Predicting the risk of postoperative recurrence and high-grade histology in patients with intracranial meningiomas using routine preoperative MRI.

Risk factors for prediction of prognosis in meningiomas derivable from routine preoperative magnetic resonance imaging (pMRI) remain elusive. Correlations of tumor and edema volume, disruption of the arachnoid layer, heterogeneity of contrast enhancement, enhancement of the capsule, T2-intensity, tumor shape, and calcifications on pMRI with tumor recurrence and high-grade (WHO grade II/III) histology were analyzed in 565 patients who underwent surgery for WHO grade I (N = 516, 91%) or II/III (high-grade histology, N = 49, 9%) meningioma between 1991 and 2018. Edema volume (OR, 1.00; p = 0.003), heterogeneous contrast enhancement (OR, 3.10; p < 0.001), and an irregular shape (OR, 2.16; p = 0.015) were associated with high-grade histology. Multivariate analyses confirmed edema volume (OR, 1.00; p = 0.037) and heterogeneous contrast enhancement (OR, 2.51; p = 0.014) as risk factors for high-grade histology. Tumor volume (HR, 1.01; p = 0.045), disruption of the arachnoid layer (HR, 2.50; p = 0.003), heterogeneous contrast enhancement (HR, 2.05; p = 0.007), and an irregular tumor shape (HR, 2.57; p = 0.001) were correlated with recurrence. Multivariate analyses confirmed tumor volume (HR, 1.01; p = 0.032) and disruption of the arachnoid layer (HR, 2.44; p = 0.013) as risk factors for recurrence, independent of histology. Subgroup analyses revealed disruption of the arachnoid layer (HR, 9.41; p < 0.001) as a stronger risk factor for recurrence than high-grade histology (HR, 5.15; p = 0.001). Routine pMRI contains relevant information about the risk of recurrence or high-grade histology of meningioma patients. Loss of integrity of the arachnoid layer on MRI had a higher prognostic value than the WHO grading, and underlying histological or molecular alterations remain to be determined.

Clinical, radiological, and histopathological predictors for long-term prognosis after surgery for atypical meningiomas.

BACKGROUND: Despite considerable rates of recurrence and mortality in atypical meningiomas, reliable predictors for estimating postoperative long-term prognosis remain elusive. METHODS: Clinical, histopathological, and radiological variables from 138 patients, including 64 females and 74 males (46% and 54%, median age 62 years), who underwent surgery for intracranial atypical meningioma were retrospectively analyzed. Associations between variables and recurrence and mortality were investigated using uni- and multivariate analyses. RESULTS: Gross total (GTR) and subtotal resection (STR) was achieved in 81% and 19% of cases, respectively. Within a median follow-up of 62 months, recurrence occurred in 52 (38%) and mortality in 22 (16%) cases. In patients who did not receive adjuvant irradiation, recurrence rates were higher after STR than after GTR (32% vs 63%, p = 0.025). In univariate analyses, only intratumoral calcifications on preoperative MRI (p = 0.012) and the presence of brain invasion in the absence of other histological grading criteria (p = 0.010) were correlated with longer progression-free intervals (PFI). In multivariate analyses, patient age was positively (HR 1.03, 95%CI 1.04-1.05; p = 0.018) and the presence of brain invasion as the only grading criterion (HR 0.37, 95%CI 0.19-0.74; p = 0.005) was negatively related with progression, while rising age at the time of surgery (HR 1.07, 95%CI 1.03-1.12; p = 0.001) was prognostic for mortality. CONCLUSIONS: PFI was longer in brain invasive but otherwise histological benign meningiomas and in tumors displaying calcifications on preoperative MRI. Advancing patient age and lower Karnofsky Performance Score were associated with higher overall mortality.

Risk factors for preoperative seizures in intracranial meningiomas.

