IDH wild-type lower-grade gliomas with glioblastoma molecular features: a systematic review and meta-analysis.

The WHO 2021 classification defines IDH wild type (IDHw) histologically lower-grade glioma (hLGG) as molecular glioblastoma (mGBM) if TERT promoter mutation (pTERTm), EGFR amplification or chromosome seven gain and ten loss aberrations are indicated. We systematically reviewed articles of IDHw hLGGs studies (49 studies, N = 3748) and meta-analyzed mGBM prevalence and overall survival (OS) according to the PRISMA statement. mGBM rates in IDHw hLGG were significantly lower in Asian regions (43.7%, 95% confidence interval [CI: 35.8-52.0]) when compared to non-Asian regions (65.0%, [CI: 52.9-75.4]) (P = 0.005) and were significantly lower in fresh-frozen specimen when compared to formalin-fixed paraffin-embedded samples (P = 0.015). IDHw hLGGs without pTERTm rarely expressed other molecular markers in Asian studies when compared to non-Asian studies. Patients with mGBM had significantly longer OS times when compared to histological GBM (hGBM) (pooled hazard ratio (pHR) 0.824, [CI: 0.694-0.98], P = 0.03)). In patients with mGBM, histological grade was a significant prognostic factor (pHR 1.633, [CI: 1.09-2.447], P = 0.018), as was age (P = 0.001) and surgical extent (P = 0.018). Although bias risk across studies was moderate, mGBM with grade II histology showed better OS rates when compared to hGBM.

Diagnostic accuracy of cerebrospinal fluid liquid biopsy and MRI for leptomeningeal metastases in solid cancers: A systematic review and meta-analysis.

Background: Cerebrospinal fluid (CSF) cytology remains the gold standard approach for diagnosing of leptomeningeal metastases (LM), but has clinical problems due to its low sensitivity. This systemic review and meta-analysis evaluated the diagnostic accuracy of the novel CSF biomarkers of liquid biopsy and magnetic resonance imaging (MRI) for detecting LM in patients with solid cancers. Methods: A systematic search of electronic databases was conducted to identify all published diagnostic accuracy studies on CSF liquid biopsies and MRI since January 2000 with registration for PROSPERO (#CRD42022301988). Articles were selected based on pre-defined inclusion and exclusion criteria following the PRISMA 2020 statement. Results: The search yielded 3790 citations, and 10 studies with 668 patients were included in the final analysis. The pooled prevalence of LM was 50.9% (340/668). The respective sensitivity and specificity for index tests were as follows: circulating tumor cells (CTC), 87.0% (95% confidence interval [CI] 77.9-92.6%) and 93.8% (86.9-97.2%); cell-free tumor DNA, 97.9% (19.3-100%) and 89.0% (25.3-99.5%); MRI 59.4% (60.7-76.9%) and 97.6% (77.3-99.8%); cytology, 71.9% (54.7-82.9%) and 100%. The diagnostic odds ratio was 100.6 (29.38-344.09) for CTC and 93.3 (88.42-1034.05) for MRI. Conclusion: Novel CSF liquid biopsies and MRI may offer improved diagnostic accuracy for LM from solid cancers; however, further research is required to specify the threshold values and to construct standards for individual primary cancers.

Incidental diffuse low-grade gliomas: A systematic review and meta-analysis of treatment results with correction of lead-time and length-time biases.

