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1.
Sci Rep ; 14(1): 21430, 2024 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271763

RESUMEN

The stiffness of human cancers may be correlated with their pathology, and can be used as a biomarker for diagnosis, malignancy prediction, molecular expression, and postoperative complications. Neurosurgeons perform tumor resection based on tactile sensations. However, it takes years of surgical experience to appropriately distinguish brain tumors from surrounding parenchymal tissue. Haptics is a technology related to the touch sensation. Haptic technology can amplify, transmit, record, and reproduce real sensations, and the physical properties (e.g., stiffness) of an object can be quantified. In the present study, glioblastoma (SF126-firefly luciferase-mCherry [FmC], U87-FmC, U251-FmC) and malignant meningioma (IOMM-Lee-FmC, HKBMM-FmC) cell lines were transplanted into nude mice, and the stiffness of tumors and normal brain tissues were measured using our newly developed surgical forceps equipped with haptic technology. We found that all five brain tumor tissues were stiffer than normal brain tissue (p < 0.001), and that brain tumor pathology (three types of glioblastomas, two types of malignant meningioma) was significantly stiffer than normal brain tissue (p < 0.001 for all). Our findings suggest that tissue stiffness may be a useful marker to distinguish brain tumors from surrounding parenchymal tissue during microsurgery, and that haptic forceps may help neurosurgeons to sense minute changes in tissue stiffness.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Meningioma , Ratones Desnudos , Microcirugia , Animales , Humanos , Microcirugia/métodos , Microcirugia/instrumentación , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Glioblastoma/cirugía , Glioblastoma/patología , Ratones , Meningioma/cirugía , Meningioma/patología , Línea Celular Tumoral , Instrumentos Quirúrgicos
2.
Int J Mol Sci ; 25(17)2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39273661

RESUMEN

Glioblastoma (GBM) is one of the most aggressive malignant tumors of the brain. We queried PubMed for articles about molecular predictor markers in GBM. This scoping review aims to analyze the most important outcome predictors in patients with GBM and to compare these factors in terms of absolute months of survival benefit and percentages. Performing a gross total resection for patients with GBM undergoing optimal chemo- and radiotherapy provides a significant benefit in overall survival compared to those patients who received a subtotal or partial resection. However, compared to IDH-Wildtype GBMs, patients with IDH-Mutant 1/2 GBMs have an increased survival. MGMT promoter methylation status is another strong outcome predictor for patients with GBM. In the reviewed literature, patients with methylated MGMT promoter lived approximately 50% to 90% longer than those with an unmethylated MGMT gene promoter. Moreover, KPS is an important predictor of survival and quality of life, demonstrating that we should refrain from aggressive surgery in important brain areas. As new therapies (such as TTFs) emerge, we are optimistic that the overall median survival will increase, even for IDH-Wildtype GBMs. In conclusion, molecular profiles are stronger outcome predictors than the extent of neurosurgical resection for GBM.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Imagen por Resonancia Magnética , Humanos , Glioblastoma/genética , Glioblastoma/cirugía , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Glioblastoma/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Metilasas de Modificación del ADN/genética , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Biomarcadores de Tumor/genética , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Pronóstico , Metilación de ADN , Isocitrato Deshidrogenasa/genética , Mutación , Regiones Promotoras Genéticas
3.
BMJ Open ; 14(9): e081689, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39260848

RESUMEN

INTRODUCTION: There are no guidelines or prospective studies defining the optimal surgical treatment for glioblastomas in older patients (≥70 years), for those with a limited functioning performance at presentation (Karnofsky Performance Scale ≤70) or for those with tumours in certain locations (midline, multifocal). Therefore, the decision between resection and biopsy is varied, among neurosurgeons internationally and at times even within an institution. This study aims to compare the effects of maximal tumour resection versus tissue biopsy on survival, functional, neurological and quality of life outcomes in these patient subgroups. Furthermore, it evaluates which modality would maximise the potential to undergo adjuvant treatment. METHODS AND ANALYSIS: This study is an international, multicentre, prospective, two-arm cohort study of an observational nature. Consecutive patients with glioblastoma will be treated with resection or biopsy and matched with a 1:1 ratio. Primary endpoints are (1) overall survival and (2) proportion of patients that have received adjuvant treatment with chemotherapy and radiotherapy. Secondary endpoints are (1) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months after surgery; (2) progression-free survival (PFS); (3) quality of life at 6 weeks, 3 months and 6 months after surgery and (4) frequency and severity of serious adverse events. The total duration of the study is 5 years. Patient inclusion is 4 years; follow-up is 1 year. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media. TRIAL REGISTRATION NUMBER: NCT06146725.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Calidad de Vida , Humanos , Glioblastoma/cirugía , Glioblastoma/patología , Glioblastoma/terapia , Estudios Prospectivos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Biopsia/métodos , Estudios Multicéntricos como Asunto , Procedimientos Neuroquirúrgicos/métodos , Anciano , Femenino , Masculino
5.
Acta Neurochir (Wien) ; 166(1): 357, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39215803

