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OBJECTIVE: Some patients unexpectedly display an unfavorable cognitive course after epilepsy surgery subsequent to any direct cognitive sequelae of the surgical treatment. Therefore, we conducted in-depth neuropathological examinations of resective specimens from corresponding patients to provide insights as to the underlying disease processes. METHODS: In this study, cases with significant cognitive deterioration following a previous postoperative assessment were extracted from the neuropsychological database of a longstanding epilepsy surgical program. An extensive reanalysis of available specimens was performed using current, state-of-the-art neuropathological examinations. Patients without cognitive deterioration but matched in regard to basic pathologies served as controls. RESULTS: Among the 355 operated patients who had undergone more than one postoperative neuropsychological examination, 30 (8%) showed significant cognitive decline in the period after surgery. Of the 24 patients with available specimens, 71% displayed further neuropathological changes in addition to the typical spectrum (ie, hippocampal sclerosis, focal cortical dysplasias, vascular lesions, and low-grade tumors), indicating (1) a secondary, putatively epilepsy-independent neurodegenerative disease process; (2) limbic inflammation; or (3) the enigmatic pathology pattern of "hippocampal gliosis" without segmental neurodegeneration. In the controls, the matched individual principal epilepsy-associated pathologies were not found in combination with the secondary pathology patterns of the study group. INTERPRETATION: Our findings indicate that patients who unexpectedly displayed unfavorable cognitive development beyond any direct surgical effects show rare and very particular pathogenetic causes or parallel, presumably independent, neurodegenerative alterations. A multicenter collection of such cases would be appreciated to discern presurgical biomarkers that help with surgical decision-making. ANN NEUROL 2023;93:536-550.
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Disfunção Cognitiva , Epilepsia , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/patologia , Epilepsia/etiologia , Hipocampo/patologia , Disfunção Cognitiva/patologia , CogniçãoRESUMO
PURPOSE: Intraoperative radiation therapy (IORT) is an emerging alternative to adjuvant stereotactic external beam radiation therapy (EBRT) following resection of brain metastases (BM). Advantages of IORT include an instant prevention of tumor regrowth, optimized dose-sparing of adjacent healthy brain tissue and immediate completion of BM treatment, allowing an earlier admission to subsequent systemic treatments. However, prospective outcome data are limited. We sought to assess long-term outcome of IORT in comparison to EBRT. METHODS: A total of 35 consecutive patients, prospectively recruited within a study registry, who received IORT following BM resection at a single neuro-oncological center were evaluated for radiation necrosis (RN) incidence rates, local control rates (LCR), distant brain progression (DBP) and overall survival (OS) as long-term outcome parameters. The 1 year-estimated OS and survival rates were compared in a balanced comparative matched-pair analysis to those of our institutional database, encompassing 388 consecutive patients who underwent adjuvant EBRT after BM resection. RESULTS: The median IORT dose was 30 Gy prescribed to the applicator surface. A 2.9% RN rate was observed. The estimated 1 year-LCR was 97.1% and the 1 year-DBP-free survival 73.5%. Median time to DBP was 6.4 (range 1.7-24) months in the subgroup of patients experiencing intracerebral progression. The median OS was 17.5 (0.5-not reached) months with a 1 year-survival rate of 61.3%, which did not not significantly differ from the comparative cohort (p = 0.55 and p = 0.82, respectively). CONCLUSION: IORT is a safe and effective fast-track approach following BM resection, with comparable long-term outcomes as adjuvant EBRT.
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Neoplasias Encefálicas , Humanos , Estudos Prospectivos , Análise por Pareamento , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/secundário , Intervalo Livre de Progressão , Encéfalo , Recidiva Local de Neoplasia/radioterapia , Radioterapia AdjuvanteRESUMO
PURPOSE: Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time. METHODS: Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups. RESULTS: Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001). CONCLUSION: IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.
