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Brain and Spinal Cord Tumours

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Childhood Brain Tumours
Pituitary Tumours
Primary CNS Lymphoma
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Lin CY, Chang CC, Su PL, et al.
Brain MRI imaging characteristics predict treatment response and outcome in patients with de novo brain metastasis of EGFR-mutated NSCLC.
Medicine (Baltimore). 2019; 98(33):e16766 [PubMed] Related Publications
Patients with non-small cell lung cancer (NSCLC) and de novo brain metastasis (BM) have poor prognosis. We aim to investigate the characteristic of brain magnetic resonance (MR) imaging and the association with the treatment response of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for lung cancer with BM.EGFR-mutated NSCLC patients with BM from October 2013 to December 2017 in a tertiary referral center were retrospectively analyzed. Patient's age, sex, cell type, EGFR mutation status, treatment, and characteristics of BM were collected. Survival analysis was performed using Kaplan-Meier method. The efficacy of different EGFR-TKIs were also analyzed.Among the 257 eligible patients, 144 patients with Exon 19 deletion or Exon 21 L858R were included for analysis. The erlotinib group had the best progression free survival (PFS) (median PFS 13 months, P = .04). The overall survival (OS) revealed no significant difference between three EGFR-TKI groups. Brain MR imaging features including tumor necrosis, rim enhancement and specific tumor locations (frontal lobe, putamen or cerebellum) were factors associated with poor prognosis. Patients with poor prognostic imaging features, the high-risk group, who received erlotinib had the best PFS (median PFS 12 months, P < .001). However, the OS revealed no significant difference between 3 EGFR-TKI groups. The low risk group patients had similar PFS and OS treated with three different EGFR-TKIs.In NSCLC patients with common EGFR mutation and de novo BM, those with poor prognostic brain MR characteristics, erlotinib provided better PFS than afatinib or gefitinib.
Related: Lung Cancer EGFR

Oyemolade TA, Shokunbi MT, Badejo OA, Adeolu AA
Brainstem Glioma: Clinical Profile and Challenges of Management in a Developing Country.
West Afr J Med. 2019 May-Aug; 36(2):172-175 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Brainstem gliomas are relatively rare tumours of the central nervous system which have varying presentations and clinical course. This study aims to analyse the clinical profile and challenges of management of these tumours in a resource-limited country.
METHIODS: We retrospectively analysed the data from the records of the patients managed for briainstem glioma between January 2010 and July 2017.
RESULTS: There were 11 patients in the study (7 males and 4 females). The median age at diagnosis was 9 years. Eight of the patients were less than 15 years. The duration of symptoms ranged from 1 month to 2 years. All the patients had cranial nerve deficits at presentation, while 7 patients had cerebellar signs. Hydrocephalus was present in 4 patients. The lesion was pontine in 9 patients and tectal in 2. Three of the patients with hydrocephalus had ventriculoperitoneal shunt insertion while one patient refused surgery. Only one of the patients had radiotherapy. None of the patients received chemotherapy. A patient was dishcarged against medical advice. One patient is still alive after 4 years while another patient is alive after 2 years. The other 9 patients are dead with a mean survival period of 6 months.
CONCCLUSION: Most of the tumours in this series were located in the pons and ran aggressive courses. Majority of our patients did not have access to radiotherapy while none had chemotherapy.
Related: Brain Stem Glioma - Childhood

Okuda T, Fujita M, Kato A
Significance of Elevated HMGB1 Expression in Pituitary Apoplexy.
Anticancer Res. 2019; 39(8):4491-4494 [PubMed] Related Publications
BACKGROUND/AIM: High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein that exerts a range of proinflammatory actions when it is secreted extracellularly. We hypothesized that HMGB1 released from damaged cells in pituitary apoplexy would exacerbate the neurological symptoms due to acute inflammation.
PATIENTS AND METHODS: All the patients included in this study suffered from non-functioning pituitary adenoma. Four patients with apoplexy and three patients without apoplexy were included in this study. They underwent endonasal transsphenoidal endoscopic surgery to resect the tumors. We conducted enzyme-linked immunosorbent assay (ELISA) to measure HMGB1 in the surgical specimens.
RESULTS: Patients with apoplexy expressed HMGB1 at significantly higher levels than those in the non-apoplexy group (p=0.0478).
CONCLUSION: HMGB1 may be involved in subacute inflammation of pituitary apoplexy. Further work is needed to elucidate the detailed biological significance of HMGB1 in this disease.
Related: Pituitary Tumors