RESUMEN

PURPOSE: Patients with glioblastomas (GBMs) have poor prognosis despite various treatments; therefore, attention should be paid to maintaining the quality of survival. Neurocognitive deficits can affect the quality of life (QOL) in patients with GBM. Most studies concerning QOL and neurocognitive functions have demonstrated a relationship between QOL and self-reported neurocognitive decline, although this method does not accurately reflect damaged functional domains. Therefore, this study aimed to clarify the neurocognitive functions that influence the QOL in patients with GBMs using an objective assessment of neurocognitive functions. METHODS: Data from 40 patients newly diagnosed with GBMs were analyzed. All patients completed the assessment of QOL and various neurological and neurocognitive functions including general cognitive function, processing speed, attention, memory, emotion recognition, social cognition, visuospatial cognition, verbal fluency, language, motor function, sensation, and visual field at 6 months postoperatively. QOL was assessed using the 36-Item Short Form Survey (SF-36). In the SF-36, the physical, mental, and role and social component summary (PCS, MCS, and RCS, respectively) scores were calculated. Multiple logistic regression analyses and chi-square tests were used to evaluate the association between SF-36 scores and neurocognitive functions. RESULTS: The MCS was maintained, while the PCS and RCS scores were significantly lower in patients with GBMs than in healthy controls (p = 0.0040 and p < 0.0001, respectively). Among several neurocognitive functions, motor function and processing speed were significantly correlated with PCS and RCS scores, respectively (p = 0.0048 and p = 0.030, respectively). Patients who maintained their RCS or PCS scores had a higher probability of preserving motor function or processing speed than those with low RCS or PCS scores (p = 0.0026). CONCLUSIONS: Motor function and processing speed may be predictors of QOL in patients with GBMs.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Calidad de Vida , Humanos , Calidad de Vida/psicología , Masculino , Femenino , Persona de Mediana Edad , Glioblastoma/cirugía , Glioblastoma/psicología , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/psicología , Anciano , Adulto , Pruebas Neuropsicológicas/estadística & datos numéricos , Cognición/fisiología , Velocidad de Procesamiento
6.
Acta Neurochir (Wien) ; 166(1): 331, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120826

RESUMEN

Herein, we present two cases of isolated suprasellar dissemination of glioblastoma in patients with well-controlled primary lesions. A 22-year-old woman and a 56-year-old woman developed rapid growth of suprasellar glioblastoma dissemination 26 and 17 months after initial surgery, respectively. Both patients presented with acute visual impairment (decreased acuity and visual field disturbances) but lacked severe pituitary dysfunction. During surgery for the disseminated tumors, gross total tumor resection was difficult due to intraoperative findings suggesting optic pathway invasion. Both patients developed further intracranial dissemination within several months post-surgery. The presence of solitary sellar and suprasellar dissemination may indicate a terminal stage.


Asunto(s)
Glioblastoma , Neoplasias Hipofisarias , Silla Turca , Humanos , Femenino , Glioblastoma/cirugía , Glioblastoma/patología , Glioblastoma/diagnóstico por imagen , Persona de Mediana Edad , Silla Turca/cirugía , Silla Turca/patología , Silla Turca/diagnóstico por imagen , Adulto Joven , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/diagnóstico por imagen , Imagen por Resonancia Magnética , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/diagnóstico por imagen , Trastornos de la Visión/etiología , Trastornos de la Visión/cirugía , Invasividad Neoplásica , Procedimientos Neuroquirúrgicos/métodos
7.
J Neurooncol ; 169(3): 517-529, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39105956

