Gross Total Resection Promotes Subsequent Recovery and Further Enhancement of Impaired Natural Killer Cell Activity in Glioblastoma Patients.

Glioblastoma is the most common primary malignant brain tumor, and median survival is relatively short despite aggressive standard treatment. Natural killer (NK) cell dysfunction is strongly associated with tumor recurrence and metastasis but is unclear in glioblastoma. NK activity (NKA) represents NK cell-secreted interferon-γ (IFN-γ), which modulates immunity and inhibits cancer progression. This study aimed to analyze NKA in glioblastoma patients to obtain a clearer overview of immunity surveillance. From 2020 to 2021, a total of 20 patients and six healthy controls were recruited. Peripheral blood samples were collected preoperatively and on postoperative days (POD) 3 and 30. Then, NKA was measured using the NK VUE kit. Although NKA decreased on POD3, it recovered and further significantly enhanced on POD30, with a nearly five-fold increase compared to baseline (p = 0.004). Furthermore, the percentage of CD56brightCD16- NK cells decreased significantly on POD3 (p = 0.022) and further recovered on PO30. Subgroup analysis of extent surgical resection further revealed that the recovery of impaired NKA was attributable to gross total resection (GTR) rather than subtotal resection (STR). In conclusion, NKA is significantly impaired in glioblastoma, and GTR has demonstrated superior benefit in improving the suppressed NKA and increased CD56brightCD16- NK subset in glioblastoma patients, which may be associated with subsequent patients' prognosis. Therefore, the goal of performing GTR for glioblastoma should be achieved when possible since it appears to increase NKA cell immunity.

Delayed Progressive Mass Effect After Secured Ruptured Middle Cerebral Artery Aneurysm: Risk Factors and Outcomes.

Objective: Delayed progressive mass effect (DPME) after securing an aneurysm is uncommon following microsurgical or endovascular repair and leads to a poor clinical outcome. Patients with ruptured middle cerebral artery (MCA) aneurysms have a high risk of postoperative oedema and mass effect, which may require decompressive treatment. Because few studies have discussed the risk and predictive factors, we focused on ruptured MCA aneurysms and evaluated the outcomes of these patients and the necessity of salvage surgery when DPME presented. Methods: Data on 891 patients with aneurysmal subarachnoid haemorrhage (aSAH) treated between January 2011 and February 2020 were extracted from the medical database of a tertiary referral centre. A total of 113 patients with aSAH resulting from at least one MCA aneurysm were identified. After excluding patients with several clinical confounders, we enrolled 80 patients with surgically treated aSAH. We examined the characteristics of aneurysms and hematomas, perioperative contrast pooling patterns, presence of distal hematomas, perisylvian low density, occlusive treatment modality, management strategies, the need for salvage surgical decompression, and postoperative 90-day outcomes to identify possible risk factors. Results: DPME was observed in 27 of the 80 patients (33.7%). The DPME and non-DPME group differed significantly in some respects. The DPME group had a higher risk of salvage surgery (p < 0.001) and poorer outcomes (mRS at day 90; p = 0.0018). The univariate analysis indicated that the presence of hematoma, CTA spot signs, perisylvian low density, and distal hematoma were independent risk factors for DPME. We also noted that DPME remained an independent predictor of a poorer 90-day functional outcome (mRS ≤ 2). Conclusion: DPME can lead to salvage decompression surgery and directly relates to poor outcomes for patients with a ruptured MCA aneurysm. Distal hematoma, perisylvian low density, and CTA spot signs on preoperative images can predict DPME.

Effect of Intracranial Pressure Control on Improvement of Cerebral Perfusion After Acute Subarachnoid Hemorrhage: A Comparative Angiography Study Based on Temporal Changes of Intracranial Pressure and Systemic Pressure.

