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The aim of this case series was to provide a modern cohort of patients with cerebral aspergillosis and show the effectiveness of modern treatment concepts. In a 10-year period from January 2009 to January 2019, we identified 10 patients (6 male, 4 female) who received surgery or frameless stereotactic drainage of a cerebral aspergilloma at our center. Patients' and disease characteristics were recorded. The median age was 65 (range 45 to 83). We conducted 133 cranial surgeries in 100 patients due to cerebral brain abscess (BA) during that time, which leads to a percentage of 10% of aspergilloma within BAs in our patient sample. We performed 3.1 surgeries per patient followed by antifungal treatment for 6 months (= median) according to the microbiological findings. Regarding comorbidities, the mean Charlson comorbidity index (CCI) at the time of admission was 5, representing an estimated 10-year survival of 21%. Six (60%) of 10 patients showed conditions of immunosuppression, one suffered endocarditis after replacement of aortic valves. Four patients showed associated frontobasal bone destruction, mycotic aneurysms, or thromboses. The mean duration of hospital stay was 37 days. Mortality was much lower than in literature. Sixty percent of the patients died during the follow-up period. The outcome of the two immunocompetent patients was more favorable. Cerebral aspergillosis is a rare, but still life-threatening, condition, which predominantly occurs in immunosuppressive conditions. Due to radical surgical and antifungal therapy for several months, mortality can be reduced dramatically.
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Encéfalo , Micoses , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Intraventricular neuroepithelial tumors (IVT) are rare lesions and comprise different pathological entities such as ependymomas, subependymomas and central neurocytomas. The treatment of choice is neurosurgical resection, which can be challenging due to their intraventricular location. Different surgical approaches to the ventricles are described. Here we report a large series of IVTs, its postoperative outcome at a single tertiary center and discuss suitable surgical approaches. METHODS: We performed a retrospective chart review at a single tertiary neurosurgical center between 03/2009-05/2019. We included patients that underwent resection of an IVT emphasizing on surgical approach, extent of resection, clinical outcome and postoperative complications. RESULTS: Forty five IVTs were resected from 03/2009 to 05/2019, 13 ependymomas, 21 subependymomas, 10 central neurocytomas and one glioependymal cyst. Median age was 52,5 years with 55.6% (25) male and 44.4% (20) female patients. Gross total resection was achieved in 93.3% (42/45). 84.6% (11/13) of ependymomas, 100% (12/21) of subependymomas, 90% (9/10) of central neurocytomas and one glioependymal cyst were completely removed. Postoperative rate of new neurological deficits was 26.6% (12/45). Postoperative new permanent cranial nerve deficits occurred in one case with 4th ventricle subependymoma and one in 4th ventricle ependymoma. Postoperative KPSS was 90% (IR 80-100). 31.1% of the patients improved in KPSS, 48.9% remained unchanged and 20% declined. Postoperative adverse events rate was 20.0%. Surgery-related mortality was 2.2%. The rate of shunt/cisternostomy-dependent hydrocephalus was 13.3% (6/45). 15.4% of resected ependymomas underwent adjuvant radiotherapy. Mean follow-up was 26,9 (±30.1) months. CONCLUSION: Our surgical findings emphasize satisfactory complete resection throughout all entities. Surgical treatment can remain feasible, if institutional experience is given. Satisfying long-term survival and cure is possible by complete removal. Gross total resection should always be performed under function-remaining aspects due to mostly benign or slow growing nature of IVTs. Further data is needed to evaluate standard of care and alternative therapy options in rare cases of tumor recurrence or in case of patient collective not suitable for operative resection.
