Prognostic and predictive impact of MGMT promoter methylation in grade 3 gliomas

BackgroundGrade 3 gliomas are aggressive primary brain tumors. Promoter methylation of methyl guanine methyl transferase (MGMT) has been associated with a favorable prognosis in patients with glioblastoma, but the impact of MGMT promoter methylation in patients with grade 3 gliomas is less clear. The purpose of the present study was to evaluate the utilization of MGMT testing in patients with Grade 3 glioma, as well its prognostic and predictive value.MethodsThe National Cancer Database (NCDB) was queried (2004–2016) for patients with newly diagnosed grade 3 glioma without 1p19q codeletion. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling.ResultsOf 20,488 total patients, 1,209 (5.0%) had MGMT testing. Of these patients, 561 (46.4%) were MGMT methylated (mMGMT), and 648 (53.6%) were MGMT unmethylated (uMGMT). mMGMT patients experienced greater median overall survival (OS) than both uMGMT patients as well as patients with no MGMT status reported (p < 0.05 for both). mMGMT was associated with improved OS for patients receiving adjuvant chemoradiation or adjuvant radiation, but not for patients receiving adjuvant chemotherapy or no adjuvant treatment.ConclusionsThis is the largest study to date describing the utilization of and outcomes for mMGMT patients with grade 3 glioma. The present results demonstrate that mMGMT is a prognostic factor and possibly a predictive biomarker, and is currently under-utilized within the US. MGMT methylation status could be used to risk-stratify and select patients for treatment intensification.Importance of studyThe present study is the largest of its kind to examine the prognostic and predictive impact of MGMT methylation (mMGMT) amongst patients with Grade 3 Glioma. The results suggest that mMGMT is prognostic, as amongst all patients, mMGMT was associated with improved overall survival. These results also suggest that mMGMT is predictive, as patients treated with adjuvant chemoradiation or adjuvant radiation therapy did have improved overall survival with mMGMT, though there was no difference in overall survival observes amongst patients receiving adjuvant chemotherapy or those patients receiving no adjuvant treatment. The study also found that only 5% of patients nationwide with Grade 3 Glioma are tested for MGMT.     

Methylation Status of the O6-Methylguanine-Deoxyribonucleic Acid Methyltransferase Gene Promoter in World Health Organization Grade III Gliomas

Objective

We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter in World Health Organization (WHO) grade III gliomas in association with other molecular markers to evaluate their prevalence.

Methods

The samples of a total of 36 newly WHO grade III glioma patients including 19 anaplastic oligodendrogliomas (AO), 7 anaplastic oligoastrocytomas (AOA), and 10 anaplastic astrocytomas (AA) were analyzed. The methylation status of the MGMT gene promoter was confirmed by methylation-specific polymerase chain reaction. The 1p/19q chromosomal deletion status and EGFR amplification were assessed by Fluorescence In-Situ Hybridization. MGMT, EGFR, EGFRvIII, and p53 expression were analyzed by immunohistochemical staining.

Results

The MGMT gene promoter was methylated in 32 (88.9%) and unmethylated in 4 (11.2%). Among them, all of the AO and AOA had methylated MGMT gene promoter without exception. Significant associations between MGMT gene promoter hypermethylation and 1p/19q deletion was observed (p = 0.003). Other molecular markers failed to show significant associations between MGMT gene promoter statuses.

Conclusion

There was extensive epigenetic silencing of MGMT gene in high grade gliomas with oligodendroglial component. Together with frequent 1p/19q co-deletion in oligodendroglial tumors, this may add plausible explanations supporting the relative favorable prognosis in oligodendroglial tumors compared with pure astrocytic tumors.     