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Neoplasias Encefálicas , Radiocirurgia , Humanos , Corticosteroides/uso terapêutico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Radiocirurgia/métodos , Radioterapia Adjuvante , Resultado do Tratamento , Estudos ProspectivosRESUMO
Surgical resection is a common treatment modality for brain metastasis (BM). Location of the BM might significantly impact patient survival and therefore might be considered in clinical decision making and patient counseling. In the present study, the authors analyzed infra- and supratentorial BM location for a potential prognostic difference. Between 2013 and 2019, 245 patients with solitary BM received BM resection at the authors' neuro-oncological center. In order to produce a covariate balance for commonly-known prognostic variables (tumor entity, age, preoperative Karnofsky Performance Score, and preoperative Charlson Comorbidity Index), a propensity score matching at a ratio of 1:1 between the cohort of patients with infra- and supratentorial BM location was performed using R. Overall survival (OS) rates were assessed for both matched cohorts of patients with BM. Sixty-one of 245 patients (25%) with solitary BM exhibited an infratentorial tumor location; 184 patients (75%) suffered from supratentorial solitary BM. Patients with infratentorial BM revealed a median OS of 11 months (95% confidence interval (CI) 7.4-14.6 months). Compared with this, median OS for the group of 61 individually matched patients with solitary supratentorial solitary BM was 13 months (95% CI 10.9-15.1 months) (p = 0.32). The present study suggests that the prognostic value of infra- and supratentorial BMs does not significantly differ in patients that undergo surgery for solitary BM. These results might encourage physicians to induce surgical therapy of supra- and infratentorial BM in a similar manner.
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Neoplasias Encefálicas , Neoplasias Infratentoriais , Humanos , Estudos Retrospectivos , Neoplasias Encefálicas/patologia , Prognóstico , Taxa de SobrevidaRESUMO
Surgical resection is highly effective in the treatment of tumor-related epilepsy (TRE) in patients with brain metastases (BM). Nevertheless, some patients suffer from postoperative persistent epilepsy which negatively impacts health-related quality of life. Therefore, early identification of patients with potentially unfavorable seizure outcome after BM resection is important. Patients with TRE that had undergone surgery for BM at the authors' institution between 2013 and 2018 were analyzed with regard to preoperatively identifiable risk factors for unfavorable seizure outcome. Tumor tissue and tumor necrosis ratios were assessed volumetrically. According to the classification of the International League Against Epilepsy (ILAE), seizure outcome was categorized as favorable (ILAE 1) and unfavorable (ILAE 2-6) after 3 months in order to avoid potential interference with adjuvant cancer treatment. Among all 38 patients undergoing neurosurgical treatment for BM with concomitant TRE, 34 patients achieved a favorable seizure outcome (90%). Unfavorable seizure outcome was significantly associated with larger tumor volumes (p = 0.012), a midline shift > 7 mm (p = 0.025), and a necrosis/tumor volume ratio > 0.2 (p = 0.047). The present study identifies preoperatively collectable risk factors for unfavorable seizure outcome in patients with BM and TRE. This might enable to preselect for highly vulnerable patients with postoperative persistent epilepsy who might benefit from accompanying neuro-oncological expertise during further systemical treatment regimes.
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Neoplasias Encefálicas , Epilepsia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Epilepsia/etiologia , Epilepsia/cirurgia , Liberdade , Humanos , Necrose , Procedimentos Neurocirúrgicos , Qualidade de Vida , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/cirurgia , Resultado do TratamentoRESUMO
Increasing evidence indicates the pathogenetic relevance of regulatory genomic motifs for variability in the manifestation of brain disorders. In this context, cis-regulatory effects of single nucleotide polymorphisms (SNPs) on gene expression can contribute to changing transcript levels of excitability-relevant molecules and episodic seizure manifestation in epilepsy. Biopsy specimens of patients undergoing epilepsy surgery for seizure relief provide unique insights into the impact of promoter SNPs on corresponding mRNA expression. Here, we have scrutinized whether two linked regulatory SNPs (rs2744575; 4779C > G and rs4646830; 4854C > G) located in the aldehyde dehydrogenase 5a1 (succinic semialdehyde dehydrogenase; ALDH5A1) gene promoter are associated with expression of corresponding mRNAs in epileptic hippocampi (n = 43). The minor ALDH5A1-GG haplotype associates with significantly lower ALDH5A1 transcript abundance. Complementary in vitro analyses in neural cell cultures confirm this difference and further reveal a significantly constricted range for the minor ALDH5A1 haplotype of promoter activity regulation through the key epileptogenesis transcription factor Egr1 (early growth response 1). The present data suggest systematic analyses in human hippocampal tissue as a useful approach to unravel the impact of epilepsy candidate SNPs on associated gene expression. Aberrant ALDH5A1 promoter regulation in functional terms can contribute to impaired γ-aminobutyric acid homeostasis and thereby network excitability and seizure propensity.
