial and repeat surgery for brain tumors to establish their individual risks that might impact management. In total, 835 patients underwent operations, and 139 (16.6%) required rehabilitation during the inpatient stay. The Karnofsky performance status, Barthel index, and the modified Rankin scale were used to assess functional status, and the gait index was used to assess gait efficiency. Motor skills, postoperative complications, and length of hospital stay were recorded. Patients were classified into two groups: first surgery (n = 103) and repeat surgery (n = 30). Eighteen percent of patients required reoperations, and these patients required prolonged postoperative rehabilitation as often as those operated on for the first time. Rehabilitation was more often complicated in the repeat surgery group (p = 0.047), and the complications were more severe and persistent. Reoperated patients had significantly worse motor function and independence in activities of daily living before surgery and at discharge, but the deterioration after surgery affected patients in the first surgery group to a greater extent according to all metrics (p < 0.001). The length of hospital stay was similar in both groups. These results will be useful for tailoring postoperative rehabilitation during a hospital stay on the neurosurgical ward as well as planning discharge requirements after leaving the hospital.


Assuntos
Atividades Cotidianas , Neoplasias Encefálicas , Neoplasias Encefálicas/reabilitação , Neoplasias Encefálicas/cirurgia , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
7.
Mol Diagn Ther ; 26(6): 699-713, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36053463

RESUMO

INTRODUCTION: The accurate detection of genetic variants such as single substitutions (IDH1/2, TERT), chromosomal abnormalities (CDKN2A, 1p/19q deletions, and EGFR amplifications), or promoter methylations (MGMT) is critical for glioma patient management, as emphasized in the World Health Organization's (WHO's) most recent classification in 2021 (WHO CNS5). The purpose of this study was to evaluate novel innovative methods for determining IDH1/2 status in the context of WHO CNS5. METHODS: Multiple biomarkers were simultaneously screened using next-generation sequencing (NGS) on 34 glioma samples. In cases where the IDH1/2 status determined by immunohistochemistry (IHC) or multiplex ligation-dependent probe amplification (MLPA) was inconsistent with the NGS results, quantitative polymerase chain reaction (qPCR) and Sanger sequencing were performed to resolve the adjudicated discrepancy. RESULTS: IDH1/2 NGS results differ from IHC (7/13 samples) as well as MLPA reports (1/4 samples). All NGS findings were confirmed by qPCR and Sanger sequencing. WHO CNS5 requires assessment of multiple mutations for glioma classification. CONCLUSIONS: We demonstrated that qPCR or NGS performed in reference genetic laboratories, rather than IHC, is the most reliable method for IDH1/2 analysis. Clinicians should be aware of discrepancies in MLPA or IHC results and seek reconsultation in facilities with extensive access to advanced molecular technologies. Moreover, we proposed a new algorithm for the molecular diagnostic procedures in glioma patients based on the WHO CNS5.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico , Imuno-Histoquímica , Glioma/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Organização Mundial da Saúde , Isocitrato Desidrogenase/genética
8.
Front Surg ; 9: 969244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157428

RESUMO

Purpose: Intervertebral disc degeneration can manifest as sequestration. In most cases, the material could be found ipsilateral to the annular tear; however, a contralateral migration is also possible. We present an anatomical description of anterior meningovertebral ligaments (MVLs) as a possible barrier for disc migration. Methods: Anatomical dissection of 20 fresh human cadavers was carried out. Complete lumbar laminectomies with facetectomies were performed. All lumbar segments were exposed. Morphologic and morphometric descriptions of anterior MVLs were presented, with special attention to possible routes of herniated disc migration. Results: Anterior MVLs were present in all cases. They were divided in three separate groups: medial, lateral, and attached to the nerve roots. The medial group was the thickest, its mean length was 26.2 ± 1.2 mm, and it had no attachment to the disc in 51% of cases. The lateral group was less firm than the medial group, its mean length was 26.9 ± 1.0 mm, and it had no relation with the disc in 47% of cases. Ligaments related to the nerve root were the most delicate and always attached to the intervertebral disc. Their mean length was 14.9 ± 1.8 mm. Conclusions: The medial group of anterior MVLs are strong connective tissue bands dividing the anterior epidural space. The lateral group is more delicate, and in most cases, lateral MVLs lack annular attachment. MVLs could be an anatomical barrier for disc migration in particular cases.

