The inhibition of Aurora A kinase regulates phospholipid remodeling by upregulating LPCAT1 in glioblastoma.

Metabolic reprogramming is a common feature of glioblastoma (GBM) progression and metastasis. Altered lipid metabolism is one of the most prominent metabolic alterations in cancer. Understanding the links between phospholipid remodeling and GBM tumorigenesis may help develop new anticancer strategies and improve treatments to overcome drug resistance. We used metabolomic and transcriptomic analyses to systematically investigate metabolic and molecular changes in low-grade glioma (LGG) and GBM. We then re-established the reprogrammed metabolic flux and membrane lipid composition in GBM based on metabolomic and transcriptomic analyses. By inhibiting Aurora A kinase via RNA interference (RNAi) and inhibitor treatment, we investigated the effect of Aurora A kinase on phospholipid reprogramming LPCAT1 enzyme expression and GBM cell proliferation in vitro and in vivo. We found that GBM displayed aberrant glycerophospholipid and glycerolipid metabolism compared with LGG. Metabolic profiling indicated that fatty acid synthesis and uptake for phospholipid synthesis were significantly increased in GBM compared to LGG. The unsaturated phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels were significantly decreased in GBM compared to LGG. The expression level of LPCAT1, which is required for the synthesis of saturated PC and PE, was upregulated in GBM, and the expression of LPCAT4, which is required for the synthesis of unsaturated PC and PE, was downregulated in GBM. Notably, the inhibition of Aurora A kinase by shRNA knockdown and treatment with Aurora A kinase inhibitors such as Alisertib, AMG900, or AT9283 upregulated LPCAT1 mRNA and protein expression in vitro. In vivo, the inhibition of Aurora A kinase with Alisertib increased LPCAT1 protein expression. Phospholipid remodeling and a reduction in unsaturated membrane lipid components were found in GBM. Aurora A kinase inhibition increased LPCAT1 expression and suppressed GBM cell proliferation. The combination of Aurora kinase inhibition with LPCAT1 inhibition may exert promising synergistic effects on GBM.

Effects of Sevoflurane and Propofol on Neurological Recovery of Traumatic Brain Injury Patients in the Early Postoperative Stage: A Retrospective Cohort Study.

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury (TBI) patients in the early postoperative stage.Methods We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy. Generalized additive mixed model (GAMM) was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale (GCS) on postoperative days 1, 3, and 7. Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale (GOS) at discharge.Results A total of 340 TBI patients were enrolled in this study. There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group, and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group. It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients (ß = 0.75, 95%CI: -0.55 to 2.05, P = 0.260). However, elevation in GCS from baseline was 1.73 points (95%CI: -2.81 to -0.66, P = 0.002) less in the sevoflurane group than that in the propofol group on postoperative day 1, 2.03 points (95%CI: -3.14 to -0.91, P < 0.001) less on day 3, and 1.31 points (95%CI: -2.43 to -0.19, P = 0.022) less on day 7. The risk of unfavorable GOS (GOS 1, 2, and 3) at discharge was higher in the sevoflurane group (OR = 4.93, 95%CI: 1.05 to 23.03, P = 0.043). No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS.Conclusions Compared to propofol, sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy. This difference was not detected in TBI patients undergoing decompressive craniectomy.

The clinicoradiological features and surgical outcomes of primary intracranial fibrosarcoma: a single-institute experience with a systematic review.

Primary intracranial fibrosarcoma (PIF) was a rare tumor with a high relapse rate and dismal survival rate. This study aimed to delineate the clinical characteristics of primary intracranial fibrosarcoma (PIF) and the risk factors for outcomes. We reviewed 15 PIF patients, who underwent surgical treatment at our institution from January 2009 to December 2018. Meanwhile, 36 cases from the prior literature between November 1962 and December 2019 were also retrieved and pooled to identify the risk factors. In our cohort, while cystic component (46.7%), perilesional edema (83.3%), and vascular flow void (66.7%) were commonly observed, no patient was accurately diagnosed. The 2-year relapse-free survival (RFS) and overall survival (OS) were 12.2% and 30.2%, respectively. Based on the pooled data, tumor size (p = 0.006), Ki-67 index (p = 0.004), and radiotherapy dose (p = 0.029) were prognostic factors for RFS in univariate analysis. In the univariate analysis, tumor size (p = 0.002), NGTR (p = 0.049), and high Ki-67 index (p = 0.019) were significant predictors for OS; and further multivariate analysis (n = 18) showed that large tumor size (≥ 5 cm; HR 14.613, p = 0.022) and high Ki-67 index (≥ 30%; HR 5.879, p = 0.020) were the independent risk factors for OS. Due to the rarity and nonspecific clinicoradiological features, the correct diagnosis of PIF before surgery was challenging. The outcomes of PIF were poor, and GTR plus radiotherapy (at least 60 Gy) might benefit to the outcomes and were recommended. Future study with a large cohort was needed to verify our findings.

