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BACKGROUND AND OBJECTIVES: Cavernous malformations (CMs) occurring in the cranial nerve (CN) are extremely rare, and there is currently no comprehensive review on CN CMs, leading to a lack of sufficient understanding of CN CMs. We aimed to systematically review all published CN CM cases; summarize the epidemiology, clinical manifestations, treatment, and prognosis of CN CMs; and identify factors influencing the prognosis of CN CMs. METHODS: This systematic review identified all cases potentially diagnosed with CN CM through a systematic search of PubMed, SCOPUS, Web of Science, and Cochrane databases. This represents the most comprehensive systematic review to date. We classified CN CMs based on their anatomic origins. Patient characteristics, disease manifestations, treatment approaches, and prognosis were summarized descriptively. Further analysis was conducted to identify factors influencing the prognosis of CN CMs. RESULTS: The final analysis included 108 articles (127 individual patient cases). The optic nerve (49/128, 38.3%) is the most commonly affected nerve. Notably, CN CMs can be categorized into 3 types: Intraneural, Perineural, and Extraneural. Preoperative nerve function status and novel classification were associated with the prognosis of CN CMs (P = .001; P < .001). The postoperative neurological deterioration rate for the Intraneural type was 19/37 (51.4%); for the Extraneural type, it was 13/69 (18.8%); and for the Perineural type, it was 1/22 (4.5%) (P < .001). CONCLUSION: We reviewed all the published CN CMs to date, offering a comprehensive description of CN CMs for the first time and identifying prognostic factors. The classification of CN CMs proposed in this study could serve as guidance for the selection of intraoperative treatment regimens. The findings of this systematic review are expected to provide a foundation for clinical decision-making in this crucial rare disease and lay the groundwork for developing relevant clinical guidelines.
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Background: Lung adenocarcinoma (LUAD) is the most common form of lung cancer and is often accompanied by brain metastasis (BM). The heterogeneity of the tumor renders all current conventional treatments less effective. This study aims to dissect tumor cell heterogeneity and identify potential therapeutic targets. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) in 8 patients with treatment-naïve LUAD BM and included scRNA-seq data of 10 primary LUAD samples and their matched adjacent normal tissue from GSE131907 to determine the tumor cell heterogeneity. Results: Our analyses revealed tumor cells derived from brain metastases were more heterogeneous. Tumor cells from BM harbored significantly more copy number variants (CNVs), and cells of magnoid subtype were the critical source of malignant cells both in BM and the primary lung tumor. Pseudo-time trajectory analysis revealed that malignant cells had upregulated genes enriched for cell cycle and cell division. Integrated analysis of tumor cells revealed 2 distinct malignant cell clusters (cluster 4 and cluster 6) and their marker genes. The signatures identified in the single-cell profile had prognostic value in the bulk tumor profiles. Moreover, the signature of cluster 4 had significant prognostic value in predicting patients surviving longer than 3.5 years, while the signature of cluster 6 showed better predictive ability within 1 year. Magnoid-type cells are most likely to develop into the riskiest cell type and potentially promote tumor progression. Conclusions: scRNA profiling that integrates LUAD BM and primary LUAD can provide information on those malignant cells with BM potential, offering additional prognostic information at cellular level, and may serve as a foundational resource for further tumor cell dissection and therapeutic target exploration.
