Sphenoid wing meningiomas: peritumoral brain edema as a prognostic factor in surgical outcome.

Sphenoidal meningiomas constitute 18% of intracranial masses, and still present a difficult surgical challenge. PTBE has been associated with several complications and future recurrence. This study aims to evaluate the outcome of the operatively treated sphenoid wing meningiomas in relation to PTBE as a prognostic factor in a series of 65 patients. The clinical materials of 65 patients with SWM treated microsurgically between 2007 and 2020 were analyzed retrospectively. Follow-up ranged from 6 to 156 months (median, 86). Clinical outcomes include postoperative major neurological deficit, quality of life using KPS, recurrence, and mortality rates. The mean age of patients was 53.9 years (range 20-74), males 24.6% and females75.4%. An edema index (EI) of 1 (40%) was considered as absent edema, and EI > 1 (60%) indicated present edema. Total resection (Simpson I-II) was achieved in 64.6% and subtotal (Simpson IV) in 13.8%. Postoperative complications included vision impairment in 3 patients, motor weakness 6, third nerve palsy 6, intraoperative bleeding and edema 5, and MCA infarct 2, recurrence in 17% and 7.7% died. In univariate analysis, we found that the PTBE is one of the serious risk factors in the immediate surgical outcomes and complication, though more data is needed to support this claim, while having a negative effect on postoperative KPS at short-term follow up (χ2 = 6.44, p = 0.011). PTBE was associated with decline in KPS and quality of life in the early postoperative period (three months) while showing no significant effect at long-term outcomes.

Natural history and volumetric analysis of meningiomas in neurofibromatosis type 2.

OBJECTIVE: The objective of this paper was to describe the volumetric natural history of meningiomas in patients with neurofibromatosis type 2 (NF2). METHODS: The authors performed a retrospective descriptive study by reviewing NF2 patients with meningiomas at their institution between 2000 and 2019. Demographic data were collected from the electronic medical records. Tumor volume was collected using volumetric segmentation software. Imaging characteristics including peritumoral brain edema (PTBE) and tumor calcification were collected for each patient from their first to most recent MRI at the authors' institution. An increase of 15% or more per year from original tumor size was used as the cutoff to define growth. RESULTS: A total of 137 meningiomas from 48 patients were included in the analysis. The average number of tumors per person was 2.9. Ninety-nine (72.3%) tumors were in female patients. The median length of follow-up from first imaging to last imaging was 32 months (IQR 10.9, 68.3 months). Most tumors were located in the cerebral convexity (24.8%), followed by the falcine region (18.2%) and spine (10.2%). The median tumor growth was 0.12 cm3/yr (IQR 0.03, 0.52 cm3/yr). At the time of first imaging, 21.9% of tumors had calcifications, while 13.9% of meningiomas had PTBE. Of 137 tumors, 52 showed growth. Characteristics associated with tumor growth included PTBE (OR 9.12, 95% CI 1.48-56.4), tumor volume (per cm3) at first imaging (OR 0.91, 95% CI 0.83-0.99), and 10-year increased age at first imaging (OR 0.57, 95% CI 0.43-0.74). PTBE had the shortest median time to growth at 9.2 months. CONCLUSIONS: Although the majority of NF2-associated meningiomas do not grow in the short term, a wide range of growth patterns can be seen. Younger age at first imaging and presence of PTBE are associated with growth. Patients with these characteristics likely benefit from closer follow-up.

Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Analysis of Microvascular Permeability in Peritumor Brain Edema of Fibrous Meningiomas.