9.
Biomedicines ; 10(8)2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36009577

RESUMO

Glioblastoma is the most malignant central nervous system tumor, which represents 50% of all glial tumors. The understanding of glioma genesis, prognostic evaluation, and treatment planning has been significantly enhanced by the discovery of molecular genetic biomarkers. This study aimed to evaluate survival in patients with primary glioblastoma concerning O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and other clinical factors. The study included 41 newly diagnosed glioblastoma patients treated from 2011 to 2014 in the 10th Military Research Hospital and Polyclinic, Poland. All patients underwent surgical resection followed by radiation and chemotherapy with alkylating agents. The MGMT promoter methylation was evaluated in all patients, and 43% were found to be methylated. In 26 and 15 cases, gross total resection and subtotal resection were conducted, respectively. Patients with a methylated MGMT promoter had a median survival of 504 days, while those without methylation had a median survival of 329 days. The group that was examined had a median age of 53. In a patient group younger than 53 years, those with methylation had significantly longer overall survival (639 days), compared to 433.5 days for patients without methylation. The most prolonged survival (551 days) was in patients with MGMT promoter methylation after gross total resection. The value of MGMT promoter methylation as a predictive biomarker is widely acknowledged. However, its prognostic significance remains unclear. Our findings proved that MGMT promoter methylation is also an essential positive prognostic biomarker.

10.
Surg Oncol ; 42: 101771, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35512545

RESUMO

PURPOSE: Glioblastoma multiforme (GBM) is the most common malignant brain tumor. Moreover, GBM recurs in nearly all patients. Although a standard STUPP protocol has been widely used for newly diagnosed GBM, no standard regimen has been established for recurrent patients. Here we evaluated the clinical value of recurrent GBM reoperation by comparing overall survival and quality of life (QoL) in patients with recurrent GBM undergoing repeat surgery or conservative treatment. METHODS: This was a prospective study of 165 patients with GBM receiving first operations for their disease between 2011 and 2013 at two tertiary neurosurgery centers in Poland. Thirty-five eligible patients were re-operated for recurrence (the study group), and 35 patients were selected as the control group using propensity score matching. A model was created to determine advantageous prognostic factors for longer survival of patients qualifying for reoperation using stepwise linear regression. RESULTS: The mean overall survival of patients undergoing repeat surgery was 528 days compared to 297 days in patients who did not undergo repeat surgery. Reoperation did not result in a significant deterioration in performance status as measured by the Karnofsky Performance Scale. Older age, the presence of symptoms of increased intracranial pressure, and a shorter period between initial operation and reoperation were independent predictors of a worse outcome. CONCLUSION: In selected patients, reoperation for recurrent GBM prolongs survival with no significant deteriorations in performance status.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Qualidade de Vida , Reoperação
11.
Molecules ; 27(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35408649

RESUMO

Brain tumors are neoplasms with one of the highest mortality rates. Therefore, the availability of methods that allow for the quick and effective diagnosis of brain tumors and selection of appropriate treatments is of critical importance for patient outcomes. In this study, coated blade spray-mass spectrometry (CBS-MS), which combines the features of microextraction and fast ionization methods, was applied for the analysis of brain tumors. In this approach, a sword-shaped probe is coated with a sorptive material to enable the extraction of analytes from biological samples. The analytes are then desorbed using only a few microliters of solvent, followed by the insertion of the CBS device into the interface on the mass spectrometer source. The results of this proof-of-concept experiment confirmed that CBS coupled to high-resolution mass spectrometry (HRMS) enables the rapid differentiation of two histologically different lesions: meningiomas and gliomas. Moreover, quantitative CBS-HRMS/MS analysis of carnitine, the endogenous compound, previously identified as a discriminating metabolite, showed good reproducibility with the variation below 10% when using a standard addition calibration strategy and deuterated internal standards for correction. The resultant data show that the proposed CBS-MS technique can be useful for on-site qualitative and quantitative assessments of brain tumor metabolite profiles.