Rades D, Hansen HC, Dziggel L, et al.
Prognostic Role of Pre-Treatment Symptoms for Survival of Patients Irradiated for Brain Metastases.
Anticancer Res. 2019; 39(8):4273-4277 [PubMed] Related Publications
BACKGROUND/AIM: For treatment of brain metastases, a patient's survival prognosis should be considered. Existing survival scores appear complex and require complete tumor staging. For many patients, a faster and simpler tool would be helpful.
PATIENTS AND METHODS: This retrospective study investigated the prognostic value of the number of pre-treatment symptoms plus eight other factors on survival of patients irradiated for brain metastases. Other factors included whole-brain radiotherapy (WBRT) regimen, age, gender, performance score, primary tumor type, number of brain metastases, extracranial metastases, and interval between cancer diagnosis and WBRT.
RESULTS: The number of symptoms (p=0.002) and all other factors were significantly associated with survival on univariate analyses. On multivariate analysis, all factors but the number of symptoms (p=0.47) and primary tumor type (p=0.48) were significant.
CONCLUSION: Since the number of symptoms was not an independent predictor of survival, it cannot replace existing scoring tools and may only serve for orientation.
Related: Cancer Prevention and Risk Reduction

Cortinovis D, Chiari R, Catino A, et al.
Italian Cohort of the Nivolumab EAP in Squamous NSCLC: Efficacy and Safety in Patients With CNS Metastases.
Anticancer Res. 2019; 39(8):4265-4271 [PubMed] Related Publications
BACKGROUND/AIM: Brain metastases are an additional challenge in patients with non-small-cell lung cancer (NSCLC) because most chemotherapy agents cannot cross the blood-brain barrier. Nivolumab has demonstrated efficacy in patients with advanced squamous NSCLC, but because patients with central nervous system (CNS) metastases are typically excluded from registration trials, 'field-practice' data are needed.
PATIENTS AND METHODS: Patients in the Italian cohort of the Expanded Access Program (EAP) who had CNS metastases at baseline were analyzed.
RESULTS: Thirty-seven patients with CNS metastases received a median of six doses of nivolumab. Three patients (8%) had grade 3-4 adverse events and one patient discontinued due to an adverse event. The objective response rate was 19%. Median overall survival was 5.8 (95% confidence interval=1.9-9.8) months and median progression-free survival was 4.9 (95% confidence interval=2.7-7.1) months.
CONCLUSION: The safety and efficacy of nivolumab in patients with CNS metastases appear to be similar to those seen in the overall EAP cohort in Italy.
Related: Non-Small Cell Lung Cancer

Lemelin A, Lapoirie M, Abeillon J, et al.
Pheochromocytoma, paragangliomas, and pituitary adenoma: An unusual association in a patient with an SDHD mutation. Case report.
Medicine (Baltimore). 2019; 98(30):e16594 [PubMed] Related Publications
RATIONALE: Pituitary adenomas and paragangliomas are both rare endocrine diseases. Paragangliomas (PGL)/pheochromocytomas (PHEO) are part of an inherited syndrome in about 30% to 40% of cases. Among familial cases, mutations of the succinate dehydrogenase (SDH) subunit genes (succinate dehydrogenase subunit [SDH]B, SDHC, SDHD, succinate dehydrogenase subunit AF2 [SDHAF2] , and SDHA) are the most common cause.
PATIENT CONCERNS: We here report a 31-year-old patient with a known SDHD mutation whose disease has been revealed by a left PHEO during childhood and who presented at age 29 years a large paraganglioma of the right jugular foramen, a concomitant PHEO of the left adrenal and 2 retroperitoneal paragangliomas. A pituitary incidentaloma was found during investigations on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) (FDG-PET).
DIAGNOSIS: A pituitary magnetic resonance imaging (MRI) confirmed the presence of a 14 mm pituitary macroadenoma. The pituitary function was normal except for hypogonadotropic hypogonadism. On examination of the fundus, a diagnosis of Pseudo Foster-Kennedy syndrome was made due to a venous compression of the right jugular vein caused by the paraganglioma (PGL). The pituitary adenoma was not compressive to the optic chiasm.
INTERVENTIONS: A treatment with acetazolamide was started in order to improve intracranial hypertension. The patient couldn't benefit of a surgical approach for the paraganglioma of the right jugular foramen; the patient has been treated with stereotactic radiosurgery (Gamma Knife).
OUTCOMES: The most recent MRI revealed that the right jugular foramen PGL is stable and the latest visual assessment demonstrated stability despite a recent reduction in acetazolamide dosage. A surveillance by MRI of the pituitary adenoma has been planned.
LESSONS: The association of a pituitary adenoma to paragangliomas within a same patient is very uncommon and raises the question of related physiopathological mechanisms.
Related: Pheochromocytoma and Paraganglioma Pituitary Tumors

Kwon SM, Ko Y, Bang SS
Primary intraosseous osteolytic meningioma: a case report and review of the literature.
BMC Neurol. 2019; 19(1):176 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Primary intraosseous meningioma is a subset of extradural meningioma that arises in the bone, and only a few cases have been reported to date.
CASE PRESENTATION: An 80-year-old man presented with decreased hearing on the right side accompanied by a disturbance of balance 10 months prior to admission. Magnetic resonance imaging revealed an 8 × 7 cm osteolytic mass in the right posterior fossa related to the petrous bone, with extension to the cervical region. During surgery, the tumor was found to be located extradurally, with no invasion of the dura. The tumor was removed entirely, apart from a small portion around the jugular foramen to avoid lower cranial nerve injury.
CONCLUSION: The final diagnosis was primary intraosseous osteolytic meningioma with atypical pathology. Here, we report a rare case of an osteolytic skull lesion in the skull base not invading the dura and with extensive bone destruction.