INTRODUCTION: This study aims to analyze the permeability of intra- and peri-meningiomas regions and compare the microvascular permeability between peritumoral brain edema (PTBE) and non-PTBE using DCE-MRI. METHODS: This was a retrospective of patients with meningioma who underwent surgery. The patients were grouped as PTBE and non-PTBE. The DCE-MRI quantitative parameters, including volume transfer constant (Ktrans), rate constant (Kep), extracellular volume (Ve), and mean plasma volume (Vp), obtained using the extended Tofts-Kety 2-compartment model. Logistic regression analysis was conducted to explore the risk factor of PTBE. RESULTS: Sixty-three patients, diagnosed as fibrous meningioma, were included in this study. They were 17 males and 46 females, aged from 32 to 88 years old. Kep and Vp were significantly lower in patients with PTBE compared with those without (Kep: 0.1852 ± 0.0369 vs. 0.5087 ± 0.1590, p = 0.010; Vp: 0.0090 ± 0.0020 vs. 0.0521 ± 0.0262, p = 0.007), while there were no differences regarding Ktrans and Ve (both p > 0.05). The multivariable analysis showed that tumor size ≥10 cm3 (OR = 4.457, 95% CI: 1.322-15.031, p = 0.016) and Vp (OR = 0.572, 95%CI: 0.333-0.981, p = 0.044) were independently associated with PTBE in patients with meningiomas. CONCLUSION: DCE-magnetic resonance imaging·Meningioma·Blood vessel MRI can be used to quantify the microvascular permeability of PTBE in patients with meningioma.

Systemic therapy for relapsed/refractory meningioma: Is there potential for antiangiogenic agents?

Effective therapies for relapsed/refractory meningioma after surgery and radiation therapy represent an unmet need. Most meningiomas are highly vascularized tumors and, therefore, potentially amenable to antiangiogenic therapy. Herein, we review comprehensively the scientific literature on systemic therapy options for relapsed, persistent or metastatic meningioma, not amenable to local therapy. Also, this review offers insights into the function of vascular endothelial growth factor/receptor pathway both in health and disease. Further, we address the current status of the preclinical and clinical studies targeting vascular endothelial growth factor/receptor signaling in meningioma. Most relevant publications were identified through searching the PubMed/Medline database for articles published from inception to 1 February 2018. Vascular endothelial growth factor pathway activation might represent the primary driver of angiogenesis in meningioma. Positive findings of two prospective phase II trials, supported by the results of several retrospective cohorts, suggest a clinical benefit for the vascular endothelial growth factor inhibitor bevacizumab in refractory meningioma. Bevacizumab causes both peritumoral brain edema reduction and true meningioma shrinkage. Patients with WHO grades II-III meningioma appear to benefit more than patients with grade I disease. Similarly, responses have been documented with certain oral targeted anti-vascular endothelial growth factor/receptor agents. Further exploration of the role of vascular endothelial growth factor/receptor inhibitors in refractory meningioma seems warranted.

Clinical features, surgical management, and prognostic factors of secretory meningiomas: a single-center case series of 149 patients.

Secretory meningioma (SM) is a rare histological subtype of the meningioma family. Few reports investigating SM have been published due to its extremely low incidence; thus, the current understanding of this disease is poor. We analyzed the incidence and clinical, radiological, pathological, and prognostic features of SM. Approximately 12,380 intracranial meningiomas were surgically resected at Beijing Tiantan Hospital between April 2008 and January 2017. All pathologically confirmed SM cases were identified. SMs accounted for approximately 1.2% of the intracranial meningiomas (149 of 12,380). The patients with SM had a mean age of 51.0 years and were predominantly female (112 female and 37 male). Radiologically, peritumoral brain edema was observed in 49 (32.9%) patients. Gross total resection was achieved in 115 (77.2%) cases. At the 35-months median follow-up (range 4-109 months), six patients had tumor recurrence, and one patient died from the tumor recurrence. The 5-year progression-free survival rates were 95.9%, and the 5-year overall survival rate was 99.3%. A skull base location and a tumor size ≥ 3.5 cm were significantly associated with poor short-term outcomes, and a skull base location was significantly associated with an increased risk of poor long-term outcomes (P < 0.05). A skull base location (OR 3.797; 95% CI 1.071-13.468; P = 0.039) and tumor size ≥ 3.5 cm (OR 2.616; 95% CI 1.107-6.181; P = 0.028) were independent risk factors for non-gross total resection. A son-skull base location (OR 0.070; 95% CI 0.028-0.177; P = 0.001) was the only independent risk factor that correlated with more severe peritumoral brain edema. SM is a rare subtype of meningiomas with a female predominance and low recurrence. Our results highlight the risk factors for short- and long-term outcomes, which can be useful for selecting treatments and predicting prognosis. Microsurgical treatment of a skull base SM remains a formidable challenge due to a large tumor size and critical neurovascular structure encasement.