Overall Survival of Primary Intracranial Atypical Teratoid Rhabdoid Tumor Following Multimodal Treatment: A Pooled Analysis of Individual Patient Data.

No standard treatment protocol to guide the management of the primary central nervous system atypical teratoid rhabdoid tumors (ATRTs). To evaluate the efficacy of GTR (gross total resection), RT (radiotherapy), CCMT (conventional chemotherapy), or intensified chemotherapy (ICMT) and verify the optimal treatment strategy. A total of 501 cases (18 cases from our center and 483 cases from published literature) were eligible for analysis. Clinical characteristics were reviewed, and overall survival (OS) of each combined treatment modality was compared. These prior publication data were processed according to PRISMA guidelines. This study included 265 (52.9%) males and 216 (43.1%) females. The median age of the cohort was 2.2 years with 295 (58.9%) cases younger than 3 years. GTR was achieved in 217 (43.3%) patients. Initial adjuvant CCMT, CCMT plus intrathecal chemotherapy (ITCMT), CCMT plus high-dose chemotherapy (HDCMT), and CCMT plus ITCMT and HDCMT were administered in 228 (45.5%), 78 (15.6%), 55 (11.0%), and 24 (4.8%) patients, respectively. Radiotherapy (RT) was prescribed in 266 (53.1%) patients. Fewer patients younger than 3 years old received RT (21.9% vs 33.0%, p < 0.001, chi-square test). The OS of the entire cohort at 1, 3, and 5 years were 56.6, 35.9, and 30.8%, respectively. After adjusting for age and sex, GTR (HR 0.630; p < 0.001), RT (HR = 0.295; p < 0.001), CCMT (HR = 0.382; p < 0.001), and ICMT (HR = 0.209; p < 0.001) were independent prognostic factors. The 3-year OS of surgery alone, surgery plus CCMT, surgery plus RT, surgery plus ICMT, surgery plus CCMT and RT, and surgery plus ICMT and RT were 8.9, 13.4, 23.7, 37.4, 48.3, and 68.5%, respectively. When taking into consideration the extent of tumor resection (n = 462), GTR followed by RT, CCMT, intrathecal chemotherapy, and high-dose chemotherapy provided the best OS (5-year OS 88.2%). In younger children, adjuvant ICMT had a greater 3-year OS than adjuvant RT alone (34.0% vs 0%, p = .001). This study identified independent favorable predictors for OS of ATRTs and distinguished significantly different OS following various treatment modalities. If tolerable, intensive treatment with GTR followed by adjuvant RT and ICMT is recommended. Intensified CCMT could be an alternative to avoid radiological radiotoxicity for younger children CRD42018098841.

Correction to: Clinical features, radiological profiles, and surgical outcomes of primary intracranial solitary plasmacytomas: a report of 17 cases and a pooled analysis of individual patient data.

The article Clinical features, radiological profiles, and surgical outcomes of primary intracranial solitary plasmacytomas: a report of 17 cases and a pooled analysis of individual patient data, written by Xiu-Jian Ma, Da Li, Liang Wang, Shu-Yu Hao, Li-Wei Zhang, Jun-Ting Zhang, Zhen Wu, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 7 January 2019 with open access. With the authors' decision to step back from Open Choice, the copyright of the article changed on 25 January 2019 to © Springer Science + Business Media, LLC, part of Springer Nature 2019 and the article is forthwith distributed under the terms of copyright.

Clinical features, radiological profiles, and surgical outcomes of primary intracranial solitary plasmacytomas: a report of 17 cases and a pooled analysis of individual patient data.