Nawal CL, Chejara RS, Meena PD, et al.
Severe Hyponatremia as an Uncommon Presenting Feature of Pituitary Macroadenoma.
J Assoc Physicians India. 2018; 66(8):96-98 [PubMed] Related Publications
Hyponatremia is a common electrolyte disturbance, but less commonly utilized and require a thorough evaluation to unmask etiology. It has variety of causes and is rarely due to hypopituitarism. Hyponatremia is a very early complication of pituitary tumor. Here, we report a case, who presented to us with hyponatremia and eventually thorough work-up led us to a diagnosis of Non-functioning pituitary macroadenoma.
Related: Pituitary Tumors

Benenemissi IH, Sifi K, Sahli LK, et al.
Angiotensin-converting enzyme insertion/deletion gene polymorphisms and the risk of glioma in an Algerian population.
Pan Afr Med J. 2019; 32:197 [PubMed] Free Access to Full Article Related Publications
Introduction: Just recently, it has been established that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is linked to the pathogenesis and to the evolution of human cancers. Therefore, the present study was concerned with the investigation of an eventual association between glioma and I/D polymorphism of the ACE gene.
Methods: The expression of ACE gene was detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis in 36 Algerian patients with glioma and 195 healthy controls.
Results: In glioma cases, allelic frequencies and genotypes distribution of the ACE I/D polymorphism were different from controls cases. ACE DD genotype were highly presented in glioma cases (63.9%) than controls (33.8%) and conferred 3.64-fold risk for predisposition in glioma cases (vs ID genotype, p<0.001). Recessive model (ACE II + ID genotypes vs DD) was associated with a 72% reduced risk of glioma (OR = 0.28, 95% CI: 0.13-0.60, p <0.001). Per copy D allele frequency was found higher in glioma cases (79.2%) than in controls (63.3 %), OR = 2.20, 95% CI: 1.20 - 4.03, p = 0.009.
Conclusion: The obtained data showed that the presence of the D allele might be a risk factor for the development of glioma. Further studies considering different ethnic groups with large samples are required to confirm this finding.
Related: Polymorphisms

Gunawat PV, Shaikh ST, Deopujari CE
Tumour-induced Osteomalacia Secondary to Intracranial Tumours - Report of 2 Cases.
J Assoc Physicians India. 2019; 67(4):85-86 [PubMed] Related Publications
Tumor induced osteomalacia (TIO) is a paraneoplastic syndrome which is mostly caused by a phosphaturic mesenchymal tumour mixed connective tissue variant (PMTMCT). These tumours do not have any specific site predilection but their presence in cranial compartment is very rare. Two cases of TIO secondary to phosphaturic mesenchymal tumour at the skull base are described ahead, one of which was in the posterior fossa and the other in middle cranial fossa. Early diagnosis and complete excision of PMT is essential in preventing morbidity secondary to osteomalacia. This case report stands distinct in highlighting a rare site of a phosphaturic mesenchymal tumour and the need to keep a high index of suspicion in cases of TIO especially wherein localization of the tumour is unsuccessful.

Lindström MS
Expanding the scope of candidate prognostic marker IGFBP2 in glioblastoma.
Biosci Rep. 2019; 39(7) [PubMed] Free Access to Full Article Related Publications
Glioblastoma is the most common malignant brain tumor in adults. Unfortunately, it has a very poor prognosis and no cure. In a recent paper by Yuan et al. (

Tong Y, Ye L, Li S, et al.
The association of 6 variants of 8q24 and the risk of glioma: A meta-analysis.
Medicine (Baltimore). 2019; 98(27):e16205 [PubMed] Free Access to Full Article Related Publications
With the advances in sequencing technologies and genome-wide association studies (GWAS), several inherited variants that increase glioma risk have been identified. Ten studies including 8818 cases and 17,551 controls were collected to conduct a meta-analysis to evaluate the associations between 6 variants in 8q24 and glioma risk. Of the 6 variants located in 8q24, 2 have strong significant associations with the risk of glioma, including rs4295627 (P = .003, odds ratio [OR] = 1.21), rs55705857 (P = 2.31 × 10, OR = 3.54). In particular, both homozygous GG (P = 1.91 × 10, OR1 = 2.01) and heterozygous GT (P = 7.75 × 10, OR2 = 1.35) genotypes of rs4295627 were associated with glioma risk. Further studies are needed to explore the role of the 8q24 variants involved in the etiology of glioma.
Related: Chromosome 8

