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1.
Asian J Neurosurg ; 18(3): 614-620, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38152534

RESUMO

Background Postoperative surgical site infections are a recognized complication following craniotomies with an associated increase in morbidity and mortality. Several studies have attempted to identify bundles of care to reduce the incidence of infections. Our study aims to clarify which perioperative measures play a role in reducing surgical infection rates further. Methods This study is a retrospective audit of all elective craniotomies in years 2018 to 2019. The primary endpoint was the surgical site infection rate at 30 days and 4 months after the procedure. Univariate analysis was used to identify factors predictive of postoperative infection. Results 344 patients were included in this study. Postoperative infections were observed in 5.2% of our cohort. No postoperative infections occurred within 4 months in patients receiving perioperative hair wash and intrawound vancomycin powder. In univariate analysis, craniotomy size (Fisher's exact test, p = 0.05), lack of perioperative hair wash, and vancomycin powder use (Fisher's exact test, p = 0.01) were predictive of postoperative infection. No complications relative to the use of intrawound vancomycin were observed. Conclusion Our study demonstrates that simple measures such as perioperative hair wash combined with intrawound vancomycin powder in addition to standard practice can help reducing infection rates with negligible risks and acceptable costs. Our results should be validated further in future prospective studies.

2.
Acta Neurochir (Wien) ; 165(7): 1683-1693, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37162609

RESUMO

OBJECTIVE: We sought to determine the 1-year survival following craniotomy for tumour resection in a public healthcare system and analyse the effect of indices of multiple deprivation (IMD) as well as smoking, alcohol, BMI, ASA grade and medical co-morbidities on post-operative morbidity and mortality. METHODS: This is a retrospective, single-centre study in a high volume neurosurgical centre, over a 2-year period. All patients undergoing a craniotomy for a brain tumour were included. Data was collected from the neuro-oncology database and electronic patient records. Individual patient IMD data was obtained using their postcode from a national government database. Each English postcode being ranked from 1 to 32,844, with 1 being the most deprived and 32,844 the most affluent. Descriptive results are described along with further data analysis using multiple linear and logistic regression analyses. RESULTS: 630 patients underwent an elective or urgent craniotomy for tumour. 10% of all patients underwent urgent surgery. 68% (95% CI: 64 to 71%) survived at least 1-year post-surgery. Our study found that social deprivation (IMD postcode rank) was not associated with mortality at 1 year after adjusting for potential confounding factors. Those from decile 1 had the lowest risk of death at 12 months for all tumour types (p = 0.0070). Previous smokers carried an increased risk of death at 12 months when compared with people who had never smoked RR 1.40 CI 1.10-1.78 (p = 0.006) but this risk was not evident in current smokers RR 0.92 CI 0.65-1.31 (p = 0.64). Increasing age and male gender were also found to be associated with higher mortality at 1 year (p = < 0.001). CONCLUSIONS: In the UK despite the discrepancy in the health of the general population between the north and south, social deprivation does not appear to be detrimental to neurooncological outcomes although smoking status, advancing age and male sex are.


Assuntos
Neoplasias Encefálicas , Fumar , Humanos , Masculino , Estudos Retrospectivos , Fumar/efeitos adversos , Fumar/epidemiologia , Neoplasias Encefálicas/cirurgia , Atenção à Saúde , Craniotomia/efeitos adversos , Fatores de Risco
3.
Clin Transl Radiat Oncol ; 39: 100585, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36845633