Background: Better overall survival (OS) reported in patients with incidental diffuse low-grade glioma (iLGG) in comparison to symptomatic LGG (sLGG) may be overestimated by lead-time and length-time. Methods: We performed a systematic review and meta-analysis of studies on adult hemispheric iLGGs according to the PRISMA statement to adjust for biases in their outcomes. Survival data were extracted from Kaplan-Meier curves. Lead-time was estimated by 2 methods: Pooled data of time to become symptomatic (LTs) and time calculated from the tumor growth model (LTg). Results: We selected articles from PubMed, Ovid Medline, and Scopus since 2000. Five compared OS between patients with iLGG (n = 287) and sLGG (n = 3117). The pooled hazard ratio (pHR) for OS of iLGG to sLGG was 0.40 (95% confidence interval [CI] {0.27-0.61}). The estimated mean LTs and LTg were 3.76 years (n = 50) and 4.16-6.12 years, respectively. The corrected pHRs were 0.64 (95% CI [0.51-0.81]) by LTs and 0.70 (95% CI [0.56-0.88]) by LTg. In patients with total removal, the advantage of OS in iLGG was lost after the correction of lead-time. Patients with iLGG were more likely to be female pooled odds ratio (pOR) 1.60 (95% CI [1.25-2.04]) and have oligodendrogliomas (pOR 1.59 [95% CI {1.05-2.39}]). Correction of the length-time bias, which increased the pHR by 0.01 to 0.03, preserved the statistically significant difference in OS. Conclusions: The reported outcome in iLGG was biased by lead-time and length-time. Although iLGG had a longer OS after correction of biases, the difference was less than previously reported.

Malignant Progression of Diffuse Low-grade Gliomas: A Systematic Review and Meta-analysis on Incidence and Related Factors.

Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent in literature. According to the PRISMA guidelines, we systematically reviewed articles from 2009, meta-analyzed the incidence of malignant progression, and clarified factors related to the transformation. Forty-one articles were included in this study (n = 7,122; n, number of patients). We identified two definitions of malignant progression: histologically proven (Htrans) and clinically defined (Ctrans). The malignant progression rate curves of Htrans and Ctrans were almost in parallel when constructed from the results of meta-regression by the mean follow-up time. The true transformation rate was supposed to lie between the two curves, approximately 40% at the 10-year mean follow-up. Risk of malignant progression was evaluated using hazard ratio (HR). Pooled HRs were significantly higher in tumors with a larger pre- and postoperative tumor volume, lower degree of resection, and notable preoperative contrast enhancement on magnetic resonance imaging than in others. Oligodendroglial histology and IDH mutation (IDHm) with 1p/19q codeletion (Codel) also significantly reduced the HRs. Using Kaplan-Meier curves from eight studies with molecular data, we extracted data and calculated the 10-year malignant progression-free survival (10yMPFS). The 10yMPFS in patients with IDHm without Codel was 30.4% (95% confidence interval [95% CI]: 22.2-39.0) in Htrans and 38.3% (95% CI: 32.3-44.3) in Ctrans, and that with IDHm with Codel was 71.7% (95% CI: 61.7-79.5) in Htrans and 62.5% (95% CI: 55.9-68.5) in Ctrans. The effect of adjuvant radiotherapy or chemotherapy could not be determined.

Outcomes of Preserving the Hypertrophic Arachnoid Membrane in the Brain-meningioma Interface: Long-term Follow-up.

Abnormal hypertrophic arachnoid membranes are often observed in the brain-meningioma interface during microsurgery. They contain fibrosis and tumor cell clusters; however, preservation of the membranes does not always cause recurrence from the brain surface, and the optimal treatments in the interface remain unclear. We investigated the incidence of recurrence on the brain surface following extra-arachnoid dissection with an approach emphasizing preservation of the arachnoid membranes in meningiomas of World Health Organization (WHO) Grade I. The features of dissection cleavages in the interface were prospectively recorded at surgery. The patients were followed up with MR imaging regularly. In total, 111 patients were included. The median follow-up time was 97.0 (interquartile range [IQR] 70.0-124.0) months. The cleavages in the interface were classified into three subgroups: the Extra-H group (n = 56) with extra-arachnoid resection and preservation of hypertrophic arachnoid membranes, the Extra-N group (n = 39) with extra-arachnoid resection having normal membranes, and the Subpial resection group (n = 16). Tumors recurred in 13 (11.7%) patients at both the brain and dura mater (n = 1) or at the dura mater alone (n = 12). The median recurrence-free survival (RFS) of all recurrences was significantly related to the Simpson grades (P <0.01). For brain surface recurrence, the median RFS was not related to the subgroups. The Karnofsky Performance Scores (KPSs) significantly improved in the patients except for the Subpial group at 3 months after surgery. This study revealed that hypertrophic arachnoid membranes preserved on the brain surface rarely caused recurrence from the brain in WHO Grade I meningiomas after a long-term follow-up.