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BACKGROUND: Laser interstitial thermal therapy (LITT) has been used to treat brain metastases (BMs) in several countries, and its safety and effectiveness have been confirmed. In most cases, magnetic resonance imaging (MRI) reveals an increase in tumor volume with an enhanced margin after LITT. However, little is known about the relationship between this MRI change and tumor recurrence. OBJECTIVE: We report the first case series of BMs treated by LITT in China to evaluate the clinical characteristics and predictive factors of tumor recurrence. MATERIAL AND METHODS: Patients with less than four brain metastatic lesions and a Karnofsky performance status (KPS) > 70 were eligible for study inclusion. Standard LITT procedures were performed, and a follow-up MRI was performed to analyze the radiographic changes, especially the volume ratio of the enhanced margin and the whole lesion on MRI at 30 days postoperatively. All the volume-related data were delineated and calculated using 3D Slicer software. Related predictors were also collected to evaluate the correlation with local tumor control. RESULTS: Eighteen patients with nineteen lesions were enrolled for treatment and follow-up. Primary tumor histology included pulmonary carcinoma (n = 11) and breast cancer (n = 4). On average, the tumor size measured 3.01 cm3 (range, 0.40-7.40 cm3), the total ablation time was 13.58 min (range, 2.88-37.15 min), and the complete ablation rate was 92.4% (range, 29.2-100%). Comparing 3s0-day follow-up MRI results with preoperative MRI findings, 18 lesions showed a 2.28-fold (range, 1.21-4.88) volume increase; all the lesions displayed an enhanced component with a volume ratio of 42.35% (range, 10.14-100%). Five patients experienced tumor recurrence, and the local tumor control rates at 90 days and 180 days of follow-up were 68.4% and 66.7%, respectively. Univariate analysis indicated that the primary tumor, ablation rate, and enhanced volume ratio (EVR) > 40% in the 30-day MRI were associated with tumor recurrence, whereas multivariate analysis showed that only EVR > 40% was a predictive factor of local control. CONCLUSION: LITT is a minimally invasive method used to ablate brain metastases which can be used as the first-line treatment for BM patients under certain indications. After LITT, most tumors showed volume enlargement on the 30-day MRI scan, and EVR > 40% on the 30-day MRI may indicate late tumor recurrence.
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Neoplasias Encefálicas , Terapia a Laser , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/etiologia , Terapia a Laser/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Imageamento por Ressonância Magnética/métodos , Lasers , Resultado do TratamentoRESUMO
BACKGROUND: Gonadotrophic pituitary adenoma is a major subtype of pituitary adenoma in the sellar region, but it is rarely involved in the hypersecretion of hormones into blood; thus, it is commonly regarded as "non-functioning." Its tumorigenic mechanisms remain unknown. The aim of this study was to identify human gonadotrophic pituitary adenoma stem cells (hPASCs) and explore the underlying gene expression profiles. In addition, the potential candidate genes involved in the invasive properties of pituitary adenoma were examined. METHODS: The hPASCs from 14 human gonadotrophic pituitary adenoma clinical samples were cultured and verified via immunohistochemistry. Genetic profiling of hPASCs and the matched tumor cells was performed through RNA-sequencing and subjected to enrichment analysis. By aligning the results with public databases, the candidate genes were screened and examined in invasive and non-invasive gonadotrophic pituitary adenomas using Real-time polymerase chain reaction. RESULTS: The hPASCs were successfully isolated and cultured from gonadotrophic pituitary adenoma in vitro, which were identified as positive for generic stem cell markers (Sox2, Oct4, Nestin and CD133) via immunohistochemical staining. The hPASCs could differentiate into the tumor cells expressing follicle-stimulating hormone in the presence of fetal bovine serum in the culture medium. Through RNA-sequencing, 1352 differentially expressed genes were screened and identified significantly enriched in various gene ontologies and important pathways. The expression levels of ANXA2, PMAIP1, SPRY2, C2CD4A, APOD, FGF14 and FKBP10 were significantly upregulated while FNDC5 and MAP3K4 were downregulated in the invasive gonadotrophic pituitary adenomas compared to the non-invasive ones. CONCLUSION: Genetic profiling of hPASCs may explain the tumorigenesis and invasiveness of gonadotrophic pituitary adenoma. ANXA2 may serve as a potential therapeutic target for the treatment of gonadotrophic pituitary adenoma.
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Adenoma , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/metabolismo , Perfilação da Expressão Gênica , Análise em Microsséries , Adenoma/genética , Células-Tronco/metabolismo , RNA , Proteínas de Membrana/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , FibronectinasRESUMO
Pituitary adenomas in Knosp grade 4 are difficult to resect completely and are generally involved in poor prognosis, because of the close relationship between the tumor and internal carotid. In this study, the authors retrospectively reviewed the outcome of different transcranial approaches in the management of large-to-giant pituitary adenomas in Knosp grade 4. A total of 42 patients with large-to-giant pituitary adenomas in Knosp grade 4, who underwent craniotomy in the Pituitary Disease Subdivision, Department of Neurosurgery, Beijing Tiantan Hospital, between March 2012 and March 2015 were included in this study. Clinical characteristics, surgical methods, complications, and outcomes were evaluated. The median age was 45 years (range, 19-73 years old), and 42.9% of the enrolled cases were men. The mean tumor diameter was 43.6 mm, and the mean volume was 30.9 cm3. 26 patients underwent the frontolateral approach, while 16 cases accepted the frontotemporal approach. Gross total resection was achieved in 11 patients (26.2%), near total in 26 (61.9%), and subtotal in 5 (11.9%). The adenomas were larger, and the distance of the tumor extending to the lateral skull base was also further in the frontotemporal approach cases. The surgical time was shorter, and the bleeding volume was less in the frontolateral approach cases. Subsellar extension was associated with incomplete resection in pituitary macroadenomas of Knosp grade 4. The craniotomy is still an effective treatment for pituitary macroadenomas in Knosp grade 4.