RESUMEN

PURPOSE: Post-operative MRI is used to assess extent of resection, monitor treatment response and detect progression in high-grade glioma. However, compliance with accepted guidelines for follow-up MRI, and impact on management/outcomes is unclear. METHODS: Multi-center, retrospective observational cohort study of patients with confirmed WHO grade 4 glioma (August 2018-February 2019) receiving oncological treatment. PRIMARY OBJECTIVE: investigate follow-up MRI surveillance practice and compliance with recommendations from NICE (Post-operative scan < 72h, MRI every 3-6 months) and EANO (Post-operative scan < 48h, MRI every 3 months). RESULTS: There were 754 patients from 26 neuro-oncology centers with a median age of 63 years (IQR 54-70), yielding 10,100 (median, 12.5/person, IQR 5.2-19.4) person-months of follow-up. Of patients receiving debulking surgery, most patients had post-operative MRI within 72 h of surgery (78.0%, N = 407/522), and within 48 h of surgery (64.2%, N = 335/522). The median number of subsequent follow-up MRI scans was 1 (IQR 0-4). Compliance with NICE and EANO recommendations for follow-up MRI was 52.8% (N = 398/754) and 24.9% (N = 188/754), respectively. On multivariable Cox regression analysis, increased time spent in recommended follow-up according to NICE guidelines was associated with longer OS (HR 0.56, 95% CI 0.46-0.66, P < 0.001), but not PFS (HR 0.93, 95% CI 0.79-1.10, P = 0.349). Increased time spent in recommended follow-up according to EANO guidelines was associated with longer OS (HR 0.54, 95% CI 0.45-0.63, P < 0.001) but not PFS (HR 0.99, 95% CI 0.84-1.16, P = 0.874). CONCLUSION: Regular surveillance follow-up for glioblastoma is associated with longer OS. Prospective trials are needed to determine whether regular or symptom-directed MRI influences outcomes.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Imagen por Resonancia Magnética , Humanos , Persona de Mediana Edad , Femenino , Masculino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Anciano , Glioblastoma/cirugía , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Irlanda , Estudios Retrospectivos , Reino Unido , Estudios de Seguimiento , Factores de Tiempo , Estudios de Cohortes , Adhesión a Directriz/estadística & datos numéricos
8.
Sci Rep ; 14(1): 19079, 2024 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154028

RESUMEN

Not all patients with glioblastoma multiforme (GBM) eligible for systemic chemotherapy after upfront surgery and radiotherapy finally receive it. The information on patients with GBM was retrieved from the surveillance, epidemiology, and end results database. Patients who underwent upfront surgery or biopsy and external beam radiotherapy between 2010 and 2019 were eligible for systemic chemotherapy. The available patient and tumor characteristics were assessed using multivariable logistic regression and chi-squared test. Out of the 16,682 patients eligible, 92.1% underwent systemic chemotherapy. The characteristics linked to the lowest systemic chemotherapy utilization included tumors of the brain stem/cerebellum (P = 0.01), former years of diagnosis (P = 0.001), ≥ 80 years of age (P < 0.001), Hispanic, Non-Hispanic Asian, Pacific Islander, or Black race (P < 0.001), non-partnered status (P < 0.001), and low median household income (P = 0.006). Primary tumor site, year of diagnosis, age, race, partnered status, and median household income correlated with the omission of systemic chemotherapy in GBM in adult patients.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/cirugía , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/epidemiología , Factores Socioeconómicos , Anciano de 80 o más Años , Disparidades en Atención de Salud , Programa de VERF
9.
Medicina (Kaunas) ; 60(8)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39202515

RESUMEN

Background and Objectives: Notwithstanding the major progress in the management of cancerous diseases in the last few decades, glioblastoma (GBM) remains the most aggressive brain malignancy, with a dismal prognosis, mainly due to treatment resistance and tumoral recurrence. In order to diagnose this disease and establish the optimal therapeutic approach to it, a standard tissue biopsy or a liquid biopsy can be performed, although the latter is currently less common. To date, both tissue and liquid biopsy have yielded numerous biomarkers that predict the evolution and response to treatment in GBM. However, despite all such efforts, GBM has the shortest recorded survival rates of all the primary brain malignancies. Materials and Methods: We retrospectively reviewed patients with a confirmed histopathological diagnosis of glioblastoma between June 2011 and June 2023. All the patients were treated in the Third Neurosurgical Department of the Clinical Emergency Hospital "Bagdasar-Arseni" in Bucharest, and their outcomes were analyzed and presented accordingly. Results: Out of 518 patients in our study, 222 (42.8%) were women and 296 (57.14%) were men. The most common clinical manifestations were headaches and limb paralysis, while the most frequent tumor locations were the frontal and temporal lobes. The survival rates were prolonged in patients younger than 60 years of age, in patients with gross total tumoral resection and less than 30% tumoral necrosis, as well as in those who underwent adjuvant radiotherapy. Conclusions: Despite significant advancements in relation to cancer diseases, GBM is still a field of great interest for research and in great need of new therapeutic approaches. Although the multimodal therapeutic approach can improve the prognosis, the survival rates are still short and the recurrences are constant.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/cirugía , Glioblastoma/mortalidad , Glioblastoma/terapia , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/mortalidad , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Procedimientos Neuroquirúrgicos/métodos , Resultado del Tratamiento , Anciano de 80 o más Años , Lituania/epidemiología
10.
World Neurosurg ; 189: e872-e877, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38986934

