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The bidirectional relationship between the gut microbiota and the nervous system is known as the microbiota-gut-brain axis (MGBA). The MGBA controls the complex interactions between the brain, the enteric nervous system, the gut-associated immune system, and the enteric neuroendocrine systems, regulating key physiological functions such as the immune response, sleep, emotions and mood, food intake, and intestinal functions. Psychobiotics are considered tools with the potential to modulate the MGBA through preventive, adjunctive, or curative approaches, but their specific mechanisms of action on many aspects of health are yet to be characterized. This narrative review and perspectives article highlights the key paradigms needing attention as the scope of potential probiotics applications in human health increases, with a growing body of evidence supporting their systemic beneficial effects. However, there are many limitations to overcome before establishing the extent to which we can incorporate probiotics in the management of neuropsychiatric disorders. Although this article uses the term probiotics in a general manner, it remains important to study probiotics at the strain level in most cases.
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Supplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix of Bifidobacterium animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 on high-fat (HF) diet -induced metabolic disease in mice. Supplementation with the probiotic mix in HF diet-fed mice (HF-Pr2) reduced weight and fat mass gains, decreased hepatic lipid accumulation, and lowered plasma triglyceride peak during an oral lipid tolerance test. At the molecular level, the probiotic mix protected against HF-induced rise in mRNA levels of genes related to lipid uptake, metabolism, and storage in the liver and white adipose tissues, and strongly decreased mRNA levels of genes related to inflammation in the white adipose tissue and to oxidative stress in the liver. Regarding intestinal homeostasis, the probiotic mix did not prevent HF-induced gut permeability but slightly modified microbiota composition without correcting the dysbiosis induced by the HF diet. Probiotic supplementation also modified the cecal bile acid (BA) profile, leading to an increase in the Farnesoid-X-Receptor (FXR) antagonist/agonist ratio between BA species. In agreement, HF-Pr2 mice exhibited a strong inhibition of FXR signaling pathway in the ileum, which was associated with lipid metabolism protection. This is consistent with recent reports proposing that inhibition of intestinal FXR activity could be a potent mechanism to overcome metabolic disorders. Altogether, our results demonstrate that the probiotic mix evaluated, when administered preventively to HF diet-fed mice could limit obesity and associated lipid metabolism disorders, likely through the inhibition of FXR signaling in the intestinal tract.
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Microbioma Gastrointestinal , Probióticos , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Aumento de Peso , Probióticos/farmacologia , Probióticos/uso terapêutico , Fígado/metabolismo , Triglicerídeos , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , Camundongos Endogâmicos C57BL , Ácidos e Sais Biliares/metabolismoRESUMO
We compared endogenous ω-3 PUFA production to supplementation for improving obesity-related metabolic dysfunction. Fat-1 transgenic mice, who endogenously convert exogenous ω-6 to ω-3 PUFA, and wild-type littermates were fed a high-fat diet and a daily dose of either ω-3 or ω-6 PUFA-rich oil for 12 wk. The endogenous ω-3 PUFA production improved glucose intolerance and insulin resistance but not hepatic steatosis. Conversely, ω-3 PUFA supplementation fully prevented hepatic steatosis but failed to improve insulin resistance. Both models increased hepatic levels of ω-3 PUFA-containing 2-monoacylglycerol and N-acylethanolamine congeners, and reduced levels of ω-6 PUFA-derived endocannabinoids with ω-3 PUFA supplementation being more efficacious. Reduced hepatic lipid accumulation associated with the endocannabinoidome metabolites EPEA and DHEA, which was causally demonstrated by lower lipid accumulation in oleic acid-treated hepatic cells treated with these metabolites. While both models induced a significant fecal enrichment of the beneficial Allobaculum genus, mice supplemented with ω-3 PUFA displayed additional changes in the gut microbiota functions with a significant reduction of fecal levels of the proinflammatory molecules lipopolysaccharide and flagellin. Multiple-factor analysis identify that the metabolic improvements induced by ω-3 PUFAs were accompanied by a reduced production of the proinflammatory cytokine TNFα, and that ω-3 PUFA supplementation had a stronger effect on improving the hepatic fatty acid profile than endogenous ω-3 PUFA. While endogenous ω-3 PUFA production preferably improves glucose tolerance and insulin resistance, ω-3 PUFA intake appears to be required to elicit selective changes in hepatic endocannabinoidome signaling that are essential to alleviate high-fat diet-induced hepatic steatosis.