PURPOSE: We aim to delineate the clinical characteristics of patients with primary intracranial solitary plasmacytoma (PISPC) and prognostic factors for their outcomes. METHODS: This study retrospectively reviewed 17 patients with PISPC from our center and an additional 70 cases of PISPC published previously to analyze outcome predictors. RESULTS: The entire cohort included 38 (43.7%) males and 49 (56.3%) females with a mean age of 54 years. Skull base tumors were found in 49 (56.3%) patients. Gross total resection (GTR) was achieved in 31 (35.6%) patients. Postoperative adjuvant treatments, including radiotherapy (RT) alone, chemotherapy (CMT) alone, and RT + CMT were administered in 49 (56.3%) patients, 3 (3.5%) patients, and 16 (18.4%) patients, respectively. After a median follow-up of 24 (mean 42.4) months, the 5-year disease progression-free survival (PFS), recurrence-free survival (RFS), multiple myeloma (MM)-free survival (MMFS), and overall survival (OS) were 52.9%, 76.2%, 69.6%, and 76.1%, respectively. Multivariate analysis unveiled that a skull base tumor location (HR 2.395, p = 0.040) and no RT (HR 3.115, p = 0.004) were negative prognostic factors for PFS, no RT (HR 10.526, p = 0.003) for RFS, each 1-year increase in age (HR 1.039, p = 0.049) for MMFS, and increasing age (HR 1.052, p = 0.043) and CMT (HR 6.022, p = 0.005) were risk factors for OS. However, GTR did not benefit the aforementioned outcomes. CONCLUSION: For patients with presumed PISPC, a biopsy followed by RT is recommended for skull base PISPC. However, the role of CMT is still not clear. Our findings need to be verified in a larger prospective cohort in the future. Systematic review registration number CRD42018098782.

Recurrent petroclival meningiomas: clinical characteristics, management, and outcomes.

This study seeks to elucidate the prognostic predictors and outcomes of recurrent/progressive petroclival meningiomas (PCMs). We reviewed our cohort of 39 recurrent/progressive PCMs (27 females, 69.2%) and analyzed the results from the literature. Twenty-three patients underwent reoperations, 2 received radiotherapy alone, and 14 declined any treatment. During a follow-up of 70.4 months, 7 patients experienced a 2nd recurrence/progression (R/P) and 18 patients died. In the 23 patients, gross total resection (GTR), subtotal resection (STR), and partial resection (PR) were achieved in 8, 8, and 7 patients, respectively. The percentage of the 2nd R/P-free survival of GTR, STR, and PR was 88%, 67%, and 40%, respectively. The overall survival following the 1st R/P of GTR, STR, and PR was 88%, 63%, and 33%, respectively. Patients rejecting treatment suffered from significantly poor overall survival (7%; p = 0.001) and short survival duration (42.0 months; p = 0.016) compared with that of the patients receiving treatment (67% and 86.9 months). The GTR was the only independent favorable predictor. In the 21 included studies with 98 recurrent/progressive PCM patients, 17 patients presented with a 2nd R/P and 10 died of a 2nd R/P; patients undergoing observation had a significantly poor tumor regrowth control rate compared with patients undergoing surgery (p = 0.004) or radiotherapy alone (p < 0.001). Proactive treatment should be performed for patients with recurrent/progressive PCMs. Observation can lead to relentless outcome. GTR as a preferential therapeutic strategy should be pursued as far as possible on the condition of minimal functional impairment.