Prevalence of incidental meningiomas and gliomas on MRI: a meta-analysis and meta-regression analysis.

BACKGROUND: The chance of incidentally detecting brain tumors is increasing as the utilization of magnetic resonance imaging (MRI) becomes more prevalent. In this background, knowledge is accumulating in relation to the prediction of their clinical sequence. However, their prevalence-especially the prevalence of glioma-has not been adequately investigated according to age, sex, and region. METHOD: We systematically reviewed the articles according to the PRISMA statement and calculated the prevalence of meningiomas and diffuse gliomas in adults using a generalized linear mixed model. Specifically, the differences related to age, sex, and region were investigated. RESULTS: The pooled prevalence of incidental meningiomas in MRI studies was 0.52% (95% confidence interval (CI) [0.34-0.78]) in 37,697 individuals from 36 studies. A meta-regression analysis showed that the prevalence was significantly higher in elderly individuals, women, and individuals outside Asia; this remained statistically significant in the multivariate meta-regression analysis. The prevalence reached to 3% at 90 years of age. In contrast, the prevalence of gliomas in 30,918 individuals from 18 studies was 0.064% (95%CI [0.040 - 0.104]). The meta-regression analysis did not show a significant relationship between the prevalence and age, male sex, or region. The prevalence of histologically confirmed glioma was 0.026% (95%CI [0.013-0.052]). CONCLUSIONS: Most of meningiomas, especially those in elderlies, remained asymptomatic, and their prevalence increased with age. However, the prevalence of incidental gliomas was much lower and did not increase with age. The number of gliomas that developed and the number that reached a symptomatic stage appeared to be balanced.

Prognostic significance of brain invasion in meningiomas: systematic review and meta-analysis.

The WHO 2016 classification introduced brain invasion as a standalone criterion for grade II meningioma (GIIM). We systematically reviewed studies published after 2000 and performed a PRISMA-compliant meta-analysis of the hazard ratios (HRs) for progression-free survival (PFS) between brain-invasive and noninvasive meningiomas. In five studies that included both benign and higher-grade meningiomas, brain invasion was a significant risk factor for recurrence (HR = 2.45, p = 0.0004). However, in 3 studies comparing "brain-invasive meningioma with otherwise benign histology (BIOB)" with grade I meningioma, brain invasion was not a significant predictor of PFS (HR = 1.49, p = 0.23). Among GIIM per the WHO 2000 criteria, brain invasion was a significant predictor of shorter PFS than noninvasive GIIM (HR = 3.40, p = 0.001) but not per the WHO 2016 criteria (HR 1.13, p = 0.54), as the latter includes BIOB. Meta-regression analysis of seven studies of grade II meningioma showed that more frequent BIOB was associated with lower HRs (p < 0.0001). Hence, there is no rationale for brain invasion as a standalone criterion for grade II meningioma, although almost all studies were retrospective and exhibited highly heterogeneous HRs due to differences in brain-tumor interface data availability.

Malignant transformation of WHO grade I meningiomas after surgery or radiosurgery: systematic review and meta-analysis of observational studies.

BACKGROUND: The incidence and clinical features of the malignant transformation of benign meningiomas are poorly understood. This study examined the risk of the malignant transformation of benign meningiomas after surgery or stereotactic radiosurgery. METHODS: We systematically reviewed studies published between 1979 and 2019 using PubMed, Scopus, and other sources. We analyzed pooled data according to the PRISMA guideline to clarify the incidence rate of malignant transformation (IMT) and factors affecting malignant transformation in surgically or radiosurgically treated benign meningiomas. RESULTS: IMT was 2.98/1000 patient-years (95% confidence interval [CI] = 1.9-4.3) in 13 studies in a single-arm meta-analysis. Although the evidence level of the included studies was low, the heterogeneity of the incidence was mostly explained by the tumor location. In meta-regression analysis, skull base tumors had a significantly lower IMT than non-skull base tumors, but no gender association was observed. IMT after radiosurgery in 9 studies was 0.50/1000 person-years (95% CI = 0.02-1.38). However, a higher proportion of skull base tumors, lower proportion of males, and lower salvage surgery rate were observed in the radiosurgery group than in the surgery group. The median time to malignant change was 5 years (interquartile range = 2.5-8.2), and the median survival after malignant transformation was 4.7 years (95% CI = 3.7-8) in individual case data. CONCLUSION: IMT of benign meningioma was significantly affected by the tumor location. Radiosurgery did not appear to increase IMT, but exact comparisons were difficult because of differences in study populations.