RESUMEN

OBJECTIVE: Brain tumors display remarkable cellular and molecular diversity, significantly impacting the progression and outcomes of the disease. The utilization of tumor tissue acquired through surgical handheld devices for tumor characterization raises important questions regarding translational research. This study seeks to evaluate the integrity of tissue resected using a microdebrider (MD) in the context of establishing tumor organoids from glioblastomas (GBM). METHODS: Tumor samples were collected from patients with GBM using both tumor forceps (en bloc) and a MD. The time required to protocol completion and cell viability of paired samples was measured. H&E staining was performed to examine histologic morphology. RESULTS: Ten paired samples were obtained from GBM patients using tumor forceps and the MD. Samples collected with the MD demonstrated significantly shorter processing times compared to those obtained through en bloc resection, with overall means of 31.7 ± 2.4 mins and 38.8±3 mins, respectively (P < 0.001). Cell viability measured at the end of protocol completion was comparable between tissues obtained using both the MD and en bloc, with mean viabilities of 80.2 ± 12.4% and 79.1 ± 12.5%, respectively (P = 0.848). H&E examination of tissues revealed no significant differences in the cellular and histologic characteristics of paired samples obtained using both methods across GBM tumors, nor in the corresponding established organoids. CONCLUSIONS: Tumor tissues obtained using the MD and en bloc methods demonstrate a high success rate in establishing GBM organoids, with the MD offering the advantage of significantly reduced processing time. Both methods display comparable cell viability and maintain consistent histologic characteristics in the resected tissue and the corresponding organoids.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Organoides , Humanos , Glioblastoma/patología , Glioblastoma/cirugía , Organoides/patología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Femenino , Masculino , Persona de Mediana Edad , Recolección de Tejidos y Órganos/métodos , Supervivencia Celular/fisiología , Anciano , Adulto
11.
J Neurooncol ; 169(3): 469-487, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38990444

RESUMEN

PURPOSE: Maximal-safe resection has been shown to improve overall survival in elderly patients with glioblastoma in observational studies, however, the only clinical trial comparing resection versus biopsy in elderly patients with surgically-accessible glioblastoma showed no improvements in overall survival. A meta-analysis is needed to assess whether surgical resection of glioblastoma in older patients improves surgical outcomes when compared to biopsy alone. METHODS: A search was conducted until October 9th, 2023, to identify published studies reporting the clinical outcomes of glioblastoma patients > 65 years undergoing resection or biopsy (PubMed, MEDLINE, EMBASE, and COCHRANE). Primary outcomes were overall survival (OS), progression-free survival (PFS), and complications. We analyzed mean difference (MD) and hazard ratio (HR) for survival outcomes. Postoperative complications were analyzed as a dichotomic categorical variable with risk ratio (RR). RESULTS: From 784 articles, 20 cohort studies and 1 randomized controlled trial met our inclusion criteria, considering 20,523 patients for analysis. Patients undergoing surgical resection had an overall survival MD of 6.13 months (CI 95%=2.43-9.82, p = < 0.001) with a HR of 0.43 (95% CI = 0.35-0.52, p = < 0.00001). The progression-free survival MD was 2.34 months (95%CI = 0.79-3.89, p = 0.003) with a 0.50 h favoring resection (95%CI = 0.37-0.68, p = < 0.00001). The complication RR was higher in the resection group favoring biopsy (1.49, 95%CI = 1.06-2.10). CONCLUSIONS: Our meta-analysis suggests that upfront resection is associated with improved overall survival and progression-free survival in elderly patients with newly diagnosed glioblastoma over biopsy. However, postoperative complications are more common with resection. Future clinical trials are essential to provide more robust evaluation in this challenging patient population.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Procedimientos Neuroquirúrgicos , Humanos , Glioblastoma/cirugía , Glioblastoma/patología , Glioblastoma/mortalidad , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/mortalidad , Pronóstico , Anciano , Biopsia , Procedimientos Neuroquirúrgicos/métodos
12.
J Neurooncol ; 169(3): 633-646, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39037687