Kim HY, Kim ST, Kim HJ, et al.
Differentiation of postoperative changes and residual tumors in dynamic contrast-enhanced sella MRI after transsphenoidal resection of pituitary adenoma.
Medicine (Baltimore). 2019; 98(27):e16089 [PubMed] Free Access to Full Article Related Publications
To establish magnetic resonance imaging (MRI) features that differentiate residual tumors from postoperative surgical changes following the transsphenoidal approach of a pituitary adenoma.We analyzed residual enhancements at the tumor bed in 52 patients who underwent dynamic contrast-enhanced sella MRI within 48 hours after surgery and at 6 to 28 months. Patients were divided into 2 groups defined by either peripheral or nodular enhancement patterns. For each group, we measured the maximum thickness of the residual enhancing portion and compared differences in the residual tumor and postoperative changes.Among the tumors examined in the 52 patients, 19 residual tumors showed nodular (n = 16) and peripheral (n = 3) enhancement patterns, and 33 postoperative changes showed nodular (n = 3) and peripheral (n = 30) enhancement patterns. The mean residual tumor thickness was 7.1 mm (range, 2.9-16.8 mm) and 1.9 mm (range, 1.0-7.4 mm) in the postoperative change. Receiver operating characteristic curve analysis revealed that a 3.9-mm thickness was associated with 89% sensitivity, 97% specificity, and 94% accuracy for diagnosis of residual tumor.On immediate postoperative MRI, residual enhancement with greater than 3.9-mm thickness and nodular pattern suggest residual pituitary adenoma tumor.
Related: Pituitary Tumors

Poel R, Stuessi Lobmaier A, Andratschke N, et al.
Dosimetric comparison of protons vs photons in re-irradiation of intracranial meningioma.
Br J Radiol. 2019; 92(1100):20190113 [PubMed] Related Publications
OBJECTIVES: Re-irradiation of recurrent intracranial meningiomas represents a major challenge due to dose limits of critical structures and the necessity of sufficient dose coverage of the recurrent tumor for local control. The aim of this study was to investigate dosimetric differences between pencil beam scanning protons (PBS) and volumetric modulated arc therapy (VMAT) photons for intracranial re-irradiation of meningiomas.
METHODS: Nine patients who received an initial dose >50 Gy for intracranial meningioma and who were re-irradiated for recurrence were selected for plan comparison. A volumetric modulated arc therapy photon and a pencil beam scanning proton plan were generated (prescription dose: 15 × 3 Gy) based on the targets used in the re-irradiation treatment.
RESULTS: In all cases, where the cumulative dose exceeded 100 or 90 Gy, these high dose volumes were larger for the proton plans. The integral doses were significantly higher in all photon plans (reduction with protons: 48.6%,
CONCLUSIONS: The dosimetric results of the accumulated dose for a re-irradiation with protons and with photons were very similar. The photon plans had a steeper dose falloff directly outside the target and were superior in minimizing the high dose volumes. The proton plans achieved a lower integral dose. Clinically relevant OAR sparing was extremely case specific. The optimal treatment modality should be assessed individually.
ADVANCES IN KNOWLEDGE: Dose sparing in re-irradiation of intracranial meningiomas with protons or photons is highly case specific and the optimal treatment modality needs to be assessed on an individual basis.

de Oliveira Junior ER, Nascimento TL, Salomão MA, et al.
Increased Nose-to-Brain Delivery of Melatonin Mediated by Polycaprolactone Nanoparticles for the Treatment of Glioblastoma.
Pharm Res. 2019; 36(9):131 [PubMed] Related Publications
PURPOSE: Intranasal administration has been extensively applied to deliver drugs to the brain. In spite of its unfavorable biopharmaceutic properties, melatonin (MLT) has demonstrated anticancer effects against glioblastoma. This study describes the nose-to-brain delivery of MLT-loaded polycaprolactone nanoparticles (MLT-NP) for the treatment of glioblastoma.
METHODS: MLT-NP were prepared by nanoprecipitation. Following intranasal administration in rats, brain targeting of the formulation was demonstrated by fluorescence tomography. Brain and plasma pharmacokinetic profiles were analyzed. Cytotoxicity against U87MG glioblastoma cells and MRC-5 non-tumor cells was evaluated.
RESULTS: MLT-NP increased the drug apparent water solubility ~35 fold. The formulation demonstrated strong activity against U87MG cells, resulting in IC50 ~2500 fold lower than that of the free drug. No cytotoxic effect was observed against non-tumor cells. Fluorescence tomography images evidenced the direct translocation of nanoparticles from nasal cavity to the brain. Intranasal administration of MLT-NP resulted in higher AUC
CONCLUSIONS: Nanoencapsulation of MLT was crucial for the selective antitumoral activity against U87MG. In vivo evaluation confirmed nose-to-brain delivery of MLT mediated by nanoparticles, highlighting the formulation as a suitable approach to improve glioblastoma therapy.