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Epilepsia do Lobo Temporal/genética , Hipocampo/metabolismo , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Succinato-Semialdeído Desidrogenase/genética , Animais , Linhagem Celular , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Perfilação da Expressão Gênica , Haplótipos , Hipocampo/patologia , Humanos , Técnicas In Vitro , Camundongos , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Ratos , EscleroseRESUMO
INTRODUCTION: The postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures. METHODS: Between 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors' institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2-6). RESULTS: Overall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4-515.9). CONCLUSIONS: ATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma.
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Lobectomia Temporal Anterior/métodos , Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Convulsões/etiologia , Convulsões/cirurgia , Adulto , Idoso , Neoplasias Encefálicas/complicações , Feminino , Glioblastoma/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The impact of midline shift (MLS) on long-term survival and progression in glioblastoma (GBM) is unknown. The objective of this study was to analyze the influence of mass effect on survival and progression with consideration of the patient demographics, tumor morphology, operative techniques, molecular pathology, and postoperative treatment. One hundred ninety-eight patients with GBM were analyzed retrospectively. Both MLS groups (< or ≥ 10 mm) were compared with regard to survival, progression-free survival (PFS), and postoperative course of Karnofsky Performance Status (KPS). A two-sided Fisher exact test showed no statistically significant differences in the confounders between the low- and high-MLS groups. The median survival was 18.0 months (95% confidence interval (CI) = 15.3-20.7) in the low-MLS group (n = 173) and 9.0 months (95% CI = 4.8-13.2) in the high-MLS group (n = 25) (p = 0.045). In the high-MLS group, 59.1% (13/22) with an initially high MLS had a KPS of less than 70% after 3 months, whereas 20.5% of the low-MLS group had a KPS of less than 70% (p < 0.001). Binary logistic regression analysis including the O-6-methylguanine-DNA methyltransferase (MGMT) status, extent of resection, baseline KPS, and MIB-I index showed low MLS as the only predictor for survival at 12 months (p = 0.046, odds ratio (OR) = 2.70, 95% CI = 1.0-7.2). Median PFS was 6.0 months in the high-MLS group and 9.0 months in the low-MLS group (log-rank test; p = 0.08). An initial midline shift of 10 mm or greater seems to be an imaging characteristic that independently predicts the survival in glioblastoma.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Feminino , Glioblastoma/mortalidade , Humanos , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética/mortalidade , Imageamento por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Neuronavegação/mortalidade , Neuronavegação/tendências , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
INTRODUCTION: Supra-total resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma. However, aggressive onco-surgical approaches-geared beyond conventional gross total resections (GTR)-may be associated with peri- and postoperative unfavorable events which significantly worsen initial favorable postoperative outcome. In the current study we analyzed our institutional database with regard to patient safety indicators (PSIs), hospital-acquired conditions (HACs) and specific cranial surgery-related complications (CSC) as high standard quality metric profiles in patients that had undergone surgery for temporal glioblastoma. METHODS: Between 2012 and 2018, 61 patients with temporal glioblastoma underwent GTR or temporal lobectomy at the authors' institution. Both groups of differing resection modalities were analyzed with regard to the incidence of PSIs, HACs and CSCs. RESULTS: Overall, we found 6 PSI and 2 HAC events. Postoperative hemorrhage (3 out of 61 patients; 5%) and catheter-associated urinary tract infection (2 out 61 patients; 3%) were identified as the most frequent PSIs and HACs. PSIs were present in 1 out of 41 patients (5%) for the temporal GTR and 2 out of 20 patients for the lobectomy group (p = 1.0). Respective rates for PSIs were 5 of 41 (12%) and 1 of 20 (5%) (p = 0.7). Further, CSCs did not yield significant differences between these two resection modalities (p = 1.0). CONCLUSION: With regard to ATL and GTR as differing onco-surgical approaches these data suggest ATL in terms of an aggressive supra-total resection strategy to preserve perioperative standard safety metric profiles.