Natural History of Meningiomas: Review with Meta-analyses.

Observation has been a mainstay in asymptomatic meningiomas, but it may increase the risk associated with treatment due to tumor enlargement and the aging of patients. Understanding the natural course of meningiomas is important to provide appropriate treatment. The majority of previous studies investigated factors related to their growth, but failed to demonstrate their relationship with symptomatic progression (sympP) because of its rarity. We reviewed and meta-analyzed 27 studies that investigated natural courses in asymptomatic or untreated meningiomas to find clinico-radiological factors predictive of radiological progression (radioP), growth speed, and sympP. In results of time-growth analysis, two-thirds of meningiomas showed radioP defined by a volume criterion and the rate approached a plateau at 4-5 years. In growth curve analyses, about half of incidental meningiomas presented decelerating or no growth, while less than one-quarter of them grew exponentially. RadioP, growth speed [annual volume change (AVC) or relative growth rate], and sympP each had different factors related to them. Younger age, non-calcification, and high intensity on T2-weighted image were related to radioP and rapid growth speed, but not to sympP. Tumors in males and those of larger size were likely to be symptomatic in the meta-analysis. AVC (≥2.1 cm3/year) was the strongest indicator of sympP. Apart from perifocal edema, radiological features at up-front imaging may not be useful for predicting sympP. This may be due to dynamic changes of those radiological markers in the long term. Quantified tumor size and growth speed, especially AVC, are important markers for deciding on treatment.

A practical predictor of the growth potential of benign meningiomas: Hypointensity of surface layer in T2-weighted magnetic resonance imaging.

BACKGROUND: Accurate evaluation of proliferative potential is particularly important in the clinical management of individual patients with meningiomas. We introduce a new feature in the parenchyma of meningioma, namely, hypointensity of the surface layer (HSL), on T2-weighted MR images and compare it with a cellular proliferation index and growth speed. MATERIALS AND METHODS: We retrospectively analyzed the records of consecutive patients with WHO grade I meningiomas in two institutes: an operated group with 124 meningiomas resected in one institute, and an observed group with 89 meningiomas monitored without surgery in the other. Proliferative potential was evaluated using the MIB-1 labeling index (MIB-1 LI) for the operated group and using the relative growth rate on serial MR images for the observed group. RESULTS: In the operated group, 60 (48.4%) meningiomas exhibited HSL. HSL-positive meningiomas were significantly smaller in size and more often calcified than HSL-negative ones. Univariate analysis showed that HSL negativity, large size, no calcification, and surrounding brain edema were significantly associated with high MIB-1 LI (p < 0.05). Multivariate analysis demonstrated that only HSL was significantly related to MIB-1 LI (p = 0.001). HSL did not correlate with tumor recurrence after resection. In the observed group, 43 (48.3%) meningiomas exhibited HSL and they presented a significantly slow relative growth rate. CONCLUSIONS: HSL is a simple and new radiological feature indicative of low proliferative potential and a low risk of enlargement of meningiomas. The presence or absence of HSL may serve as a key parameter for the selection of aggressive treatment or active observation.

CT Hounsfield Unit Is a Good Predictor of Growth in Meningiomas.