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Adenoma , Neoplasias Hipofisárias , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Objectives: To explore the effectiveness and safety of the combined application of sodium fluorescein and neuronavigation techniques in the resection of brain gliomas in different locations and patients of different ages. Methods: Fifty clinical cases of brain gliomas treated at the Department of Neurosurgery of Beijing Tiantan Hospital were collected from March 2014 to March 2019. These cases were divided into a supratentorial group (24 cases) and a brainstem group (26 cases) based on location and an adult group (28 cases) and a pediatric group (22 cases) based on age. Fluorescein-guided surgery was performed: the adult group received 5 mg/kg sodium fluorescein before opening the dura, while the pediatric group received 2.5 mg/kg during resection. Tumor visualization was evaluated by the enhancement of yellow fluorescein and considered "satisfactory" if the illumination demarcated the tumor boundary. Additionally, the consistency between fluorescein and neuronavigation was analyzed. The Karnofsky performance score (KPS) of all patients was recorded and assessed at admission, discharge, and the 6-month follow-up. Results: In the 28 adult cases, 4 were unsatisfactory, while in the 22 pediatric cases, 2 were unsatisfactory; in 7 cases, there was an inconsistency between yellow fluorescein enhancement and neuronavigation, 6 were in the supratentorial group, and 1 was in the brainstem group. Statistical analysis showed no significant differences in the satisfactory rate between the adult and pediatric groups (P = 0.575), whereas there were significant differences inconsistency between the supratentorial group and brainstem group (P = 0.031). The mean KPS at admission was between 70 and 100, which was not significantly different from that at discharge (P = 0.839), but the KPS at the 6-month follow-up was significantly higher than that at admission (P = 0.041). Conclusions: The consistency between sodium fluorescein and the neuronavigation system was higher in the brainstem group than in the supratentorial group; a half dose of sodium fluorescein (2.5 mg/kg) was sufficient for pediatric patients. The combined utilization of sodium fluorescein and neuronavigation techniques may confer glioma patients the opportunity to obtain better clinical outcomes after surgery.
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PURPOSE: The aim of this study was to investigate an imaging biomarker based on contrast enhanced T1-weighted and T2-weighted magnetic resonance imaging (MRI) to determine the hearing loss related to acoustic neuromas (AN). METHODS: In this retrospective study, 441 acoustic neuromas treated with microsurgery were included. The diagnostic and follow-up MRI and audiometry of these patients were compared. RESULTS: We discovered a new MRI grading biomarker based on the percentage of tumor filling the inner auditory canal (TFIAC classification). The area under the receiver operating characteristics (AUROC) curve was highest for TFIAC (0.675), followed by period of observation (0.615) and tumor size (0.6) (Pâ¯< 0.001). The percentage of patients in TFIAC grade III (90.1%) experiencing hypoacusis prior to microsurgery was significantly higher than that in TFIAC grade I (72.7%, Pâ¯= 0.037) and TFIAC grade IV patients had a higher rate of non-serviceable hearing compared to TFIAC grade III patients (Pâ¯< 0.001). During the follow-up, TFIAC grade IV patients experienced a significantly higher rate of non-serviceable hearing than TFIAC grade III patients in all ANs (Pâ¯< 0.001) and in serviceable hearing acoustic neuroma cases prior to surgery (TFIAC grade IV 55.4%, TFIAC grade III 69.0%, Pâ¯= 0.045). The TFIAC grade IV patients experienced a significantly higher rate of facial nerve dysfunction than TFIAC grade III patients after surgery (grade IV 48.0%, grade III 26.1%, Pâ¯< 0.001). CONCLUSION: The TFIAC classification serves as a potential imaging biomarker for preoperative and postoperative hearing prediction in ANs, which may aid neurosurgeons in predicting hearing loss and selecting optimal surgical strategies.