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Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Hospitalização/estatística & dados numéricos , Procedimentos Neurocirúrgicos/normas , Segurança do Paciente/normas , Qualidade da Assistência à Saúde/normas , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: Cavernoma-related epilepsy (CRE) is a frequent symptom in patients with cerebral cavernous malformations (CCMs). Reports on surgical management and seizure outcome of epileptogenic CCM often focus on intracranial cavernoma in general. Therefore, data on CCMs within the temporal lobe are scarce. The authors therefore analyzed their institutional data. METHODS: From 2003 to 2018, 52 patients suffering from CCMs located within the temporal lobe underwent surgery for CRE at University Hospital Bonn. Information on patient characteristics, preoperative seizure history, preoperative evaluation, surgical strategies, postoperative complications, and seizure outcome was assessed and further analyzed. Seizure outcome was assessed 12 months after surgery according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class I) versus unfavorable (ILAE classes II-VI). RESULTS: Overall, 47 (90%) of 52 patients with CCMs located in the temporal lobe and CRE achieved favorable seizure outcome. Pure lesionectomy was performed in 5 patients, extended lesionectomy with resection of the hemosiderin rim in 38 patients, and anterior temporal lobectomy in 9 patients with temporal lobe CCM. Specifically, 36 patients (69%) suffered from drug-resistant epilepsy (DRE), 3 patients (6%) from chronic CRE, and 13 patients (25%) sustained sporadic CRE. In patients with DRE, favorable seizure outcome was achieved in 32 (89%) of 36 patients. Patients with DRE were significantly older than patients with CCM-associated chronic or sporadic seizures (p = 0.02). Furthermore, patients with DRE more often underwent additional amygdalohippocampectomy following the recommendation of presurgical epileptological evaluation. CONCLUSIONS: Favorable seizure outcome is achievable in a substantial number of patients with epileptogenic CCM located in the temporal lobe, even if patients suffered from drug-resistant CRE. For adequate counseling and monitoring, patients with CRE should undergo a thorough pre- and postsurgical evaluation in dedicated epilepsy surgery programs.
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Epilepsia Resistente a Medicamentos/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Hemangioma Cavernoso/cirurgia , Convulsões/cirurgia , Lobo Temporal/cirurgia , Adolescente , Adulto , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: Supra-total glioblastoma resection has gained growing attention with regard to superior long-term disease control. However, aggressive onco-surgical approaches-geared beyond conventional gross total resections (GTR)-are limited by the impairment of adjacent eloquent areas at risk that may entail severe postoperative functional morbidity. Against this backdrop we analyzed our institutional database with regard to potential survival benefits of anterior temporal lobectomy as a paradigm for supra-total resection in patients with precisely temporal-located, non-eloquent glioblastoma. METHODS: Between 2012 and 2017, 38 patients with isolated temporal glioblastoma underwent GTR or temporal lobectomy at the authors' institution. Both groups of differing resection modalities were compared with regard to postoperative Karnofsky performance score (KPS), progression-free survival (PFS), and overall survival (OS). RESULTS: Patients with temporal lobectomy exhibited significantly superior median KPS at the 12 months follow-up compared to the GTR group (median KPS of 80 vs. 60, p = 0.04). Temporal lobectomy was associated with significantly prolonged PFS (p = 0.005) and OS (p = 0.002) coming up to 15 months (95% CI 9.7-22.1) and 23 months (95% CI 14.8-34.5) compared to 7 months (95% CI 3.3-8.3) and 11 months (95% CI 9.2-17.9) for the GTR group. Multivariate analysis revealed temporal lobectomy as the only predictor for both superior PFS (p = 0.037, OR 7.3, 95% CI 1.1-47.4) and OS (p = 0.04, OR 7.8, 95% CI 1.1-55.2). CONCLUSIONS: These results strongly suggest temporal lobectomy as an aggressive supra-total resection policy to constitute the surgical modality of choice for isolated temporal-located glioblastoma.