OBJECTIVE: Increased intracranial pressure (ICP) is a well-known complication after aneurysmal subarachnoid hemorrhage (aSAH). This study focused on the different temporal changes in ICP, mean arterial pressure, and cerebral perfusion pressure at the early stage of aSAH, throughout aneurysm embolization, and their effects on improvement in angiographic perfusion patterns. METHODS: Twenty-seven patients with aSAH were evaluated who underwent coiling and cerebrospinal fluid (CSF) drainage. Diagnostic angiography was performed to confirm the presence and location of the vascular lesion. The transit time of the capillary filling phase was defined as a surrogate of cerebral perfusion. Capillary filling transit times were compared before and after CSF drainage. Univariate and multivariate analyses were performed to identify associations between different physical parameters and capillary filling transit times. RESULTS: By univariate analysis, average capillary transit time before CSF drainage had a significant correlation with initial ICP (P = 0.0004; R2 = 0.398) but not systemic pressure (mean arterial pressure or cerebral perfusion pressure). Improvement in capillary filling pattern (i.e., a decrease in angiographic capillary transit time after CSF drainage) was seen in patients with high initial ICP and correlated with ICP difference after ventricular drainage (P = 0.0001 and P < 0.0001, respectively). Using multivariate regression analysis, improved control in postprocedural ICP levels significantly correlated with angiographic evidence of improved cerebral perfusion (P = 0.0243). CONCLUSIONS: Decreasing ICP by CSF drainage strongly correlated with improved cerebral microcirculation after aSAH. Further development of ICP control protocols that can provide better ICP management of patients with aSAH is warranted.

Anterior Skull Base Tumor Resection by Transciliary Supraorbital Keyhole Craniotomy: A Single Institutional Experience.

BACKGROUND: The prognosis and recurrence rate after resection of an anterior skull base lesion via transciliary supraorbital keyhole craniotomy depend on residual tumor volume. The extent to which pathology and size of tumor influence the resection rate using this approach is unknown. METHODS: Sixty-two patients underwent a total of 64 operations using the supraorbital keyhole approach in this retrospective study. Meningioma was the most common tumor, followed by pituitary adenoma and craniopharyngioma. Age, sex, tumor volume, operative duration, blood loss, and complication rates were evaluated. Pre- and postoperative residual tumor volumes were measured using OsiriX software (medical image viewer system) based on magnetic resonance imaging. A 15-mL cut value divided the subjects into large versus small meningioma groups. RESULTS: The average resection rate for meningiomas was 95.2% compared with 83.9% for craniopharyngiomas and 53.2% for pituitary adenomas. The major complication rate (primarily blindness and hemiplegia) was 4.48% in all tumors. No operative-related deaths occurred. There were no surgical revisions to traditional large craniotomies. No significant differences in age, sex, postoperative volumes, resection rates, or recurrence rates were noted between small and large meningioma groups. However, longer operative times and hospital stays, and greater blood loss occurred in the large meningioma group. CONCLUSIONS: Transciliary keyhole craniotomy is a safe and effective approach for anterior skull base tumors, especially meningiomas. Excellent resection results were achieved even in cases of large meningiomas. Although longer operative times, longer hospital stays, and greater blood loss occurred in larger compared with smaller meningioma cases, recurrence rates were similar.

The venous delay phenomenon in computed tomography angiography: a novel imaging outcome predictor for poor cerebral perfusion after severe aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Diverse treatment results are observed in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). Significant initial perfusion compromise is thought to predict a worse treatment outcome, but this has scant support in the literature. In this cohort study, the authors correlate the treatment outcomes with a novel poor-outcome imaging predictor representing impaired cerebral perfusion on initial CT angiography (CTA). METHODS: The authors reviewed the treatment results of 148 patients with poor-grade aSAH treated at a single tertiary referral center between 2007 and 2016. Patients with the "venous delay" phenomenon on initial CTA were identified. The outcome assessments used the modified Rankin Scale (mRS) at the 3rd month after aSAH. Factors that may have had an impact on outcome were retrospectively analyzed. RESULTS: Compared with previously identified outcome predictors, the venous delay phenomenon on initial CTA was found to have the strongest correlation with posttreatment outcomes on both univariable (p < 0.0001) and multivariable analysis (OR 4.480, 95% CI 1.565-12.826; p = 0.0052). Older age and a higher Hunt and Hess grade at presentation were other factors that were associated with poor outcome, defined as an mRS score of 3 to 6. CONCLUSIONS: The venous delay phenomenon on initial CTA can serve as an imaging predictor for worse functional outcome and may aid in decision making when treating patients with poor-grade aSAH.

Corpus callosum involvement and postoperative outcomes of patients with gliomas.

