Immune factors preceding diagnosis of glioma: a Prostate Lung Colorectal Ovarian Cancer Screening Trial nested case-control study.

BackgroundEpidemiological studies of adult glioma have identified genetic and environmental risk factors, but much remains unclear. The aim of the current study was to evaluate anthropometric, disease-related, and prediagnostic immune-related factors for relationship with glioma risk.MethodsWe conducted a nested case-control study among the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. One hundred and twenty-four glioma cases were identified and each matched to four controls. Baseline characteristics were collected at enrollment and were evaluated for association with glioma status. Serum specimens were collected at yearly intervals and were analyzed for immune-related factors including TGF-β1, TNF-α, total IgE, and allergen-specific IgE. Immune factors were evaluated at baseline in a multivariate conditional logistic regression model, along with one additional model that incorporated the latest available measurement.ResultsA family history of glioma among first-degree relatives was associated with increased glioma risk (OR = 4.41, P = .002). In multivariate modeling of immune factors at baseline, increased respiratory allergen-specific IgE was inversely associated with glioma risk (OR for allergen-specific IgE > 0.35 PAU/L: 0.59, P = .03). A logistic regression model that incorporated the latest available measurements found a similar association for allergen-specific IgE (P = .005) and showed that elevated TGF-β1 was associated with increased glioma risk (P-value for trend <.0001).ConclusionThe results from this prospective prediagnostic study suggest that several immune-related factors are associated with glioma risk. The association observed for TGF-β1 when sampling closer to the time of diagnosis may reflect the nascent brain tumor's feedback on immune function

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Background: Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma. Methods: We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events. Results: The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified. Conclusions: 5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives

Increased burden of familial-associated early-onset cancer risk among minority americans compared to non-latino whites

Background: The role of race/ethnicity in genetic predisposition of early-onset cancers can be estimated by comparing family-based cancer concordance rates among ethnic groups. Methods: We used linked California health registries to evaluate the relative cancer risks for first-degree relatives of patients diagnosed between ages 0 and 26, and the relative risks of developing distinct second primary malignancies (SPMs). From 1989 to 2015, we identified 29,631 cancer patients and 62,863 healthy family members. We calculated the standardized incident ratios (SIRs) of early-onset primary cancers diagnosed in proband siblings and mothers, as well as SPMs detected among early-onset patients. Analyses were stratified by self-identified race/ethnicity. Results: Given probands with cancer, there were increased relative risks of any cancer for siblings and mothers (SIR = 3.32; 95% confidence interval [CI]: 2.85–3.85) and of SPMs (SIR = 7.27; 95% CI: 6.56–8.03). Given a proband with solid cancer, both Latinos (SIR = 4.98; 95% CI: 3.82–6.39) and non-Latino Blacks (SIR = 7.35; 95% CI: 3.36–13.95) exhibited significantly higher relative risk of any cancer in siblings and mothers when compared to non-Latino White subjects (SIR = 3.02; 95% CI: 2.12–4.16). For hematologic cancers, higher familial risk was evident for Asian/Pacific Islanders (SIR = 7.56; 95% CI: 3.26–14.90) compared to non-Latino whites (SIR = 2.69; 95% CI: 1.62–4.20). Conclusions: The data support a need for increased attention to the genetics of early-onset cancer predisposition and environmental factors in race/ethnic minority families in the United States.</p

The endoscope-assisted supraorbital “keyhole” approach for anterior skull base meningiomas: an updated meta-analysis

Abstract: Introduction: The gold-standard treatment for symptomatic anterior skull base meningiomas is surgical resection. The endoscope-assisted supraorbital “keyhole” approach (eSKA) is a promising technique for surgical resection of olfactory groove (OGM) and tuberculum sellae meningioma (TSM) but has yet to be compared with the microscopic transcranial (mTCA) and the expanded endoscopic endonasal approach (EEA) in the context of existing literature. Methods: An updated study-level meta-analysis on surgical outcomes and complications of OGM and TSM operated with the eSKA, mTCA, and EEA was conducted using random-effect models. Results: A total of 2285 articles were screened, yielding 96 studies (2191 TSM and 1510 OGM patients). In terms of effectiveness, gross total resection incidence was highest in mTCA (89.6% TSM, 91.1% OGM), followed by eSKA (85.2% TSM, 84.9% OGM) and EEA (83.9% TSM, 82.8% OGM). Additionally, the EEA group had the highest incidence of visual improvement (81.9% TSM, 54.6% OGM), followed by eSKA (65.9% TSM, 52.9% OGM) and mTCA (63.9% TSM, 45.7% OGM). However, in terms of safety, the EEA possessed the highest cerebrospinal fluid leak incidence (9.2% TSM, 14.5% OGM), compared with eSKA (2.1% TSM, 1.6% OGM) and mTCA (1.6% TSM, 6.5% OGM). Finally, mortality and intraoperative arterial injury were 1% or lower across all subgroups. Conclusions: In the context of diverse study populations, the eSKA appeared not to be associated with increased adverse outcomes when compared with mTCA and EEA and offered comparable effectiveness. Case-selection is paramount in establishing a role for the eSKA in anterior skull base tumours

Venous thromboembolism and intracranial hemorrhage after craniotomy for primary malignant brain tumors: a National Surgical Quality Improvement Program analysis