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Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Procedimentos Neurocirúrgicos/mortalidade , Procedimentos Neurocirúrgicos/métodos , Idoso , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/classificação , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: The best time for cranioplasty (CP) after decompressive craniectomy (DC) is controversial, and there are no authoritative guidelines yet. Both complications as well as outcome may depend on the timing of CP. The aim of this single-center study was to evaluate the impact of late CP on procedural safety as well as on patient outcome. METHODS: All patients receiving CP at a tertiary university medical center between 01/2015 and 12/2022 were included retrospectively. Patients' conditions were assessed according to the modified Rankin Scale (mRS) prior to CP and 6 months after. Baseline characteristics, indication for DC, time from DC to CP, and postoperative complications according to the Landriel Ibañez Classification were analyzed. RESULTS: CP was performed in 271 patients who previously underwent DC due to traumatic brain injury (25.5%), ischemic stroke (29.5%), aneurysmal subarachnoid hemorrhage (26.9%), or intracerebral hemorrhage (18.1%). The median interval between DC and CP was 143 days (interquartile range 112-184 days). Receiver operating characteristic analysis revealed a cut-off of 149 days, where CP performed within 149 days after DC led to an improvement on mRS after CP (p = 0.001). In multivariate analysis, additional rehabilitation after and better mRS before CP were independently associated with improvement of outcome. The rate of complications was similar between early and late CP (24.8% and 25.4%, respectively, p = 0.562). CONCLUSIONS: Late cranioplasty is a safe procedure. The outcome was improved when additional rehabilitation was performed after cranioplasty and was not associated with the timing of cranioplasty.
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BACKGROUND AND AIMS: Brain metastases are prevalent in the late stages of malignant melanoma. Multimodal therapy remains challenging. Patient-derived organoids (PDOs) represent a valuable pre-clinical model, faithfully recapitulating key aspects of the original tumor, including the heterogeneity and the mutational status. This study aimed to establish PDOs from melanoma brain metastases (MBM-PDOs) and to test the feasibility of using them as a model for in vitro targeted-therapy drug testing. METHODS: Surgical resection samples from eight patients with melanoma brain metastases were used to establish MBM-PDOs. The samples were enzymatically dissociated followed by seeding into low-attachment plates to generate floating organoids. The MBM-PDOs were characterized genetically, histologically, and immunohistologically and compared with the parental tissue. The MBM-PDO cultures were exposed to dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) followed by a cell viability assessment. RESULTS: Seven out of eight cases were successfully cultivated, maintaining the histological, immunohistological phenotype, and the mutational status of the parental tumors. Five out of seven cases harbored BRAF V600E mutations and were responsive to BRAF and MEK inhibitors in vitro. Two out of seven cases were BRAF wild type: one case harboring an NRAS mutation and the other harboring a KIT mutation, and both were resistant to BRAF and MEK inhibitor therapy. CONCLUSIONS: We successfully established PDOs from melanoma brain metastases surgical specimens, which exhibited a consistent histological and mutational profile with the parental tissue. Using FDA-approved BRAF and MEK inhibitors, our data demonstrate the feasibility of employing MBM-PDOs for targeted-therapy in vitro testing.