Predicting the growth rate of meningiomas is important in treatment planning. Although calcification may be an important sign of slow growth in meningiomas, the developmental process and its relation to the tumor growth pattern have not been elucidated. We retrospectively examined the location and degree of calcification in 150 meningiomas (131 asymptomatic tumors) using computed tomography (CT) scans and mean Hounsfield units (mHU). Tumor growth was evaluated using serial imaging studies wherein we calculated tumor doubling time (Td) and identified the growth curve pattern as exponential, intermediate, or decelerating. Tumors in women more frequently had calcification and showed higher mHU than those in men. The mHU was measured at least twice in 57 tumors. Tumors in women showed greater mHU increases than those in men. We found a significant correlation between Td and mHU (R = 0.49). Tumors in men and those in patients in the younger age group grew significantly faster. Multivariate analysis revealed that mHU was the only significant factor affecting Td (P <0.0001). The growth pattern was significantly related to calcification (n = 61, P = 0.0042). Tumors with decelerating growth more frequently showed calcification and had higher mHU than those with exponential growth. Receiver operating characteristic curve analysis revealed that mHU was a better predictor of growth pattern change compared with calcification on CT scan. Meningiomas with high mHU, even without calcification, were likely to show growth deceleration. Mean Hounsfield unit correlated with Td and may be a good quantitative indicator of the growth rate and pattern.

Diagnosis of demyelinating brain lesion simulating brain tumors on fast imaging employing steady-state acquisition magnetic resonance imaging.

BACKGROUND: A single inflammatory demyelinating brain lesion sometimes mimics a brain tumor on conventional magnetic resonance imaging (MRI), and thus poses a considerable diagnostic challenge. We assessed the usefulness of a new MRI technique, fast imaging employing steady-state acquisition (FIESTA), for the diagnosis of inflammatory demyelinating disease (IDD). METHODS: Three patients (2 males, 1 female) with a histopathologically proven inflammatory demyelinating brain lesion which mimicked a brain tumor on MRI were evaluated with a post-contrast three-dimensional FIESTA sequence before biopsy and treatment. Those images were compared with the images of intra-axial brain tumors (n = 147). RESULTS: Preoperative FIESTA showed an iso- or slightly hyperintense distinct intralesional structure that appeared reticulate or broad-line in patients with IDD. These structures traversed a hyperintense demyelinating lesion in the deep grey matter (DGM) and were connected to the surrounding extralesional area, which appeared to be dense fibers between DGM. Such distinct intralesional structures were not observed in most brain tumors. CONCLUSION: Reticulate or broad-line-like intralesional structures on FIESTA may, therefore, be suggestive of IDD rather than indicate a brain tumor.

mTORC1 signaling in primary central nervous system lymphoma.

BACKGROUND: Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) acts as a downstream effector of phosphatidyl-inositol-3 kinase, which is frequently hyperactivated in glioblastoma multiforme and links to cell signaling in cellular proliferation, differentiation, metabolism, and survival. Although many studies have suggested the importance of mTORC1 in tumorigenesis, its role remains unclear in brain tumors other than glioblastoma. METHODS: In the present study, we evaluated the activation of mTORC1 in 24 cases of primary central nervous system lymphoma (PCNSL). RESULTS: Immunohistochemical analysis showed overexpression of Rheb, which is immediately upstream of mTORC1, in 20 cases of PCNSL. Immunohistochemical analysis also showed overexpression of phospho-4E-BP1 (Thr37/46) and phospho-S6 (Ser235/236), which are increased after mTORC1 activation as mTORC1 downstream effectors in 17 and 21 cases, respectively. CONCLUSION: Our data suggest that abnormal activation of the mTORC1 signaling pathway may cause tumor growth in patients with PCNSL.

Response-adapted treatment with upfront high-dose chemotherapy followed by autologous stem-cell transplantation rescue or consolidation phase high-dose methotrexate for primary central nervous system lymphoma: a long-term mono-center study.