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Perda Auditiva , Neuroma Acústico , Biomarcadores , Perda Auditiva/diagnóstico por imagem , Humanos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSES: Immunotherapies for solid tumor are gaining traction in the clinic, however, the immunological landscape of pituitary adenomas (PAs) is not well defined. In the present study, we used the RNA-seq data of PAs to investigate the impact of immunological landscape on clinical features of pituitary adenomas and aim to evaluate the potential immunotherapy for PAs. METHODS: We analyzed tumor-infiltrating immune cells in 115 PA samples using RNA-seq. Main immune cell types (B cells, CD8+ T cells, CD4+ T cells, macrophages and NK cells) were detected from the expression of genes. The association between immune cells abundance and immune checkpoint, as well as inflammatory factors were analyzed. 10 additional patients were enrolled for validation. RESULTS: In RNA sequencing data, landscape of PAs were identified. Our computationally inferred immune infiltrates significantly associate with patient clinical features. Growth hormone-secreting adenomas (GHomas) were found with higher B cells and CD8+ T cells infiltration. Moreover, GHomas showed relative different genetic background, significant invasive behavior and independently correlated with reduced progress-free time. Tumor progression was related to increased expression of PD-1/PD-L1 and was associated with higher immune infiltration. Analysis of cancer-testis antigen expression and CD8+ T-cell abundance suggested CTAG2 and TSPYL6 were potential immunotherapeutic targets in GHomas and non-functioning adenomas, respectively. CONCLUSIONS: Tumor-infiltrating immune cells confer important clinical and biological implications. Our results of immune-infiltrate levels in PAs may inform effective cancer vaccine and checkpoint blockade therapies and make it possible to take immunotherapy into invasive PAs.
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Adenoma/imunologia , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/imunologia , Regulação Neoplásica da Expressão Gênica , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Hipofisárias/imunologia , Adenoma/genética , Adenoma/patologia , Adulto , Biomarcadores Tumorais/imunologia , Feminino , Seguimentos , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Prognóstico , Estudos Retrospectivos , Análise de Sequência de RNARESUMO
The controversy of adjuvant radiotherapy of meningiomas is at least partially due to the insufficient understanding on meningioma cells' response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in meningiomas has yet to be confirmed. Therefore, the malignant meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors, and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo. Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression, and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee's radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for malignant meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.
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Glioblastoma (GBM) is one of the most common aggressive cancers of the central nervous system in adults with a high mortality rate. Bortezomib is a boronic acid-based potent proteasome inhibitor that has been actively studied for its anti-tumour effects through inhibition of the proteasome. The proteasome is a key component of the ubiquitin-proteasome pathway that is critical for protein homeostasis, regulation of cellular growth, and apoptosis. Overexpression of polo-like kinase 4 (PLK4) is commonly reported in tumour cells and increases their invasive and metastatic abilities. In this study, we established a cell model of PLK4 knockdown and overexpression in LN-18, A172 and LN-229 cells and found that knockdown of PLK4 expression enhanced the anti-tumour effect of bortezomib. We further found that this effect may be mediated by the PTEN/PI3K/AKT/mTOR signalling pathway and that the apoptotic and oxidative stress processes were activated, while the expression of matrix metalloproteinases (MMPs) was down-regulated. Similar phenomenon was observed using in vitro experiments. Thus, we speculate that PLK4 inhibition may be a new therapeutic strategy for GBM.
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Bortezomib/farmacologia , Proliferação de Células/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Proteínas Serina-Treonina Quinases/genética , Animais , Apoptose/efeitos dos fármacos , Ácidos Borônicos/farmacologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Xenoenxertos , Humanos , Camundongos , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Inibidores de Proteassoma/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genéticaRESUMO
BACKGROUND: Intracranial fibrosarcoma is an extremely rare neoplasm in the central nervous system. Insofar there were only sporadic case reports describing its features. The purpose of this study is to review the clinical and surgical features of cases who were treated in our department. METHOD: The authors retrospectively reviewed and detailed the clinical and surgical data obtained from 5 patients with fibrosarcoma who underwent treatment at our institute between January 2009 and January 2019. RESULTS: There were 3 males and 2 females including 2 juvenile and 3 senior patients. The most frequent sign was intermittent pain and vomiting. The location of the tumor included middle fossa, thalamus and midbrain, sellar and suprasellar region and right parietal-occipital lobe. Surgical observation demonstrated the consistency of the tumor was tenacious with abundant blood supply. Gross total resection was achieved in 2 cases. Pathological analysis showed spindle cells in a herringbone form with positive Vimentin staining in all 5 cases, with the absence of GFAP or S-100. All 5 patients were deceased eventually after a varied period of time after the first surgery. CONCLUSION: Intracranial fibrosarcoma was a highly malignant entity presented in the central nervous system. Surgery still remains the first-line treatment followed by radiotherapy, however, the prognostic outcome was very poor. Future studies should be more focused on accumulation of the relevant information on this disease thus hopefully in assisting to developing more optimized treatment.