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Neoplasias do Ventrículo Cerebral/cirurgia , Neoplasias Neuroepiteliomatosas/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
PURPOSE: To investigate the in vivo correlation between 18F-fluoroethyl-tyrosine (18F-FET) uptake and amino acid transporter expression and vascularization in treatment-naive glioblastomas. METHODS: A total of 43 stereotactic biopsies were obtained from 13 patients with suspected glioblastoma prior to therapy. All patients underwent a dynamic 18F-FET PET/MRI scan before biopsy. Immunohistochemistry was performed using antibodies against SLC7A5 (amino acid transporter), MIB-1 (Ki67, proliferation), CD31 (vascularization) and CA-IX (hypoxia). The intensity of staining was correlated with 18F-FET uptake and the dynamic 18F-FET uptake slope at the biopsy target point. RESULTS: In all patients, the final diagnosis was IDH-wildtype glioblastoma, WHO grade IV. Static 18F-FET uptake was significantly correlated with SLC7A5 staining (r = 0.494, p = 0.001). While the dynamic 18F-FET uptake slope did not show a significant correlation with amino acid transporter expression, it was significantly correlated with the number of CD31-positive vessels (r = -0.350, p = 0.031), which is line with earlier results linking 18F-FET kinetics with vascularization and perfusion. Besides, static 18F-FET uptake also showed correlations with CA-IX staining (r = 0.394, p = 0.009) and CD31 positivity (r = 0.410, p = 0.006). While the correlation between static 18F-FET uptake and SLC7A5 staining was confirmed as significant in multivariate analysis, this was not the case for the correlation with CD31 positivity, most likely because of the lower effect size and the relatively low number of samples. No significant correlation between 18F-FET uptake and Ki67 proliferation index was observed in our cohort. CONCLUSION: Our results support the findings of preclinical studies suggesting that specific 18F-FET uptake in glioblastomas is mediated by amino acid transporters. As proposed previously, dynamic 18F-FET parameters might be more influenced by perfusion and therefore related to properties of the tumour neovascularization.
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Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Tirosina/análogos & derivados , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Transportador 1 de Aminoácidos Neutros Grandes/genética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Neovascularização Patológica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Ligação Proteica , Tirosina/farmacocinéticaRESUMO
Although Schwann cell-derived tumors show typical histological features, the broad variety of spindle cell tumors that exist can impede the diagnostic procedure. In this study, we present aldehyde dehydrogenase 1 (ALDH1) as a new, viable diagnostic marker for Schwann cell tumors. Protein expression was examined by immunohistochemistry in schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (MPNST) as well as in non-neoplastic peripheral nerve sheath specimens. Meningiomas and other spindle cell-like tumors served as control tissue. ALDH1 immunohistochemistry was performed on human FFPE samples. Staining evaluation was performed according to a defined immunoreactive score. All schwannomas and neurofibromas were strongly positive for ALDH1. MPNST were positive too, but with a clear reduction of ALDH1 expression. All non-Schwann-cell-derived tumors showed no immunoreaction. This leads to the conclusion that ALDH1 can serve a as viable diagnostic marker for schwannomas and neurofibromas as it was expressed and detected by IHC in all samples. Furthermore, ALDH1 expression seems to be a sign for differentiation as it diminishes during malignization of Schwann cell tumors. Hence, its expression level provides information about the biological behavior of the tumor.
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Família Aldeído Desidrogenase 1/metabolismo , Biomarcadores Tumorais/análise , Neurilemoma/patologia , Células de Schwann/metabolismo , Adulto , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico , Meningioma/patologia , Neoplasias de Bainha Neural/diagnóstico , Neoplasias de Bainha Neural/patologia , Neurilemoma/diagnóstico , Neurofibroma/patologiaRESUMO
PURPOSE: The aim of this study is to investigate the association between postoperative tumor volume and overall survival (OS) of O6-methylguanine DNA methyltransferase (MGMT)-unmethylated glioblastoma patients. METHODS: One hundred-twenty-six patients with MGMT-unmethylated glioblastoma who were treated either with surgical resection or needle biopsy between 2006 and 2015 were included in this retrospective cohort. Pre- and postcontrast T1 weighted images were evaluated in order to determine pre- and postoperative contrast-enhancing tumor volumes (CE-TV). Cox regression models adjusted for other significant prognostic factors were used to investigate the association between postoperative tumor volume and survival. RESULTS: Complete resection of CE-TV was significantly associated with longer OS in the univariate analysis (HR 0.61; 95% CI 0.40-0.94; p = 0.02). However, this fact could not be confirmed after adjusting the model for other relevant prognostic factors (HR 1.01; 95% CI 0.65-1.55; p = 0.962). Postoperative CE-TV was significantly associated with survival in both univariate (HR: 1.04; 95% CI 1.025-1.055; p < 0.001) and multivariate analyses (HR: 1.027; 95% CI 1.005-1.049; p = 0.014). CONCLUSIONS: Although complete resection of tumor tissue was not significantly associated with longer OS in MGMT-unmethylated GBM patients, maximum safe resection should always be attempted, since postoperative tumor volume is strongly associated with OS.
