Zenghui Qian

Aneurysm Characteristics Associated with the Rupture Risk of Intracranial Aneurysms: A Self-Controlled Study

This study analyzed the rupture risk of intracranial aneurysms (IAs) according to aneurysm characteristics by comparing the differences between two aneurysms in different locations within the same patient. We utilized this self-controlled model to exclude potential interference from all demographic factors to study the risk factors related to IA rupture. A total of 103 patients were diagnosed with IAs between January 2011 and April 2015 and were enrolled in this study. All enrolled patients had two IAs. One IA (the case) was ruptured, and the other (the control) was unruptured. Aneurysm characteristics, including the presence of a daughter sac, the aneurysm neck, the parent artery diameter, the maximum aneurysm height, the maximum aneurysm width, the location, the aspect ratio (AR, maximum perpendicular height/average neck diameter), the size ratio (SR, maximum aneurysm height/average parent diameter) and the width/height ratio (WH ratio, maximum aneurysm width/maximum aneurysm height), were collected and analyzed to evaluate the rupture risks of the two IAs within each patient and to identify the independent risk factors associated with IA rupture. Multivariate, conditional, backward, stepwise logistic regression analysis was performed to identify the independent risk factors associated with IA rupture. The multivariate analysis identified the presence of a daughter sac (odds ratio [OR], 13.80; 95% confidence interval [CI], 1.65–115.87), a maximum aneurysm height ≥7 mm (OR, 4.80; 95% CI, 1.21–18.98), location on the posterior communicating artery (PCOM) or anterior communicating artery (ACOM; OR, 3.09; 95% CI, 1.34–7.11) and SR (OR, 2.13; 95% CI, 1.16–3.91) as factors that were significantly associated with IA rupture. The presence of a daughter sac, the maximum aneurysm height, PCOM or ACOM locations and SR (>1.5±0.7) of unruptured IAs were significantly associated with IA rupture.

ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for astrocytic tumors

Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. Malignant astrocytic tumors such as glioblastoma (GBM) are the most lethal intracranial tumors. However, the clinical practicability and significance of molecular parameters for the diagnostic and prognostic prediction of astrocytic tumors is still limited. In this study, we detected ATRX, IDH1-R132H and Ki-67 by immunohistochemistry and observed the association of IDH1-R132H with ATRX and Ki-67 expression. There was a strong association between ATRX loss and IDH1-R132H (p<0.0001). However, Ki-67 high expression restricted in the tumors with IDH1-R132H negative (p=0.0129). Patients with IDH1-R132H positive or ATRX loss astrocytic tumors had a longer progressive- free survival (p<0.0001, p=0.0044, respectively). High Ki-67 expression was associated with shorter PFS in patients with astrocytic tumors (p=0.002). Then we characterized three prognostic subgroups of astrocytic tumors (referred to as A1, A2 and A3). The new model demonstrated a remarkable separation of the progression interval in the three molecular subgroups and the distribution of patients’ age in the A1-A2-A3 model was also significant different. This model will aid predicting the overall survival and progressive time of astrocytic tumors’ patients.

Progressive Occlusion of Enterprise Stent-Assisted Coiling of Ruptured Wide-Necked Intracranial Aneurysms and Related Factors on Angiographic Follow-Up: A Single-Center Experience with 468 Patients