RESUMEN

PURPOSE: PreOperative radiotherapy (RT) is commonly used in the treatment of brain metastasis and different cancer types but has never been used in primary glioblastoma (GBM). Here, we aim to establish, describe, and validate the use of PreOperative RT for the treatment of GBM in a preclinical model. METHODS: Rat brains were locally irradiated with 30-Gy, hypofractionated in five doses 2 weeks before or after the resection of intracranial GBM. Kaplan-Meier analysis determined survival. Hematoxylin-eosin staining was performed, and nuclei size and p21 senescence marker were measured in both resected and recurrent rodent tumors. Immunohistochemistry assessed microglia/macrophage markers, and RNAseq analyzed gene expression changes in recurrent tumors. Akoya Multiplex Staining on two human patients from our ongoing Phase I/IIa trial served as proof of principle. RESULTS: PreOperative RT group median survival was significantly higher than PostOperative RT (p < 0.05). Radiation enlarged cytoplasm and nuclei in PreOperative RT resected tumors (p < 0.001) and induced senescence in PostOperative RT recurrent tumors (p < 0.05). Gene Set Enrichment Analysis (GSEA) suggested a more proliferative profile in PreOperative RT group. PreOperative RT showed lower macrophage/microglia recruitment in recurrent tumors (p < 0.01) compared to PostOperative RT. Akoya Multiplex results indicated TGF-ß accumulation in the cytoplasm of TAMs and CD4 + lymphocyte predominance in PostOperative group. CONCLUSIONS: This is the first preclinical study showing feasibility and longer overall survival using neoadjuvant radiotherapy before GBM resection in a mammalian model. This suggests strong superiority for new clinical radiation strategies. Further studies and trials are required to confirm our results.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioblastoma/radioterapia , Glioblastoma/patología , Glioblastoma/metabolismo , Glioblastoma/cirugía , Animales , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirugía , Humanos , Ratas , Modelos Animales de Enfermedad , Masculino , Recurrencia Local de Neoplasia/patología , Cuidados Preoperatorios , Femenino
13.
J Clin Neurosci ; 127: 110746, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39079422

RESUMEN

BACKGROUND: Glioblastoma patients may develop functional deficits post-operatively that affect activities of daily living and result in worse outcomes. The Activity Measure for Post-Acute Care (AM-PAC) instrument assigns patients basic mobility and daily activity scores, but it is unknown if these scores correlate with post-operative outcomes in glioblastoma patients. METHODS: Adult (≥18 years) glioblastoma patients evaluated by physical/occupational therapy after resection at a single instution (June 2008-December 2020) were identified. Patient demographics, post-operative AM-PAC scores, and clinical outcomes were collected. Multivariate regression identified associations between AM-PAC scores and post-operative outcomes. RESULTS: 600 patients were included (mean age 59.3 years, 59.2 % male); 151 (25.3 %) and 246 (43.8 %) patients had low mobility (<42.9) and activity (<39.4) scores, respectively. 103 (17.2 %) and 177 (29.5 %) patients experienced extended lengths of stay (LOS) in the ICU (≥2 days) and overall (≥7 days), respectively. 154 (25.7 %) patients had non-home discharges. The 30-day readmission rate was 13.7 %. In multivariate analysis, low mobility scores correlated with increased odds of extended overall (p < 0.0001) and ICU (p = 0.0004) LOS, non-home discharge (p < 0.0001), and 30-day readmission (p = 0.0405). Low activity scores correlated with extended overall LOS (<0.0001) and non-home discharge (p < 0.0001). In log-rank analysis, median survival time was shorter for patients with low mobility (9.5 vs. 14.7 months, p < 0.0001) and activity (10.6 vs. 16.3 months, p < 0.0001) scores than for high-scoring patients. CONCLUSION: AM-PAC basic mobility and daily activity scores are associated with outcomes after glioblastoma resection. These easily obtainable scores may be useful for prognosticating and guiding decision making in post-operative glioblastoma patients.