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Ácidos Graxos Ômega-3 , Fígado Gorduroso , Resistência à Insulina , Camundongos , Animais , Fígado Gorduroso/tratamento farmacológico , Camundongos Transgênicos , Suplementos NutricionaisRESUMO
BACKGROUND: Facial nerve schwannomas account for about 0.8% of all petrous mass lesions. Schwannomas of the greater superficial petrosal nerve (GSPN) are a rare subtype with few case-reports up to date. CASE PRESENTATIONS: A retrospective analysis of clinical outcomes, radiographic findings and postoperative complication between June 2007 and December 2020 was performed. Four cases of GSPN schwannomas were reported. The presenting symptoms were facial nerve palsy and hearing loss. Imaging studies showed a subtemporal mass on the anterosuperior aspect of the petrous bone, in one case with extraordinary petrous bone and mastoid infiltration and destruction. Three cases were removed through a subtemporal extra- or intradural approach, one case via a combined pre- and retrosigmoid approach. Improvement of facial nerve palsy occurred in one case; new hearing loss was observed in another case. Xeropthalmia was a short-term temporary deficit in three cases. Short- to mid-term follow-up of the patients has not shown any tumor recurrence. CONCLUSIONS: GSPN schwannomas are rare entities presenting with heterogenous symptoms. Our surgical findings emphasize safe resection. Complete remission is possible by GTR. Since the small data set limits the expressiveness of statements regarding standard of care and alternative therapy options, additional data is needed.
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Paralisia Facial , Neurilemoma , Humanos , Gânglio Geniculado/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia , Neurilemoma/cirurgia , Neurilemoma/diagnósticoRESUMO
Introduction: Surgical treatment for CCS in patients with an underlying cervical stenosis without instability remains controversial. Research question: The aim was to assess the incidence of concomitant discoligamentous injury (DLI) in patients with CCS and underlying degenerative cervical spinal stenosis and to determine the sensitivity of MRI by comparing intraoperative site inspection to preoperative imaging findings. Material and methods: We performed a retrospective analysis of our clinical prospective database. Fifty-one patients (39 male, 12 female) between January 2010 and June 2019 were included. Age, sex, neurological deficits, preoperative MRI, and surgical treatment were recorded. Sensitivity was determined by the quotient of patients in whom all levels of DLI were correctly identified on MRI and the total number of patients with intraoperatively confirmed DLI. Results: Mean age at surgery was 64.1 â± â11.3 (range 41-86). DLI was suspected in 33 (62.1%) patients based on MRI findings, which could be confirmed intraoperatively in 29 patients (56.9%). In 2 patients, DLI was detected intraoperatively that was not suspected in preoperative MRI; in 5 patients, another level was affected intraoperatively than was indicated by MRI. The overall specificity and sensitivity of preoperative MRI imaging to identify discoligamentous lesions of the cervical spine was 73% and 79%, respectively. Discussion and conclusion: The incidence of DLI in patients with traumatic CCS based on preexisting spinal stenosis was 60.78%, which is higher than previously reported. The sensitivity of MRI imaging to detect DLI of 79% suggests that these patients are at risk of missing traumatic DLI on imaging.
