- Volumetric voxelwise apparent diffusion coefficient histogram analysis for differentiation of the fourth ventricular tumors. [Journal Article]
- NJNeuroradiol J 2018 Sep 19; :1971400918800803
- Purpose We applied voxelwise apparent diffusion coefficient (ADC) histogram analysis in addition to structural magnetic resonance imaging (MRI) findings and patients' age for differentiation of intra...
Purpose We applied voxelwise apparent diffusion coefficient (ADC) histogram analysis in addition to structural magnetic resonance imaging (MRI) findings and patients' age for differentiation of intraaxial posterior fossa tumors involving the fourth ventricle. Participants and methods Pretreatment MRIs of 74 patients with intraaxial brain neoplasm involving the fourth ventricle, from January 1, 2004 to December 31, 2015, were reviewed. The tumor solid components were segmented and voxelwise ADC histogram variables were determined. Histogram-driven variables, structural MRI findings, and patient age were combined to devise a differential diagnosis algorithm. Results The most common neoplasms were ependymomas ( n = 21), medulloblastoma ( n = 17), and pilocytic astrocytomas ( n = 13). Medulloblastomas followed by atypical teratoid/rhabdoid tumors had the lowest ADC histogram percentile values; whereas pilocytic astrocytomas and choroid plexus papillomas had the highest ADC histogram percentile values. In a multivariable multinominal regression analysis, the ADC 10th percentile value from voxelwise histogram was the only independent predictor of tumor type ( p < 0.001). In separate binary logistic regression analyses, the 10th percentile ADC value, tumor morphology, enhancement pattern, extension into Luschka/Magendie foramina, and patient age were predictors of different tumor types. Combining these variables, we devised a stepwise diagnostic model yielding 71% to 82% sensitivity, 91% to 95% specificity, 75% to 78% positive predictive value, and 89% to 95% negative predictive value for differentiation of ependymoma, medulloblastoma, and pilocytic astrocytoma. Conclusion We have shown how the addition of quantitative voxelwise ADC histogram analysis of the tumor solid component to structural findings and patient age can help with accurate differentiation of intraaxial posterior fossa neoplasms involving the fourth ventricle based on pretreatment MRI.
- Central nervous system manifestations of tuberous sclerosis complex. [Journal Article]
- AJAm J Med Genet C Semin Med Genet 2018 Sep 19
- Tuberous sclerosis complex (TSC) is a neurocutaneous autosomal-dominant genetic syndrome marked by development of hamartomatous lesions arising from dysfunction of the mammalian target of rapamycin (...
Tuberous sclerosis complex (TSC) is a neurocutaneous autosomal-dominant genetic syndrome marked by development of hamartomatous lesions arising from dysfunction of the mammalian target of rapamycin (mTOR) pathway. Although TSC remains a heterogeneous clinical entity, the recent inclusion of genetic diagnostic criteria reflects advancement in our understanding of its underlying etiopathogenesis. Abnormal cellular growth, differentiation, and migration result in multisystem sequelae, with neurologic manifestations of TSC representing the primary cause of morbidity and mortality for the majority of individuals. Modern imaging techniques aid in the diagnosis of TSC and guide treatment strategies by revealing central nervous system findings. Cortical tubers are the namesake lesion of the disorder and occur in up to 90% of cases, often exerting significant epileptogenic potential. Subependymal nodules are found in 80% of patients as calcified tumors lining the ependyma of the lateral ventricles. In some cases, these nodules are thought to progress to subependymal giant cell astrocytomas and may present with obstructive hydrocephalus. Retinal astrocytic hamartomas are also common, present in 50% of patients. Surgery remains the treatment of choice for large or symptomatic lesions, though clinical trials have highlighted a potential role for mTOR pathway antagonism. A multidisciplinary approach is necessary for achieving optimal patient outcomes.
- Everolimus (Afinitor) [BOOK]
- BOOKCanadian Agency for Drugs and Technologies in Health: Ottawa (ON)
- The objective of this review is to perform a systematic review of the beneficial and harmful effects of everolimus for the treatment of patients three years of age or older with subependymal giant ce...
The objective of this review is to perform a systematic review of the beneficial and harmful effects of everolimus for the treatment of patients three years of age or older with subependymal giant cell astrocytoma (SEGAs) associated with tuberous sclerosis complex (TSC) that have demonstrated serial growth, who are not candidates for surgical resection and for whom immediate surgery is not required.
- Discovery of novel human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2) inhibitors as potential anticancer agents. [Journal Article]
- EJEur J Med Chem 2018 Sep 07; 158:286-301
- The enzyme inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the de novo biosynthesis of guanine nucleotides, and thus regulates the guanine nucleotide pool required for c...