RESUMO

Background: Glioblastoma is a high-grade aggressive neoplasm whose outcomes have not changed in decades. In the current treatment pathway, tumour growth continues and remains untreated for several weeks post-diagnosis. Intensified upfront therapy could target otherwise untreated tumour cells and improve the treatment outcome. POBIG will evaluate the safety and feasibility of single-fraction preoperative radiotherapy for newly diagnosed glioblastoma, assessed by the maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV). Methods: POBIG is an open-label, dual-centre phase I dose and volume escalation trial that has received ethical approval. Patients with a new radiological diagnosis of glioblastoma will be screened for eligibility. This is deemed sufficient due to the high accuracy of imaging and to avoid treatment delay. Eligible patients will receive a single fraction of preoperative radiotherapy ranging from 6 to 14 Gy followed by their standard of care treatment comprising maximal safe resection and postoperative chemoradiotherapy (60 Gy/30 fr) with concurrent and adjuvant temozolomide). Preoperative radiotherapy will be directed to the part of the tumour that is highest risk for remaining as postoperative residual disease (hot spot). Part of the tumour will remain unirradiated (cold spot) and sampled separately for diagnostic purposes. Dose/volume escalation will be guided by a Continual Reassessment Method (CRM) model. Translational opportunities will be afforded through comparison of irradiated and unirradiated primary glioblastoma tissue. Discussion: POBIG will help establish the role of radiotherapy in preoperative modalities for glioblastoma. Trial registration: NCT03582514 (clinicaltrials.gov).

4.
Br J Neurosurg ; 37(2): 182-187, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34918613

RESUMO

BACKGROUND: The combination of awake craniotomy with multimodal neurophysiological mapping and monitoring in intra-axial tumour resection is not well described, but may have theoretical benefits which we sought to investigate. METHODS: All patients undergoing awake craniotomy for tumour resection with cortical and/or subcortical stimulation together with one or more of electrocorticography (ECoG/EEG), motor or somatosensory evoked potentials were identified from the operative records of two surgeons at two centres over a 5 year period. Patient, operative and outcome data were collated. Statistical analysis was performed to evaluate factors predictive of intra-operative seizures and surgical outcomes. RESULTS: 83 patients with a median age 50 years (18-80 years) were included. 80% had gliomas (37% low grade) and 13% metastases. Cortical mapping was negative in 35% (language areas) and 24% (motor areas). Complete or near total resection was achieved in 80% with 5% severe long-term neurological deficits. Negative cortical mapping was combined with positive subcortical mapping in 42% with no significant difference in extent of resection rates to patients undergoing positive cortical mapping (p = 0.95). Awake mapping could not be completed in 14%, but with no compromise to extent of resection (p = 0.55) or complication rates (p = 0.09). Intraoperative seizures occurred in 11% and were significantly associated with intra-operative EEG spikes (p = 0.003). CONCLUSIONS: Awake multi-modal monitoring is a safe and well tolerated technique. It provides preservation of extent of resection and clinical outcomes in cases of aborted awake craniotomy. Negative cortical mapping in combination with positive subcortical mapping was also shown to be safe, although not hitherto well described. Electrocorticography further enables the differentiation of seizure activity from true positive mapping, and the successful treatment of spikes prior to full clinical seizures occurring.


Assuntos
Neoplasias Encefálicas , Monitorização Neurofisiológica Intraoperatória , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Vigília , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Craniotomia/métodos , Convulsões/etiologia , Convulsões/cirurgia , Mapeamento Encefálico/métodos
5.
World Neurosurg ; 162: e246-e250, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35259507

RESUMO

BACKGROUND: Surgical site infection (SSI) is a significant cause of postoperative morbidity and mortality. As oncologic care advances, the use of surgical adjuncts such as intraoperative ultrasound (US), 5-aminolevulinic acid (5-ALA), and neurophysiologic monitoring has increased. This study set out to identify whether the use of surgical adjuncts in supratentorial tumor surgery lead to increased operative time or increased rates of SSI. METHODS: This is a retrospective study at a large tertiary clinical neurosciences center in the UK. We included all patients who underwent an elective supratentorial craniotomy for a tumor over a 12 month period. We retrospectively assessed whether patients had had a postoperative infection at 30 days or 4 months using our electronic patient record system. RESULTS: A total of 267 patients were included. The median age was 58 years (range: 17-87 years) with roughly equal numbers of men and women (men: 138 of 267, 52%). Most operations were carried out for gliomas (149 of 267, 56%) or metastases (61 of 267, 23%). The median length of surgery was 3 hours 6 minutes, with 24% lasting >4 hours. The overall infection rate was 4.5%. Intraoperative monitoring and 5-ALA was associated with longer operative times although not necessarily larger craniotomy sizes, whereas intraoperative US was associated with a shorter operative time and smaller craniotomy size. These adjuncts were not associated with an increased risk of infection. CONCLUSIONS: This study adds reassurance that although some surgical adjuncts lead to increased operative times, in our study there was no apparent increased risk of infection as a result of this.