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(1) Background: Plasma cell neoplasia can be separated into independent subtypes including multiple myeloma (MM) and solitary plasmacytoma of the bone (SBP). The first clinical signs patients present with are skeletal pain, most commonly involving ribs and vertebrae. (2) Methods: Retrospective analysis of 114 patients (38 female, 76 male) receiving spinal surgery from March 2006 until April 2020. Neurological impairments and surgical instability were the criteria for intervention in this cohort. Analysis was based on demographic data, Spinal Instability Neoplastic Score (SINS), location of the lesion, spinal levels of tumor involvement, surgical treatment, histopathological workup, adjuvant therapy, functional outcome, and overall survival (OS). (3) Results: The following surgical procedures were performed: posterior stabilization only in 9 patients, posterior stabilization and decompression without vertebral body replacement in 56 patients, tumor debulking and decompression only in 8 patients, anterior approach in combined approach without vertebral body replacement and without biopsy and/or without kyphoplasty in 33 patients, 3 patients received biopsies only, and 5 patients received kyphoplasty only. The histopathology diagnoses were MM in 94 cases and SBP in 20 cases. Median OS was 72 months (53.4-90.6 months). Preoperative KPSS was 80% (range 40-100%), the postoperative KPSS was 80% (range 50-100%). (4) Conclusions: Surgery for patients with plasma cell neoplasia is beneficial in case of neurological impairment and spinal instability. Moreover, we were able to show that patients with MM and a low number of spinal levels to be supplied have a better prognosis as well as a younger age at the time of the surgical intervention.
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Mieloma Múltiplo , Plasmocitoma , Neoplasias da Coluna Vertebral , Feminino , Humanos , Masculino , Mieloma Múltiplo/patologia , Plasmócitos/patologia , Plasmocitoma/patologia , Plasmocitoma/cirurgia , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/patologia , Coluna Vertebral/cirurgia , Resultado do TratamentoRESUMO
Introduction: Glioblastoma (GBM) is the most common malignant primary brain tumor. Treatment includes maximally safe surgical resection followed by radiation and/or chemotherapy. However, resection can lead to ventricular opening, potentially increasing the risk for development of communicating hydrocephalus (CH). Complications such as rebleeding and infection may also lead to CH and, eventually, the need for cerebrospinal fluid (CSF) diversion surgery. In this study, we evaluated the incidence of different types of hydrocephalus and potential risk factors for the development of CH following glioblastoma resection. Methods: 726 GBM patients who underwent tumor resection at our department between 2006 and 2019 were analyzed retrospectively. Potential risk factors that were determined for each patient were age, sex, tumor location, the number of resection surgeries, ventricular opening during resection, postoperative CSF leak, ventriculitis, and rebleeding. Uni- as well as multivariate analyses were performed to identify associations with CH and independent risk factors. Results: 55 patients (7.6%) needed CSF diversion surgery (implantation of a ventriculoperitoneal or ventriculoatrial shunt) following resection surgery. 47 patients (6.5%) had CH, on median, 24 days after the last resection (interquartile range: 17-52 days). 3 patients had obstructive hydrocephalus (OH) and 5 patients had other CSF circulation disorders. Ventricular opening (odds ratio (OR): 7.9; p=0.000807), ventriculitis (OR 3.3; p=0.000754), and CSF leak (OR 2.3; p=0.028938) were identified as significant independent risk factors for the development of post-resection CH. Having more than one resection surgery was associated with CH as well (OR 2.1; p=0.0128), and frontal tumors were more likely to develop CH (OR 2.4; p=0.00275), while temporal tumors were less likely (OR 0.41; p=0.0158); However, none of those were independent risk factors. Age, sex, or rebleeding were not associated with postoperative CH. Conclusion: Postoperative CH requiring CSF shunting is not infrequent following GBM resection and is influenced by surgery-related factors. It typically occurs several weeks after resection. If multiple risk factors are present, one should discuss the possibility of postoperative CH with the patient and maybe even consider pre-emptive shunt implantation to avoid interruption of adjuvant tumor therapy. The incidence of CH requiring shunting in GBM patients could rise in the future.
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Although glioblastoma multiforme (GBM) is not an invariably cold tumor, checkpoint inhibition has largely failed in GBM. In order to investigate T cell-intrinsic properties that contribute to the resistance of GBM to endogenous or therapeutically enhanced adaptive immune responses, we sorted CD4+ and CD8+ T cells from the peripheral blood, normal-appearing brain tissue, and tumor bed of nine treatment-naive patients with GBM. Bulk RNA sequencing of highly pure T cell populations from these different compartments was used to obtain deep transcriptomes of tumor-infiltrating T cells (TILs). While the transcriptome of CD8+ TILs suggested that they were partly locked in a dysfunctional state, CD4+ TILs showed a robust commitment to the type 17 T helper cell (TH17) lineage, which was corroborated by flow cytometry in four additional GBM cases. Therefore, our study illustrates that the brain tumor environment in GBM might instruct TH17 commitment of infiltrating T helper cells. Whether these properties of CD4+ TILs facilitate a tumor-promoting milieu and thus could be a target for adjuvant anti-TH17 cell interventions needs to be further investigated.