This study was designed to assess the effect of the Enterprise stent on progressive occlusion of wide-necked aneurysms and to evaluate the association between dubious factors and progressive occlusion, which is a consecutive, retrospective, single-center study. Data from 468 patients with 495 wide-necked aneurysms, who had undergone Enterprise stent-assisted coiling (SAC) were reviewed, and the clinical outcomes and the angiographic results were analyzed. A 14-month clinical follow-up was achieved in 421 of the 468 patients (90.0%), showing modified Rankin Scale (mRS) 0–1 in 364 (86.4%), mRS 2 in 17 (4.1%), mRS 3 in 17 (4.1%), mRS 4–5 in 9 (2.1%), and mRS 6 in 14 (3.3%) patients. Overall, the morbidity and mortality were 10.2% and 3.3%, respectively. Initial angiographic results showed Raymond scale (RS)1 in 273 (55.2%), RS2 in 194 (39.2%), and RS3 in 28 (5.6%) patients. Eight-month angiographic follow-up was available in 394 of 495 patients (79.6%), and RS1 was seen in 315 (79.9%), RS2 in 65 (16.5%) and RS3 in 14 (3.6%) cases. At the end of the follow-up, 115 of the 165 (69.7%) patients with initial RS2 and RS3 showed progressive occlusion. Statistical analysis showed no significant difference between progressive occlusion and age (p = 0.654), sex (p = 0.016), aneurysm diameter (p = 0.010), neck size (p = 0.124), dome-to neck ratio (DNR) (p = 0.018) and location (p = 0.001) at the time of follow-up. SAC using Enterprise stent is not only feasible for wide-necked aneurysms, but can achieve a high rate of progressive occlusion with good clinical outcomes at medium-term follow-up. Patient age and aneurysm neck size showed no associated with progressive occlusion at follow-up, while sex, aneurysm diameter, DNR and location were significantly associated with progressive occlusion.

MRI features can predict EGFR expression in lower grade gliomas: A voxel-based radiomic analysis

AbstractObjectiveTo identify the magnetic resonance imaging (MRI) features associated with epidermal growth factor (EGFR) expression level in lower grade gliomas using radiomic analysis.Methods270 lower grade glioma patients with known EGFR expression status were randomly assigned into training (n=200) and validation (n=70) sets, and were subjected to feature extraction. Using a logistic regression model, a signature of MRI features was identified to be predictive of the EGFR expression level in lower grade gliomas in the training set, and the accuracy of prediction was assessed in the validation set.ResultsA signature of 41 MRI features achieved accuracies of 82.5% (area under the curve [AUC] = 0.90) in the training set and 90.0% (AUC = 0.95) in the validation set. This radiomic signature consisted of 25 first-order statistics or related wavelet features (including range, standard deviation, uniformity, variance), one shape and size-based feature (spherical disproportion), and 15 textural features or related wavelet features (including sum variance, sum entropy, run percentage).ConclusionsA radiomic signature allowing for the prediction of the EGFR expression level in patients with lower grade glioma was identified, suggesting that using tumour-derived radiological features for predicting genomic information is feasible.Key Points• EGFR expression status is an important biomarker for gliomas. • EGFR in lower grade gliomas could be predicted using radiogenomic analysis. • A logistic regression model is an efficient approach for analysing radiomic features.

Assessment of Risk of Aneurysmal Rupture in Patients with Normotensives, Controlled Hypertension, and Uncontrolled Hypertension.

BACKGROUND The prevalence of hypertension in patients with intracranial aneurysms has been an increased concern, but it is not well understood if uncontrolled hypertension has impact on aneurysmal rupture. The aim of this study was to determine whether the risk of aneurysmal rupture is higher in uncontrolled hypertensive cohorts than in controlled hypertensive cohorts and normotensive cohorts. METHODS We retrospectively analyzed the records and angiographies of 456 patients with aneurysms who were treated at our center between June 2013 and June 2014. Three groups of patients were included in the study following the ESH-ESC (European Society of Hypertension-European Society of Cardiology) 2013 guidelines: normotensive group (n = 229), controlled hypertension group (n = 127), and uncontrolled hypertension group (n = 100). Paired comparisons of these 3 groups were analyzed with the Nemenyi test. Multivariate logistic regression analysis was used to exclude the impact of possible confounding factors. RESULTS The results of the univariate analysis showed that hypertension, smoking, and size of the aneurysms were significantly associated with intracranial aneurysmal rupture (P < .05). The multivariate logistic regression analysis containing clinical and aneurysmal characteristics showed that uncontrolled hypertension, smoking, and aneurysm size were statistically significant predictors of intracranial aneurysmal rupture (P < .05). The paired comparisons of 3 groups showed that the risk of rupture of intracranial aneurysms in the uncontrolled hypertension group was significantly greater than that in the normotensive group (P < .05) and in the controlled hypertension group (P < .05). CONCLUSIONS Uncontrolled hypertension is associated with increased risk of rupture of intracranial aneurysms. Given that aneurysmal rupture is a potentially fatal-but preventable-complication, these findings are of clinical relevance.