Expression of N-cadherin and ß-catenin in human meningioma in correlation with peritumoral edema.

OBJECTIVE: To analyze the expression of ß-catenin and N-cadherin in large series of meningioma cases and to investigate their correlation with peritumoral brain edema (PTBE). MATERIALS AND METHODS: Study group consists of 154 patients diagnosed with intracranial meningioma divided into: low-grade (G1) and high-grade (G2 or G3) group. PTBE was graded into four groups (0, I, II, III) using Steinhoff classification. The expression of N-cadherin, ß-catenin was analyzed and graded based on the positive ratio of immunoreactivity. The results were analyzed statistically. RESULTS: 104 cases were low-grade and 50 high-grade meningiomas. PTBE was observed in 103(66.8 %) cases: 57 grade I, 44 grade II and 2 grade III. Positive N-cadherin expression was found only in the membrane of the neoplastic cells in 50(48.1%) cases of low-grade, and in 34(68%) of high-grade group. In low-grade meningioma, ß-catenin expression was observed within the cytoplasm and nucleus in 54(51.9%) cases. In high-grade meningiomas, ß-catenin expression was observed in 33(66%) tumors only within the nucleus. N-cadherin expression was observed in 36 cases with PTBE grade I, 28 with grade II and 2 with grade III. ß-catenin expression was observed in 40 cases with PTBE grade I, 24 with grade II and 2 with grade III. The results were statistically significant. CONCLUSIONS: Significant N-cadherin expression especially in high-grade meningioma group was found. ß-catenin expression was the most evident in the nucleus rather than in cytoplasm. The degree of PTBE correlated with the N-cadherin and ß-catenin expression and was the most prominent in high-grade meningioma group.

Glucocorticoids in the management of peritumoral brain edema: a review of molecular mechanisms.

Peritumoral brain edema (PTBE) is mediated by blood-brain barrier breakdown. PTBE results from interstitial vasogenic brain edema due to vascular endothelial growth factor and other inflammatory products of brain tumors. Glucocorticoids (GCs) are the mainstay for treatment of PTBE despite significant systemic side effects. GCs are thought to affect multiple cell types in the edematous brain. Here, we review preclinical studies of GC effects on edematous brain and review mechanisms underlying GC action on tumor cells, endothelial cells, and astrocytes. GCs may reduce tumor cell viability and suppress vascular endothelial growth factor (VEGF) production in tumor cells. Modulation of expression and distribution of tight junction proteins occludin, claudin-5, and ZO-1 in endothelial cells likely plays a central role in GC action on endothelial cells. GCs may also have an effect on astrocyte angiopoietin production and limited effect on astrocyte aquaporin. A better understanding of these molecular mechanisms may lead to the development of novel therapeutics for management of PTBE with a better side effect profile.

Increased CD44 expression in primary meningioma: its clinical significance and association with peritumoral brain edema.

OBJECTIVE: CD44 is a major cell surface receptor involved in cell adhesion and migration. The overexpression of CD44 is a poor prognostic factor in many neoplasms, including meningiomas. The aim of this study was to investigate the association between CD44 gene expression and clinical signatures of primary meningiomas. METHODS: CD44 gene expression was quantitatively evaluated by snap freezing tumor tissues obtained from 106 patients with primary meningioma. The relationships between CD44 expression and clinical signatures of meningiomas, including histological malignancy, tumor volume, and peritumoral brain edema (PTBE), were analyzed. PTBE was assessed using the Steinhoff classification (SC) system (from SC 0 to SC III). RESULTS: CD44 gene expression in WHO grade 2 and 3 meningiomas was significantly higher than that in grade 1 meningiomas. In addition, CD44 expression increased with the severity of PTBE. Particularly, among the grade 1 meningiomas or small-sized tumors (maximum tumor diameter < 43 mm), CD44 expression in tumors with severe PTBE (SC II or III) was significantly higher than that in tumors without or with mild PTBE (SC 0 or I). Multivariate logistic regression analysis also revealed that overexpression of CD44 was an independent significant factor of severe PTBE development in primary meningiomas. CONCLUSIONS: In addition to tumor cell aggressiveness, CD44 expression promotes the development of PTBE in meningioma. Since PTBE is a strong factor of tumor-related epilepsy or cognitive dysfunction in patients with meningioma, CD44 is thus a potential therapeutic target in meningioma with PTBE.