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Neoplasias Encefálicas , Linfócitos T CD4-Positivos , Glioblastoma , Linfócitos T Auxiliares-Indutores , Neoplasias Encefálicas/patologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Citometria de Fluxo , Glioblastoma/patologia , Humanos , Linfócitos do Interstício Tumoral/citologia , Linfócitos T Auxiliares-Indutores/citologiaRESUMO
Background: Brain metastases were considered to be well-defined lesions, but recent research points to infiltrating behavior. Impact of postoperative residual tumor burden (RTB) and extent of resection are still not defined enough. Patients and Methods: Adult patients with surgery of brain metastases between April 2007 and January 2020 were analyzed. Early postoperative MRI (<72 h) was used to segment RTB. Survival analysis was performed and cutoff values for RTB were revealed. Separate (subgroup) analyses regarding postoperative radiotherapy, age, and histopathological entities were performed. Results: A total of 704 patients were included. Complete cytoreduction was achieved in 487/704 (69.2%) patients, median preoperative tumor burden was 12.4 cm3 (IQR 5.2-25.8 cm3), median RTB was 0.14 cm3 (IQR 0.0-2.05 cm3), and median postoperative tumor volume of the targeted BM was 0.0 cm3 (IQR 0.0-0.1 cm3). Median overall survival was 6 months (IQR 2-18). In multivariate analysis, preoperative KPSS (HR 0.981982, 95% CI, 0.9761-0.9873, p < 0.001), age (HR 1.012363; 95% CI, 1.0043-1.0205, p = 0.0026), and preoperative (HR 1.004906; 95% CI, 1.0003-1.0095, p = 0.00362) and postoperative tumor burden (HR 1.017983; 95% CI; 1.0058-1.0303, p = 0.0036) were significant. Maximally selected log rank statistics showed a significant cutoff for RTB of 1.78 cm3 (p = 0.0022) for all and 0.28 cm3 (p = 0.0047) for targeted metastasis and cutoff for the age of 67 years (p < 0.001). (Stereotactic) Radiotherapy had a significant impact on survival (p < 0.001). Conclusions: RTB is a strong predictor for survival. Maximal cytoreduction, as confirmed by postoperative MRI, should be achieved whenever possible, regardless of type of postoperative radiotherapy.
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OBJECTIVE: The role of resection in progressive glioblastoma (GBM) to prolong survival is still controversial. The aim of this study was to determine 1) the predictors of post-progression survival (PPS) in progressive GBM and 2) which subgroups of patients would benefit from recurrent resection. METHODS: We have conducted a retrospective bicentric cohort study on isocitrate dehydrogenase (IDH) wild-type GBM treated in our hospitals between 2006 and 2015. Kaplan-Maier analyses and univariable and multivariable Cox regressions were performed to identify predictors and their influence on PPS. RESULTS: Of 589 patients with progressive IDH wild-type GBM, 355 patients were included in analyses. Median PPS of all patients was 9 months (95% CI 8.0-10.0), with complete resection 12 months (95% CI 9.7-14.3, n=81), incomplete resection 11 months (95% CI 8.9-13.1, n=70) and without resection 7 months (95% CI 06-08, n=204). Multivariable Cox regression demonstrated a benefit for PPS with complete (HR 0.67, CI 0.49-0.90) and incomplete resection (HR 0.73, 95% CI 0.51-1.04) and confirmed methylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene promoter, lower age at diagnosis, absence of deep brain and multilocular localization, higher Karnofsky Performance Status (KPS) and recurrent therapies to be associated with longer PPS. In contrast, traditional eloquence and duration of progression-free survival had no effect on PPS. Subgroup analyses showed that all subgroups of confirmed predictors benefited from resection, except for patients in poor condition with a KPS <70. CONCLUSIONS: Out data suggest a role for complete and incomplete recurrent resection in progressive GBM patients regardless of methylation of MGMT, age, or adjuvant therapy but not in patients with a poor clinical condition with a KPS <70.