Treatment regimens for primary central nervous system lymphoma (PCNSL) include high-dose methotrexate (HD-MTX)-based chemotherapy, with or without radiotherapy and are based on studies of selected patient groups. This retrospective study assessed a consistent strategy of response-adapted protocol applied for patients including age >65 years in a cancer center for 10 years longitudinally. Case notes were studied of 61 consecutively treated patients with PCNSL histologically diagnosed between 2003 and 2013. Clinical follow-up during and after treatment included neurologic examination and magnetic resonance imaging. Of the patients studied, 14.8 % (9/61) were clinically unfit for chemotherapy; the remaining 85.2 % (52/61) of patients were treated with HD-MTX. Of these patients, 58 % (30/52) achieved an initial complete response, with a median survival of 100.1 months. Of these response-adapted patients, 33 % (10/30) were <65 years and were treated with upfront high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT). The remaining response-adapted patients included 53 % (16/30) who were ≥65 years underwent consolidation with HD-MTX, and 14 % (4/30) who chose radiotherapy. The median survival of patients with HDC-ASCT had not yet been reached compared with 67.6 months for patients with HD-MTX consolidation treatment (p = 0.26). At the end of the study, 75 % (39/52) of patients had died mainly owing to progression or relapse of PCNSL. Multivariate analysis showed that age younger than 65 years (p = 0.02) and complete response for up-front HD-MTX (p = 0.001) were independent prognostic indicators of overall survival. In conclusion, this single-center retrospective clinical study has shown that treatment of PCNSL with upfront HDC-ASCT and consolidation phase HD-MTX monotherapy may be feasible, even for elderly patients in a routine clinical setting, using the three-step selection by eligibility and response to initial HD-MTX, and age threshold of 65 years for ASCT.

"Comet tail sign": A pitfall of post-gadolinium magnetic resonance imaging findings for metastatic brain tumors.

A highly enhanced cap attached to the surface of metastatic tumors in the brain parenchyma is occasionally encountered on magnetic resonance (MR) images. This atypical enhanced cap tends to occur in severe peritumoral edema and may produce the characteristic bulge of a metastatic mass lesion termed the "comet tail sign" (CTS). The purpose of this study was to demonstrate the features of the CTS using MR imaging and pathological findings, and to clarify its clinical relevance. We selected 21 consecutive cases of newly diagnosed metastases from MR imaging studies that demonstrated the CTS; all had diffuse peritumoral edema. The MR T2-weighted images showed similarly homogenous and high intensity signals in both the tail and peritumoral edema. Fourteen of the 21 patients underwent surgical resection of their tumors, and 12 tails were separately removed for pathological examination, no tumor cells which revealed. We speculate that the CTS does not contain neoplastic tissues but is observed as a result of the leakage of contrast medium from the tumor body into the interstitial space of the white matter. Although CTS is a peculiar and uncommon enhancement pattern, it has clinical significance in determining the extent of the margin for invasive local treatments, such as surgical resection or stereotactic radiotherapy; this is particularly true in and near the eloquent areas.

O6-methylguanine DNA methyltransferase expression in tumor cells predicts outcome of radiotherapy plus concomitant and adjuvant temozolomide therapy in patients with primary glioblastoma.

Expression of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene has been shown to correlate with clinical outcomes in patients with glioblastoma multiforme treated with alkylating agents. We evaluated MGMT protein expression in 53 primary glioblastomas by the immunohistochemistry (IHC) and analyzed the correlation between results of immunostaining and patient outcomes. There were 28 MGMT-immunopositive and 25 negative glioblastomas. Patients with MGMT-immunonegative glioblastomas showed significantly longer progression-free survival (PFS) (P = 0.0032), but no statistically significant benefits on overall survival (OS) (P = 0.0825) were shown. In 41 glioblastomas treated with temozolomide (TMZ) therapy (MGMT-immunopositive: n = 22, negative: n = 19), both PFS and OS were significantly better in MGMT-immunonegative glioblastomas. (PFS: P = 0.0015, OS: P = 0.0384). We conclude that MGMT expression on immunohistochemistry (IHC) correlates with outcomes in patients with primary glioblastoma receiving TMZ and suggest the use of MGMT-IHC as a surrogate marker for predicting tumor chemosensitivity.

Growth curve analysis of asymptomatic and symptomatic meningiomas.