Claudin and transmembrane receptor protein gene expressions are reversely correlated in peritumoral brain edema.

INTRODUCTION: Peritumoral brain edema (PTBE) has been widely reported with many brain tumors, especially with glioma. Since the blood-brain barrier (BBB) is essential for maintaining minimal permeability, any alteration in the interaction of BBB components, specifically in astrocytes and tight junctions (TJ), can result in disrupting the homeostasis of the BBB and making it severely leaky, which subsequently generates edema. OBJECTIVE: This study aimed to evaluate the functional gliovascular unit of the BBB by examining changes in the expression of claudin (CLDN) genes and the expression of transient receptor potential (TRP) membrane channels, additionally to define the correlation between their expressions. The evaluation was conducted using in vitro spheroid swelling models and tumor samples from glioma patients with PTBE. RESULTS: The results of the spheroid model showed that the genes TRPC3, TRPC4, TRPC5, and TRPV1 were upregulated in glioma cells either wild-type isocitrate dehydrogenase 1 (IDH1) or the IDH1 R132H mutant, with or without NaCl treatment. Furthermore, TRP genes appeared to adversely correlate with the up regulation of CLDN1, CLDN3, and CLDN5 genes. Besides, the upregulation of TRPC1 and TRPC4 in IDH1mt-R132H glioma cells. On the other hand, the correlation analysis revealed different correlations between different proteins in PTBE. CLDN1 exhibits a slight positive correlation with CLDN3. Similarly, TRPV1 displays a slight positive correlation with TRPC1. In contrast, TRPC4 shows a slight negative correlation with TRPC5. On the other hand, TRPC3 demonstrates a slight positive correlation with TRPC5, while the non-PTBE analysis highlights a moderate positive correlation between CLDN1 and TRPM4 while CLDN3 exhibits a moderate negative correlation with TRPC4. Additionally, CLDN5 demonstrates a slight negative correlation with TRPC4 but a moderate positive correlation with TRPC3. Furthermore, TRPC1 have a slight negative correlation with TRPV1, TRPC3 exhibiting a slight positive correlation with TRPC4, and TRPV1 showing a slight negative correlation with TRPC5. CONCLUSION: As a conclusion, the current study provided evidence of a slight negative correlation between TRPs and CLDN gene expression in PTBE patients and confirmatory results with some of the genes in cell model of edema.

Bevacizumab reduces peritumoral brain edema in lung cancer brain metastases after radiotherapy.

BACKGROUND: The aim of this study was to investigate the efficacy of bevacizumab (Bev) in reducing peritumoral brain edema (PTBE) after stereotactic radiotherapy (SRT) for lung cancer brain metastases. METHODS: A retrospective analysis was conducted on 44 patients with lung cancer brain metastases (70 lesions) who were admitted to our oncology and Gamma Knife center from January 2020 to May 2022. All patients received intracranial SRT and had PTBE. Based on treatment with Bev, patients were categorized as SRT + Bev and SRT groups. Follow-up head magnetic resonance imaging was performed to calculate PTBE and tumor volume changes. The edema index (EI) was used to assess the severity of PTBE. Additionally, the extent of tumor reduction and intracranial progression-free survival (PFS) were compared between the two groups. RESULTS: The SRT + Bev group showed a statistically significant difference in EI values before and after radiotherapy (p = 0.0115), with lower values observed after treatment, but there was no difference in the SRT group (p = 0.4008). There was a difference in the distribution of EI grades in the SRT + Bev group (p = 0.0186), with an increased proportion of patients at grades 1-2 after radiotherapy, while there was no difference in the SRT group (p > 0.9999). Both groups demonstrated a significant reduction in tumor volume after radiotherapy (p < 0.05), but there was no difference in tumor volume changes between the two groups (p = 0.4089). There was no difference in intracranial PFS between the two groups (p = 0.1541). CONCLUSION: Bevacizumab significantly reduces the severity of PTBE after radiotherapy for lung cancer. However, its impact on tumor volume reduction and intracranial PFS does not reach statistical significance.