Assuntos
Neoplasias Encefálicas , Espectrometria de Massas em Tandem , Neoplasias Encefálicas/diagnóstico , Humanos , Reprodutibilidade dos Testes , Microextração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos
12.
Int J Mol Sci ; 23(7)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35408879

RESUMO

The development of a fast and accurate intraoperative method that enables the differentiation and stratification of cancerous lesions is still a challenging problem in laboratory medicine. Therefore, it is important to find and optimize a simple and effective analytical method of enabling the selection of distinctive metabolites. This study aims to assess the usefulness of solid-phase microextraction (SPME) probes as a sampling method for the lipidomic analysis of brain tumors. To this end, SPME was applied to sample brain tumors immediately after excision, followed by lipidomic analysis via liquid chromatography-high resolution mass spectrometry (LC-HRMS). The results showed that long fibers were a good option for extracting analytes from an entire lesion to obtain an average lipidomic profile. Moreover, significant differences between tumors of different histological origin were observed. In-depth investigation of the glioma samples revealed that malignancy grade and isocitrate dehydrogenase (IDH) mutation status impact the lipidomic composition of the tumor, whereas 1p/19q co-deletion did not appear to alter the lipid profile. This first on-site lipidomic analysis of intact tumors proved that chemical biopsy with SPME is a promising tool for the simple and fast extraction of lipid markers in neurooncology.


Assuntos
Neoplasias Encefálicas , Lipidômica , Biópsia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Humanos , Isocitrato Desidrogenase/genética , Lipídeos , Mutação
13.
Artigo em Inglês | MEDLINE | ID: mdl-35206503

RESUMO

Brain tumor location is an important factor determining the functional state after brain tumor surgery. We assessed the functional state and course of rehabilitation of patients undergoing surgery for brain tumors and assessed the location-dependent risk of loss of basic motor skills and the time needed for improvement after surgery. There were 835 patients who underwent operations, and 139 (16.6%) required rehabilitation during the inpatient stay. Karnofsky Performance Scale, Barthel Index, and the modified Rankin scale were used to assess functional status, whereas Gait Index was used to assess gait efficiency. Motor skills, overall length of stay (LOS) in hospital, and LOS after surgery were recorded. Patients were classified into four groups: cerebral hemisphere (CH), ventricular system (VS), and cerebellopontine angle (CPA) tumors; and a control group not requiring rehabilitation. VS tumor patients had the lowest scores in all domains compared with the other groups before surgery (p < 0.001). Their performance further deteriorated after surgery and by the day of discharge. They most often required long-lasting postoperative rehabilitation and had the longest LOS (35 days). Operation was most often required for CH tumors (77.7%), and all metrics and LOS parameters were better in these patients (p < 0.001). Patients with CPA tumors had the best outcomes (p < 0.001). Most patients (83.4%) with brain tumors did not require specialized rehabilitation, and LOS after surgery in the control group was on average 5.1 days after surgery. VS tumor patients represent a rehabilitation challenge. Postoperative rehabilitation planning must take the tumor site and preoperative condition into account.


Assuntos
Neoplasias Encefálicas , Ventrículos Cerebrais , Cérebro , Destreza Motora , Neuroma Acústico , Neoplasias Encefálicas/reabilitação , Neoplasias Encefálicas/cirurgia , Ventrículos Cerebrais/cirurgia , Cérebro/cirurgia , Humanos , Tempo de Internação , Neuroma Acústico/reabilitação , Neuroma Acústico/cirurgia
14.
Cancers (Basel) ; 14(2)2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35053475

RESUMO

Glioblastoma multiforme is one of the most malignant neoplasms among humans in their third and fourth decades of life, which is evidenced by short patient survival times and rapid tumor-cell proliferation after radiation and chemotherapy. At present, the diagnosis of gliomas and decisions related to therapeutic strategies are based on genetic testing and histological analysis of the tumor, with molecular biomarkers still being sought to complement the diagnostic panel. This work aims to enable the metabolomic characterization of cancer tissue and the discovery of potential biomarkers via high-resolution mass spectrometry coupled to liquid chromatography and a solvent-free sampling protocol that uses a microprobe to extract metabolites directly from intact tumors. The metabolomic analyses were performed independently from genetic and histological testing and at a later time. Despite the small cohort analyzed in this study, the results indicated that the proposed method is able to identify metabolites associated with different malignancy grades of glioma, as well as IDH and 1p19q codeletion mutations. A comparison of the constellation of identified metabolites and the results of standard tests indicated the validity of using the characterization of one comprehensive tumor phenotype as a reflection of all diagnostically meaningful information. Due to its simplicity, the proposed analytical approach was verified as being compatible with a surgical environment and applicable for large-scale studies.