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Purpose: A correct placement of the applicator during intraoperative radiation therapy for brain metastasis is of paramount importance, to deliver a precise and safe treatment. The applicator-to-surface contact assessment cannot be performed under direct observation because the applicator itself limits the visual range. No image guided verification is currently performed intracranially. We hypothesize that image guided intraoperative radiation therapy would assure a more precise delivery in the target area. We describe our workflow in a first in-human experience. Methods and Materials: Phantom-based measurements were performed to reach the best cone beam computed tomography imaging quality possible. Once defined, a clinical feasibility study was initiated. An in-room cone beam computed tomography device is used to acquire intraoperative images after placing the applicator. Repositioning the applicator is thereafter discussed with the surgeon, according to the imaging outcomes, if required. Results: An optimal image quality was achieved with 120-kV voltage, 20-mA current, and a tube current time product of 150 mAs. An additional 0.51 mSv patient exposure was calculated for the entire procedure. The wide dynamic range (-600 HU to +600 HU) of cone beam computed tomography and a 27 HU mean computed tomography values difference between brain tissue and spherical applicator allows distinguishing both structures. In this first in-human experience, the applicator was repositioned after evidencing air gaps, assuring full applicator-to-surface contact. Conclusions: This first in-human procedure confirmed the feasibility of kilovoltage image guided intraoperative radiation therapy in a neurosurgical setting. A prospective study has been initiated and will provide further dosimetric details.
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PURPOSE: Patients with spinal metastases (SM) from solid neoplasms typically exhibit progression to an advanced cancer stage. Such metastases can either develop concurrently with an existing cancer diagnosis (termed metachronous SM) or emerge as the initial indication of an undiagnosed malignancy (referred to as synchronous SM). The present study investigates the prognostic implications of synchronous compared to metachronous SM following surgical resection. METHODS: From 2015 to 2020, a total of 211 individuals underwent surgical intervention for SM at our neuro-oncology facility. We conducted a survival analysis starting from the date of the neurosurgical procedure, comparing those diagnosed with synchronous SM against those with metachronous SM. RESULTS: The predominant primary tumor types included lung cancer (23%), prostate cancer (21%), and breast cancer (11.3%). Of the participants, 97 (46%) had synchronous SM, while 114 (54%) had metachronous SM. The median overall survival post-surgery for those with synchronous SM was 13.5 months (95% confidence interval (CI) 6.1-15.8) compared to 13 months (95% CI 7.7-14.2) for those with metachronous SM (p = 0.74). CONCLUSIONS: Our findings suggest that the timing of SM diagnosis (synchronous versus metachronous) does not significantly affect survival outcomes following neurosurgical treatment for SM. These results support the consideration of neurosurgical procedures regardless of the temporal pattern of SM manifestation.
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Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Segunda Neoplasia Primária , Neoplasias da Coluna Vertebral , Masculino , Humanos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/patologia , Prognóstico , Análise de Sobrevida , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Neoplasias Primárias Múltiplas/patologia , Estudos RetrospectivosRESUMO
PURPOSE: After surgical resection of brain metastases (BMs), intraoperative radiation therapy (IORT) provides a promising alternative to adjuvant external beam radiation therapy by enabling superior organ-at-risk preservation, reduction of in-hospital times, and timely admission to subsequent systemic treatments, which increasingly comprise novel targeted immunotherapeutic approaches. We sought to assess the safety and efficacy of IORT in combination with immune checkpoint inhibitors (ICIs) and other targeted therapies (TTs). METHODS AND MATERIALS: In a multicentric approach incorporating individual patient data from 6 international IORT centers, all patients with BMs undergoing IORT were retrospectively assessed for combinatorial treatment with ICIs/TTs and evaluated for toxicity and cumulative rates, including wound dehiscence, radiation necrosis, leptomeningeal spread, local control, distant brain progression (DBP), and estimated overall survival. RESULTS: In total, 103 lesions with a median diameter of 34 mm receiving IORT combined with immunomodulatory systemic treatment or other TTs were included. The median follow-up was 13.2 (range, 1.2-102.4) months, and the median IORT dose was 25 (range, 18-30) Gy prescribed to the applicator surface. There was 1 grade 3 adverse event related to IORT recorded (2.2%). A 4.9% cumulative radiation necrosis rate was observed. The 1-year local control rate was 98.0%, and the 1-year DBP-free survival rate was 60.0%. Median time to DBP was 5.5 (range, 1.0-18.5) months in the subgroup of patients experiencing DBP, and the cumulative leptomeningeal spread rate was 4.9%. The median estimated overall survival was 26 (range, 1.2 to not reached) months with a 1-year survival rate of 74.0%. Early initiation of immunotherapy/TTs was associated with a nonsignificant trend toward improved DBP rate and overall survival. CONCLUSIONS: The combination of ICIs/TTs with IORT for resected BMs does not seem to increase toxicity and yields encouraging local control outcomes in the difficult-to-treat subgroup of larger BMs. Time gaps between surgery and systemic treatment could be shortened or avoided. The definitive role of IORT in local control after BM resection will be defined in a prospective trial.