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), frequently complicates the postoperative course of primary malignant brain tumor patients. Thromboprophylactic anticoagulation is commonly used to prevent VTE at the risk of intracranial hemorrhage (ICH). We extracted all patients who underwent craniotomy for a primary malignant brain tumor from the National Surgical Quality Improvement Program (NSQIP) registry (2005–2015) to perform a time-to-event analysis and identify relevant predictors of DVT, PE, and ICH within 30 days after surgery. Among the 7376 identified patients, the complication rates were 2.6, 1.5, and 1.3% for DVT, PE, and ICH, respectively. VTE was the second-most common major complication and third-most common reason for readmission. ICH was the most common reason for reoperation. The increased risk of VTE extends beyond the period of hospitalization, especially for PE, whereas ICH occurred predominantly within the first days after surgery. Older age and higher BMI were overall predictors of VTE. Dependent functional status and longer operative times were predictive for VTE during hospitalization, but not for post-discharge events. Admission two or more days before surgery was predictive for DVT, but not for PE. Preoperative steroid usage and male gender were predictive for post-discharge DVT and PE, respectively. ICH was associated with various comorbidities and longer operative times. This multicenter study demonstrates distinct critical time periods for the development of thrombotic and hemorrhagic events after craniotomy. Furthermore, the VTE risk profile depends on the type of VTE (DVT vs. PE) and clinical setting (hospitalized vs. post-discharge patients)

The endoscopic endonasal approach is not superior to the microscopic transcranial approach for anterior skull base meningiomas—a meta-analysis

Object In the past decade, the endonasal transsphenoidal approach (eTSA) has become an alternative to the microsurgical transcranial approach (mTCA) for tuberculum sellae meningiomas (TSMs) and olfactory groove meningiomas (OGMs). The aim of this meta-analysis was to evaluate which approach offered the best surgical outcomes. Methods: A systematic review of the literature from 2004 and meta-analysis were conducted in accordance with the PRISMA guidelines. Pooled incidence was calculated for gross total resection (GTR), visual improvement, cerebrospinal fluid (CSF) leak, intraoperative arterial injury, and mortality, comparing eTSA and mTCA, with p-interaction values. Results: Of 1684 studies, 64 case series were included in the meta-analysis. Using the fixed-effects model, the GTR rate was significantly higher among mTCA patients for OGM (eTSA: 70.9% vs. mTCA: 88.5%, p-interaction < 0.01), but not significantly higher for TSM (eTSA: 83.0% vs. mTCA: 85.8%, p-interaction = 0.34). Despite considerable heterogeneity, visual improvement was higher for eTSA than mTCA for TSM (p-interaction < 0.01), but not for OGM (p-interaction = 0.33). CSF leak was significantly higher among eTSA patients for both OGM (eTSA: 25.1% vs. mTCA: 10.5%, p-interaction < 0.01) and TSM (eTSA: 19.3%, vs. mTCA: 5.81%, p-interaction < 0.01). Intraoperative arterial injury was higher among eTSA (4.89%) than mTCA patients (1.86%) for TSM (p-interaction = 0.03), but not for OGM resection (p-interaction = 0.10). Mortality was not significantly different between eTSA and mTCA patients for both TSM (p-interaction = 0.14) and OGM resection (p-interaction = 0.88). Random-effect models yielded similar results. Conclusion: In this meta-analysis, eTSA was not shown to be superior to mTCA for resection of both OGMs and TSMs. Electronic supplementary material The online version of this article (10.1007/s00701-017-3390-y) contains supplementary material, which is available to authorized users

Visual outcomes after endoscopic endonasal pituitary adenoma resection: a systematic review and meta-analysis

Purpose Patients with pituitary adenomas often present with visual deficits. While the aim of endoscopic endonasal transsphenoidal surgery (EETS) is to improve these deficits, permanent worsening is a possible outcome. The aim of this meta-analysis was to evaluate the effect of EETS for pituitary adenomas on visual outcomes. Methods: A meta-analysis was conducted according to the PRISMA guidelines. Pooled prevalence was calculated for complete recovery, improvement, and deterioration of visual field deficits, visual acuity and unspecified visual function in fixed- and random-effect models, including assessment of heterogeneity (I2) and publication bias (Begg’s test). Results: Out of 2636 articles, 35 case series were included in the meta-analysis. Results are described for fixed-effect models. For patients with impaired visual acuity, only one study reported complete recovery (27.2%). Pooled prevalence for improvement was 67.5% (95% CI = 59.1–75.0%), but with considerable heterogeneity (I2: 86.0%), and 4.50% (95% CI = 1.80–10.8%) for patients experiencing deterioration. For patients with visual field deficits, the prevalence was 40.4% (95% CI = 34.8–46.3%) for complete recovery, 80.8% (95% CI = 77.7–83.6%) for improvement, and 2.3% (95% CI = 1.1–4.7%) for deterioration. For the unspecified visual outcomes, pooled prevalence of complete recovery was 32.9% (95% CI: 28.5–37.7%), but with considerable heterogeneity (I2 = 84.2%). The prevalence was 80.9% (95% CI = 77.9–83.6) for improvement and 2.00% (95% CI = 1.10–3.40%) for deterioration. Random-effect models yielded similar results. Publication bias was non-significant for all the outcomes. Conclusion: While visual deficits improved after EETS in the majority of patients, complete recovery was only achieved in less than half of the patients and some patients even suffered from visual deterioration. Electronic supplementary material The online version of this article (doi:10.1007/s11102-017-0815-9) contains supplementary material, which is available to authorized users