Stent-assisted coiling of very small wide-necked intracranial aneurysms: Complications, anatomical results and clinical outcomes

BACKGROUND AND OBJECTIVE Treatment of very small (≤3mm) wide-necked intracranial aneurysms remains controversial, we investigated the efficacy and safety of stent-assisted coiling of such aneurysms. METHODS From September 2008 to December 2012, 112 very small wide-necked intracranial aneurysms in 108 patients were embolized with stent-assisted coiling. We assessed the initial neurological conditions, complications and anatomic results. The follow-up results were evaluated with DSA and mRS. RESULTS Stent deployment was successful in 104 of 108 procedures (96.3%). 11 complications (10.2%) occurred during procedures, including 5 events of aneurysm rupture, 3 events of thromboembolism. The rate of complication, rupture and thromboembolism was not statistically different between the ruptured and unruptured patients (P=0.452, P=0.369, P=1.000, respectively). The initial aneurysmal occlusion was Raymond scale (RS) 1 in 34 patients (31.5%), RS2 in 53 patients (49.1%), and RS3 in 21 patients (19.4%). 79 aneurysms were available for anatomic follow-up of 12-47 months, stable occlusion in 45 aneurysms (57.0%), progressive complete occlusion in 34 aneurysms (43.0%). 95 patients(88.0%) were available for a clinical follow-up of 12-52 months, 92 patients (96.8%) had favorable clinical outcomes (mRS ≤2), 3 patients (3.2%) had morbidity (mRS: 3-5). The morbidity was not statistically different between the ruptured and unruptured patients (P=1.000). CONCLUSIONS Stent-assisted coiling of very small wide-necked intracranial aneurysms may be effective and safe. Because of low risk of rupture in such aneurysms, the coiling of unruptured such aneurysms must be selective. The long-term efficacy and safety of coiling such aneurysms remains to be determined in larger prospective series.

Molecular and clinical characterization of IDH associated immune signature in lower-grade gliomas

ABSTRACT Background: Mutations in isocitrate dehydrogenase (IDH) affect the development and prognosis of gliomas. We investigated the role of IDH mutations in the regulation of immune phenotype in lower-grade gliomas (LGGs).Method and patients: A total of 1,008 cases with clinical and IDH mutation data from five cohorts were enrolled. Samples with RNA sequencing data from the Chinese Glioma Genome Atlas (CGGA) were used as training set, whereas RNA data from the Cancer Genome Atlas, Repository for Molecular Brain Neoplasia, GSE16011, and CGGA microarray databases were used for validation. R language tools and bioinformatics analysis were used for gene signature construction and biological function annotation.Results: We found that IDH mutations caused down-regulation of local immune response as among 332 immune system-related genes, 196(59.0%) were differentially expressed according to IDH mutation status. Nearly 70% of those differentially expressed genes exhibited prognostic value in LGGs. An immune response-based gene signature was constructed that distinguished cases with high- or low-risk of unfavorable prognosis and remained an independent prognostic factor in multivariate analyses in both training and validation cohorts. Samples from high-risk cases exhibited elevated expression of genes involved in immune response and NF-κB pathway activation. Furthermore, we found a strong correlation between the risk score and T cells, macrophage-related immune response, and expression of several prominent immune checkpoints.Conclusion: Our results indicated that mutant IDH is highly associated with the regulation of the immune microenvironment in LGGs. The observed immune system gene signature, which was sensitive to IDH mutation status, efficiently predicted patient survival.