Assuntos
Procedimentos Neurocirúrgicos , Infecção da Ferida Cirúrgica , Craniotomia/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia
6.
Acta Neurochir (Wien) ; 164(4): 1115-1123, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35039959

RESUMO

INTRODUCTION: Depending on severity of presentation, pituitary apoplexy can be managed with acute surgery or non-operatively. We aim to assess long-term tumour control, visual and endocrinological outcomes following pituitary apoplexy with special emphasis on patients treated non-operatively. METHODS: Multicentre retrospective cohort study. All patients with symptomatic pituitary apoplexy were included. Patients were divided into 3 groups: group 1: surgery within 7 days; group 2: surgery 7 days-3 months; group 3: non-operative. Further intervention for oncological reasons during follow-up was the primary outcome. Secondary outcome measures included visual and endocrinological function at last follow-up. RESULTS: One hundred sixty patients were identified with mean follow-up of 48 months (n = 61 group 1; n = 34 group 2; n = 64 group 3). Factors influencing decision for surgical treatment included visual acuity loss (OR: 2.50; 95% CI: 1.02-6.10), oculomotor nerve palsy (OR: 2.80; 95% CI: 1.08-7.25) and compression of chiasm on imaging (OR: 9.50; 95% CI: 2.06-43.73). Treatment for tumour progression/recurrence was required in 17%, 37% and 24% in groups 1, 2 and 3, respectively (p = 0.07). Urgent surgery (OR: 0.16; 95% CI: 0.04-0.59) and tumour regression on follow-up (OR: 0.04; 95% CI: 0.04-0.36) were independently associated with long-term tumour control. Visual and endocrinological outcomes were comparable between groups. CONCLUSION: Urgent surgery is an independent predictor of long-term tumour control following pituitary apoplexy. However, 76% of patients who successfully complete 3 months of non-operative treatment may not require any intervention in the long term.


Assuntos
Apoplexia Hipofisária , Neoplasias Hipofisárias , Acidente Vascular Cerebral , Humanos , Apoplexia Hipofisária/diagnóstico por imagem , Apoplexia Hipofisária/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
7.
Pituitary ; 25(2): 267-274, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34843070

RESUMO

PURPOSE: There is no compelling outcome data or clear guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using low molecular weight heparin (chemoprophylaxis) in patients undergoing pituitary surgery. Here we describe our experience of early chemoprophylaxis (post-operative day 1) following trans-sphenoidal pituitary surgery. METHODS: Single-centre review of a prospective surgical database and VTE records. Adults undergoing first time trans-sphenoidal pituitary surgery were included (2009-2018). VTE was defined as either deep vein thrombosis and/or pulmonary embolism within 3 months of surgery. Postoperative haematomas were those associated with a clinical deterioration together with radiological evidence. RESULTS: 651 Patients included with a median age of 55 years (range 16-86 years). Most (99%) patients underwent trans-sphenoidal surgery using a standard endoscopic single nostril or bi-nostril trans-sphenoidal technique. More than three quarters had pituitary adenomas (n = 520, 80%). Postoperative chemoprophylaxis to prevent VTE was administered in 478 patients (73%). Chemoprophylaxis was initiated at a median of 1 day post-procedure (range 1-5 days postoperatively; 92% on postoperative day 1). Tinzaparin was used in 465/478 patients (97%) and enoxaparin was used in 14/478 (3%). There were no cases of VTE, even in 78 ACTH-dependent Cushing's disease patients. Six patients (1%) developed postoperative haematomas. Chemoprophylaxis was not associated with a significantly higher rate of postoperative haematoma formation (Fisher's Exact, p = 0.99) or epistaxis (Fisher's Exact, p > 0.99). CONCLUSIONS: Chemoprophylaxis after trans-sphenoidal pituitary surgery on post-operative day 1 is a safe strategy to reduce the risk of VTE without significantly increasing the risk of postoperative bleeding events.


Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/prevenção & controle , Fatores de Risco , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Adulto Jovem
8.
Endocrine ; 75(3): 872-882, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34741239

RESUMO

PURPOSE: To assess and compare outcome of surgical management of non-functioning pituitary adenohypophyseal tumours in patients under 65-years, and 65-years and older at tertiary neurosurgical referral centre. METHODS: Data was retrospectively analysed from pituitary database. Forty-four patients aged 65 or older (Group 1) and 93 patients under 65 (Group 2) underwent endoscopic trans-sphenoidal surgery (ETSS) between January 2017 and July 2019. The surgical, endocrinological, ophthalmological and radiological outcomes were compared. RESULTS: 6.8% of Group 1 patients had peri-operative surgical complications compared to 12.9% in Group 2 (p = 0.29). Improved visual fields and acuity were seen in 65.2% and 82.8% of Group 1 and Group 2 respectively (p = 0.124), although there were pre-existing ocular problems in 15.9% of Group 1. New hormone deficiencies were observed in 31.8% of Group 1 patients, and 24.7% of Group 2 (p = 0.555). Tumour regrowth/recurrence was seen in 2.3% of Group 1 (p = 0.553). The rate of repeat surgery was 6.8% in the Group 1 and 12.9% in Group 2 (p = 0.28). There was no significant relationship between extent of resection, complications or hormonal deficiency. The mean duration of follow-up was 10.5 ± 13.0 months for Group 1 patients and 13.0 ± 16.0 months for Group 2 patients (p = 0.526). CONCLUSIONS: ETSS for non-functioning pituitary adenohypophyseal tumours is safe and well tolerated in the patients aged 65 and older. Advanced age by itself should not be a contra-indication for ETSS. It is however highly recommended that the care of such patients to be offered at a high volume, dedicated pituitary surgical units.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/patologia , Idoso , Humanos , Recidiva Local de Neoplasia/complicações , Neoplasias Hipofisárias/patologia , Estudos Retrospectivos , Resultado do Tratamento , Reino Unido
9.
World Neurosurg ; 154: e718-e723, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34343689

RESUMO

BACKGROUND: The insular cortex is an eloquent island of mesocortex surrounded by vital structures making this region relatively challenging to neurosurgeons. Historically, lesions in this region were considered too high risk to approach given the strong chance of poor surgical outcome. Advances in recent decades have meant that surgeons can more safely access this eloquent region. Seizure outcome after excision of insular low-grade gliomas is well reported, but little is known about seizure outcomes after excision of insular high-grade gliomas. METHODS: A retrospective analysis was performed of all patients presenting with new-onset seizures during 2015-2019 who underwent excision of an insular high-grade glioma at 3 regional neurosurgical centers in the United Kingdom. RESULTS: We identified 38 patients with a mean (SD) age of 45.7 (15.3) years with median follow-up of 21 months. At long-term follow-up, of 38 patients, 23 were seizure-free (Engel class I), 2 had improved seizures (Engel class II), 6 had poor seizure control (Engel class III/IV), and 7 died. CONCLUSIONS: Excision of insular high-grade gliomas is safe and results in excellent postoperative seizure control.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Córtex Insular/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias , Convulsões/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Neurooncol Adv ; 3(1): vdab014, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34056602