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BACKGROUND: For recurrent glioblastoma (GB) patients, several therapy options have been established over the last years such as more aggressive surgery, re-irradiation or chemotherapy. Age and the Karnofsky Performance Status Scale (KPSS) are used to make decisions for these patients as these are established as prognostic factors in the initial diagnosis of GB. This study's aim was to evaluate preoperative patient comorbidities by using the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for recurrent GB patients. METHODS: In this retrospective analysis we could include 123 patients with surgery for primary recurrence of GB from January 2007 until December 2016 (43 females, 80 males, mean age 57 years (range 21-80 years)). Preoperative age, sex, ACCI, KPSS and adjuvant treatment regimes were recorded for each patient. Extent of resection (EOR) was recorded as a complete/incomplete resection of the contrast-enhancing tumor part. RESULTS: Median overall survival (OS) was 9.0 months (95% CI 7.1-10.9 months) after first re-resection. Preoperative KPSS > 80% (P < 0.001) and EOR (P = 0.013) were associated with significantly improved survival in univariate analysis. Including these factors in multivariate analysis, preoperative KPSS < 80 (HR 2.002 [95% CI: 1.246-3.216], P = 0.004) and EOR are the only significant prognostic factor (HR 1.611 [95% CI: 1.036-2.505], P = 0.034). ACCI was not shown as a prognostic factor in univariate and multivariate analyses. CONCLUSION: For patients with surgery for recurrent glioblastoma, the ACCI does not add further information about patient's prognosis besides the well-established KPSS and extent of resection.
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Neoplasias Encefálicas , Glioblastoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Comorbidade , Feminino , Glioblastoma/epidemiologia , Glioblastoma/cirurgia , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest. METHOD: Eighteen consecutive patients undergoing BM resection followed by immediate lex-IORT with 16-30 Gy applied to the spherical applicator were retrospectively analyzed. Demographic, RT-specific, radiographic and clinical data were reviewed to evaluate the effectiveness and safety of IORT for BM. Descriptive statistics and Kaplan-Meyer analysis were applied. RESULTS: The mean follow-up time was 10.8 months (range, 0-39 months). The estimated local control (LC), distant brain control (DBC) and overall survival (OS) at 12 months post IORT were 92.9% (95%-CI 79.3-100%), 71.4% (95%-CI 50.2-92.6%) and 58.0% (95%-CI 34.1-81.9%), respectively. Two patients developed radiation necrosis (11.1%) and wound infection (CTCAE grade III); both had additional adjuvant treatment after IORT. For five patients (27.8%), the time to the start or continuation of systemic treatment was ≤15 days and hence shorter than wound healing and adjuvant RT would have required. CONCLUSION: In accordance with previous series, this study demonstrates the effectiveness and safety of IORT in the management of brain metastases despite the small cohort and the retrospective characteristic of this analysis.
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OBJECTIVE: The exact role of the extent of resection or residual tumor volume on overall survival in glioblastoma patients is still controversial. Our aim was to create a statistical model showing the association between resection extent/residual tumor volume and overall survival and to provide a nomogram that can assess the survival benefit of individual patients and serve as a reference for non-randomized studies. METHODS: In this retrospective multicenter cohort study, we used the non-parametric Cox regression and the parametric log-logistic accelerated failure time model in patients with glioblastoma. On 303 patients (training set), we developed a model to evaluate the effect of the extent of resection/residual tumor volume on overall survival and created a score to estimate individual overall survival. The stability of the model was validated by 20-fold cross-validation and predictive accuracy by an external cohort of 253 patients (validation set). RESULTS: We found a continuous relationship between extent of resection or residual tumor volume and overall survival. Our final accelerated failure time model (pseudo R2 = 0.423; C-index = 0.749) included residual tumor volume, age, O6-methylguanine-DNA-methyltransferase methylation, therapy modality, resectability, and ventricular wall infiltration as independent predictors of overall survival. Based on these factors, we developed a nomogram for assessing the survival of individual patients that showed a median absolute predictive error of 2.78 (mean: 1.83) months, an improvement of about 40% compared with the most promising established models. CONCLUSIONS: A continuous relationship between residual tumor volume and overall survival supports the concept of maximum safe resection. Due to the low absolute predictive error and the consideration of uneven distributions of covariates, this model is suitable for clinical decision making and helps to evaluate the results of non-randomized studies.