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Neoplasias Encefálicas , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Terapia Combinada , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Imunoterapia/efeitos adversos , Necrose , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: Two common valve types used to treat hydrocephalus include gravity assisted valves (GAV) and medium pressure valves (MPV). Despite their different mechanism of action, differentiated surgical indications per type are not well defined. One could assume that due to a higher complexity of the GAV system, it may be more prone to valve-related malfunction. The purpose of this retrospective study was to compare the valve-related complication rates of GAV and MPV in patients with communicating hydrocephalus. METHOD: Patients aged 16 years or older undergoing their first shunt implantation using GAV or MPV were included. We recorded demographic data, implantation diagnosis, outcome, complications, valve type and valve adjustments. Symptoms were documented at discharge and follow-up. Valve-related malfunctions were distinguished from other shunt complications. RESULTS: N = 252 patients (range 16.6-88.4, mean 65.0 years, 116 male and 136 female) underwent shunt placement for the first time. N = 122 GAV (48.4 %) and n = 130 MPV were implanted (51.6 %) over a period of 5 years. The most frequent diagnoses were normal pressure hydrocephalus (NPH) in 86 cases (34.1 %) and posthemorrhagic hydrocephalus in 114 cases (45.2 %). About two thirds of patients were free of hydrocephalus-related symptoms at follow-up. N = 66 subjects (26.2 %) underwent at least one shunt revision. N = 29 revisions (11.5 %) were due to valve-related malfunction. Valve-related revisions were the main cause for revision in 18/37 cases (48.6 %) in the GAV group and in 11/29 (37.9 %) in the MPV group. Neither clinical improvement nor valve-related malfunctions were found to be statistically different among groups. CONCLUSIONS: Despite their technical differences, GAV and MPV show similar valve-related revision rates in the treatment of communicating hydrocephalus.
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Derivações do Líquido Cefalorraquidiano , Hidrocefalia/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Derivações do Líquido Cefalorraquidiano/métodos , Feminino , Seguimentos , Gravitação , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Pressão , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a known complication of posterior fossa surgery near the sigmoid and transverse sinus. The incidence and treatment of postoperative asymptomatic CVST are controversial. OBJECTIVE: To analyze incidence, risk factors, and management of asymptomatic postoperative CVST after posterior fossa tumor surgery. METHODS: In this retrospective, single-center study, we included all patients who underwent posterior fossa tumor surgery in the semisitting position between January 2013 and December 2020. All patients underwent preoperative and postoperative imaging using MRI with/without additional computed tomography angiography. We analyzed the effect of demographic and surgical data on the incidence of postoperative CVST. Furthermore, therapeutic anticoagulation or conservative treatment for postoperative CVST and the incidence of intracranial hemorrhage were investigated. RESULTS: In total, 266 patients were included. Thirty-three of 266 (12.4%) patients developed postoperative CVST. All patients were asymptomatic. Thirteen of 33 patients received therapeutic anticoagulation, and 20 patients did not. Univariate analysis showed that age ( P = .56), sex ( P = .20), American Society of Anesthesiology status ( P = .13), body mass index ( P = .60), and length of surgery ( P = .176) were not statistically correlated with postoperative CVST. Multivariate analysis revealed that meningioma ( P < .001, odds ratio 11.3, CI 95% 4.1-31.2) and vestibular schwannoma ( P = .013, odds ratio 4.4, CI 95% 1.3-16.3) are risk factors for the development of new postoperative CVST. The use of therapeutic anticoagulation to treat postoperative CVST was associated with a higher rate of intracranial hemorrhage (n = 4, P = .017). CONCLUSION: Tumor entity influences the incidence of postoperative CVST. In clinically asymptomatic patients, careful decision making is necessary whether to initiate therapeutic anticoagulation or not.