RESUMO

BACKGROUND: The COVID-19 pandemic has profoundly affected cancer services. Our objective was to determine the effect of the COVID-19 pandemic on decision making and the resulting outcomes for patients with newly diagnosed or recurrent intracranial tumors. METHODS: We performed a multicenter prospective study of all adult patients discussed in weekly neuro-oncology and skull base multidisciplinary team meetings who had a newly diagnosed or recurrent intracranial (excluding pituitary) tumor between 01 April and 31 May 2020. All patients had at least 30-day follow-up data. Descriptive statistical reporting was used. RESULTS: There were 1357 referrals for newly diagnosed or recurrent intracranial tumors across 15 neuro-oncology centers. Of centers with all intracranial tumors, a change in initial management was reported in 8.6% of cases (n = 104/1210). Decisions to change the management plan reduced over time from a peak of 19% referrals at the start of the study to 0% by the end of the study period. Changes in management were reported in 16% (n = 75/466) of cases previously recommended for surgery and 28% of cases previously recommended for chemotherapy (n = 20/72). The reported SARS-CoV-2 infection rate was similar in surgical and non-surgical patients (2.6% vs. 2.4%, P > .9). CONCLUSIONS: Disruption to neuro-oncology services in the UK caused by the COVID-19 pandemic was most marked in the first month, affecting all diagnoses. Patients considered for chemotherapy were most affected. In those recommended surgical treatment this was successfully completed. Longer-term outcome data will evaluate oncological treatments received by these patients and overall survival.

11.
Virchows Arch ; 478(5): 977-984, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32918169

RESUMO

Primary non-neuroendocrine tumours of the pituitary gland and sella are rare lesions often challenging to diagnose. We describe two cases of clinically aggressive primary glomus tumour of the pituitary gland. The lesions occurred in a 63-year-old male and a 30-year-old female who presented with headache, blurred vision and hypopituitarism. Neuroimaging demonstrated large sellar and suprasellar tumours invading the surrounding structures. Histologically, the lesions were characterised by angiocentric sheets and nests of atypical cells that expressed vimentin, smooth muscle actin and CD34. Perivascular deposition of collagen IV was also a feature. Case 2 expressed synaptophysin. INI-1 (SMARCB1) expression was preserved. Both lesions were mitotically active and demonstrated a Ki-67 labelling index of 30%. Next-generation sequencing performed in case 1 showed no mutations in the reading frame of 37 commonly mutated oncogenes, including BRAF and KRAS. Four pituitary glomus tumours have previously been reported, none of which showed features of malignant glomus tumour. Similar to our two patients, three previous examples displayed aggressive behaviour.


Assuntos
Tumor Glômico/patologia , Neoplasias Hipofisárias/patologia , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Diagnóstico Diferencial , Evolução Fatal , Feminino , Tumor Glômico/química , Tumor Glômico/diagnóstico por imagem , Tumor Glômico/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Hipofisárias/química , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/genética , Valor Preditivo dos Testes
12.
J Clin Neurosci ; 82(Pt A): 49-51, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33317738

RESUMO

There has been a growing anxiety in carrying out awake craniotomy surgeries during the SARS-CoV-2 pandemic, not only due to airway management but also close proximity to the team in theatre. We set out to safely perform the first documented awake craniotomy in the UK since the beginning of lockdown. We performed a thorough workup of the patient with minimal hospital visits, using remote communication wherever possible. We modified our existing awake craniotomy protocol/technique guided by local/national policies. An asleep-awake-asleep craniotomy for tumour resection was performed successfully without compromising patient and staff safety with excellent post-operative outcome. With appropriate pre- and peri-operative modifications to established protocols, awake craniotomies with functional mapping can be safely carried out. By incorporating novel aspects to our technique, we believe that this service can safely resume in carefully selected patients.