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BACKROUND: Median overall survival (OS) after diagnosis of glioblastoma (GBM) remains 15 months amongst patients receiving aggressive surgical resection, chemotherapy and irradiation. Treatment of patients with a poor preoperative Karnofsky Performance Status Scale (KPSS) is still controversial. Therefore, we retrospectively assessed the outcome after surgical treatment in patients with a KPSS of ≤60%. METHODS: We retrospectively included patients with a de-novo glioblastoma WHO °IV and preoperative KPSS ≤60%, who underwent surgery at two neurosurgical centres between September 2006 and March 2016. We recorded pre- and postoperative tumour volume, pre- and postoperative KPSS, OS, age and MGMT promoter status. RESULTS: One hundred twenty-three patients (58 females/65 males, mean age 67.4 ± 13.4 years) met the inclusion criteria. Seventy-five of the 123 patients (61%) underwent surgical resection. 48/123 patients (39%) received a biopsy. The median preoperative and postoperative tumour volume of all patients was 33.0 ± 31.3 cm3 (IR 15.0-56.5cm3) and 3.1 ± 23.8 cm3 (IR 0.2-15.0 cm3), respectively. The median KPSS was 60% (range 20-60%) preoperatively and 50% (range 0-80%) postoperatively. Patients who received a biopsy showed a median OS for patients who received a biopsy only was 3.0 months (95% CI 2.0-4.0 months), compared to patients who had a resection and had a median OS of 8 months (95% CI 3.1-12.9 months). Age (p < 0.001, HR: 1.045 [95% CI 1.022-1.068]), postoperative tumour volume (p = 0.02, HR: 1.016 [95% CI 1.002-1.029]) and MGMT promotor status (p = 0.016, HR: 0.473 [95% CI 0.257-0.871]) were statistically significant in multivariate analysis. In subgroup analyses only age was shown as a significant prognostic factor in multivariate analyses for patients receiving surgery (p < 0.001, HR: 1.046 [95% CI 1.022-1.072]). In the biopsy group no significant prognostic factors were shown in multivariate analysis. CONCLUSION: GBM patients with a preoperative KPSS of ≤60% might profit from surgical reduction of tumour burden.
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Neoplasias Encefálicas , Glioblastoma , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/cirurgia , Feminino , Glioblastoma/cirurgia , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Carga TumoralRESUMO
Manifestation of malignant lymphoma in the spine is rare; there have only been a few cases reported in the literature. Due to its rarity, there is no gold standard for the management of patients suffering from spinal lymphoma manifestations. Methods: We retrospectively reviewed the data for 37 patients (14 female, 23 male) with malignant lymphoma in the spine receiving intervention in our center from March 2006 until June 2020. Neurological impairment, pain, diagnostics, and/or surgical instability were the criteria for surgery in this patient cohort. Otherwise, only CT-guided biopsies were conducted. Analysis of the patient cohort was based on the Karnofsky performance status scale (KPSS), location of the lesion, spinal levels involved, spinal instability neoplastic score (SINS), surgical treatment, histopathological workup, adjuvant therapy, and overall survival. The following surgical procedures were performed: posterior stabilization and decompression in nine patients; decompression and/or tumor debulking in 18 patients; a two-staged procedure with dorsal stabilization and vertebral body replacement in four patients; decompression and biopsy in one patient; a two-stage procedure with kyphoplasty and posterior stabilization for one patient; posterior stabilization without decompression for one patient; a vertebroplasty and cement-augmented posterior stabilization for one patient; and a CT-guided biopsy alone for two patients. Twenty-one patients (56.78%) had ≥1 lesion in the thoracic spine, 10 patients (27.03%) had lesions in the lumbar spine, two patients had lesions in the cervicothoracic junction, two patients had lesions in the thoracolumbar junction, one patient had a lesion in the lumbosacral junction, and one patient had a lesion in the sacrum. The diagnoses of the histopathological workup were diffuse large B-cell lymphoma in 23 (62.16%) cases, indolent lymphoma in 11 (29.74%) cases, anaplastic T-cell lymphoma in one case (2.70%), T-cell lymphoma in one case (2.70%), and Burkitt lymphoma in one (2.70%) case. The median overall survival was 7.2 months (range 0.1-266.7 months). Pre- and postoperative KPSS scores were 70% (IQR 60-80%). Manifestation of malignant lymphomas in the spine is rare. Similar to the approach taken for spine metastases, a surgical intervention in cases of neurological impairment or manifest or potential instability is indicated, followed by chemoimmunotherapy and radiotherapy.