Assuntos
Neoplasias Infratentoriais , Trombose dos Seios Intracranianos , Humanos , Estudos Retrospectivos , Incidência , Trombose dos Seios Intracranianos/epidemiologia , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Neoplasias Infratentoriais/complicações , Neoplasias Infratentoriais/tratamento farmacológico , Hemorragias Intracranianas/complicações , Anticoagulantes/uso terapêuticoRESUMO
STUDY DESIGN: Retrospective single center cohort study. PURPOSE: Spinal instrumentation in combination with antibiotic therapy is a treatment option for acute or chronic pyogenic spondylodiscitis (PSD). This study compares the early fusion outcome for multi-level and single-level PSD after urgent surgical treatment with interbody fusion in combination with fixation. METHODS: This is a retrospective cohort study. Over a 10 year period at a single institution, all surgically treated patients received surgical debridement, fusion und fixation of the spine to treat PSD. Multi-level cases were either adjacent to each other on the spine or distant. Fusion rates were assessed at 3 and 12 months after surgery. We analyzed demographic data, ASA status, duration of surgery, location and length of spine affected, Charlson comorbidity index (CCI), and early complications. RESULTS: A total of 172 patients were included. Of these, 114 patients suffered from single-level and 58 from multi-level PSD. The most frequent location was the lumbar spine (54.0%) followed by the thoracic spine (18.0%). The PSD was adjacent in 19.0% and distant in 81.0% of multi-level cases. Fusion rates at the 3 month follow-up did not differ among the multi-level group (p = 0.27 for both adjacent and distant sites). In the single-level group, sufficient fusion was achieved in 70.2% of cases. Pathogen identification was possible 58.5% of the time. CONCLUSIONS: Surgical treatment of multi-level PSD is a safe option. Our study demonstrates that there was no significant difference in early fusion outcomes between single-level and multi-level PSD, whether adjacent or distant.
Assuntos
Discite , Fusão Vertebral , Humanos , Discite/cirurgia , Discite/complicações , Estudos de Coortes , Estudos Retrospectivos , Resultado do Tratamento , Fusão Vertebral/efeitos adversos , Vértebras Lombares/cirurgia , DesbridamentoRESUMO
BACKGROUND: Delayed cerebral ischemia (DCI) is usually caused by cerebral vasospasm (CVS). To detect DCI and CVS a cranial CT scan will be performed, but cervical vessels are not necessarily displayed. PATIENT: A 63-year-old female patient who suffered from aneurysmal subarachnoid hemorrhage (SAH) was treated at the authors' institution. After an initially unremarkable clinical course, she developed aphasia on day 11. CT angiography (CTA) and perfusion imaging revealed significant hypoperfusion of the left hemisphere. In addition, the CTA showed a subtotal stenosis of the internal carotid artery (ICA) at the level of the petrous segment, suspicious for a dissection. This was not detectable angiographically in the final control of the intervention and was also not clinically evident until day 11. Cerebral perfusion as well as the clinical symptoms normalized rapidly after stent reconstruction of the ICA. CONCLUSION: Even though CVS is the most frequent cause of hypoperfusion in patients after SAH, a periinterventional dissection can also lead to relevant stenosis and thus to a disturbed cerebral perfusion and corresponding neurological deficits. The time delay between the intervention and the clinical as well as CT-angiographical manifestation in our case is remarkable.