Prognostic value of a microRNA signature as a novel biomarker in patients with lower-grade gliomas

MicroRNAs (miRNAs) may act as prognostic biomarkers in a variety of cancers. The aim of this study was to identify and evaluate a prognostic miRNA signature in patients with lower-grade gliomas (LGGs). miRNA expression profiles and clinical data of patients with LGGs from the Chinese Glioma Genome Atlas (CGGA; the training cohort) and The Cancer Genome Atlas (TCGA; the validation cohort) were analyzed, and the least absolute shrinkage and selection operator Cox regression model was used to identify the miRNA signature, which was combined with clinical prognostic factors to develop an individualized survival prediction model. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to reveal the biological implications of the signature. We identified a four-miRNA signature that stratified patients in the training cohort into low- or high-risk groups according to overall survival time, a finding that was verified in the validation cohort. Multivariate Cox regression analysis indicated that the four-miRNA signature was an independent prognostic biomarker, and a nomogram combining this miRNA signature with clinicopathological and molecular factors showed high prognostic accuracy for individualized survival prediction in both TCGA (C-index = 0.83) and CGGA (C-index = 0.68) cohorts. Functional annotation indicated that the major biological processes of this prognostic miRNA signature were enriched in cell cycle and DNA repair-associated biological processes. Our findings indicated that our newly discovered four-miRNA signature may be an effective independent prognostic factor for the prediction of patients with LGGs.

Genotype prediction of ATRX mutation in lower-grade gliomas using an MRI radiomics signature

ObjectivesTo predict ATRX mutation status in patients with lower-grade gliomas using radiomic analysis.MethodsCancer Genome Atlas (TCGA) patients with lower-grade gliomas were randomly allocated into training (n = 63) and validation (n = 32) sets. An independent external-validation set (n = 91) was built based on the Chinese Genome Atlas (CGGA) database. After feature extraction, an ATRX-related signature was constructed. Subsequently, the radiomic signature was combined with a support vector machine to predict ATRX mutation status in training, validation and external-validation sets. Predictive performance was assessed by receiver operating characteristic curve analysis. Correlations between the selected features were also evaluated.ResultsNine radiomic features were screened as an ATRX-associated radiomic signature of lower-grade gliomas based on the LASSO regression model. All nine radiomic features were texture-associated (e.g. sum average and variance). The predictive efficiencies measured by the area under the curve were 94.0 %, 92.5 % and 72.5 % in the training, validation and external-validation sets, respectively. The overall correlations between the nine radiomic features were low in both TCGA and CGGA databases.ConclusionsUsing radiomic analysis, we achieved efficient prediction of ATRX genotype in lower-grade gliomas, and our model was effective in two independent databases.Key Points• ATRX in lower-grade gliomas could be predicted using radiomic analysis.• The LASSO regression algorithm and SVM performed well in radiomic analysis.• Nine radiomic features were screened as an ATRX-predictive radiomic signature.• The machine-learning model for ATRX-prediction was validated by an independent database.

Curative glubran 2 embolization of cerebral arteriovenous malformations patient selection and initial results.

The liquid embolic agents currently used for embolization of cerebral arteriovenous malformations are Onyx and NBCA. Glubran 2, a cyanoacrylate-based synthetic glue, has recently been applied for embolization of cerebral arteriovenous malformations (AVMs). We report the clinical results of selected cerebral AVMs treated with Glubran 2 targeting for curative embolization. Between October 2011 and March 2013, 31 patients with cerebral AVMs were selected for curative embolization with Glubran 2. There were 19 men and 12 women with a mean age of 32 years (range 4–65 years). Initial clinical presentation included hemorrhage in 28 and seizures in three patients. AVM location was frontal in eight patients, parietal in four, occipital in eight temporal in six, cerebellar in two and cerebellar vermis in three patients. Follow-up was performed clinically and with angiography examination at three to six months. Clinical outcomes were evaluated based on the modified Rankin Scale (mRS). A mean of 2.5 (range, 1–12) feeding pedicles were embolized per patient. Complete angiographic obliteration of AVM was achieved in 27 patients. A hemorrhagic complication was observed in one patient, an ischemic complication in one patient and technical complications in four patients. There was no procedure-related disabling neurological deficit or death at discharge. Additional gamma knife radiosurgery was performed in five patients, including one patient with recurrent AVM. All of the patients had favorable clinical outcomes at three to six month follow-up (mRS≤2). The curative embolization technique with Glubran 2 for selected cerebral AVMs achieved a high initial complete obliteration rate with an acceptable complication frequency.