BACKGROUND: About 25% of patients with intracranial meningioma display seizures at the time of initial presentation. Hence, identification of risk factors for preoperative seizures is crucial during perioperative care of meningioma patients. METHODS: Associations of preoperative seizures with clinical, radiological and histological variables were analyzed in 945 patients (689 females, 73% and 256 males, 27%; median age: 58 years) who underwent surgery for primary diagnosed intracranial meningioma. RESULTS: Preoperative seizures were found in 189 patients (20%). In univariate analyses, male gender (OR=1.91, 95% CI: 1.37-2.68; P<0.001), grade II/III histology (OR=2.24, 95% CI: 1.46-3.46; P<0.001), brain invasion (OR=2.59, 95% CI: 1.45-4.63; P=001), non-skull base tumor location (OR=3.07, 95% CI: 2.13-4.41; P<0.001), heterogeneous contrast-enhancement (OR=1.60, 95% CI: 1.04-2.46; P=0.031), intratumoral calcifications (OR=1.91, 95% CI: 1.17-3.10; P=0.009), an irregular shape (OR=2.07, 95% CI: 1.32-3.26; P=0.002) as well as tumor (OR=1.01 per ccm, 95% CI: 1.00-1.02; P=0.001) and edema volumes (OR=1.01 per ccm, 95% CI: 1.00-1.01; P<0.001) were correlated with seizures. Semiology was not related to any of the analyzed variables (P>0.05, each). No associations were found between seizures and histological subtype of 832 grade I meningiomas (P=0.391). In multivariate analyses, only non-skull base tumor location (OR=3.12, 95% CI: 1.74-5.59; P<0.001) and a rising peritumoral edema volume (OR=1.01 per ccm, 95% CI: 1.00-1.01; P<0.001) were identified as independent predictors for preoperative seizures. CONCLUSIONS: Several mostly radiological variables were identified as risk factors for epilepsy. However, multivariate analyses confirmed only peritumoral edema and non-skull base tumor location as independent predictors for preoperative seizures. None of the variables predicts semiology.

Predicting postoperative seizure development in meningiomas - Analyses of clinical, histological and radiological risk factors.

INTRODUCTION: Seizures after meningioma surgery are common, with a distinct impact on postoperative life quality. Sufficient risk factors for seizure development are sparsely known but needed to improve perioperative patient counseling and, eventually, antiepileptic treatment. MATERIALS AND METHODS: Correlations between clinical, radiological and histological variables and the onset of new seizures following surgery for initially diagnosed cranial meningioma were retrospectively analyzed in uni- and multivariate analyses. RESULTS: 752 preoperatively seizure-naïve patients (569 females, 76 % and 183 males, 24 %) with a median age of 57 years were included. Postoperative seizures occurred in 69 cases (9 %). In univariate analyses, seizures were correlated with preoperative Karnofsky Score < 80 (OR: 1.91, 95 % CI 1.01-3.59; p = .045), convexity/parasagittal tumor location (OR: 1.77, 95 % CI 1.06-2.95; p = .030), heterogenous contrast-enhancement of the tumor (OR: 2.24, 95 % CI 1.14-4.39; p = .019) and intratumoral calcifications (OR: 3.35, 95 % CI 1.59-7.05; p = .001). Multivariable analyses revealed age at the time of surgery (OR: 1.04, 95 % CI 1.01-1.07; p = .009) and intratumoral calcifications on preoperative imaging (OR: 3.70, 95 % CI 1.73-7.92; p = .001) as risk factors for postoperative seizures. Based on multivariate analyses, a score for discrimination of patients at low (3 %), intermediate (11 %) and high risk (17 %) of postoperative seizures (AUC: 0.7, p < .001) was conducted. In subgroup analyses, postoperative hemorrhage (OR: 2.90, 95 % CI 1.13-7.46; p = .028) and hydrocephalus (OR: 3.65, 95 % CI 1.48-9.01; p = .005) were correlated with postoperative seizures. CONCLUSION: Risk factors for postoperative seizures after meningioma surgery are sparse and can be basically taken from preoperative imaging. Among surgical complications, postoperative hemorrhage and hydrocephalus are strong seizure predictors.

Occurrence of Fibrotic Tumor Vessels in Grade I Meningiomas Is Strongly Associated with Vessel Density, Expression of VEGF, PlGF, IGFBP-3 and Tumor Recurrence.