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Fibrossarcoma/diagnóstico por imagem , Neoplasias Cranianas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Feminino , Fibrossarcoma/metabolismo , Fibrossarcoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/metabolismo , Lobo Occipital/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias Cranianas/metabolismo , Neoplasias Cranianas/cirurgia , Vimentina/metabolismo , Adulto JovemRESUMO
BACKGROUND: Ocular motor dysfunction is one of the most common postoperative complications of petroclival meningioma. However, its incidence, recovery rate, and independent risk factors remain poorly explored. METHODS: A prospective analysis of 31 petroclival meningiomas was performed. Operative approaches were selected by utilizing a new 6-region classification of petroclival meningiomas we proposed. Two scores were used to evaluate the functions of the oculomotor and abducens nerves. Pearson correlation analysis and binary logistic regression analysis were used to identify independent risk factors for intraoperative oculomotor and abducens nerve injury. RESULTS: Postoperative new-onset dysfunctions in the pupillary light reflex and eye/eyelid movements as well as abducens paralysis were detected in eight (25.8%), ten (32.3%) and twelve (38.7%) cases, respectively. Their corresponding recovery rates after 6 months of follow-up were 75% (6/8), 80% (8/10), and 83.3% (10/12), respectively, and their mean times to start recovery were 4.03, 2.43, and 2.5 months, respectively. Tumor invasion into the suprasellar region/sphenoid sinus was the only risk factor for dysfunctions in both the pupillary light reflex (p = 0.001) and eye/eyelid movements (p = 0.002). Intraoperative utilization of the infratrigeminal interspace was the only risk factor for dysfunction in eyeball abduction movement (p = 0.004). CONCLUSIONS: Dysfunctions of the oculomotor and abducens nerves recovered within 6 months postoperatively. Tumor extension into the suprasellar region/sphenoid sinus was the only risk factor for oculomotor nerve paralysis. Eye/eyelid movements were more sensitive than the pupillary light reflex in reflecting nerve dysfunctions. Intraoperative utilization of the infratrigeminal interspace was the only risk factor for abducens nerve paralysis.
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Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Traumatismos do Nervo Oculomotor/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Neoplasias da Base do Crânio/cirurgia , Nervo Abducente/patologia , Traumatismo do Nervo Abducente/etiologia , Traumatismo do Nervo Abducente/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Nervo Oculomotor/patologia , Traumatismos do Nervo Oculomotor/etiologia , Complicações Pós-Operatórias/etiologia , Reflexo PupilarRESUMO
Context: Primary spinal primitive neuroectodermal tumor (PNET) of the central nervous system has a low incidence. The intraspinal case is very rare. Around 30 cases have been reported so far. We summarized the cases of primary spinal PNET available in the database of our institute, either intramedullary or extramedullary cases. Then we did literature review of the same disease. Findings: There were eight cases of primary spinal PNET available in our database, with one intramedullary case and seven extramedullary cases. Surgical resection was performed. The histology diagnosis was PNET. Peri-operative image examinations of the whole central nervous system (CNS) were performed to exclude tumors other than spinal cord origin. Then during literature review, 33 reports of the disease were included. The pre-operative diagnosis rate was low. The disease had a high recurrence rate and poor prognosis given available treatment. Conclusion: Primary spinal primitive neuroectodermal tumor is of high malignancy. Little is known due to its quite low incidence. The prognosis is poor due to lacking of effective treatment strategy. Present treatment strategy is referred to other common CNS malignancies like glioma. Further investigation of the disease is necessary.