Factors influencing the growth rate of vestibular schwannoma in patients with neurofibromatosis type 2.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a devastating disease with no well-accepted management guidelines. Better understanding of the disease process provides the basis for how or when to initiate treatment. Only few studies have addressed the factors influencing the growth rate of NF2-related vestibular schwannomas (VSs), and these studies have reported variable results. This study aimed to assess the clinical factors influencing the growth rate of NF2-related VSs. METHODS: The medical records of 66 patients (totalling 74 VSs) were retrospectively analysed. The tumours were measured according to a two-component box model. The tumour growth rate was estimated by linear regression analysis of the changes in VS volumes over time. The clinical characteristics of all the patients were recorded. The relationship between the tumour growth rate and clinical factors were analysed. Linear regression, Pearson's correlation and Student's t-test were conducted using the SPSS 19.0 statistical package. RESULTS: The median follow-up duration was 4.9 years. The VSs growth rate was highly correlated with the initial VS volume (r = 0.97, p < 0.01). However, it was inversely correlated with the age at symptom onset (r = -0.41, p < 0.01). The average VS growth rate in patients with spinal tumours was 13.18 cm(3)/year compared with 0.19 cm(3)/year in patients without spinal tumours (p < 0.01). The VS growth rate in patients who had resection of a contralateral VS was slightly higher than that of patients with untreated VSs (p < 0.01). Other factors including sex, vestibular symptom, presence of other cranial schwannomas, family history and dermal abnormalities did not affect the VS growth rate. CONCLUSIONS: The potential clinical factors influencing the VS growth rate are the age at symptom onset, initial tumour volume and presence of spinal tumours. Surgical resection of VSs might accelerate the growth rate of contralateral tumours. The effects of these factors require further experimental confirmation.

Clinical, radiological, and pathological features of 16 papillary glioneuronal tumors.

BACKGROUND: Papillary glioneuronal tumors (PGNTs) are a novel distinct intracranial neoplastic entity. In this study, the authors aimed to analyze the clinical, radiological, and pathological features of PGNT. METHODS: Clinical charts and radiographs of 16 cases of PGNT surgically treated between 2006 and 2013 were retrospectively reviewed. Follow-up evaluations and a literature review were performed. RESULTS: The study included nine males and seven females with a mean age of 23.8 years. The most common preoperative symptom was headache (68.8 %, 11 of 16 patients). Radiological results showed that the frontal lobe (25.0 %) was the most common portion of the brain involved, and 13 lesions (81.3 %) presented with cystic appearance with or without solid elements. All patients were misdiagnosed as non-PGNT tumors. Complete resection was achieved in 12 patients (75.0 %). Ki67 staining was positive in <1 % of cells present in eight lesions and varied in the other eight lesions, with a range of 1 % to 13 %. The mean follow-up duration was 56.2 months, and no recurrence was observed. Seventy-seven PGNTs (40 males, 51.9 %) have been reported, and 49 patients stained positive for Ki67/MIB-1. Of these cases, 28 (57.1 %) had positive staining rates of ≥1 %. In 51 patients for whom outcome information was available, six (11.8 %) exhibited recurrence, and the recurrence rates for complete resection and incomplete resection were 5.1 % and 33.3 %, respectively. CONCLUSIONS: PGNTs displayed a wide spectrum of clinical and radiological phenotypes, and they were more frequently observed in the frontal lobe and in young patients without sex predilection. Fair outcomes could be achieved by complete resection. Although PGNT displayed indolent pathobiology, atypical appearances were observed. More patients and longer follow-up periods are needed to further elucidate the biological features of PGNTs.

Quantitative computer tomography analysis of post-operative subdural fluid volume predicts recurrence of chronic subdural haematoma.

BACKGROUND: Post-operative volume of subdural fluid is considered to correlate with recurrence in chronic subdural haematoma (CSDH). Information on the applications of computer-assisted volumetric analysis in patients with CSDHs is lacking. OBJECTIVE: To investigate the relationship between haematoma recurrence and longitudinal changes in subdural fluid volume using CT volumetric analysis. METHODS: Fifty-four patients harbouring 64 CSDHs were studied prospectively. The association between recurrence rate and CT findings were investigated. RESULTS: Eleven patients (20.4%) experienced post-operative recurrence. Higher pre-operative (over 120 ml) and/or pre-discharge subdural fluid volumes (over 22 ml) were significantly associated with recurrence; the probability of non-recurrence for values below these thresholds were 92.7% and 95.2%, respectively. CSDHs with larger pre-operative (over 15.1 mm) and/or residual (over 11.7 mm) widths also had significantly increased recurrence rates. Bilateral CSDHs were not found to be more likely to recur in this series. On receiver-operating characteristic curve, the areas under curve for the magnitude of changes in subdural fluid volume were greater than a single time-point measure of either width or volume of the subdural fluid cavity. CONCLUSIONS: Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the 'self-resolution' period can be used as significantly radiological predictors of recurrence.