Angiogenesis is a key feature during oncogenesis and remains a potential target of antiangiogenic therapy. While commonly described in high-grade lesions, vascularization and its correlation with prognosis in grade I meningiomas is largely unexplored. In the histological classification, not only the number but also the composition of blood vessels seems to be important. Therefore, tumor vessel density and fibrosis were correlated with clinical and imaging variables and prognosis in 295 patients with intracranial grade I meningioma. Expression of pro-angiogenic proteins within the meningiomas was investigated by proteome analyses and further validated by immunohistochemical staining. Fibrotic tumor vessels (FTV) were detected in 48% of all tumors and strongly correlated with vessel density, but not with the histopathological tumor subtype. Occurrence of FTV was correlated with a 2-fold increased risk of recurrence in both univariate and multivariate analyses. Explorative proteome analyses revealed upregulation of VEGF (vascular endothelial growth factor), PlGF (placental growth factor), and IGFBP-3 (insulin-like growth factor-binding protein-3) in tumors displaying FTV. Immunohistochemical analyses confirmed strong correlations between tumor vessel fibrosis and expression of VEGF, PlGF, and IGFBP-3. Presence of FTV was strongly associated with disruption of the arachnoid layer on preoperative MRI in univariate and multivariate analyses. In summary, the occurrence of fibrotic tumor vessels in grade I meningiomas is strongly associated with vessel density, disruption of the arachnoid layer, expression of VEGF, PlGF, IGFBP-3 and tumor recurrence.

Prediction of brain invasion in patients with meningiomas using preoperative magnetic resonance imaging.

Brain invasion (BI) in meningiomas impacts WHO grading and therefore adjuvant treatment. However, BI is rare and neurosurgical sampling and neuropathological analyses are not standardised. Moreover, associations with imaging findings are sparsely known. Associations between BI and findings on preoperative MRI were investigated in 617 meningioma patients. BI was strongly correlated with other high-grade criteria (p<.001). Presence of a contrast enhancing tumour capsule, disruption of the arachnoid layer, intratumoural calcifications and T2-intensity were not related to high-grade histology or BI (p>.05, each). High-grade histology (p=.033) but not BI (p=.354) was associated with tumour location. Irregular tumour shape (OR: 3.33, 95%CI 1.33-8.30; p=.007), heterogeneous contrast enhancement (OR: 2.82, 95%CI 1.19-6.70; p=.015) and peritumoural edema (OR: 1.005 per ccm, 95%CI 1.001-1.008); p=.011) were associated with BI. Multivariable analyses identified only increasing edema volume (OR: 1.005 per ccm, 95%CI 1.002-1.009; p=.010) as a predictor for BI, independent of other histopathological high-grade criteria. We finally provide a new model to estimate the risk of BI using routine preoperative MRI. Several imaging characteristics were identified as predictors for BI. Consideration in clinical routine can increase the accuracy of the detection in neuropathological analyses.

Spinal meningiomas - Risks and potential of an increasing age at the time of surgery.

Although the majority of surgeries for spinal meningiomas are performed in geriatric patients, age-related analyzes of preoperative symptoms and functional outcome are sparse. Clinical, neuropathological and radiological data of 88 patients who underwent surgery for spinal meningiomas were reviewed. Correlations between the patients' age and preoperative symptoms as well as functional outcome were investigated. 14 males (16%) and 74 females (84%) with a median age of 67 years were included. Age at the time of surgery was independent of the tumor location and volume, intra-/extradural tumor location, spinal cord compression or signal change on T2-weighted MRI (p > 0.05, each). Preoperative McCormick score (p = 0.001), motor (p = 0.005) and sensory (p = 0.025) deficits and incontinence (p = 0.010) increased, while frequency of radicular pain decreased with increasing age (p = 0.020). Multivariate analyses confirmed an increasing risk of motor (OR: 1.05, p = 0.017) and, with borderline significance, of sensory deficits (OR: 1.04, 95%CI 1.00-1.10; p = 0.056) with rising age. Simpson grades I, II, III and IV were achieved in 12 (14%), 54 (64%), 14 (17%) and 4 (5%) individuals, respectively. Only 3 of 12 patients (25%) with perioperative complications were younger than 65 years. Rising age was associated with improvement of motor (p = 0.006) and sensory deficits (p = 0.045). In multivariate analyzes, probability of improvement of preoperative motor weakness (OR = 1.05, p = 0.031) and sensory deficits (OR = 1.07, p = 0.014) increased with rising age. Despite more frequent preoperative neurological deficits, older patients with spinal meningiomas recover most noticeably after surgery. However, stratification of the medical condition is urgent to reduce complications.

Brain invasion and the risk of seizures in patients with meningioma.