Sollfrank L, Lettmaier S, Erdmann M, Uslu U
Panniculitis Under Successful Targeted Inhibition of the MAPK/ERK Signaling Pathway in a Patient With BRAF V600E-mutated Spindle Cell Oncocytoma of the Pituitary Gland.
Anticancer Res. 2019; 39(7):3955-3959 [PubMed] Related Publications
BACKGROUND: Spindle cell oncocytoma (SCO) is a rare non-neuroendocrine neoplasm of the pituitary gland. In general, surgical excision and radiation therapy is performed. However, local recurrences are frequently seen, requiring repeated surgical and radio-oncological interventions. Thus, mutational analysis of the tumor and targeted therapy may represent a valuable therapy option in these patients.
CASE REPORT: A 38-year-old female patient with past medical history of 6 surgeries (two transsphenoidal and four transcranial), radiation therapy, and chemoradiation therapy due to several recurrences of a SCO, presented for follow-up imaging. MRI of the brain showed growth of a tumor in the right parasellar region consistent with a new local recurrence, which due to its size and location was considered to be not resectable. Molecular analysis of a previously surgically removed tumor showed a BRAF V600E mutation and thus, combined targeted inhibition of the MAPK/ERK signaling pathway using a BRAF inhibitor and a MEK inhibitor was started. Due to drug-induced panniculitis, MEK inhibitor had to be stopped and BRAF inhibitor only was continued, which was well tolerated by the patient. Subsequent imaging revealed tumor regression already four weeks after therapy initiation and no disease progression has been observed to date.
CONCLUSION: A SCO patient with BRAF V600E mutation was successfully treated using targeted inhibition of the MAPK/ERK signaling pathway. Under therapy, tumor regression was observed and the patient has been free of progressive disease for more than two years now. Thus, mutational analysis and targeted inhibition may offer an effective treatment option for SCO patients, while potential side-effects to this therapy, like observed in our case, can occur and needs to be adequately treated.
Related: Pituitary Tumors BRAF

Helson L, Majeed M
Pleiotropic Chemotherapy to Abrogate Glioblastoma Multiforme Migration/Invasion.
Anticancer Res. 2019; 39(7):3423-3427 [PubMed] Related Publications
Current clinical failure to cure primary glioblastoma multiforme in virtually all adult patients is due to genetic aberrations, molecular heterogeneity, and clonal evolution of tumor stem and differentiated cells within the core tumor, leading to their migration, invasion and proliferation in normal surrounding and in distant cerebral tissue sites. These factors are the causes of targeted drug resistance, inadequate surgical removal, and inadequate radio-therapeutic interventions. Resolution of this clinical conundrum may be found in administration of Withaferin A alone or in combination with pleiotropic drugs which address aberrant molecules and pathways promoting tumor cell motility, migration, invasion and proliferation.

Hu Y, Zhang N, Zhang S, et al.
Differential circular RNA expression profiles of invasive and non-invasive non-functioning pituitary adenomas: A microarray analysis.
Medicine (Baltimore). 2019; 98(26):e16148 [PubMed] Free Access to Full Article Related Publications
Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors, and some exhibit locally invasive or even clinically aggressive behavior. Circular RNAs (circRNAs) are a reinvented class of non-coding RNAs that play important roles in tumor initiation and progression.CircRNA microarray assays were performed in 4 invasive and 4 non-invasive NFPAs, and 4 typically differential expression circRNAs were selected for validation using quantitative reverse transcription-polymerase chain reaction. The diagnostic and prognostic values of tested cirRNAs were further evaluated. Bioinformatics analysis and a literature review of potential miRNAs targets involved in pituitary tumor invasion were performed.A specific circRNA expression profile was detected between invasive and non-invasive NFPAs, including 91 upregulated and 61 downregulated circRNAs in invasive tumors. The dysregulation of the 4 circRNAs has been confirmed. The expression of hsa_circRNA_102597, a downregulated circRNA, was significantly correlated with tumor diameter (P < .05) and Knosp grade (P < .01). Hsa_circRNA_102597 alone or in combined with Ki-67 index was able to accurately differentiate invasive from non-invasive NFPAs as well as predict tumor progression/recurrence. Fourteen aberrantly expressed circRNAs might be involved in the invasiveness of pituitary adenomas via seven predicted potential miRNA targets.CircRNAs are participated in pituitary tumor invasion, and may be used as novel diagnostic and prognostic biomarkers in NFPAs.
Related: Pituitary Tumors

Li S, Zhong N, Xu W, et al.
The impact of surgical timing on neurological outcomes and survival in patients with complete paralysis caused by spinal tumours: evaluation of surgery on patients with complete paralysis due to neoplastic epidural spinal cord compression.
Bone Joint J. 2019; 101-B(7):872-879 [PubMed] Related Publications
AIMS: The aim of this study was to explore the prognostic factors for postoperative neurological recovery and survival in patients with complete paralysis due to neoplastic epidural spinal cord compression.
PATIENTS AND METHODS: The medical records of 135 patients with complete paralysis due to neoplastic cord compression were retrospectively reviewed. Potential factors including the timing of surgery, muscular tone, and tumour characteristics were analyzed in relation to neurological recovery using logistical regression analysis. The association between neurological recovery and survival was analyzed using a Cox model. A nomogram was formulated to predict recovery.
RESULTS: A total of 52 patients (38.5%) achieved American Spinal Injury Association Impairment Scale (AIS) D or E recovery postoperatively. The timing of surgery (p = 0.003) was found to be significant in univariate analysis. In multivariate analysis, surgery within one week was associated with better neurological recovery than surgery within three weeks (p = 0.002), with a trend towards being associated with a better neurological recovery than surgery within one to two weeks (p = 0.597) and two to three weeks (p = 0.055). Age (p = 0.039) and muscle tone (p = 0.018) were also significant predictors. In Cox regression analysis, good neurological recovery (p = 0.004), benign tumours (p = 0.039), and primary tumours (p = 0.005) were associated with longer survival. Calibration graphs showed that the nomogram did well with an ideal model. The bootstrap-corrected C-index for neurological recovery was 0.72.
CONCLUSION: In patients with complete paralysis due to neoplastic spinal cord compression, whose treatment is delayed for more than 48 hours from the onset of symptoms, surgery within one week is still beneficial. Surgery undertaken at this time may still offer neurological recovery and longer survival. The identification of the association between these factors and neurological recovery may help guide treatment for these patients. Cite this article:

Malinverno M, Maderna C, Abu Taha A, et al.
Endothelial cell clonal expansion in the development of cerebral cavernous malformations.
Nat Commun. 2019; 10(1):2761 [PubMed] Free Access to Full Article Related Publications
Cerebral cavernous malformation (CCM) is a neurovascular familial or sporadic disease that is characterised by capillary-venous cavernomas, and is due to loss-of-function mutations to any one of three CCM genes. Familial CCM follows a two-hit mechanism similar to that of tumour suppressor genes, while in sporadic cavernomas only a small fraction of endothelial cells shows mutated CCM genes. We reported that in mouse models and in human patients, endothelial cells lining the lesions have different features from the surrounding endothelium, as they express mesenchymal/stem-cell markers. Here we show that cavernomas originate from clonal expansion of few Ccm3-null endothelial cells that express mesenchymal/stem-cell markers. These cells then attract surrounding wild-type endothelial cells, inducing them to express mesenchymal/stem-cell markers and to contribute to cavernoma growth. These characteristics of Ccm3-null cells are reminiscent of the tumour-initiating cells that are responsible for tumour growth. Our data support the concept that CCM has benign tumour characteristics.
Related: PDCD10

Qu Y, Zhou L, Jiang J, et al.
Combination of three-dimensional arterial spin labeling and stretched-exponential model in grading of gliomas.
Medicine (Baltimore). 2019; 98(25):e16012 [PubMed] Free Access to Full Article Related Publications
To evaluate the diagnostic value of combining 3D arterial spin labeling (ASL) and stretched-exponential diffusion model in grading of gliomas.A total of 72 patients with histo-pathology proved gliomas (34 low-grade, 38 high-grade) were included in this study. 3D ASL and multi-b diffusion weighted imaging (DWI) images were retrospectively analyzed. The ASL and DWI parameters-tumor blood flow (TBF), distributed diffusion coefficient (DDC), and diffusion heterogeneity α were compared between high-grade and low-grade groups and P < .05 was regarded as statistically significant. TBF was also normalized to the corresponding values in contralateral mirror regions of interest (ROI) (M-TBF), normal grey matter (G-TBF), and white matter (W-TBF) and were compared between high and low-grade tumors.TBF values were significantly higher in high-grade gliomas (P < .001). In stretched-exponential model, the α value of low-grade gliomas showed significant higher than high-grade gliomas group (P < .001), but there was no difference of DDC (P > .05). When TBF values were normalized to contralateral mirror ROI, normal grey matter and white matter, G-TBF showed the highest sensitivity and specificity for differentiation high-grade and low-grade gliomas. The area under area under curve (AUC) of G-TBF and α for glioma grading were 0.926 and 0.892, respectively. The area under AUC of the G-TBF combination with α was 0.960 and corresponding sensitivity and specificity were 94.1% and 98.7%.The combination of 3D ASL and stretched-exponential model parameters can be used to differentiate high-grade and low-grade gliomas. Combination G-TBF and α value can obtain best diagnostic performance.

Li D, Xu S, Sun M, et al.
MAID chemotherapy regimen as a treatment strategy for metastatic malignant ameloblastoma: A case report.
Medicine (Baltimore). 2019; 98(25):e15873 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Ameloblastoma is generally characterized as a benign tumor originating in odontogenic epithelium. However, few cases of metastatic malignant ameloblastoma have also been reported. Due to the low incidence of malignant ameloblastoma, there is no established treatment regimen. To explore effective treatment for malignant ameloblastoma, we reported this case study.
PATIENTS CONCERNS: This report described a case of a 28-year-old malignant ameloblastoma female patient with multiple metastasis (brain and lung).
DIAGNOSES: The patient presented ameloblastoma of the left mandible in 2012. Three years later, local recurrence and brain metastasis was observed during a follow-up examination. Five years later, malignant ameloblastoma was detected by imaging and immunohistochemistry in the bilateral multiple pulmonary nodules and mediastinal lymph nodes.
INTERVENTIONS: The patient was initially treated with tumor resection. Three years later after local recurrence and brain metastasis, she was accepted the extensive mandibulectomy supplemented with brain stereotactic body radiotherapy (SBRT). When diagnosed with pulmonary metastasis, the patient received combined chemotherapy regimen of MAID (mesna, adriamycin, ifosfamide and dacarbazine) for 6 cycles.
OUTCOMES: The efficacy evaluation was partial remission (PR) after the 6 cycles of MAID. The last patient follow-up was July 24th 2018, and no evidence of progression was observed. The progression-free survival (PFS) of the patient was more than 9 months.
LESSONS: Surgical resection is the optimal treatment for locally recurrent ameloblastoma. SBRT may be an effective treatment for unresectable oligometastasis of malignant ameloblastoma. Finally, combined chemotherapy of MAID showed encouraging effects in the management of metastatic malignant ameloblastoma.
Related: Dacarbazine Doxorubicin Ifosfamide Mesna