Apnea as an uncommon preoperative manifestation of medulla cavernous malformation: surgical treatment and literature review.

OBJECTIVE: Apnea is not a common preoperative manifestation of medulla cavernous malformations (CMs). The role of surgical resection in patients suffering from apnea secondary to hemorrhage from medulla CMs requires further definition. METHODS: Medical records and radiographs were reviewed retrospectively for four patients treated surgically for medulla CMs in our institution between 2008 and 2011. Recent outcomes for these patients were also evaluated. The modified Rankin Scale (mRS) was used to evaluate neurological function. RESULTS: All four patients (3 male, 1 female; mean age: 41.3 years) suffered two or three hemorrhages with a preoperative mRS of five and, due to the loss of autonomous respiration and consciousness, underwent a preoperative tracheotomy for mechanical ventilation, which lasted an average of 4.5 days. Prior to surgery, all patients had recovered to the point of maintaining spontaneous breath and normal blood gas values with oxygen supplementation. Lesions were totally resected in all patients via the posterior suboccipital approach. Postoperative ventilation was continued in one patient for 1 day. The mean postoperative mRS score at discharge was 3.5, and all patients had improved from their previous scores. The tracheostomy was closed in three patients at 15, 16, and 35 days after surgery. After a mean follow-up of 34.7 months, the most recent mRS scores were 3, 2, 2, and 2; no recurrent hemorrhage was noted, and three patients lived independently. CONCLUSION: In carefully selected patients with hemorrhage due to medulla CMs, favorable outcomes can be achieved even if apnea was a part of the preoperative clinical presentation. Surgery should be considered in these patients, particularly in those with repeated hemorrhages, and apnea should not be considered an absolute contraindication to surgery.

Surgical management and outcomes of petroclival meningiomas: a single-center case series of 259 patients.

BACKGROUND: Surgical management of petroclival meningiomas is challenging. Various and inconsistent outcome and prognostic factors of the lesions have been evaluated previously. In the present study, the surgical outcome, philosophy, and experience of petroclival meningiomas are detailed based on a large patient series. METHODS: A series of 259 patients with petroclival meningiomas (70 males and 189 females) were surgically treated. Clinical charts and radiographs were reviewed. Follow-up results were evaluated. RESULTS: The preoperative Karnofsky Performance Scale (KPS) score was 74.2 ± 10.5. The mean tumor size was 4.3 ± 1.0 cm. The gross total resection (GTR) rate was 52.5%. During a mean follow-up period of 55.3 months, recurrence/progression (R/P) occurred in 11 patients. The recent KPS score was 78.4 ± 22.7, it improved in 139 (57.2%) patients and stabilized in 53 (21.8%) patients, and 201 (82.7%) patients lived independently. The risk factors affecting the KPS score included (but were not limited to) age ≥ 60, preoperative KPS ≤ 60, and brainstem edema. The adverse factors contributing to R/P-free survival included (but were not limited to) non-total resection and the absence of the subarachnoid space. The R/P-free survival rate was 94.5% at 5 years and 91.2% at 9 years. The overall survival rate was 94.7% at 5 years and 94.7% at 9 years. CONCLUSIONS: Favorable outcomes from petroclival meningiomas could be achieved by microsurgery. Neurological function and quality of life were prioritized, and GTR was attempted. Risk factors should be considered in surgical schemes, and tumor recurrence should be aggressively monitored and treated.

[Microsurgical treatment for jugular foramen meningiomas].

OBJECTIVE: To explore the microsurgical treatment and clinical efficacies of jugular foramen meningiomas. METHODS: A total of 28 patients with jugular foramen meningiomas undergoing microsurgical operations at Beijing Tiantan Hospital during the period from April 1996 to April 2011 were analyzed retrospectively. The retrosigmoid suboccipital (n = 13), far lateral (n = 9), postauricular trans-supracondylar (n = 4) and trans-paracondylar approaches (n = 2) were used. RESULTS: Complete tumor resection was achieved in 18 patients and subtotal tumor resection in 10 patients. Twenty-two patients were followed up for a mean follow-up period of 3 years. The postoperative Karnofsky performance scale was above 80 in 19 patients. Twelve patients experienced hoarseness or bucking, 11 lived independently and 2 died of tumor recurrence. CONCLUSION: Jugular foramen meningiomas have a higher recurrence rate and severe cranial nerve damages may occur postoperatively. It is important to classify them into different clinical entities and choose appropriate surgical approaches and techniques so as to achieve satisfactory outcomes.