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Tumores Neuroectodérmicos Primitivos , Traumatismos da Medula Espinal , Neoplasias da Medula Espinal , Humanos , Tumores Neuroectodérmicos Primitivos/diagnóstico , Tumores Neuroectodérmicos Primitivos/epidemiologia , Tumores Neuroectodérmicos Primitivos/cirurgia , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/epidemiologia , Neoplasias da Medula Espinal/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the independent risk factors for recurrence in intracranial atypical meningiomas (AMs) treated with gross total resection (GTR) and early external beam radiotherapy (EBRT). METHODS: Clinical, radiological, and pathological data of intracranial AMs treated with GTR-plus-early-EBRT between January 2008 and July 2016 were reviewed. Immunohistochemical staining for Ki-67 was performed. Kaplan-Meier curves and univariate and multivariate Cox proportional hazards regression analyses were used to explore independent predictors of tumor recurrence. Chi square test was performed to compare variables between subgroups. RESULTS: Forty-six patients with intracranial AMs underwent GTR and early EBRT. Ten (21.7%) recurred and three (6.5%) died during a median follow-up of 76.00 months. Univariate and multivariate Cox analyses revealed that malignant progression (MP) (P = 0.009) was the only independent predictor for recurrence, while Ki-67 was of minor value in this aspect (P = 0.362). MP-AMs had a significantly higher recurrence rate (P = 0.008), a higher proportion of irregularly shaped tumors (P = 0.013) and significantly lower preoperative Karnofsky Performance Scale (KPS) scores (P = 0.040) than primary (Pri) AMs. No significant difference in Ki-67 expression was detected between these subgroups (P = 0.713). CONCLUSIONS: MP was significantly correlated with an increased incidence of recurrence in GTR-plus-early-EBRT-treated intracranial AMs. Significantly higher frequencies of tumor relapse and irregularly shaped tumors and lower preoperative KPS scores were observed in MP-AMs compared with Pri-AMs. Ki-67 expression is of minor value in predicting tumor recurrence or distinguishing tumor origins in AMs.
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OBJECTIVE: To develop a method to distinguish atypical meningiomas (AMs) with malignant progression (MP) from primary AMs without a clinical history. METHODS: The clinical, radiologic, and pathologic data of 33 previously Simpson grade I resected (if any) as well as no radiotherapy treated intracranial AMs between January 2008 and December 2015 were reviewed. Immunohistochemical staining for connexin 43 (Cx43) and Ki-67 was performed. Descriptive analysis and univariate and multivariate logistic regression analyses were used to explore independent predictors of MP. A multivariable logistic model was developed to estimate the risk of MP, and its diagnostic value was determined from a receiver operating characteristic curve. RESULTS: There were 11 AMs (33.3%) with histopathologically confirmed MP from benign meningiomas. The other 22 (66.7%) were initially diagnosed AMs with no histopathologically confirmed MP during a median 60.5 months (range, 42-126 months) of follow-up. Univariate and multivariate logistic analyses showed that irregular tumor shape (P = 0.010) and low Cx43 expression (P = 0.010) were independent predictors of the presence of MP, and the predicted probability was calculated by the following formula: P = 1/[1+exp.{1.218-(3.202×Shape)+(3.814×Cx43)}]. P > 0.5 for an irregularly shaped (score 1) AM with low Cx43 expression (score 0) indicated a high probability of MP. The sensitivity, specificity, positive predictive value, negative predictive value, and overall predictive accuracy were 63.6, 95.6, 87.5, 84.0, and 84.8%, respectively. CONCLUSIONS: Low Cx43 expression and irregular tumor shape were independent predictors of the presence of MP. The relevant logistic regression model was found to be effective in distinguishing MP-AMs from primary AMs.
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Modelos Logísticos , Neoplasias Meníngeas/patologia , Meningioma/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Conexina 43/biossíntese , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Lymphocytic hypophysitis (LYH) is a rare autoimmune inflammatory disease of the pituitary gland. In this study, we aim to characterize LYH at presentation and focus on the management and prognosis of LYH. METHODS: A retrospective study of patients with LYH was conducted between 2011 and 2018 at a single institute. The patients were included by pathologic conformation and strict exclusion criteria. Clinical profile, imaging, and management data were collected. RESULTS: Twenty patients with LYH (16 women and 4 men) were included. Ten patients were diagnosed histologically and the remaining 10 patients were confirmed clinically of exclusion criteria. The median age at diagnosis was 37 years (range, 16-58 years). Presenting symptoms were followed by polyuria/polydipsia (11, 55%), vision changes (10, 50%), headache (8, 40%), menstrual irregularities and amenorrhea (4, 20%), diplopia (1, 5%), or sexual dysfunction (1, 5%). Eight patients had partial anterior pituitary hormone dysfunction. The thyroid-stimulating hormone axis was most involved. Ten patients received transsphenoidal surgery, 5 patients experienced steroid pulse therapy, and observation was performed on 5 patients. Only 5 patients (25%) showed improvement of anterior pituitary dysfunction after initial management. Recovery of diabetes insipidus occurred in 2 patients (18%). The overall recurrence rate was 22.2%. CONCLUSIONS: Nonoperative treatment is a better option for most patients with LYH because it is effective and noninvasive. Surgery is recommended for definitive diagnosis, severe or rapid progression of neurologic impairment, and glucocorticoid insensitivity. Periodic follow-up is mandatory in a patient's long-term management.