BRAF V600E mutation is a significant prognosticator of the tumour regrowth rate in brainstem gangliogliomas

BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma’s clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma’s clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation. The volume of tumours was calculated accurately by using 3D Slicer software. The clinical data of these patients were retrospectively analysed. In tumours with BRAF V600E mutations, the tumour regrowth rate was significantly faster than that of the wild type group (p = 0.001). Moreover, the BRAF V600E mutant group had shorter progression-free survival (PFS) compared with wild type (p = 0.012). On multivariate analysis, no factor was found to be an independent prognostic factor; however, tumours with faster regrowth rates had a strong trend towards an increased risk for shorter PFS (HR = 1.027, p = 0.056). No statistical analysis could be performed to evaluate factors affecting overall survival (OS). These data suggest that BRAF V600E can predict the regrowth rate of brainstem gangliogliomas after microsurgery, and a BRAF V600E-targeted therapeutic may be a promising early intervention measure for patients who harbour BRAF V600E mutation after microsurgery.     

Short-term outcomes and predictors of post-surgical seizures in patients with supratentorial low-grade gliomas

To explore the predictive factors and short-term outcomes of post-surgical seizures in patients with supratentorial low-grade gliomas (LGGs). A consecutive series of 70 supratentorial LGG patients with seizures were reviewed to determine the predictors and short-term outcomes of seizures. Univariate analyses and multivariate logistic regression analyses were performed to determine the predictive factors associated with postoperative seizure outcomes. We identified the preoperative seizure frequency threshold by plotting a receiver operating characteristic curve. A Kaplan-Meier curve was constructed to illustrate the seizure-free survival rate of our cohort over time. 54 patients who remained seizure -free post-surgery were classified into the Engel class I, and the other 16 patients whose seizures relapsed were classified into Engel classes II–IV. Univariate and multivariate logistic regression analyses showed that the preoperative seizure frequency (X² = 16.069, P = 0.001), extent of resection (x² = 5.031, P = 0.025), IDH1 mutation (x² = 4.435, P = 0.035) and adjuvant chemotherapy of temozolomide (X² = 4.081, P = 0.043) were related to the postoperative short-term seizure outcome. The ROC curve indicated that the area under the curve for the preoperative seizure frequency test was 0.805 (95% confidence interval 0.690–0.920, p < 0.05), which corresponded to an optimal threshold of 2 preoperative seizures. The IDH1^WT status and adjuvant chemotherapy with temozolomide were related to a better post-operative seizure outcome. Within the first year after the surgical resection, seizures reoccurred among 16 patients (22.9%) with a mean time of 10.8 months. The preoperative seizure frequency, extent of resection, IDH1 status, and adjuvant chemotherapy with temozolomide were predictive factors of short-term postoperative seizure outcomes for supratentorial LGGs. To obtain a favorable seizure outcome, early intervention and removal are warranted. IDH1 mutation is the predictive biomarker of postoperative seizure outcomes. The adjuvant chemotherapy with temozolomide appears to be associated with better seizure outcomes, and it may be useful in helping to control the postoperative seizures.     

The utility of magnetic resonance spectroscopy in frame-less stereotactic needle biopsy of glioma

ObjectiveProton magnetic resonance spectroscopy (¹H—MRS) can benefit the differentiation of gliomas preoperative grading and facilitate guiding biopsy. This study was to investigate the optimal metabolite or metabolic ratios of MRS for the biopsy target delineating by using the technique of MRS imaging guided frame-less stereotactic biopsy.MethodsDuring a 4 year period between the Sep 2012 and Oct 2016, 57 patients (25 women, 32 men; mean age, 46.4) with histologic diagnosis of glioma, who underwent the ¹H—MRS imaging guided frameless stereotactic biopsy, were retrospectively reviewed. The metabolite or metabolic ratios values of MRS was measured. And the sensitivity, specificity, accuracy as well as the area under the curve (AUC) of those parameters for glioma grading are calculated based on the receiver operating characteristic curve (ROC) analysis.Results65 stereotactic biopsy samples from 57 patients were histopathologically clarified to HGGs (25) or LGGs (40) for quantitative analysis. The Cho, Cho/NAA and Cho/Cr values of LGGs group were significantly lower than that of HGGs (P = 0.09, 0.001, 0.003), and the NAA value of LGGs group was significantly higher than that of HGGs (P = 0.001). The cutoff value of 3.65 for the Cho/NAA ratio provided the best combination of sensitivity (92.0%), specificity (95.0%), and diagnostic accuracy (93.8%) for identifying glioma grade, which was superior to other parameters.ConclusionThe results of our study provided evidence that Cho/NAA ratio had the superior diagnostic performance in distinguishing glioma grade, indicating that the spot of highest Cho/NAA ratio was optimal metabolic targets for spectroscopic guided tissue sampling in homogenous glioma.     