OBJECTIVE: Identification of risk factors for perioperative epilepsy remains crucial in the care of patients with meningioma. Moreover, associations of brain invasion with clinical and radiological variables have been largely unexplored. The authors hypothesized that invasion of the cortex and subsequent increased edema facilitate seizures, and they compared radiological data and perioperative seizures in patients with brain-invasive or noninvasive meningioma. METHODS: Correlations of brain invasion with tumor and edema volumes and preoperative and postoperative seizures were analyzed in univariate and multivariate analyses. RESULTS: Totals of 108 (61%) females and 68 (39%) males with a median age of 60 years and harboring totals of 92 (52%) grade I, 79 (45%) grade II, and 5 (3%) grade III tumors were included. Brain invasion was found in 38 (22%) patients and was absent in 138 (78%) patients. The tumors were located at the convexity in 72 (41%) patients, at the falx cerebri in 26 (15%), at the skull base in 69 (39%), in the posterior fossa in 7 (4%), and in the ventricle in 2 (1%); the median tumor and edema volumes were 13.73 cm3 (range 0.81-162.22 cm3) and 1.38 cm3 (range 0.00-355.80 cm3), respectively. As expected, edema volume increased with rising tumor volume (p < 0.001). Brain invasion was independent of tumor volume (p = 0.176) but strongly correlated with edema volume (p < 0.001). The mean edema volume in noninvasive tumors was 33.0 cm3, but in invasive tumors, it was 130.7 cm3 (p = 0.008). The frequency of preoperative seizures was independent of the patients' age, sex, and tumor location; however, the frequency was 32% (n = 12) in patients with invasive meningioma and 15% (n = 21) in those with noninvasive meningioma (p = 0.033). In contrast, the probability of detecting brain invasion microscopically was increased more than 2-fold in patients with a history of preoperative seizures (OR 2.57, 95% CI 1.13-5.88; p = 0.025). In univariate analyses, the rate of preoperative seizures correlated slightly with tumor volume (p = 0.049) but strongly with edema volume (p = 0.014), whereas seizure semiology was found to be independent of brain invasion (p = 0.211). In multivariate analyses adjusted for age, sex, tumor location, tumor and edema volumes, and WHO grade, rising tumor volume (OR 1.02, 95% CI 1.00-1.03; p = 0.042) and especially brain invasion (OR 5.26, 95% CI 1.52-18.15; p = 0.009) were identified as independent predictors of preoperative seizures. Nine (5%) patients developed new seizures within a median follow-up time of 15 months after surgery. Development of postoperative epilepsy was independent of all clinical variables, including Simpson grade (p = 0.133), tumor location (p = 0.936), brain invasion (p = 0.408), and preoperative edema volume (p = 0.081), but was correlated with increasing preoperative tumor volume (p = 0.004). Postoperative seizure-free rates were similar among patients with invasive and those with noninvasive meningioma (p = 0.372). CONCLUSIONS: Brain invasion was identified as a new and strong predictor for preoperative, but not postoperative, seizures. Although also associated with increased peritumoral edema, seizures in patients with invasive meningioma might be facilitated substantially by cortical invasion itself. Consideration of seizures in consultations between the neurosurgeon and neuropathologist can improve the microscopic detection of brain invasion.

Survey of 2582 cases of acute orthopedic trauma.

BACKGROUND: Orthopedic injuries are among the most common causes of mortality, morbidity, hospitalization, and economic burden in societies. OBJECTIVES: In this research, we study the prevalence of different types of trauma requiring orthopedic surgery. PATIENTS AND METHODS: We conducted a cross-sectional study on 2582 patients with acute orthopedic injuries admitted to the orthopedic emergency ward at the Poursina Hospital (a referral center in Guilan province (northern Iran), during December 2010 through September 2011. Patients were examined and the data collection form was filled for each patient. Data were analyzed by SPSS software version 19 and were listed in tables. RESULTS: Of 2582 included cases, 1940 were male and 642 were female, with a mean age of 34.5 years. Most injuries were seen in the 25 to 44 year age group from rural areas. The highest frequency of trauma related to falls. On the other hand, bicycling and shooting had the lowest frequencies. There were 18 cases with limb amputation. Overall, 66.5% of patients had fractures, 5% had soft tissue lacerations, and 10% had dislocations. CONCLUSIONS: Identification of risk factors and methods of prevention is one of the most important duties of healthcare systems. Devising plans to minimize these risk factors and familiarizing people with them is prudent.