Kamoun S, Azouz H, Zemmali M, et al.
Desmoplastic infantile ganglioglioma.
Pan Afr Med J. 2019; 32:113 [PubMed] Free Access to Full Article Related Publications
The term desmoplastic infantile ganglioglioma was coined by VandenBerg et al in 1987. In their first report these authors referred to a rare, distinct brain tumor. About 60 cases of desmoplastic infantile ganglioglioma have been described in the literature since its first description. We report a case of a 6-year-old girl who was admitted for seizure without family history. Magnetic resonance imaging scan showed a hypodense area in the right temporal region. A right temporal craniotomy was performed and the tumor was excised. The pathologic examination revealed the diagnosis of desmoplastic infantile ganglioglioma.
Related: Childhood Brain Tumours Childhood Brain Tumors

Liu Z, Liu H, Liu Z, Zhang J
Oligodendroglial tumours: subventricular zone involvement and seizure history are associated with CIC mutation status.
BMC Neurol. 2019; 19(1):134 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: CIC-mutant oligodendroglial tumours linked to better prognosis. We aim to investigate associations between CIC gene mutation status, MR characteristics and clinical features.
METHODS: Imaging and genomic data from the Cancer Genome Atlas and the Cancer Imaging Archive (TCGA/TCIA) for 59 patients with oligodendroglial tumours were used. Differences between CIC mutation and CIC wild-type were tested using Chi-square test and binary logistic regression analysis.
RESULTS: In univariate analysis, the clinical variables and MR features, which consisted 3 selected features (subventricular zone[SVZ] involvement, volume and seizure history) were associated with CIC mutation status (all p < 0.05). A multivariate logistic regression analysis identified that seizure history (no vs. yes odd ratio [OR]: 28.960, 95 confidence interval [CI]:2.625-319.49, p = 0.006) and SVZ involvement (SVZ- vs. SVZ+ OR: 77.092, p = 0.003; 95% CI: 4.578-1298.334) were associated with a higher incidence of CIC mutation status. The nomogram showed good discrimination, with a C-index of 0.906 (95% CI: 0.812-1.000) and was well calibrated. SVZ- group has increased (SVZ- vs. SVZ+, hazard ratio [HR]: 4.500, p = 0.04; 95% CI: 1.069-18.945) overall survival.
CONCLUSIONS: Absence of seizure history and SVZ involvement (-) was associated with a higher incidence of CIC mutation.
Related: CIC

Liang W, Guo B, Ye J, et al.
Vasorin stimulates malignant progression and angiogenesis in glioma.
Cancer Sci. 2019; 110(8):2558-2572 [PubMed] Free Access to Full Article Related Publications
Glioma, the most common human primary brain tumor, is characterized by invasive capabilities and angiogenesis. Vasorin (VASN), a transmembrane protein, is reported to be associated with vascular injury repair and is overexpressed in some human tumors. However, its role in tumor progression and angiogenesis in glioma is unknown. In this study, VASN was shown to be overexpressed in high-grade gliomas, and the expression level correlated with tumor grade and microvessel density in glioma specimens. Glioma patients with high VASN expression had a shorter overall survival time. Knockdown of VASN in glioma cells by shRNA significantly inhibited the malignancy of glioma, including cell proliferation, colony formation, invasion, and sphere formation. Ectopic expression of VASN increased glioma progression in vitro. The expression of VASN correlated with the mesenchymal type of glioblastoma multiforme (GBM) subtyped by gene set enrichment analysis (GSEA). Our results showed that the concentration of VASN was increased in the conditioned medium (CM) from glioma cells with VASN overexpression, and the CM from glioma cells with knockdown or overexpressed VASN inhibited or promoted HUVEC migration and tubulogenesis in vitro, respectively. Glioma growth and angiogenesis were stimulated upon ectopic expression of VASN in vivo. The STAT3 and NOTCH pathways were found to be activated and inhibited by VASN overexpression. Our findings suggest that VASN stimulates tumor progression and angiogenesis in glioma, and, as such, represents a novel therapeutic target for glioma.
Related: Angiogenesis and Cancer