Effects of and prognostic factors affecting endovascular mechanical thrombectomy of acute vertebrobasilar artery occlusion

PurposeTo investigate the clinical outcome and factors affecting the prognosis of endovascular mechanical thrombectomy of acute vertebrobasilar artery occlusion.Materials and methodsEighty-three patients with acute vertebrobasilar artery occlusion were treated with endovascular mechanical thrombectomy, and the recanalization rate, clinical outcomes at three months, modified DWI-PC-ASPECTS, and MRA-BATMAN scores were analyzed.ResultsFollowing acute mechanical thrombectomy, the TICI 2B-3 score was achieved in all patients (100%). At three-month evaluation, 56 (67.5%) patients had good prognosis with the mRS score of 0–2, including 13 (23.2%) patients who had arterial occlusion caused by emboli and 43 (76.8%) who had atherosclerotic stenosis. In analyzing factors affecting the prognosis, a significant difference (P < 0.05) existed between patients with good (mRS 0–2) and poor (mRS 3–6) prognosis in the NIHSS (17.3 vs. 31.2, P = 0.000001), modified DWI-PC-ASPECTS (10.4 vs. 7.8, P = 0.021), and MRA-BATMAN (6.3 vs. 4.6, P = 0.003) scores. Univariate Logistic regression analysis demonstrated NIHS score ≥ 21, modified DWI-PC-ASPECTS score ≤ 8.5, and MRA-BATMAN score ≤ 6.5 to be the risk factors for poor prognosis. Multivariate Logistic regression analysis revealed NIHSS score ≥ 21 as an independent risk factor for poor prognosis.ConclusionEndovascular mechanical thrombectomy is safe and effective in recanalizing occluded vertebrobasilar artery occlusion, and NIHS score ≥ 21, modified DWI-PC-ASPECTS score ≤ 8.5, and MRA-BATMAN score ≤ 6.5 are the risk factors for poor prognosis.     

Cerebellar anaplastic astrocytoma in adult patients: 15 consecutive cases from a single institution and literature review

Adult cerebellar anaplastic astrocytomas (cAA) are rare entities and their clinical and genetic appearances are still ill defined. Previously, malignant gliomas of the cerebellum were combined and reviewed together (cAA and cerebellar glioblastomas (cGB), that could have possibly affected overall survival (OS) and progression-free survival (PFS). We present characteristics of 15 adult patients with cAA and compared them to a series of 45 patients with a supratentorial AA (sAA) in order to elicit the effect of tumor location on OS and PFS. The mean age at cAA diagnosis was 39.3 years (range 19–72). A history of neurofibromatosis type I was noted in 1 patient (6.7%). An IDH-1 mutation was identified in 6/15 cases and a methylated MGMT promoter in 5/15 cases. Patients in study and control groups were matched in age, sex and IDH-1 mutation status. Patients in a study group tended to present with longer overall survival (50 vs. 36.5 months), but the difference did not reach statistical significance. In both cAA and supratentorial AA groups presence of the IDH-1 mutation remains a positive predictor for the prolonged survival. The present study suggests that adult cAA constitute a group of gliomas with relatively higher rate of IDH-1 mutations and prognosis similar to supratentorial AA. The present study is the first to systematically compare cAA and supratentorial AA with respect to their genetic characteristics and suggests that both groups show a similar survival prognosis.     