15.
Neurosurg Rev ; 45(3): 2211-2219, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35061140

RESUMO

Dural sinus thrombosis is one of the complications after posterior fossa surgery. However, that topic is not described well with regard to vestibular schwannoma surgery using the unique suboccipital retrosigmoid approach. We analyzed retrospectively medical records and radiological investigations of 116 patients. The including criteria were histopathologically confirmed vestibular schwannoma operated on using the retrosigmoid approach, preoperative and postoperative contrast-enhanced MRI, and at least 1-year follow-up. The patient group included 36% males and 64% females. The average age was 47.3 ± 13.9 years. Sixty percent of the tumors were classified as T4b according to the Hannover scale and their mean volume was 13.73 ± 10.28 cm3. There were no signs of thrombosis preoperatively. Postoperative changes in the dural sinuses were found in 26 (22%) cases. In 7 (27%) cases, there was an external compression by the hemostatic agent, and in 19 (73%) cases, a thrombus was visualized in the sinus lumen. The size of the sinus, age, and the tumor size were not risk factors for thrombosis, whereas an intraoperative sinus injury was a statistically significant risk factor (p = 0.0012). All of the patients diagnosed with thrombosis were in good clinical condition in long-term follow-up, except one fatal case. Complete recanalization was observed in 58% of cases after 1-year follow-up. Postoperative changes in the dural venous sinuses are a frequent finding after vestibular schwannoma surgery using the suboccipital retrosigmoid approach. Intraoperative dural injury is a risk factor for thrombosis. Thrombosis in that group of patients is usually asymptomatic and does not influence the prognosis.


Assuntos
Neuroma Acústico , Trombose dos Seios Intracranianos , Trombose , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/complicações , Neuroma Acústico/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Trombose dos Seios Intracranianos/complicações
16.
Brain Sci ; 11(11)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34827431

RESUMO

Stereotactic biopsy of posterior fossa lesions is often regarded as hazardous due to the critical structures in that area. Therefore, the aim of the study was to evaluate the diagnostic accuracy and safety of infratentorial stereotactic biopsy of brainstem or cerebellar lesions and its associations with other clinical, laboratory, and radiological parameters. From January 2000 to May 2021, 190 infratentorial stereotactic biopsies of posterior fossa tumors, including 108 biopsies of brainstem lesions, were performed. Moreover, 63 supratentorial biopsies of cerebral peduncle lesions were analyzed to compare the safety and efficacy of both approaches. Additionally, the presence of antibodies against Toxoplasma gondii and Epstein-Barr Virus (EBV) were documented in 67 and 66 patients, respectively, and magnetic resonance imaging (MRI) scans were evaluated in 114 patients. Only 4% of patients had minor complications and 1.5% had major complications, including one patient who died from intracranial bleeding. Nine (4.7%) biopsies were non-diagnostic. Isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were assessed in 29 patients, and were non-diagnostic in only 3 (10.3%) cases. Patients with high-grade gliomas (HGG) were more frequently seropositive for T. gondii than individuals with low-grade gliomas (LGG; p < 0.001). A total of 27% of HGG and 41% of LGG were non-enhancing on MRI. The infratentorial approach is generally safe and reliable for biopsy of brainstem and cerebellar lesions. In our study, the safety and efficacy of supratentorial biopsy of the cerebral peduncle and infratentorial biopsy of lesions below the cerebral peduncle were comparably high. Moreover, patients with HGG were more frequently seropositive for T. gondii than patients with LGG, and the relationship between toxoplasmosis and gliomagenesis requires further investigation.

17.
Sci Rep ; 11(1): 19522, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593948

RESUMO

It is extremely challenging to perform chemical analyses of the brain, particularly in humans, due to the restricted access to this organ. Imaging techniques are the primary approach used in clinical practice, but they only provide limited information about brain chemistry. Solid-phase microextraction (SPME) has been presented recently as a chemical biopsy tool for the study of animal brains. The current work demonstrates for the first time the use of SPME for the spatially resolved sampling of the human brain in vivo. Specially designed multi-probe sampling device was used to simultaneously extract metabolites from the white and grey matter of patients undergoing brain tumor biopsies. Samples were collected by inserting the probes along the planned trajectory of the biopsy needle prior to the procedure, which was followed by metabolomic and lipidomic analyses. The results revealed that studied brain structures were predominantly composed of lipids, while the concentration and diversity of detected metabolites was higher in white than in grey matter. Although the small number of participants in this research precluded conclusions of a biological nature, the results highlight the advantages of the proposed SPME approach, as well as disadvantages that should be addressed in future studies.