Tao L, Chen Y, Huang Q, et al.
Constant expression of somatostatin receptor 2a in minute pulmonary meningothelial-like nodules.
J Clin Pathol. 2019; 72(8):525-528 [PubMed] Related Publications
AIMS: Although ultrastructural studies showed that minute pulmonary meningothelial-like nodules (MPMNs) cells closely resembled meningothelial cells, their immunophenotype has not been well characterised, partly due to their rarity.
METHODS: Somatostatin receptor 2a (SSTR2a) and other markers of meningioma, including epithelial membrane antigen (EMA), progesterone receptor (PR) and S100, were analysed retrospectively in 19 MPMN cases from two institutions in China.
RESULTS: The median age of patients with MPMNs was 62.5 years (32-73 years), with a male-to-female ratio of 1:8.5. Most (15/19) patients with MPMNs had coexisting diseases, including adenocarcinomas (12 cases), bronchiectasis (1 case) and tuberculosis (2 cases). Just over half of the cases (10/19) were multifocal lesions (2-5 lesions). An additional 53 cases with 123 lesions from the literature were reviewed with reported immunophenotype information. In total, 162 lesions were included in the analysis. The size of nodules was 1-4 mm. All MPMN lesions (39/39) in the 19 cases showed strong and diffuse cytoplasmic expression of SSTR2a. The expression rate of SSTR2a was higher than that of conventional markers of meningioma, including EMA (86/138), PR (32/68) and S100 (1/125).
CONCLUSIONS: Our observations expand the spectrum of recognised SSTR2a-positive lesions and once again demonstrated that MPMNs show immunohistochemical characteristics similar to meningothelial cells.
Related: Lung Cancer

Xingyi J, Guonan C, Xin Z, Naijie L
Ab
J Biomed Nanotechnol. 2019; 15(7):1468-1481 [PubMed] Related Publications
Glioblastoma (GBM) is the most common and aggressive primary brain tumor, temozolomide (TMZ) is widely used for the treatment of GBM, but the effects of TMZ for GBM are limited by the presence of rapid resistance. It was reported that a small percentage of glioma cells which called glioma stem cells (GSCs) lead GBM resistance to TMZ, and sensitizes GSCs to TMZ was an effective way to solve the TMZ resistance and cure the GBM. A polypeptide
Related: Dacarbazine Temozolomide

Chen YS, Chiu YH, Li YS, et al.
Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors.
Int J Nanomedicine. 2019; 14:3601-3613 [PubMed] Free Access to Full Article Related Publications

Yang Q, Wang R, Wei B, et al.
Gene and microRNA Signatures Are Associated with the Development and Survival of Glioblastoma Patients.
DNA Cell Biol. 2019; 38(7):688-699 [PubMed] Related Publications
This study was aimed to identify hub genes associated with the development of glioblastoma (GBM) by conducting a bioinformatic analysis. The raw gene expression data were downloaded from the Gene Expression Omnibus database and The Cancer Genome Atlas project. After the differentially expressed genes (DEGs) were identified, the functional enrichment analysis of DEGs was conducted. Subsequently, the protein-protein interaction (PPI) network, molecular complex detection clusters, and transcriptional factor (TF)-miRNA-target regulatory network were constructed, respectively. Furthermore, the survival analysis of prognostic outcomes and genes was analyzed. In addition, the expression of key genes was validated by quantitative real-time PCR (qRT-PCR) analysis. A total of 884 DEGs, including 418 upregulated and downregulated genes, were identified between GBM and normal samples. The PPI network comprised a set of 3418 pairs involving 751 nodes, and
Related: MicroRNAs AKT1

Ueda Y, Ohira S, Yamazaki H, et al.
Dosimetric performance of two linear accelerator-based radiosurgery systems to treat single and multiplebrain metastases.
Br J Radiol. 2019; 92(1100):20190004 [PubMed] Related Publications
OBJECTIVE: To evaluate and compare the dosimetric plan quality for noncoplanar volumetric arc therapy of single and multiple brain metastases using the linear accelerator-based radiosurgery system HyperArc and a robotic radiosurgery system.
METHODS: 31 tumors from 24 patients were treated by stereotactic radiosurgery using the CyberKnife system. CT images, structure sets, and dose files were transferred to the Eclipse treatment planning system for the HyperArc system. Dosimetric parameters for both plans were compared. The beam-on time was calculated from the total monitor unit and dose rate.
RESULTS: For normal brain tissue, the received volume doses were significantly lower for HyperArc than for CyberKnife_G4 and strongly correlated with the planning target volume (PTV) for cases of single brain metastasis. In addition, the difference in volume dose between CyberKnife_G4 and HyperArc was proportional to the PTV. For multiple brain metastases, no significant difference was observed between the two stereotactic radiosurgery systems, except for high-dose region in the normal tissue. In low dose for brain minus PTV, when the maximum distance among each target was above 8.0 cm, HyperArc delivered higher dose than CyberKnife_G4. The mean ± SDs for the beam-on time were 15.8 ± 5.3 and 5.6 ± 0.8 min for CyberKnife_G4 and HyperArc, respectively (
CONCLUSION: HyperArc is best suited for larger targets in single brain metastasis and for smaller inter tumor tumor distances in multiple brain metastases.
ADVANCES IN KNOWLEDGE: The performance of HyperArc in comparison with CyberKnife_G4 was depended on defined margin and tumor distances.

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