Asunto(s)
Actividades Cotidianas , Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/cirugía , Masculino , Persona de Mediana Edad , Femenino , Neoplasias Encefálicas/cirugía , Anciano , Tiempo de Internación/estadística & datos numéricos , Atención Subaguda/métodos , Estudios Retrospectivos , Adulto , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Readmisión del Paciente/estadística & datos numéricos
14.
J Neurooncol ; 169(2): 257-267, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38960965

RESUMEN

BACKGROUND: Quantifying tumor growth and treatment response noninvasively poses a challenge to all experimental tumor models. The aim of our study was, to assess the value of quantitative and visual examination and radiomic feature analysis of high-resolution MR images of heterotopic glioblastoma xenografts in mice to determine tumor cell proliferation (TCP). METHODS: Human glioblastoma cells were injected subcutaneously into both flanks of immunodeficient mice and followed up on a 3 T MR scanner. Volumes and signal intensities were calculated. Visual assessment of the internal tumor structure was based on a scoring system. Radiomic feature analysis was performed using MaZda software. The results were correlated with histopathology and immunochemistry. RESULTS: 21 tumors in 14 animals were analyzed. The volumes of xenografts with high TCP (H-TCP) increased, whereas those with low TCP (L-TCP) or no TCP (N-TCP) continued to decrease over time (p < 0.05). A low intensity rim (rim sign) on unenhanced T1-weighted images provided the highest diagnostic accuracy at visual analysis for assessing H-TCP (p < 0.05). Applying radiomic feature analysis, wavelet transform parameters were best for distinguishing between H-TCP and L-TCP / N-TCP (p < 0.05). CONCLUSION: Visual and radiomic feature analysis of the internal structure of heterotopically implanted glioblastomas provide reproducible and quantifiable results to predict the success of transplantation.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Imagen por Resonancia Magnética , Trasplante de Neoplasias , Animales , Femenino , Humanos , Masculino , Ratones , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Glioblastoma/diagnóstico por imagen , Glioblastoma/cirugía , Glioblastoma/patología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Trasplante de Neoplasias/métodos , Radiómica
15.
EBioMedicine ; 106: 105243, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39004066

RESUMEN

BACKGROUND: Surgery is crucial for glioma treatment, but achieving complete tumour removal remains challenging. We evaluated the effectiveness of a probe targeting monocarboxylate transporter 4 (MCT4) in recognising gliomas, and of near-infrared window II (NIR-II) fluorescent molecular imaging and photothermal therapy as treatment strategies. METHODS: We combined an MCT4-specific monoclonal antibody with indocyanine green to create the probe. An orthotopic mouse model and a transwell model were used to evaluate its ability to guide tumour resection using NIR-II fluorescence and to penetrate the blood-brain barrier (BBB), respectively. A subcutaneous tumour model was established to confirm photothermal therapy efficacy. Probe specificity was assessed in brain tissue from mice and humans. Finally, probe effectiveness in photothermal therapy was investigated. FINDINGS: MCT4 was differentially expressed in tumour and normal brain tissue. The designed probe exhibited precise tumour targeting. Tumour imaging was precise, with a signal-to-background (SBR) ratio of 2.8. Residual tumour cells were absent from brain tissue postoperatively (SBR: 6.3). The probe exhibited robust penetration of the BBB. Moreover, the probe increased the tumour temperature to 50 °C within 5 min of laser excitation. Photothermal therapy significantly reduced tumour volume and extended survival time in mice without damage to vital organs. INTERPRETATION: These findings highlight the potential efficacy of our probe for fluorescence-guided surgery and therapeutic interventions. FUNDING: Jilin Province Department of Science and Technology (20200403079SF), Department of Finance (2021SCZ06) and Development and Reform Commission (20200601002JC); National Natural Science Foundation of China (92059207, 92359301, 62027901, 81930053, 81227901, U21A20386); and CAS Youth Interdisciplinary Team (JCTD-2021-08).


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Transportadores de Ácidos Monocarboxílicos , Terapia Fototérmica , Animales , Ratones , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/antagonistas & inhibidores , Humanos , Terapia Fototérmica/métodos , Glioblastoma/terapia , Glioblastoma/metabolismo , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Glioblastoma/cirugía , Línea Celular Tumoral , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Cirugía Asistida por Computador/métodos , Modelos Animales de Enfermedad , Barrera Hematoencefálica/metabolismo , Proteínas Musculares/metabolismo , Imagen Óptica/métodos , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Clin Neurol Neurosurg ; 245: 108469, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39079287