Assuntos
Neoplasias Encefálicas/cirurgia , COVID-19/epidemiologia , Craniotomia/métodos , Glioma/cirurgia , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pandemias , SARS-CoV-2/isolamento & purificação , Vigília
13.
J Clin Neurosci ; 77: 98-105, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32417129

RESUMO

Neurofibromatosis type 1 (NF1) manifests itself in many ways in the spine. This study aims to report the types of spinal lesions, clinical and demographic data in a large cohort from a complex NF1 centre. The characteristics of those with spinal neurofibromatosis, where neurofibromas are present on every spinal nerve root, were sought for comparison with the wider group of NF1 patients. This is a retrospective review of MDT minutes of 303 patients from a UK NF1 centre and the largest reported series of NF1 patients based on radiological data. Prevalence of each symptom and lesion was calculated and statistically significant associations were established. The most reported findings were cutaneous lesions (44.9%) and neurological deficit (27.4%). 28.4% had dural ectasia, 52.5% had some form of spinal deformity. 57.8% had spinal nerve root tumours, the most common of which were at C2. The most progressive lesions were spinal nerve root tumours (29.1%). The only statistically significant association found was between dural ectasia and spinal deformity (P < 0.003), where dural ectasia is associated with a 32.6% increase in spinal deformity incidence. This is the largest descriptive study of spinal lesions in NF1. Spinal tumours and spinal deformity are prevalent in NF1. The predilection of spinal tumours for flexible spinal regions suggests that repetitive movement might be an important factor in pathogenesis. Physicians and patients should be alert to the observation that although many spinal neurofibromatosis patients display no neurological deficit, they often have significant lesions which require monitoring and sometimes surgery.


Assuntos
Neurofibromatose 1/etiologia , Neurofibromatose 1/patologia , Raízes Nervosas Espinhais/patologia , Coluna Vertebral/patologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neurofibroma/patologia , Neurofibromatoses , Neurofibromatose 1/complicações , Neurofibromatose 1/epidemiologia , Estudos Retrospectivos , Neoplasias da Medula Espinal/patologia , Curvaturas da Coluna Vertebral , Reino Unido/epidemiologia
14.
Neuro Oncol ; 22(9): 1289-1301, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32227096

RESUMO

BACKGROUND: Glioblastoma (GBM) has been extensively researched over the last few decades, yet despite aggressive multimodal treatment, recurrence is inevitable and second-line treatment options are limited. Here, we demonstrate how high-throughput screening (HTS) in multicellular spheroids can generate physiologically relevant patient chemosensitivity data using patient-derived cells in a rapid and cost-effective manner. Our HTS system identified actinomycin D (ACTD) to be highly cytotoxic over a panel of 12 patient-derived glioma stemlike cell (GSC) lines. ACTD is an antineoplastic antibiotic used in the treatment of childhood cancers. Here, we validate ACTD as a potential repurposed therapeutic for GBM in 3-dimensional GSC cultures and patient-derived xenograft models of recurrent glioblastoma. METHODS: Twelve patient-derived GSC lines were screened at 10 µM, as multicellular spheroids, in a 384-well serum-free assay with 133 FDA-approved compounds. GSCs were then treated in vitro with ACTD at established half-maximal inhibitory concentrations (IC50). Downregulation of sex determining region Y-box 2 (Sox2), a stem cell transcription factor, was investigated via western blot and through immunohistological assessment of murine brain tissue. RESULTS: Treatment with ACTD was shown to significantly reduce tumor growth in 2 recurrent GBM patient-derived models and significantly increased survival. ACTD is also shown to specifically downregulate the expression of Sox2 both in vitro and in vivo. CONCLUSION: These findings indicate that, as predicted by our HTS, ACTD could deplete the cancer stem cell population within the tumor mass, ultimately leading to a delay in tumor progression. KEY POINTS: 1. High-throughput chemosensitivity data demonstrated the broad efficacy of actinomycin D, which was validated in 3 preclinical models of glioblastoma.2. Actinomycin D downregulated Sox2 in vitro and in vivo, indicating that this agent could target the stem cell population of GBM tumors.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Animais , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Criança , Dactinomicina/farmacologia , Glioblastoma/tratamento farmacológico , Humanos , Camundongos , Células-Tronco Neoplásicas , Fatores de Transcrição SOXB1/genética
15.
Br J Neurosurg ; 33(6): 641-647, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31526136