The Surgical Risk Factors of Giant Intracranial Meningiomas: A Multi-Centric Retrospective Analysis of Large Case Serie.

Giant intracranial meningiomas (GIMs) are a subgroup of meningiomas with huge dimensions with a maximum diameter of more than 5 cm. The mechanisms by which a meningioma can grow to be defined as a "giant" are unknown, and the biological, radiological profile and the different outcomes are poorly investigated. We performed a multi-centric retrospective study of a series of surgically treated patients suffering from intracranial meningioma. All the patients were assigned on the grounds of the preoperative imaging to giant and medium/large meningioma groups with a cut-off of 5 cm. We investigated whether the presence of large diameter and peritumoral brain edema (PBE) on radiological diagnosis indicates different mortality rates, grading, characteristics, and outcomes in a multi-variate analysis. We found a higher risk of developing complications for GIMs (29.9% versus 14.8%; p < 0.01). The direct proportional relationship between PBE volume and tumor volume was present only in the medium/large group (Pearson correlation with p < 0.01) and not in the GIM group (p = 0.47). In conclusion, GIMs have a higher risk of developing complications in the postoperative phase than medium/large meningioma without higher risk of mortality and recurrence.

Peritumoral Brain Edema in Relation to Tumor Size Is a Variable That Influences the Risk of Recurrence in Intracranial Meningiomas.

Peritumoral brain edema (PBE) is common in intracranial meningiomas (IM) and can increase their morbidity. It is not uncommon for a neurosurgeon to confront meningiomas with a large proportion of PBE independently from the site and size of the contrast-enhancing lesion with increased surgical risks. We performed a retrospective review of 216 surgically-treated patients suffering from IM. We recorded clinical, biological, and radiological data based on the rate of tumor and edema volume and divided the patients into a group with high Edema/Tumor ratio and a group with a low ratio. We investigated how the ratio of edema/lesion may affect the outcome. Multivariate analysis was performed for the two groups. Smokers were found to be more likely to belong to the high-rate group. The edema/tumor ratio did not affect the surgical radicality; however, independently of the biological sub-type, WHO grading, and EOR, a higher frequency of recurrence is shown in patients with a high edema/tumor ratio (70.5% vs. 8.4%. p < 0.01). There is evidence to suggest that the blood-brain barrier (BBB) damage from smoke could play a role in an increased volume of PBE. The present study demonstrates that IMs showing a high PBE ratio to tumor volume at diagnosis are associated with a smoking habit and a higher incidence of recurrence independently of their biological type and grading.

Efficacy of Bevacizumab in High-Grade Meningiomas: A Retrospective Clinical Study.

Objective: We investigated the role of bevacizumab (BV) in high-grade meningiomas (HGMs) by retrospective analysis. Methods: We retrospectively analyzed the clinical data of 139 patients with HGMs. The chi-square test was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received BV and those who did not. According to whether they received BV treatment, we divided the patients into the BV group and non-BV group, and the effect of BV on PFS and OS was compared. In addition, we compared Karnofsky performance status (KPS) and steroid doses between the BV and non-BV groups. Results: There were statistically differences in PFS and OS between the BV and non-BV groups at 12 and 36 months after surgery (P<0.05). However, there was no significant difference in PFS and OS between the two groups at 60 months postoperatively (P>0.05). Using survival curves drawn by the Kaplan Meier method, we found that the PFS and OS of the BV group were greater than those of the non-BV group, and the difference was statistically significant (P<0.05). Conclusion: BV could improve PFS and OS at 12 and 36 months after surgery in patients with HGMs. In addition, BV was associated with lower preoperative steroid use.

MRI multiparametric scoring system for pial blood supply of intracranial meningiomas.