Subarachnoid hemorrhage rebleeding in the first 24 h is associated with external ventricular drain placement and higher grade on presentation: Cohort study

BackgroundRebleeding after aneurysmal subarachnoid hemorrhage (aSAH) confers a poor prognosis; however, risk factors and differential outcomes associated with early rebleeding in the first 24 h after symptom presentation are incompletely understood.MethodsA retrospective cohort study of all aSAH presenting to our institution between 2001 and 2016 was performed. Early rebleeding events were defined as clinical neurologic decline with radiographically confirmed acute intracranial hemorrhage within 24 h after symptom presentation. Univariate and multivariate logistic regression analyses were used to assess clinical associations, with a specific focus on baseline Glasgow Coma Score (GCS), World Federation of Neurosurgical Societies (WFNS), and modified Fisher scores.ResultsOf 471 aSAH cases, 33 (7%) experienced early rebleeding. Multivariate regression identified extraventricular drain (EVD) placement (OR = 2.16, P = 0.04) and WFNS 3–5 (OR = 2.69, P = 0.02) as significant predictors of early rebleeding. Good functional outcomes were observed in 8 patients with early rebleeding (24%), all of whom underwent aneurysm treatment. Higher SAH grade prior to rebleeding (WFNS 3–5) was significantly associated with increased odds of an unfavorable functional outcome (OR = 8.09, P < 0.01). Anticoagulation, aneurysm size and location were not significantly associated with either early rebleeding incidence or functional outcome.ConclusionsEarly rebleeding in aSAH is associated with unfavorable functional outcomes. EVD placement and higher SAH grade on presentation appear to be significantly and independently associated with increased risk of rebleeding within first 24 h, as well as unfavorable long-term functional outcome; however, the clinical benefit of hyper-acute aneurysm treatment requires further investigation.     

Clinical outcome of surgically treated low-grade gliomas: A retrospective analysis of a single institute

Objective

Low grade gliomas (LGGs) are slow-growing primary brain tumors with heterogeneous clinical behaviors. The aim of our study is to review the treatment outcome of 63 patients with LGGs focusing on surgical outcome and the current therapeutic strategy.

Methods

We retrospectively enrolled 63 patients surgically treated for LGGs. The gross total resection (GTR) was performed in 35 patients (60.3%), subtotal resection (STR) was performed in 19 patients (31.7%) and partial resection (PR) or biopsy was performed in 9 patients (14.3%). We analyzed their progression-free survival (PFS), overall survival (OS), and malignant transformation with regard to age, gender, Karnofsky performance score (KPS), clinical presentation, tumor location, radiologic pattern, contrast enhancement, extent of removal, pathologic subtype, chemotherapy (CT) and radiotherapy (RT) treatment.

Results

Among all LGGs, the 3-year OS rate was 80% and the 5-year OS was 76%. The 3-year PFS rate was 83.6% and the 5-year PFS was 25%. The non-eloquent area location showed a longer PFS than the eloquent area location (p = 0.05). Oligodendroglial pathology showed a longer PFS compared to oligoastrocytomas and astrocytomas (p = 0.02). Patients older than 60 years had poorer OS than younger patients (p < 0.05). Female gender had a shorter OS than male gender (p < 0.05), and a KPS of 90 or 100 had a longer OS than a KPS of 80 (p < 0.05). Oligodendroglial pathology statistically correlated with a longer OS (p < 0.05).

Conclusion

The findings from our study, which were confirmed by uni- and multivariate analyses, demonstrated that radical tumor resection was associated with better long-term outcomes and tumor progression for patients with LGG.     

Evaluation status and prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in pediatric high grade gliomas

Introduction  

In this study, we investigated the prognostic and predictive value of MGMT promoter methylation and protein expression in 30 pediatric high grade gliomas (pHGG).     

A pilot study of glioblastoma multiforme in elderly patients: Treatments,O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and survival

Objectives

Elderly Glioblastoma multiforme (GBM) patients have a worse prognosis and receive variable treatments. MGMT gene promoter methylation is linked with improved survival in GBM. We examined treatments administered and survival including in relation to MGMT methylation status in elderly GBM patients.

Patients and methods

Patients ≥65 years with diagnosed GBM between 1/01/2007 and 30/04/2009 and undergoing either a biopsy, subtotal (STR) or gross total resection (GTR) were included. The collected information included MGMT status [methylated (ME) vs. unmethylated (UN)] and survival data. p < 0.05 was considered significant.