RESUMO

Purpose: Meningiomas are the commonest predominantly non-malignant brain tumour in adults. The use of surgery appears to be increasing, and outcomes are thought to be good, but whole nation data for England is scarce. The aim of this report is to examine the epidemiology of patients operated for cranial and spinal meningioma in England, and to assess associations between outcomes and gender, age, meningioma site (cranial or spinal), and grade.Material and methods: A search strategy encompassing all patients coded with cranial and spinal meningioma treated between January 1999 and December 2013 was obtained from data linkage between the National Cancer Registration and Analysis Service and Hospital Episode Statistics for England.Results: 25,694 patients were diagnosed with meningioma in England between 1999 and 2013, in whom 24,302 were cranial and 1392 spinal. Of these patients, 14,229 (60%) cranial and 1188 (85%) spinal meningioma received surgery. Of those operated on 70.1% were women, and, where the tumour grade was recorded, 79.5% were WHO grade I, 18.4% grade II, and 2.1% grade III. Five and ten year net survival rates for surgically treated cranial meningiomas were respectively 90% and 81% for those with WHO grade I, 80% and 63% for grade II, and 30% and 15% for WHO grade III tumours. Overall survival after surgery is better in women, younger adults, and people with spinal or lower grade meningiomas. Outcomes have improved over the time period examined.Conclusion: The outcome for patients with meningioma is good and is improving. However, there remains a significant mortality related to the disease process.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/cirurgia , Meningioma/epidemiologia , Meningioma/cirurgia , Neoplasias da Coluna Vertebral/epidemiologia , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Masculino , Meningioma/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Procedimentos Neurocirúrgicos , Sistema de Registros , Estudos Retrospectivos , Fatores Sexuais , Neoplasias da Coluna Vertebral/patologia , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
16.
World Neurosurg ; 130: e362-e367, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31233927

RESUMO

BACKGROUND: Minimally invasive resection of brain metastases aims to maximize resection while minimizing brain trauma. METHODS: Patients with 1 or more metastases that underwent resection following neuro-oncology multidisciplinary meeting discussion from September 2014 to October 2018, with pre- and postoperative magnetic resonance imaging, were included. All patients including posterior fossa metastases or multiple metastases were positioned supine. Hair was not shaved. Volumetric postcontrast T1 magnetic resonance imaging was used for incision planning and neuronavigation. The craniotomy site was tailored to tumor depth according to keyhole principles and ranged between 2 and 5 cm. Intraoperative monitoring and awake mapping were carried out in selected cases. RESULTS: Out of 320 consecutive patients with brain metastases, 44 patients were identified as suitable for minimally invasive resection. Nine patients had no postoperative imaging and were excluded. There were 38 metastases in 35 patients. There were 18 cerebellar metastases, 10 frontal, 3 parietal, 3 occipital, 2 temporal, 1 intraventricular, and 1 basal ganglia. Median length of stay was 3 days (range, 1-24). Average tumor volume was 54.7 cm3 (range, 10-240 cm3). Endoscopic assistance was used in 4 patients. Median performance status improved from 2 to 1 (range, preoperative: 0-4; postoperative: 0-2). Median survival was 14.7 months. CONCLUSIONS: Minimally invasive resection of brain metastasis is safe and effective, and in selected cases confers advantages compared with standard techniques.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Adulto , Idoso , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Análise de Sobrevida , Resultado do Tratamento
18.
J Neurosurg Spine ; 30(1): 126-132, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30485203