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Hipofisite Autoimune/patologia , Imageamento por Ressonância Magnética , Neuroimagem , Adolescente , Adulto , Hipofisite Autoimune/complicações , Hipofisite Autoimune/diagnóstico por imagem , Hipofisite Autoimune/terapia , Terapia Combinada , Diabetes Insípido/etiologia , Diagnóstico Diferencial , Diplopia/etiologia , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Hemianopsia/etiologia , Terapia de Reposição Hormonal , Humanos , Hipofisectomia/métodos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Doenças da Hipófise/etiologia , Hormônios Hipofisários/sangue , Hormônios Hipofisários/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Primary intradiploic epidermoid cyst of the central nervous system (CNS) is a rare disease. More than 200 cases have been reported so far. The lesion can affect every flat bone of the cranium. The pre-operative diagnosis is always misleading. We reported a 61-year-old female with giant primary intradiploic epidermoid cyst in the parietal bone. Surgical resection was performed. The patient recovered well with no complication nor neurologic dysfunction. A literature review of the disease will also be presented here.â©.
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Doenças Ósseas/patologia , Cisto Epidérmico/patologia , Osso Parietal/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Dysplastic gangliocytoma of the cerebellum, also called Lhermitte-Duclos disease (LDD), is known as a rare, benign brain tumor. Around 200 cases have been reported. CASE DESCRIPTION: Here we introduced a newly diagnosed adult case with intratumoral hemorrhage. Then we reviewed 18 cases diagnosed in our institute, including 12 adults and 6 children. CONCLUSIONS: Preoperative diagnosis based on magnetic resonance imaging is 50% in adults and 16.7% in pediatrics. Diagnostic tiger stripes are not always seen in pediatric cases. The prognosis of the disease is good if total resection can be achieved. Further examinations for PTEN mutation and other comorbidities are recommended.
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Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/cirurgia , Ganglioneuroma/diagnóstico por imagem , Ganglioneuroma/cirurgia , Síndrome do Hamartoma Múltiplo/diagnóstico por imagem , Síndrome do Hamartoma Múltiplo/cirurgia , Adulto , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/patologia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/cirurgia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Ganglioneuroma/complicações , Ganglioneuroma/patologia , Síndrome do Hamartoma Múltiplo/complicações , Síndrome do Hamartoma Múltiplo/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Flavonoids, despite having low nutritional value, have numerous biological activities and extremely beneficial health effects. This study investigated the anticancer activity of rutin in human glioma CHME cells. METHODS: Cytotoxicity was determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Protein expression was determined through Western blotting. Apoptosis was detected using annexin V/propidium iodide (PI) and fluorescence microscopy. RESULTS: Rutin induced maximum cytotoxicity in CHME cells, as revealed through MTT assays. Cell death induced by rutin was due to apoptosis via P53 up-regulation. Rutin induced nuclear condensation, fragmentation, and membrane blebbing, as determined through 4',6-diamidino-2-phenylindole (DAPI) staining. Furthermore, rutin increased reactive oxygen species (ROS) levels and caused a loss of mitochondrial membrane potential, activating the intrinsic apoptotic pathway in CHME cells. The induction of apoptosis by rutin was further confirmed by the release of cytochrome c, up-regulation of BAX, and down-regulation of BCL, activated caspase 9, and caspase 3. The knockdown of P53 reversed rutin-induced apoptosis in a concentration-dependent manner. CONCLUSIONS: Rutin plays an important role in the induction of apoptosis in CHME cells. Based on these data, rutin should be further investigated as an anticancer agent in human glioma CHME cells.