Assuntos
Biópsia/instrumentação , Química Encefálica , Encéfalo/metabolismo , Metabolômica/instrumentação , Biópsia/métodos , Cromatografia Líquida , Humanos , Lipidômica/instrumentação , Lipidômica/métodos , Espectrometria de Massas , Metabolômica/métodos
18.
Molecules ; 26(20)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34684691

RESUMO

Alterations in the carnitine shuttle system may be an indication of the presence of cancer. As such, in-depth analyses of this pathway in different malignant tumors could be important for the detection and treatment of this disease. The current study aims to assess the profiles of carnitine and acylcarnitines in gliomas with respect to their grade, the presence of isocitrate dehydrogenase (IDH) mutations, and 1p/19q co-deletion. Brain tumors obtained from 19 patients were sampled on-site using solid-phase microextraction (SPME) immediately following excision. Analytes were desorbed and then analyzed via liquid chromatography-high-resolution mass spectrometry. The results showed that SPME enabled the extraction of carnitine and 22 acylcarnitines. An analysis of the correlation factor revealed the presence of two separate clusters: short-chain and long-chain carnitine esters. Slightly higher carnitine and acylcarnitine concentrations were observed in the higher-malignancy tumor samples (high vs. low grade) and in those samples with worse projected clinical outcomes (without vs. with IDH mutation; without vs. with 1p/19q co-deletion). Thus, the proposed chemical biopsy approach offers a simple solution for on-site sampling that enables sample preservation, thus supporting comprehensive multi-method analyses.


Assuntos
Carnitina/metabolismo , Aberrações Cromossômicas , Glioma/patologia , Isocitrato Desidrogenase/genética , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Microextração em Fase Sólida/métodos , Adulto Jovem
19.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34638714

RESUMO

Gliomas are the most common central nervous system tumors. New technologies, including genetic research and advanced statistical methods, revolutionize the therapeutic approach to the patient and reveal new points of treatment options. Moreover, the 2021 World Health Organization Classification of Tumors of the Central Nervous System has fundamentally changed the classification of gliomas and incorporated many molecular biomarkers. Given the rapid progress in neuro-oncology, here we compile the latest research on prognostic and predictive biomarkers in gliomas. In adult patients, IDH mutations are positive prognostic markers and have the greatest prognostic significance. However, CDKN2A deletion, in IDH-mutant astrocytomas, is a marker of the highest malignancy grade. Moreover, the presence of TERT promoter mutations, EGFR alterations, or a combination of chromosome 7 gain and 10 loss upgrade IDH-wildtype astrocytoma to glioblastoma. In pediatric patients, H3F3A alterations are the most important markers which predict the worse outcome. MGMT promoter methylation has the greatest clinical significance in predicting responses to temozolomide (TMZ). Conversely, mismatch repair defects cause hypermutation phenotype predicting poor response to TMZ. Finally, we discussed liquid biopsies, which are promising diagnostic, prognostic, and predictive techniques, but further work is needed to implement these novel technologies in clinical practice.


Assuntos
Biomarcadores Tumorais , Neoplasias do Sistema Nervoso Central , Glioma , Proteínas de Neoplasias , Temozolomida/uso terapêutico , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/metabolismo , Metilação de DNA/efeitos dos fármacos , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Glioma/diagnóstico , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Humanos , Mutação , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Prognóstico
20.
Front Neurol ; 12: 706166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707553

RESUMO

Self-destructive and aggressive behaviors can have a significant impact on the quality of life of affected individuals and their carrers. While deep brain stimulation (DBS) has been applied to the treatment of self-destructive and aggressive behaviors in isolated cases, clinical data on this treatment modality are still lacking. We therefore assessed responses to treatment with bilateral DBS of the nucleus accumbens in six patients with severe self-destructive and aggressive behaviors. Three patients had Tourette syndrome and three had other underlying predispositions including obsessive compulsive disorder, cerebral palsy, encephalitis, and epilepsy. Patients were followed up for between 2 and 7 years, and patients were assessed using the Modified Overt Aggression Scale (six patients) and the Buss-Perry Aggression Questionnaire (three patients able to complete the questionnaire on their own). DBS reduced self-destructive and aggressive behaviors by 30-100% and by an average of 74.5%. Patients with Tourette syndrome responded better to DBS and improved by 27.3% according to the Buss-Perry Aggression Questionnaire. These results suggest that nuclei accumbens stimulation may be an effective treatment for aggressive and self-destructive behaviors regardless of etiology.

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