Results

59 patients were identified with median age at diagnosis being 72.68 years (65.72–85.04). Treatment included surgery (25 GTR, 8 STR, 26 biopsy), chemoradiation (22) and radiotherapy alone (20). Overall median overall survival (MOS) was 219 days. MOS with chemoradiation was 316 days vs. 143 days without it (p = 0.011). 47 patients had definite MGMT status (28 ME, 19 UN). In ME patients, 9/28 received temozolamide compared to 10/19 in UN category. Temozolamide administration in patients with definite MGMT status was based on WHO performance status (p = 0.007). MOS in UN group was 308 days vs. 167 days in ME group (p = 0.068). In a multivariate Cox model including use of temozolamide, WHO score and methylation status, only temozolamide use was significantly associated with a reduced risk for death (HR 0.443, 95% CI 0.200–0.982, p = 0.045).

Conclusions

In this small cohort of patients, chemoradiation in suitable elderly GBM patients seemed to afford a survival benefit. MGMT methylation was not associated with an improved survival with temozolamide being the only factor leading to a better survival. Temozolamide use should be considered irrespective of MGMT status in this population with future large prospective studies needed to elucidate this further.     

Gender and other risk factors associated with risky behaviours among Nigerian adolescents

Risky behaviours in adolescents, apart from substance use, and their associate factors, have not been thoroughly investigated in Nigeria. Hence, there is a need to study the prevalence of risky behaviours and their relationship with gender and other potential risk factors. Data comprising socio-demographic, risky behaviours, personality traits, religious orientation and substance use were obtained from 300 randomly selected secondary school students. Two risk groups (low and high) based on the number of risky behaviours were determined. Male was a risk factor for theft (OR = 2.1; 95%CI = 1.17–3.95), bullying (OR = 2.76; 95%CI = 1.37–5.56) and fighting (OR = 2.14; 95%CI = 1.35–3.40). Fifty-two (17.3%) of the students were of high-risk behaviour group. Furthermore, private school (β = 1.05; P = 0.010), poor perceived relationship with teachers (β = 1.21; P = 0.002), polygamy (β = 1.20; P = 0.002) and lifetime cigarette use (β = 1.07; P = 0.027) were predictors of high-risk behaviour group. Substantial proportion of adolescents in Nigeria exhibit risky behaviours of which gender and other factors play a significant role.     

脑胶质瘤CHSY1的表达变化及临床意义的生信分析

目的 探讨硫酸软骨素合酶1（CHSY1）在脑胶质瘤中的表达及临床意义。方法 从Gliovis下载CHSY1在TCGA、CGGA和Rembrandt数据库中的基因表达数据和对应的临床数据,将CHSY1表达量由低到高排序,前50%为低表达组,后50%为高表达组。利用TIMER在线网站分析CHSY1在脑胶质瘤中的表达与免疫浸润的相关性。结果 胶质瘤组织CHSY1表达水平明显高于正常脑组织（P<0.05）,且与胶质瘤病理分级呈正相关（P<0.05）。多因素Cox回归分析显示CHSY1高表达是胶质瘤病人生存预后不良的独立危险因素（P<0.05）,CHSY1高表达组中位生存期较低表达组明显缩短（P<0.05）。MGMT启动子甲基化组胶质母细胞瘤病人中,CHSY1高表达组中位生存期较低表达组明显缩短（P<0.05）。CHSY1高表达组胶质瘤病人化疗后中位生存期较低表达组明显缩短（P<0.05）。TIMER分析发现,胶质母细胞瘤组织CHST1表达水平与树突状细胞的浸润程度呈正相关,低级别胶质瘤组织CHST1表达水平与B细胞、CD8+ T细胞、嗜中性粒细胞、巨噬细胞和树突状细胞的浸润程度成正比。结论 脑胶质瘤CHSY1呈高表达,与胶质瘤的恶性程度与免疫浸润呈正相关。CHSY1可作为胶质瘤预后和对化疗反应的预测因子。     