[Microsurgical treatment of giant cell tumor of skull].

OBJECTIVE: To explore the diagnosis and microsurgical treatment of giant cell tumor (GCT) of skull. METHODS: The investigators reviewed the clinical features, operative approach and prognosis of 23 consecutive cases of GCT of skull operated at our department between July 2000 and November 2008. RESULTS: Headache was the most common presenting symptom (86.96%) found among the patients with GCT of skull. Besides, the symptoms induced by the consequent lesions of II-XII intracranial nerves were also commonly observed. The mean duration of symptoms was 29.3 months and the mean preoperative KPS (Karnofsky performance scale) was 76 +/- 6. Among these cases, 10 tumors occurred in sphenoid bone, 9 in temporal bone, 3 in posterior fossa and 1 in frontal bone. Gross total resections were achieved in 6 cases, subtotal resections in 10 cases and partial resections in 7 cases. There was no operative death case. The follow-up data of 18 patients (78.26%) were collected with a mean follow-up duration of 35.5 months. All patients lived in normal postoperative life. CONCLUSION: GCT of skull is a generally low-degree malignancy showing a local bone invasion mostly in sphenoid and temporal bones.

Prognostic and predictive value of an immune infiltration signature in diffuse lower-grade gliomas.

BACKGROUNDLower-grade gliomas (LGGs) vary widely in terms of the patient's overall survival (OS). There is no current, valid method that could exactly predict the survival. The effects of intratumoral immune infiltration on clinical outcome have been widely reported. Thus, we aim to develop an immune infiltration signature to predict the survival of LGG patients.METHODSWe analyzed 1216 LGGs from 5 public data sets, including 2 RNA sequencing data sets and 3 microarray data sets. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select an immune infiltration signature and build a risk score. The performance of the risk score was assessed in the training set (329 patients), internal validation set (140 patients), and 4 external validation sets (405, 118, 88, and 136 patients).RESULTSAn immune infiltration signature consisting of 20 immune metagenes was used to generate a risk score. The performance of the risk score was thoroughly verified in the training and validation sets. Additionally, we found that the risk score was positively correlated with the expression levels of TGF-ß and PD-L1, which were important targets of combination immunotherapy. Furthermore, a nomogram incorporating the risk score, patient's age, and tumor grade was developed to predict the OS, and it performed well in all the training and validation sets (C-index: 0.873, 0.881, 0.781, 0.765, 0.721, and 0.753).CONCLUSIONThe risk score based on the immune infiltration signature has reliable prognostic and predictive value for patients with LGGs and is a potential biomarker for the cotargeting immunotherapy.FUNDINGThis work was supported by The National Natural Science Foundation of China (grant nos. 81472370 and 81672506), the Natural Science Foundation of Beijing (grant no. J180005), the National High Technology Research and Development Program of China (863 Program, grant no. 2014AA020610), and the National Basic Research Program of China (973 Program, grant no. 2014CB542006).

MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells.

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.

Tumefactive demyelinating lesions: nine cases and a review of the literature.

Tumefactive demyelinating lesions (TDLs) are misdiagnosed frequently. To investigate the characteristics of TDLs, clinical and radiological data from nine cases with TDLs were analyzed after admission. All cases underwent surgery and pathological examination; some received postoperative steroid therapy. Onsets were mostly within 3 weeks and main presentation included intracranial hypertension, extremity weakness, epilepsy, and visual disturbance. Symptoms in children were acute and severe, frequently including headache, vomiting, and visual disturbance. Most intracephalic lesions were in cerebral hemispheres. All intraspinal lesions were in cervical segments. Radiological features included mass effect, perifocal edema and enhancement (of which open-ring enhancement was diagnostic), and decreased relative cerebral blood volume. Intraoperative frozen section did not confirm the diagnosis, while postoperative paraffin section did confirm it (by evidence of macrophage infiltration). The patients responded well to steroid therapy and no relapse was found during following up. Thus, intensive analysis of both clinical and radiological data may provide some clues for diagnosis. For suspected cases, it is advisable to take steroid therapy or undergo advanced radiological examinations, such as serial magnetic resonance spectroscopy. However, in difficult cases, pathological evidence is beneficial to a final diagnosis.