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Linfoma , Vértebras Torácicas , Feminino , Humanos , Vértebras Lombares , Linfoma/diagnóstico , Linfoma/terapia , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Resection of pure intraorbital tumors is challenging owing to the nearness of the optic apparatus. The objective of this article was to report our experience with different intraorbital tumors and discuss classic approaches and obstacles. METHODS: A retrospective case series of patients who underwent surgery for intraorbital tumors at a tertiary neurosurgical center between June 2007 and January 2020 was performed. RESULTS: The study included 34 patients (median age 58 years; range, 18-87 years; 55.9% [19/34] female, 44.1% [15/34] male). Preoperative proptosis was observed in 67.6% (23/34); visual impairment, in 52.9% (18/34); diplopia, in 41.2% (14/34); and ptosis, in 38.3% (13/34). Intraconal tumors were found in 58.8% (20/34). The most common lesions were cavernous hemangiomas in 26.5% (9/34) and metastases in 14.7% (5/34). Gross total resection rate was 73.5% (25/34). Planned biopsy was performed in 14.7% (5/34). Median follow-up time was 15.5 months (interquartile range: 0-113 months). Surgical approaches included supraorbital approach (23.5% [8/34]), pterional approach (52.9% [18/34]), lateral orbitotomy (14.7% [5/34]), transnasal approach (5.9% [2/34]), and combined transnasal approach/lateral orbitotomy (2.9% [1/34]). Excluding planned biopsies, gross total resection was achieved in 80.0% (12/15) with pterional approach, 100% (7/7) with supraorbital approach, 80.0% (4/5) with lateral orbitotomy, and 100% (1/1) with transnasal approach/lateral orbitotomy. Complication rate requiring surgical intervention was 11.8% (4/34). CONCLUSIONS: Considering the low operative morbidity and satisfactory functional outcome, gross total resection of intraorbital lesions is feasible. We support use of classic transcranial and transorbital approaches. More invasive and complicated approaches were not needed in our series.
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Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Resection of jugular foramen schwannomas (JFSs) with minimal cranial nerve (CN) injury remains difficult. Reoperations in this vital region are associated with severe CN deficits. METHODS: We performed a retrospective analysis at a tertiary neurosurgical center of patients who underwent surgery for JFSs between June 2007 and May 2020. We included nine patients (median age 60 years, 77.8% female, 22.2% male). Preoperative symptoms included hearing loss (66.6%), headache (44.4%), hoarseness (33.3%), dysphagia (44.4%), hypoglossal nerve palsy (22.2%), facial nerve palsy (33.3%), extinguished gag reflex (22.2%), and cerebellar dysfunction (44.4%). We observed Type A, B, C, and D tumors in 3, 1, 1, and 4 patients, respectively. A total of 77.8% (7/9) underwent a retrosigmoid approach, and 33.3% (3/9) underwent an extreme lateral infrajugular transcondylar (ELITE) approach. Gross total resection (GTR) was achieved in all cases. The rate of shunt-dependent hydrocephalus was 22.2% (2/9). No further complications requiring surgical intervention occurred during follow-up. The median follow-up time was 16.5 months (range 3-84 months). CONCLUSIONS: Considering the satisfying outcome, the GTR of JFSs is feasible in performing well-known skull base approaches. Additional invasive and complicated approaches were not needed. Radiosurgery may be an effective alternative for selected patients.