RESUMO

OBJECTIVEC2 nerve root neurofibromas have been reported frequently in patients with neurofibromatosis type 1 (NF1), although their genetic and imaging characteristics are unexplored. The aim of this study was to characterize genetic and spinal imaging findings in a large cohort of NF1 patients with C2 neurofibromas.METHODSThe authors performed a review of national NF1 referrals between 2009 and 2016. Inclusion criteria were at least 1 C2 root neurofibroma and cervical-spine or whole-spine MRI scans available for analysis. Blinded imaging review was performed by a neuroradiologist with an interest in NF1.RESULTSFifty-four patients with 106 C2 neurofibromas were included. The median age was 32.5 years (range 15-61 years), and there were slightly more male patients (33 vs 21 female patients). Splice-site (30%) and missense (20%) variants were frequent. Spinal neurofibromas were distributed in all spine regions (65%) or in the cervical spine alone (22%). Most (93%) C2 neurofibromas were visible on MRI scans of the head. Intradural invasion and cord compression in the cervical spine included the C2 level in 95% and 80% of patients, respectively. Compared with all other cervical spine neurofibromas in these patients, C2 neurofibromas had higher rates of intraspinal extension (75% vs 32%; OR 6.20, 95% CI 3.85-9.97; p < 0.001), intradural invasion (53% vs 26%; OR 3.20, 95% CI 2.08-4.92; p < 0.001), and cord compression (25% vs 13%; OR 2.26, 95% CI 1.35-3.79; p = 0.002). However, C2 neurofibromas had lower rates of extraforaminal growth beyond the transverse process (12% vs 62%; OR 0.09, 95% CI 0.05-0.16; p < 0.001).CONCLUSIONSC2 neurofibromas are associated with an aggressive intraspinal phenotype, limited growth outside the spinal canal, and an uncommon genetic profile. These observations require future study.


Assuntos
Neurofibroma/diagnóstico por imagem , Neurofibromatose 1/diagnóstico por imagem , Compressão da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/diagnóstico por imagem , Adolescente , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neurofibroma/complicações , Neurofibromatose 1/complicações , Fenótipo , Compressão da Medula Espinal/complicações , Neoplasias da Medula Espinal/complicações , Coluna Vertebral/patologia , Adulto Jovem
20.
Pituitary ; 20(4): 441-449, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28421421

RESUMO

PURPOSE: In pituitary apoplexy (PA), there are preliminary reports on the appearance of sphenoid sinus mucosal thickening (SSMT). SSMT is otherwise uncommon with an incidence of up to 7% in asymptomatic individuals. The aim of this study was to evaluate the incidence and clinical significance of SSMT in patients with PA and a control group of surgically treated non-functioning pituitary adenomas (NFPAs). METHODS: Retrospective review of clinical and imaging variables in PA and NFPA patients. Sphenoid sinus mucosal thickness was measured on the presenting MRI scan by a blinded neuroradiologist. Pathological SSMT was defined as >1 mm adjacent to the pituitary fossa. Forward stepwise logistic regression was used to identify factors associated with SSMT. RESULTS: There were 50 NFPA and 47 PA patients. PA patients were managed conservatively (N = 11) or surgically (N = 36). The median sphenoid sinus mucosal thickness was greater in the PA than NFPA groups (2.0 vs. 0.5 mm; p < 0.001). In multivariate analysis of both the PA and NFPA groups, the presence of PA was the only factor associated with SSMT (OR 0.043, 95% CI 0.012-0.16; p < 0.001). In multivariate analysis of the PA group alone, a shorter time from symptom onset to presenting MRI scan (OR 0.12, 95% CI 0.026-0.54; p = 0.006) and a more severe grade of apoplexy (OR 7.29, 95% CI 1.10-48.40; p = 0.04), were associated with SSMT. CONCLUSION: The incidence of SSMT is higher in patients with PA, especially during the acute phase of PA. The aetiology of SSMT in PA is unclear and may reflect inflammatory and/or infective changes.


Assuntos
Apoplexia Hipofisária/patologia , Seio Esfenoidal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias , Estudos Retrospectivos , Adulto Jovem
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