RESUMEN

OBJECTIVE: Patients with glioblastoma (GBM) often undergo surgery to prolong survival. However, the use of surgery, and more specifically achieving gross total resection (GTR), in patients >80 years old has yet to be fully assessed. Using the Surveillance, Epidemiology, and End Results (SEER) database, we aim to assess the efficacy of surgical resection, radiotherapy (RT) and chemotherapy (CT) on overall survival (OS) in very elderly GBM patients compared to elderly counterparts (age 65-79 years). METHODS: The SEER database was queried for all patients >65 years old with GBM (2000-2020). Patients not undergoing surgery or biopsy were excluded. Patients were stratified by age, and demographic relationships were assessed with chi-squared testing for categorical variables. Bivariable models were created using Kaplan-Meier survival estimates. All significant variables from bivariable analysis were included on multivariable Cox survival regression models to determine independent associations between clinical variables and OS. RESULTS: A total of 27,090 operative GBM patients were identified; 1868 patients (15.92 %) were very elderly and 10,092 patients (84.38 %) were elderly. Very elderly patients were less likely to undergo GTR (28 % vs 35 %, p<0.001), RT (59 % vs 78 %, p<0.001) and CT (40 % vs 66 %, p<0.001). In multivariable Cox regression analysis, very elderly patients who achieved GTR (HR=.696, p<0.001), received RT (HR=0.583, p<0.001) and underwent CT (HR=0.4197, p<0.001) had significantly improved OS compared to very elderly patients that did not undergo these treatment options. CONCLUSION: Currently, very elderly GBM patients undergo lower rates of aggressive surgery, RT and CT. However, very elderly patients that undergo surgery, RT and CT may have a survival advantage. These treatments should be considered as potential options for this patient population.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Procedimientos Neuroquirúrgicos , Programa de VERF , Humanos , Glioblastoma/cirugía , Glioblastoma/mortalidad , Glioblastoma/terapia , Anciano , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/mortalidad , Masculino , Anciano de 80 o más Años , Femenino , Resultado del Tratamiento , Factores de Edad
17.
World Neurosurg ; 189: e419-e426, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38906477

RESUMEN

OBJECTIVE: Adherence to combinatorial treatments are important predictors of improved long-term outcomes for patients with glioblastoma (GB); however, factors associated with refusal of surgery, chemotherapy, or radiotherapy (RT) by patients with GB have not been studied. METHODS: The National Cancer Database was queried from 2004 to 2018 to identify patients with a primary diagnosis of GB who underwent surgical resection alone or followed by either RT or chemotherapy. Adult patients who voluntarily rejected a physician's recommendations for 1 or more treatment were selected. Multivariable regression was used to identify factors associated with rejection of surgical resection, chemotherapy, and RT. Patients receiving treatment were 3:1 propensity score matched to those rejecting treatment and median overall survival (OS) was compared. RESULTS: 58,788 patients were included in the analysis. Factors associated with voluntary refusal of GB treatment included: old age, nonprivate insurance, female sex, Black race, comorbidities, treatment at a nonacademic facility, and living 55+ miles away from a treatment facility (P < 0.05). On propensity matched analysis, refusal of surgery conferred a 4 month decrease in OS (P < 0.001), RT an 8 month decrease in OS (P < 0.001), and chemotherapy a 7 month decrease in OS (P < 0.001). CONCLUSIONS: In patients with GB, age, sex, race, nonprivate insurance, medical comorbidities, distance from treatment facility, and geographic location were associated with refusal of surgery, postsurgical RT, and chemotherapy. In addition, treatment refusal had a significant impact on OS length.


Asunto(s)
Neoplasias Encefálicas , Bases de Datos Factuales , Glioblastoma , Negativa del Paciente al Tratamiento , Humanos , Glioblastoma/terapia , Glioblastoma/cirugía , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Negativa del Paciente al Tratamiento/estadística & datos numéricos , Neoplasias Encefálicas/terapia , Anciano , Estados Unidos/epidemiología , Adulto
18.
J Neurooncol ; 169(2): 445-455, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38913230

RESUMEN

BACKGROUND AND OBJECTIVES: Contrast enhancement in glioblastoma, IDH-wildtype is common but not systematic. In the era of the WHO 2021 Classification of CNS Tumors, the prognostic impact of a contrast enhancement and the pattern of contrast enhancement is not clearly elucidated. METHODS: We performed an observational, retrospective, single-centre cohort study at a tertiary neurosurgical oncology centre (January 2006 - December 2022). We screened adult patients with a newly-diagnosed glioblastoma, IDH-wildtype in order to assess the prognosis role of the contrast enhancement and the pattern of contrast enhancement. RESULTS: We included 1149 glioblastomas, IDH-wildtype: 26 (2.3%) had a no contrast enhancement, 45 (4.0%) had a faint and patchy contrast enhancement, 118 (10.5%) had a nodular contrast enhancement, and 960 (85.5%) had a ring-like contrast enhancement. Overall survival was longer in non-contrast enhanced glioblastomas (26.7 months) than in contrast enhanced glioblastomas (10.9 months) (p < 0.001). In contrast enhanced glioblastomas, a ring-like pattern was associated with shorter overall survival than in faint and patchy and nodular patterns (10.0 months versus 13.0 months, respectively) (p = 0.033). Whatever the presence of a contrast enhancement and the pattern of contrast enhancement, surgical resection was an independent predictor of longer overall survival, while age ≥ 70 years, preoperative KPS score < 70, tumour volume ≥ 30cm3, and postoperative residual contrast enhancement were independent predictors of shorter overall survival. CONCLUSION: A contrast enhancement is present in the majority (97.7%) of glioblastomas, IDH-wildtype and, regardless of the pattern, is associated with a shorter overall survival. The ring-like pattern of contrast enhancement is typical in glioblastomas, IDH-wildtype (85.5%) and remains an independent predictor of shorter overall survival compared to other patterns (faint and patchy and nodular).