The enzyme inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the de novo biosynthesis of guanine nucleotides, and thus regulates the guanine nucleotide pool required for cell proliferation. Of the two isoforms, human IMPDH type 2 (hIMPDH2) is a validated molecular target for potential immunosuppressive, antiviral and anticancer chemotherapy. In search of newer hIMPDH2 inhibitors as potential anticancer agents, three novel series (A: 5-aminoisobenzofuran-1(3H)-one, B: 3,4-dimethoxyaniline and C: benzo[d]-[1,3]dioxol-5-ylmethanamine) were synthesized and evaluated for in vitro and cell-based activities. A total of 37 molecules (29-65) were screened for their in vitrohIMPDH2 inhibition, with particular emphasis on establishing their structure-activity relationship (SAR) trends. Eight compounds (hits, 30, 31, 33-35, 37, 41 and 43) demonstrated significant enzyme inhibition (>70% @ 10 μM); especially the A series molecules were more potent than B series (<70% inhibition @ 10 μM), while C series members were found to be inactive. The hIMPDH2 IC50 values for the hits ranged from 0.36 to 7.38 μM. The hits displaying >80% hIMPDH2 inhibition (30, 33, 35, 41 and 43) were further assessed for their cytotoxic activity against cancer cell lines such as MDA-MB-231 (breast adenocarcinoma), DU145 (prostate carcinoma), U87 MG (glioblastoma astrocytoma) and a normal cell line, NIH-3T3 (mouse embryonic fibroblast) using MTT assay. Most of the compounds exhibited higher cellular potency against cancer cell lines and notably lower toxicity towards NIH-3T3 cells compared to mycophenolic acid (MPA), a prototypical hIMPDH2 inhibitor. Two of the series A hits (30 and 35) were evaluated in human peripheral blood mononuclear cells (hPBMC) assay and found to be better tolerated than MPA. The calculated/predicted molecular and physicochemical properties were satisfactory with reference to drug-likeness. The molecular docking studies clearly demonstrated crucial interactions of the hits with the cofactor-binding site of hIMPDH2, further providing critical information for refining the design strategy. The present study reports the design and discovery of structurally novel hIMPDH2 inhibitors as potential anticancer agents and provides a guide for further research on the development of safe and effective anticancer agents, especially against glioblastoma.
- Granular cell astrocytoma: an aggressive IDH-wildtype diffuse gliomarwith molecular genetic features of primary glioblastoma. [Journal Article]
- BPBrain Pathol 2018 Sep 17
- Granular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCAs. Median age of presentation was 57.8 years and most cases developed in the frontal or tempo...
Granular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We studied a series of 39 GCAs. Median age of presentation was 57.8 years and most cases developed in the frontal or temporal lobes. Tumors included grade II (n=14), grade III (n=11), and grade IV (n=14) by WHO criteria. Granular cell morphology was diffuse in 31 (79%) cases and partial in eight (21%). Immunohistochemistry showed frequent positivity for GFAP (28 of 31), OLIG2 (16 of16), and CD68 (27 of 30), but HAM56, CD163, and IBA-1 histiocytic markers were all negative (22 of 22). IDH1(R132H) was negative in all the cases tested (16 of 16), while ATRX expression was retained (12 of 12). Cytogenetics demonstrated monosomy 10 (6 of 6) cases, +7 in 4 (of 6), -13q in 4 of 6, and -14 in 4 of 6. Next generation sequencing demonstrated mutations in PTEN/PIK3 genes in 6/13 (46%), NF1 in 3 of 10 (30%), TP53 in 3 of 13 (23%), PALB2 in 3 of 10 (30%), STAG2 in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%) and AR in 2 of 10 (20%). CDKN2A/B deletion was identified in 5 of 13 (30%) cases (homozygous deletion in 4). The TERT C228T mutation was identified in 9 of 13 (69%). No mutations were encountered in IDH1, IDH2, CIC, FUBP1, H3F3A, BRAF or ATRX genes. The mean overall survival was 11.3 months. Patients >60 years old at diagnosis had a worse survival than patients <60 years (p=0.001). There were no statistically significant differences in survival by WHO grade, extent of granular cell change, sex or MIB-1 (p>0.05). GCA is a variant of IDH-wildtype diffuse glioma with aggressive behavior irrespective of grade and extent of granular cell morphology, and with molecular genetic features corresponding to primary glioblastoma. This article is protected by copyright. All rights reserved.
- [Prognostic significance of combined TERT and IDH gene mutation analysis in diffusely infiltrating gliomas]. [Journal Article]
- ZBZhonghua Bing Li Xue Za Zhi 2018 Sep 08; 47(9):658-663
- Objective: To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot mutations of TERT and IDH1/2 genes were dete...