Meningiomas sometimes appear to stop growing after attaining a large size. Commonly used exponential growth models do not reflect this phenomenon. We attempted to find the best curve to simulate their growth. Fifty-two patients with meningioma were followed up for 3.1-21.7 years (mean 7.5 years) with four or more imaging studies each. Thirty-one patients had asymptomatic tumors. The other 21 patients with residual or recurrent tumor were followed up after surgery. Time-volume curves for each tumor were plotted. Nonlinear regression analyses were performed against power, exponential, logistic, and Gompertzian curves. Time-volume curves corresponded to the Gompertzian and logistic growth curves better than to power or exponential curves. When simulating time-volume curves with Gompertzian curves, the majority of benign meningiomas began to slow their growth before patient age of 80 years. Twenty-three of 31 asymptomatic meningiomas had already passed the inflection point before diagnosis. In contrast, this happened less frequently in symptomatic tumors. Especially, all six atypical meningiomas continued to grow quasi-exponentially. Sigmoid curves that approach a plateau were better descriptors of the growth of benign meningiomas than were curves of unlimited growth. However, atypical meningiomas were unlikely to slow their growth.

Recurrence and regrowth of benign meningiomas.

The World Health Organization (WHO) grading system for meningioma is helpful for predicting aggressive subtypes. However, even benign meningiomas sometimes show relatively rapid growth and may recur after total removal. We attempted to find histopathological features that would be valuable for predicting recurrence or regrowth of WHO grade I meningiomas. We investigated 135 benign meningiomas, of which 120 were totally removed (Simpson's grade I-III). The median follow-up period was 9.7 years (1-21 years). The recurrence rate in the patients with total removal was 7.5% at 10 years and 9.3% at 20 years. The univariate analysis revealed that MIB-1 index (>or=2%), existence of mitosis, absence of calcification, and paucity of fibrosis significantly correlated with recurrence. On the other hand, the histological features of sheet-like growth, prominent nucleoli, and necrosis did not correlate with recurrence, because they were relatively rare in grade I tumors. Multivariate analysis revealed that high MIB-1 index and absence of calcification significantly correlated with recurrence. The patients with recurrent or residual tumors did not always receive adjuvant treatment. Including subtotally treated tumors, the retreatment rate was 9.8% at 10 years and 25.6% at 20 years. MIB-1 index and Simpson's grade significantly correlated with retreatment in both univariate and multivariate analyses.

[The measurement of fractional anisotropy values at the corpus callosum in an irradiated-rat model by 7T-MRI: comparison with quantitative histological evaluation].

Radiation-induced white matter injury has recently been evaluated by fractional anisotropy (FA) values using diffusion tensor image (DTI) data on magnetic resonance (MR) imaging. However, controversy remains as to which histological components affect anisotropy. FA values were compared with histological findings in rat irradiated brains. Forty Gy whole brain radiation was performed on 9 rats, with another 9 rats not subjected to irradiation prepared as the control group. DTI data for the corpus callosum were obtained using a 7.0 Tesla MR scanner at post radiation 18+2 to 48 +/- 2 weeks (p18w-p48w), and the mean FA value (mFA) was calculated. Histological parameters were assessed at p24w, p36w, and p48w in hematoxylin-eosin stained and immunohistochemically processed sections. Numbers of dilated vessels, hypertrophic glial fibrillary acidic protein (GFAP)-positive cells and Olig2-positive cells were quantitatively evaluated. Qualitative assessment of change in neurofilament (NF)-and myelin basic protein (MBP)-positive structures at each time point was also performed. The mFA decreased from p30w to p42w, significantly decreasing at p42w compared to the control group. However, It recovered to control levels at p48w. Histological examination showed that hypertrophic GFAP-positive cells and dilated vessels had increased at p48w. Olig2-positive cells decreased significantly at p48w compared to p24w and p36w (p<0.05). Although NF-positive structures continued to decrease over time, MBP-positive structures recovered at p48w in agreement with the change in mFA. In the subacute/chronic stage, rat irradiated brain FA value in the corpus callosum appears to mainly reflect the change in myelin structure.