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Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/mortalidade , Glioblastoma/patologia , Neurocirurgia/métodos , Complicações Pós-Operatórias , Proteínas Supressoras de Tumor/genética , Feminino , Seguimentos , Glioblastoma/genética , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Gliomas are primary brain tumors that present the majority of malignant adult brain tumors. Gliomas are subdivided into low- and high-grade tumors. Despite extensive research in recent years, the prognosis of malignant glioma patients remains poor. This is caused by naturally highly infiltrative capacities as well as high levels of radio- and chemoresistance. Additionally, it was shown that low linear energy transfer (LET) irradiation enhances migration and invasion of several glioma entities which might counteract today's treatment concepts. However, this finding is discussed controversially. In the era of personalized medicine, this controversial data might be attributed to the patient-specific heterogeneity that ultimately could be used for treatment. Thus, current developments in glioma therapy should be seen in the context of intrinsic and radiation-enhanced migration and invasion. Due to the natural heterogeneity of glioma cells and different radiation responses, a personalized radiation treatment concept is suggested and alternative radiation concepts are discussed.
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OBJECTIVE: Malignant peripheral nerve sheath tumors are infiltrating, aggressive tumors that are soft tissue sarcomas. This article describes 3 patients with a tumorous swelling in the entire inferior alveolar nerve suspicious for malignant peripheral nerve sheath tumor, which is particularly rare in the trigeminal nerve. Diagnostic tools, surgical proceedings, and reconstructive procedures are presented. METHODS: Three male patients (age range, 58-68 years) with numbness, pain, and mild swelling in the sensory area served by the mental nerve presented to the Department of Oral and Maxillofacial Surgery and underwent diagnostic work-up including computed tomography, magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography/computed tomography, and biopsy of the clinically visible tumor mass with histopathologic and molecular pathologic analysis. RESULTS: Magnetic resonance imaging revealed the full extent of the tumor comprising the course of the entire mandibular nerve (1 case bilateral) starting in the trigeminal ganglion through the inferior alveolar nerve and ending in the mental foramen. Both a neurosurgical and a maxillofacial intervention with jaw replacement were necessary. Adjuvant radiation of intracranial closed resection margins and, in 1 case, of parts of the mandible was required. CONCLUSIONS: To reveal the full extent of tumor spread of malignant peripheral nerve sheath tumors, sufficient preoperative imaging is crucial, as it is an important step in therapy planning. Magnetic resonance imaging and positron emission tomography/computed tomography have the best prospect of success in depicting the full extent of disease. Radical surgical management is the treatment of choice, whereas radiochemotherapy has an ancillary part.