Corpus callosum involvement is associated with poorer survival in high grade glioma (HGG), but the prognostic value in low grade glioma (LGG) is unclear. To determine the prognostic impact of corpus callosum involvement on progression free survival (PFS) and overall survival (OS) in HGG and LGG, the records of 233 glioma patients treated from 2008 to 2011 were retrospectively reviewed. Preoperative magnetic resonance (MR) images were used to identify corpus callosum involvement. Age, sex, preoperative Karnofsky performance scale, postoperative Eastern Cooperative Oncology Group (ECOG) score and extent of resection (EOR) were evaluated with respect to PFS and OS. The incidence of corpus callosum involvement was similar among HGG (14 %) and LGG (14.5 %). Univariate analysis revealed that PFS and OS were significantly shorter in both WHO grade II and grade IV glioma with corpus callosum involvement (both, p < 0.05). Multivariate analysis showed that grade II glioma with corpus callosum involvement have shorter PFS (p = 0.03), while EOR, instead of corpus callosum involvement (p = 0.16), was an independent factor associated with PFS in grade IV glioma (p < 0.05). Corpus callosum involvement was no longer significantly associated with OS after adjusting age, gender, EOR, preoperative and postoperative performance status (p = 0.16, 0.17 and 0.56 in grade II, III and IV gliomas, respectively). Corpus callosum involvement happened in both LGG and HGG, and is associated with lower EOR and higher postoperative ECOG score both in LGG and HGG. Corpus callosum involvement tends to be an independent prognostic factor for PFS in LGG, but not for OS in LGG or in HGG.

MicroRNA-495 inhibits proliferation of glioblastoma multiforme cells by downregulating cyclin-dependent kinase 6.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive type of glioma and carries the poorest chances of survival. There is therefore an urgent need to understand the mechanisms of glioma tumorigenesis and develop or improve therapeutics. The aim of this study was to assess the possible prognostic value of cyclin-dependent kinase 6 (CDK6) and the effects of microRNA-495 (miR-495) manipulation on CDK6 expression and cell survival in glioma cells. METHODS: Analyses of clinical specimens from GBM patients were used. Expression of CDK6 was analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. Expression of CDK6 was also analyzed after over-expression of miR-495 in T98 cells; both cell proliferation and RB phosphorylation were examined. Cell proliferation, cell cycle distribution, and RB phosphorylation were also examined after knockdown of CDK6 in U87-MG and T98 cells. RESULTS: Analyses of clinical specimens from GBM patients identified that CDK6 is significantly expressed in gliomas. CDK6 antigen expression was higher in tumor cores and margins than in adjacent normal brain tissues, and higher levels of CDK6 expression in the tumor margin correlated with decreased survival. Over-expression of miR-495 in T98 cells downregulated the expression of CDK6 and inhibited retinoblastoma phosphorylation, and knockdown of CDK6 in U87-MG and T98 cells by siRNAs resulted in cell cycle arrest at the G1/S transition and inhibition of cell proliferation. CONCLUSIONS: This study revealed miR-495 is down-regulated in glioma tissues. Furthermore, miR-495 regulated CDK6 expression and involved in glioma cell growth inhibition, which indicated the possible role of miR-495 in tumor progression.

Evaluation of the prognostic value of CD44 in glioblastoma multiforme.

BACKGROUND/AIM: Glioblastoma and astrocytoma are the most common brain tumors affecting adults 45-60 years of age. The poor prognosis for glioblastoma patients results from recurrence after treatment. There is therefore an urgent need to develop diagnostic and prognostic markers as well as new therapies. PATIENTS AND METHODS: Microarray analyses of clinical specimens from glioblastoma patients were used to identify potential tumor markers. Expression of candidate genes was analyzed by real-time reverse transcription-polymerase chain reaction and by immunoblotting and immunohistochemistry. RESULTS: Five potential markers (CD44 antigen (CD44), growth arrest and DNA-damage-inducible, alpha (GADD45A), fibronectin 1 (FN1), CD63 antigen (CD63) and secreted phosphoprotein 1 (SPP1)) showed expression patterns that correlated significantly with malignant glioma. In particular, expression of the CD44 antigen was elevated in more severe tumor types, and higher in tumor cores than in peripheral regions. However, lower levels of CD44 expression surprisingly correlated with lower survival. CONCLUSION: The CD44 antigen is a promising candidate for further development as a prognostic and therapeutic tool.