Skull Base Juvenile Psammomatoid Ossifying Fibroma: Clinical Characteristics, Treatment, and Prognosis.

OBJECTIVE: The diagnosis and management for juvenile psammomatoid ossifying fibroma (JPOF) of the skull base are challenging, and clinical data are limited. METHODS: A retrospective review of JPOF was performed, and the clinical characteristics, treatment strategy, and prognosis were analyzed. RESULTS: There were 23 patients pathologically confirmed with JPOF, most with JPOF located in the skull base area (19/23, 82.6%). Of those tumors, 43.5% presented with dura matter breakthrough. Most of the chief complaints were headache (n = 8, 34.8%) and visual impairment (n = 5, 21.7%). Most of the tumors were solid tumors with spherical appearance, frequently accompanied by cysts of various size (n = 14, 60.9%). Craniotomy, mostly via the frontal approach, was the most common approach in the present series, comprising 73.6% (17/23) of all cases. The endoscopic endonasal approach was performed in 6 cases (26.1%). In total, 62.5% of patients (15/23) underwent gross total resection, 8.7% of patients (2/23) underwent subtotal resection, and 26.1% of patients (6/23) underwent partial resection. After a mean follow up of 66.1 ± 36.1 months (range, 3-124), 3 patients (13.6%) suffered from tumor recurrence with a mean recurrence time of 13 months. CONCLUSIONS: The present series of skull base JPOFs showed that radical surgery combined with skull base reconstruction contributed to overall good prognosis. Further studies are needed to evaluate the long-term outcomes and to characterize its pathologic characteristics.

Treatment strategy and long-term outcomes of primary intracranial rhabdomyosarcoma: a single-institution experience and systematic review.

OBJECTIVE: Primary intracranial rhabdomyosarcoma (PIRMS) is rare, and the effects of the treatment strategy on overall survival (OS) are unclear. This study aimed to evaluate risk factors pertinent to OS and to propose an optimal treatment strategy. METHODS: Clinical data of patients with PIRMS treated at Beijing Tiantan Hospital and from the English-language literature between 1946 and 2018 were reviewed. A literature review was performed via Ovid, MEDLINE, Embase, PubMed, Web of Science, and Cochrane databases using the terms "rhabdomyosarcoma," "intracranial," "cerebral," and "brain." Previously published data were processed and used according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: There were 8 males (66.7%) and 4 females with PIRMS at our institution, with a mean age of 24.3 years. Gross-total resection was achieved in 4 patients (33.3%), and adjuvant radiation and chemotherapy were administered in 5 (45.5%) and 3 (27.3%) patients, respectively. After a mean follow-up period of 13.7 months, all patients developed local-regional recurrence and died of the disease. Twenty-nine cases (14 female and 15 male) were reported in the literature with a median age of 9.0 years. After a mean follow-up duration of 18.6 months, 13 patients (44.8%) developed recurrences, 7 patients (24.1%) had extracranial metastasis, and 14 patients (48.3%) died. In the pooled cases, adjuvant radiation (hazard ratio [HR] 0.089, 95% confidence interval [CI] 0.027-0.288, p < 0.001) and age < 10 years (HR 0.227, 95% CI 0.077-0.666, p = 0.007) were independent predictors of good local-regional progression-free survival (LR-PFS). Adjuvant radiation therapy (HR 0.301, 95% CI 0.110-0.828, p = 0.020) and age < 10 years (HR 0.359, 95% CI 0.131-0.983, p = 0.046) were significant predictors for favorable OS in the multivariate model. CONCLUSIONS: Due to the rarity of the disease, a poor outcome of PIRMS was demonstrated based on the pooled cohort. Use of radiation was associated with improved outcomes and should be considered to improve OS/LR-PFS. Further study is required to identify the optimal treatment regimen.Systematic review no.: CRD42019121249 (crd.york.ac.uk/PROSPERO/).

A Logistic Regression Model for Detecting the Presence of Malignant Progression in Atypical Meningiomas.

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.