Frontal glioblastoma multiforme may be biologically distinct from non-frontal and multilobar tumors

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and carries a grim prognosis. Lobar GBM, notably those localized to the frontal lobe, are generally more amenable to complete surgical resection, and may carry a better prognosis. The biology of differently localized GBM has been reported scarcely in terms of prognostic markers, including isocitrate dehydrogenase 1 (IDH1) mutation and O(6)-methylguanine-methyltransferase (MGMT) methylation. To our knowledge, there has been no evaluation in the literature of different proliferation indexes in different GBM locations in the brain. We performed a retrospective evaluation of our prospectively collected database to assess the rate of IDH1 positivity, MGMT methylation and Ki67 index for GBM located in the frontal lobes alone, lobar GBM in other supra-tentorial lobes and multilobar GBM. IDH1 mutated tumors were localized in the frontal lobes in 50.0%, whereas only 20.3% of IDH1 wild-type tumors were localized in the frontal lobe (p = 0.006); MGMT methylated tumors were localized in the frontal lobe in 32.0% of the cases. Only 13.75% of the MGMT unmethylated tumors were localized to the frontal lobe (p = 0.005); Tumors with higher Ki67 proliferation index were more likely to be localized in the frontal lobe (40.6% vs. 19.5%, p = 0.019). This is the largest cohort of GBM assessed for these purposes in the literature. Frontal lobe GBMs may be intrinsically biologically distinct from GBM in other lobes and from multilobar tumors.     

MGMT gene promoter methylation in pediatric glioblastomas

Purpose  

Relatively few studies have been performed on molecular properties of pediatric glioblastoma multiforme (GBM). Methylation of DNA repair gene O⁶-methylguanine-DNA methyltransferase (MGMT) promoter region has been associated with favorable prognosis and prolonged survival in adult GBM patients treated with temozolomide (TMZ). We explored the frequency of MGMT gene promoter methylation in pediatric glioblastomas and compared it with the known molecular alterations in p53.     

lncRNA RGMB-AS1在脑胶质瘤预后评估中的价值

目的 探讨长链非编码RNA（lncRNA）RGMB-AS1在脑胶质瘤病人预后评估中的作用。方法 选取2014年9月~2017年6月经术后病理检查证实的脑胶质瘤140例（低级别64例,高级别76例）,另选取颅脑损伤内减压术中切取正常脑组织25例为对照。实时荧光定量PCR法检测lncRNA RGMB-AS1的表达水平,以RGMB-AS1表达量的中位数为截断值,分为高表达组和低表达组。用Kaplan-Meier法比较总体生存期（OS）和无进展生存期（PFS）,用Cox比例回归风险模型分析影响胶质瘤病人预后的因素。结果 140例胶质瘤中,lncRNA RGMB-AS1高表达70例,低表达70例。胶质瘤组织lncRNA RGMB-AS1的相对表达量明显高于对照组（P<0.05）。多因素Cox比例回归风险模型分析结果显示年龄≥50岁、术前KPS评分<80分、WHO分级Ⅲ~Ⅳ级、lncRNA RGMB-AS1高表达是胶质瘤病人PFS和OS的独立影响因素（P<0.05）。lncRNA RGMB-AS1高表达胶质瘤病人PFS和OS较低表达病人均明显缩短（P<0.05）。无论是高级别胶质瘤,还是低级别胶质瘤,lncRNA RGMB-AS1高表达病人PFS和OS较低表达病人均明显缩短（P<0.05）。结论 lncRNA RGMB-AS1表达水平与脑胶质瘤病例级别呈正相关,lncRNA RGMB-AS1高表达脑胶质瘤病人生存期较低表达病人明显缩短。这提示lncRNA RGMB-AS1表达水平可作为脑胶质瘤病人预后评估指标。     

Comparison of clinical outcomes and characteristics between patients with and without hypertension in moyamoya disease