Objective: To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade Ⅰ, 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade Ⅱ, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade Ⅲ, 72 cases) and glioblastoma (WHO grade Ⅳ, 59 cases). The prognostic significance of TERT and IDH1/2 hot spot mutations was evaluated. Results: No IDH or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation frequency was higher in patients aged ≥40 years(60.8%, 93/153) than in patients aged <40 years (32.8%, 22/67; P<0.01). TERT promoter mutation rate was also significantly higher in oligodendroglioma (87.5% , 56/64) than that in astrocytoma(37.8%, 59/156; P<0.01). Young age (<40 years), oligodendroglioma and IDH1 mutation were favorable prognostic factors for diffusely infiltrating astrocytic and oligodendroglial tumors. TERT mutation alone was not of prognostic significance. Diffusely infiltrating astrocytic and oligodendroglial tumors were divided into four molecular subtypes according to TERT and IDH1 mutation status: IDH(+ )/TERT(+ ), IDH(+ )/TERT(-), IDH(-)/TERT(-) and IDH(-)/TERT(+ ). There was significant prognostic difference among the 4 subtypes. Conclusions: Combined IDH and TERT gene mutation analysis may be useful for prognostic subgrouping. Notably, IDH1 wild-type cases can be further subdivided into TERT(+ ) or (-) subgroups with significant prognostic difference.
- Safety of high-dose intravenous mistletoe therapy in pediatric cancer patients: A case series. [Journal Article]
- CTComplement Ther Med 2018; 40:198-202
- CONCLUSIONS: Our study underpinned the safety and feasibility of high-dose mistletoe infusion in children with advanced stages of cancer and showed noteworthy antineoplastic effects, which should be verified in a prospective clinical phase II/III-study. Because of possible side effects, the treatment should be implemented only in an in-patient setting in experienced pediatric oncology centers.
- Meningioma mimicking an intraparenchymal cystic tumor. [Journal Article]
- NJNagoya J Med Sci 2018; 80(3):431-434
- Meningiomas rarely exhibit cystic lesions with mural nodules, and may be misdiagnosed as intraparenchymal cystic tumors. We herein present a 64-year-old woman with a cystic lesion and enhancing mural...
Meningiomas rarely exhibit cystic lesions with mural nodules, and may be misdiagnosed as intraparenchymal cystic tumors. We herein present a 64-year-old woman with a cystic lesion and enhancing mural nodule in the left temporal lobe accompanied by peritumoral brain edema. Differential diagnoses included low-grade gliomas, hemangioblastoma, and cystic meningioma. Gross total resection of the tumor was achieved through a temporal surgical approach. Intraoperative findings showed that the tumor was an extraparenchymal tumor. The cyst was covered by an extraparenchymal thin membrane and the cystic fluid was yellowish in color. The final result of the pathological examination was microcystic meningioma, WHO grade I. Although intraparenchymal tumors, such as hemangioblastoma, ganglioglioma, pilocytic astrocytoma, and pleomorphic xanthoastrocytoma, commonly display this MRI pattern, meningioma needs to be included in the differential diagnosis.
- Cognitive features and surgical outcome of patients with long-term epilepsy-associated tumors (LEATs) within the temporal lobe. [Journal Article]
- EBEpilepsy Behav 2018 Sep 10; 88:25-32
- CONCLUSIONS: Patients with LEATs in the temporal lobe frequently show cognitive impairments. Predictors for pre- and postoperative cognition mostly correspond to what is known for temporal lobe epilepsy and resections in general. However, different tumor types appear to be associated with different cognitive and seizure outcomes with astrocytoma as the least benefitted group.
New Search Next
- Fluorescein-Guided Surgery for Pediatric Brainstem Gliomas: Preliminary Study and Technical Notes. [Journal Article]
- JNJ Neurol Surg B Skull Base 2018; 79(Suppl 4):S340-S346
- Introduction Brainstem gliomas (BsG) account for 10 to 15% of pediatric brain tumors. Surgery is the preferred treatment for focal and exophytic lesions. Sodium fluorescein has been proven safe and ...
Introduction Brainstem gliomas (BsG) account for 10 to 15% of pediatric brain tumors. Surgery is the preferred treatment for focal and exophytic lesions. Sodium fluorescein has been proven safe and effective in resection of malignant brain tumors. Objective The objective was to o analyze the safety and effectiveness of this approach, to evaluate intraoperative fluorescein imaging, and to measure the safety of chosen dose for pediatric patients. Methods Twelve cases were enrolled between March 2014 and September 2016 in Beijing Tiantan Hospital. All of the patients received 2.5 mg/kg of sodium fluorescein before opening the dura; the intraoperative fluorescence enhancement was observed, and the degree of satisfaction and consistency with the neuronavigation were evaluated. Results With a mean age of 7.5 years, there were eight cases located within the pontine, three in the medullary oblongata, and one in the tectal plate. Histological results were astrocytoma, glioblastoma, oligodendroglioma, and pilocytic astrocytoma. Under the fluorescein module of the microscope, the tumors were recognizable enough to help surgeons to discriminate the lesion from non-fluorescent tissue, with a consistency of 83% with the neuronavigation. Total removal was accomplished in nine cases, while the mean percentage of resection of the other cases was 93.7%. The Karnofsky performance score (KPS) showed no significant differences between pre-operation and discharge, but there was a difference between pre-operation and 6-month follow-up. Conclusion The fluorescein-guided surgery is useful for demarcating the tumor margin and works well with other navigation and monitoring devices. A safe dose of sodium fluorescein (2.5 mg/kg) was proven effective for children.