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PURPOSE: Combining imaging modalities has become an essential tool for assessment of tumor biology in glioblastoma (GBM) patients. Aim of this study is to understand how tumor cellularity and neovascularization are reflected in O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography ([18F] FET PET) and magnetic resonance imaging (MRI) parameters, including cerebral blood volume (CBV), fractional anisotropy (FA) and mean diffusivity (MD). METHODS: In this prospective cohort, 162 targeted biopsies of 43 patients with therapy-naïve, isocitrate dehydrogenase (IDH) wildtype GBM were obtained after defining areas of interest based on imaging parameters [18F] FET PET, CBV, FA and MD. Histopathological analysis of cellularity and neovascularization was conducted and results correlated to imaging data. RESULTS: ANOVA analysis showed a significant increase of CBV in areas with high neovascularization. For diffusion metrics, and in particular FA, a trend for inverse association with neovascularization was found. [18F] FET PET showed a significant positive correlation to cellularity, while CBV also showed a trend towards correlation with cellularity, not reaching significant levels. In contrast, MD and FA were negatively associated with cellularity. CONCLUSION: Our study confirms that amino acid PET and MR imaging parameters are indicative of histological tumor properties in glioblastoma and highlights the ability of multimodal imaging to assess tumor biology non-invasively.
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Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. The aim of this study was to identify chaperone- and immune-related biomarkers to improve prediction of outcome in glioblastoma. Depending on its intra- or extracellular localization the major stress-inducible heat shock protein 70 (Hsp70) fulfills different tasks. In the cytosol Hsp70 interferes with pro-apoptotic signaling pathways and thereby protects tumor cells from programmed cell death. Extracellular Hsp70 together with pro-inflammatory cytokines are reported to stimulate the expression of activatory NK cell receptors, recognizing highly aggressive human tumor cells that present Hsp70 on their cell surface. Therefore, intra-, extracellular and membrane-bound Hsp70 levels were assessed in gliomas together with activatory NK cell receptors. All gliomas were found to be membrane Hsp70-positive and high grade gliomas more frequently show an overexpression of Hsp70 in the nucleus and cytosol. Significantly elevated extracellular Hsp70 levels are detected in glioblastomas with large necrotic areas. Overall survival (OS) is more favorable in patients with low Hsp70 serum levels indicating that a high Hsp70 expression is associated with an unfavorable prognosis. The data provide a first hint that elevated frequencies of activated NK cells at diagnosis might be associated with a better clinical outcome.
RESUMO
The aim of this study was to assess pre- and postoperative cognitive functions in patients who underwent surgery for benign intracranial lesions. In total, 58 patients (21 men, 37 women, mean age 51.6 years [range 24-76 years]) with benign intracranial lesions (including benign tumors and vascular lesions) and neuralgia of the trigeminal nerve were included in this prospective study. Extensive cognitive testing was used to categorize attention, memory, and executive functions. Mood and pain were assessed preoperatively (t0, mean 3.7 days before surgery), immediately after surgery/during inpatient stay (t1, mean 7.6 days after surgery), and at first outpatient check-up (t2, mean 99.5 days after surgery). All 58 patients were tested at t0 and t1, but at t2 only 24 patients were available at t2. The data were categorized as improvement/stable condition or deterioration and shown as percentages. The pre- and postoperative values of BDI-II and mood were compared by the Wilcoxon test for paired samples. Binary logistic regression analyses were performed to identify parameters influencing cognition in the subgroup of meningioma patients. Immediately after surgery (t1), the percentage of patients with improvement/stable condition was > 50% in all categories in the majority of subtests (attention: 12/14 subtests, memory: 11/13 subtests, executive functions: 6/9 subtests). Similar results were shown at t2. Mood and pain did not change significantly after surgery. Factors like age, Karnofsky performance status, and tumor volume were not shown as significant influencing factors for cognitive functions in meningioma patients. The results of this study suggest that-in contrast to neuroepithelial tumors-cognitive functions do not deteriorate after surgery of benign intracranial lesions. Further studies are necessary to evaluate the results of this study.