ObjectiveOur study aimed to compare the disparity of patients with moyamoya disease (MMD) between hypertension group and non-hypertension group. And we attempt to explore the risk factors for MMD with hypertension.MethodsWe retrospectively analyze 542 adult patients with moyamoya disease admitted to our hospital from 2009 to 2016. In view of inclusion criteria, we divided patients with moyamoya disease into two groups (hypertension group and non-hypertension group) and summarized their clinical characteristics. Furthermore, we explore the risk factors for unfavorable outcomes in hypertension group.ResultsOf 542 adult patients with moyamoya disease, we identified 156 patients (28.8%) with hypertension and 386 patients (71.2%) without hypertension. During follow-up, we hold the views that the prognosis of non-hypertension group was obviously better than hypertension group (P = 0.005) and the complications were prone to occurring to patients with hypertension (P = 0.037). In the multivariate analysis, severe hypertension (OR, 2.746; 95% CI, 1.096–6.822; P = 0.031) and no anti-hypertensive medication (OR, 0.342; 95% CI, 0.131–1.895; P = 0.029) were the independent predictors for postoperative unfavorable outcomes. The common surgical modalities of moyamoya disease (direct and indirect bypass) had no significant difference in future unfavorable outcomes prevention in adult MMD patients with hypertension.ConclusionsWe suggested severe hypertension and no anti-hypertensive medication as the independent risk factors for unfavorable clinical outcomes in adult MMD with hypertension.     

Evaluation of radiological recurrence patterns following gamma knife radiosurgery for solitary meningioma previously treated via cranial surgery

The use of gamma knife radiosurgery (GKS) for meningiomas after cranial surgery has been extensively evaluated; however, studies on tumor progression, including recurrence out of the margin dose line, are scarce. Hence, we aimed to evaluate the meningioma recurrence after GKS within and out of the margin dose. We included 37 consecutive patients with World Health Organization (WHO) grade 1 meningiomas who were treated with GKS following cranial surgery. Radiologically indicated recurrences were classified into three patterns by their relationship to the margin dose and tumor. The median follow-up was 58.9 months; 2 (5.4%) patients died. Only 2 (5.4%) patients did not keep active daily lives because of tumor progression. Cumulative local control at 5 years was 85.2%. Local recurrence and recurrence out of the margin dose occurred in 5 (13.5%) and 13 (35.1%) patients, respectively. A larger preoperative maximum diameter was a risk factor for local recurrence (hazard ratio [HR]: 2.118; P = 0.033), adjacent progression (HR: 1.633; P = 0.015), and remote progression (HR: 2.016; P = 0.003). Symptomatic adverse radiation effects occurred in 1 patient. Salvage GKS and cranial surgery were performed in 9 (24.3%) and 8 (21.6%) patients, respectively. Progression to WHO grade 2–3 occurred in 5 (13.5%) patients. A larger preoperative maximum diameter was a risk factor for progression of WHO grade (HR: 2.016, P = 0.033). Progression out of the margin dose was associated with a larger preoperative tumor size.     

胶质母细胞瘤MGMT基因启动子甲基化、MGMT蛋白表达和预后相关性分析

目的探讨脑胶质母细胞瘤中O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因启动子甲基化状态和MGMT蛋白表达水平与临床预后的相关性。方法收集119例人脑胶质母细胞瘤石蜡包埋样本,提取基因组DNA并进行亚硫酸氢盐修饰,用MethyLight法检测MGMT基因启动子甲基化状态,用免疫组织化学染色法检测MGMT蛋白表达水平,对MGMT基因启动子甲基化状态和MGMT表达水平与患者预后行相关性分析。结果在119例胶质母细胞瘤样本中,有42例检测到MGMT基因启动子甲基化,甲基化发生率为35.3%(42/119例),MGMT基因启动子甲基化与无进展生存期(P=0.011)及总体生存期(P=0.036)延长相关。MGMT蛋白表达水平和临床预后无相关性(P0.05),与MGMT基因启动子甲基化状态之间也无相关性(P0.05)。结论 MGMT基因启动子甲基化与胶质母细胞瘤患者预后呈正相关,由免疫组化法测得的MGMT蛋白表达水平和预后及基因启动子甲基化之间无关联性,MGMT基因启动子甲基化状态可以作为评判预后的生物学指标之一。