Asunto(s)
Neoplasias Encefálicas , Medios de Contraste , Glioblastoma , Isocitrato Deshidrogenasa , Imagen por Resonancia Magnética , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Glioblastoma/mortalidad , Glioblastoma/cirugía , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Imagen por Resonancia Magnética/métodos , Pronóstico , Isocitrato Deshidrogenasa/genética , Anciano , Adulto , Organización Mundial de la Salud
19.
Acta Neurochir (Wien) ; 166(1): 260, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858238

RESUMEN

The aim of this case study was to describe differences in English and British Sign Language (BSL) communication caused by a left temporal tumour resulting in discordant presentation of symptoms, intraoperative stimulation mapping during awake craniotomy and post-operative language abilities. We report the first case of a hearing child of deaf adults, who acquired BSL with English as a second language. The patient presented with English word finding difficulty, phonemic paraphasias, and reading and writing challenges, with BSL preserved. Intraoperatively, object naming and semantic fluency tasks were performed in English and BSL, revealing differential language maps for each modality. Post-operative assessment confirmed mild dysphasia for English with BSL preserved. These findings suggest that in hearing people who acquire a signed language as a first language, topographical organisation may differ to that of a second, spoken, language.


Asunto(s)
Neoplasias Encefálicas , Craneotomía , Glioblastoma , Lengua de Signos , Lóbulo Temporal , Humanos , Glioblastoma/cirugía , Craneotomía/métodos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Lóbulo Temporal/cirugía , Lóbulo Temporal/diagnóstico por imagen , Mapeo Encefálico/métodos , Masculino , Vigilia/fisiología , Habla/fisiología , Multilingüismo , Lenguaje , Adulto
20.
World Neurosurg ; 189: e230-e237, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38857868

RESUMEN

BACKGROUND: Malignant gliomas are the most prevalent primary malignant cerebral tumors. Preoperative imaging plays an important role, and the prognosis is closely related to surgical resection and histomolecular aspects. Our goal was to correlate Ki67 indexes with tumoral volumetry in semiautomatic segmentation on preoperative magnetic resonance images and residual fluorescence in a 5-ALA-assisted resection cohort. METHODS: We included 86 IDH-wildtype glioblastoma patients with complete preoperative imaging submitted to 5-ALA assisted resections. Clinical, surgical, and histomolecular findings were also obtained. Preoperative magnetic resonance studies were preprocessed and segmented semiautomatically on Visualization and Analysis for whole tumor (WT) on 3D FLAIR, enhancing tumor (ET), and necrotic core on 3D postgadolinium T1. We performed a linear regression analysis for Ki67 and a multivariate analysis for surgical outcomes. RESULTS: Higher Ki-67 indexes correlated positively with higher WT (P = 0.048) and ET (P = 0.002). Lower Ki67 correlated with 5-ALA free margins (P = 0.045). WT and ET volumes correlated with the extent of resection (EOR; P = 0.002 and 0.002, respectively). Eloquence did not impact EOR (P = 0.14). CONCLUSIONS: There is a correlation between Ki67, the metabolically active tumoral volumes (WT and ET), and 5-ALA residual fluorescence. Methodological inconsistencies are probably responsible for contradictory literature findings, and further prospective studies are needed to validate and reproduce these findings.


Asunto(s)
Ácido Aminolevulínico , Neoplasias Encefálicas , Glioblastoma , Antígeno Ki-67 , Imagen por Resonancia Magnética , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/cirugía , Glioblastoma/patología , Glioblastoma/metabolismo , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Femenino , Masculino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Anciano , Imagen por Resonancia Magnética/métodos , Carga Tumoral , Adulto , Fluorescencia
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