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Nervo Mandibular/fisiologia , Neoplasias de Bainha Neural/patologia , Neoplasias do Sistema Nervoso Periférico/patologia , Idoso , Humanos , Imageamento por Ressonância Magnética , Masculino , Nervo Mandibular/cirurgia , Pessoa de Meia-Idade , Neoplasias de Bainha Neural/cirurgia , Neoplasias do Sistema Nervoso Periférico/cirurgiaRESUMO
Glycosylation is one of the most important posttranslational modifications of proteins and lipids that contributes to the structural diversity of cellular molecules. Enzymes of the glycosyltransferase class are responsible for altering glycosylation patterns by adding carbohydrate chains to the respective acceptor molecules. It is well known that glycosylation is commonly altered in cancerous tissue. Therefore, the present study aimed to determine the incidence of Nacetylgalactosaminyltransferase 6 (GALNT6), a prominent member of the glycosyltransferase class, in breast cancer tissue of different developmental stages by immunohistochemistry. Although no correlation was identified between tumour characteristics and GALNT6 staining intensity, to the best of our knowledge, this is the first study to demonstrate that tissue from carcinoma in situtumours and metastases were more heavily stained than latestage breast cancers. This may indicate an important role of glycosylation aberration in escaping the immune system at early phases of tumour development. The present study also hypothesised that nascent or early metastasizing tumours are normally recognized by the immune system of the patient, but glycosylation pattern changes may facilitate tumor escape from immune recognition. In followup studies, our group will aim to confirm and consolidate these results in a larger patient cohort that may give greater insight into breast cancer characterization as well as tumour treatment.
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Neoplasias da Mama/enzimologia , Transformação Celular Neoplásica/metabolismo , N-Acetilgalactosaminiltransferases/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Transformação Celular Neoplásica/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
BACKGROUND: Glycosylation is the most frequent posttranslational modification of proteins and lipids influencing inter- and intracellular communication and cell adhesion. Altered glycosylation patterns are characteristically observed in tumour cells. Normal and altered carbohydrate chains are transferred to their acceptor structures via glycosyltransferases. Here, we present the correlation between the presence of three different glycosyltransferases and tumour characteristics. METHODS: 235 breast cancer tissue samples were stained immunohistochemically for the glycosyltransferases N-acetylgalactosaminyltransferase 6 (GALNT6), ß-1,6-N-acetylglucosaminyltransferase 2 (GCNT2), and ST6 (α-N-acetyl-neuraminyl-2,3-ß-galactosyl-1,3)-N-acetylgalactosamine α-2,6-sialyltransferase 1 (ST6GALNac1). Staining was evaluated by light microscopy and was correlated to different tumour characteristics by statistical analysis. RESULTS: We found a statistically significant correlation for the presence of glycosyltransferases and tumour size and grading. Specifically smaller tumours with low grading revealed the highest incidences of glycosyltransferases. Additionally, Her4-expression but not pHer4-expression is correlated with the presence of glycosyltransferases. All other investigated parameters could not uncover any statistically significant reciprocity. CONCLUSION: Here we show, that glycosyltransferases can identify small tumours with well-differentiated cells; hence, glycosylation patterns could be used as a marker for early tumourigenesis. This assumption is supported by the fact that Her4 is also correlated to glycosylation, whereas the activated form of Her4 does not show such a connection with glycosylation.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Glicosiltransferases/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-MeierRESUMO
Altered glycosylation is a predominant feature of tumour cells; it serves for cell adhesion and detachment, respectively, and facilitates the immune escape of these cells. Therefore changes in the expression of glycosyltransferase genes could help to identify circulating tumour cells (CTCs) in the blood samples of cancer patients using a quantitative polymerase chain reaction (PCR) approach. Blood samples of healthy donors were inoculated with certain numbers of established breast cancer cell line cells, thus creating a model system. These samples were analysed by quantitative PCR for the expression of six different glycosyltransferase genes. The three genes with the best results in the model system were consecutively applied to samples from adjuvant breast cancer patients and of healthy donors. FUT3 and GALNT6 showed the highest increase in relative expression, while GALNT6 and ST3GAL3 were the first to reach statistically significant different ∆CT-values comparing the sample with and without addition of tumour cells. These three genes were applied to patient samples, but did not show any significant results that may suggest the presence of CTCs in the blood. Although the relative expression of some of the glycosyltransferase genes exhibited reasonable results in the model system, their application to breast cancer patient samples will have to be further improved, e.g. by co-analysis of patient blood samples by gold-standard methods.