Background: Meningiomas are occasionally fed by pial blood supply (PBS). It is postulated that peritumoral flow void (PTFV), peritumoral brain edema (PTBE), and absence of an arachnoid plane (AP) are useful parameters for evaluating PBS. Purpose: To determine whether conventional magnetic resonance imaging (MRI) using a multiparametric scoring system (MSS) is a useful way to predict PBS. Material and Methods: Forty-six patients were included and divided: PBS and non-PBS groups. Differences between the groups in six parameters of MR imaging were analyzed: tumor size, tumor location, PTBE grade, AP grade, PTFV, and MIB1 labeling index (MIB1-LI) grade. Cutoff values were determined using receiver operating characteristic (ROC) curve analysis for the differentiation of both groups based on statistically significant parameters. All cases were scored as 1 (PBS) or 0 (non-PBS) for each parameter according to set thresholds. Individual scores were totaled for each case, yielding a combined score for each case to obtain a cutoff value using ROC curve analysis for the MSS. Results: Peritumoral brain edema grade, AP grade, PTFV, and MIB-LI grade were statistically associated with PBS. Receiver operating characteristic curve analyses showed that PTBE grade 3 or 4, AP grade 3 or 4, and PTFV positivity had the highest accuracy of 69%, 64%, and 68%, respectively. Regarding the MSS, a cutoff value of 2 had the highest accuracy of 71%; PBS diagnosis was indicated by at least two of the three parameters, namely, PTBE grade, AP grade, and PTFV. Conclusion: The MSS is a useful way to predict PBS in intracranial meningiomas on MRI.

The Long and Winding Road: An Overview of the Immunological Landscape of Intracranial Meningiomas.

The role of immunotherapy is gaining ever-increasing interest in the neuro-oncological field, and this is also expanding to the management of intracranial meningioma. Meningiomas are still the most common primary adult tumor of the CNS, and even though surgery and/or radiotherapy still represent cornerstones of their treatment, recent findings strongly support the potential role of specific immune infiltrate cells, their features and genomics, for the application of personalized treatments and prognostic implications. According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a descriptive and complete overview about the characteristics, role and potential implications of immunology in meningioma tumors. Seventy articles were included and analyzed in the present paper. The meningioma microenvironment reveals complex immune tumor-immune cells interactions that may definitely influence tumor progression, as well as offering unexpected opportunities for treatment.

Peri-tumoral brain edema associated with glioblastoma correlates with tumor recurrence.

Glioblastoma is the most common malignant tumor of the brain. Despite advances in treatment, the prognosis for the condition has remained poor. Glioblastoma is often associated with peritumoral brain edema (PTBE), which can result in increased intracranial pressure and devastating neurological sequelae if left untreated. Surgery is the main treatment for glioblastoma, however current international surgical guidelines do not specify whether glioblastoma-induced PTBE tissue should be resected. In this study, we analyzed treatment outcomes of PTBE using surgical resection. We performed a retrospective analysis of 255 cases of glioblastoma between 2014 and 2016, and found that a significant proportion of patients had a degree of PTBE. We found that surgical resection led to reduction in midline shift that had resulted from edema, however, postoperative complications and KPS scores were not significantly different in the two conditions. We also observed a delay in glioblastoma recurrence in patients undergoing PTBE tissue resection vs patients without resection of PTBE tissue. Interestingly, there was an abnormal expression of tumor associated genes in PTBE, which has not been previously been found. Taken together, this study indicates that glioblastoma-induced PTBE should be investigated further particularly as the tumor microenvironment is a known therapeutic target and therefore interactions between the microenvironment and PTBE should be explored. This study also highlights the importance of resection of PTBE tissue to not only reduce the mechanical obstruction associated with edema but also to delay recurrence of glioblastoma.

Effect of osteoporotic conditions on the development of peritumoral brain edema after LINAC-based radiation treatment in patients with intracranial meningioma.

PURPOSE: Disruption of the tumor-brain barrier in meningioma is a crucial factor in peritumoral brain edema (PTBE). We previously reported the possible effect of osteoporosis on the integrity of the arachnoid trabeculae because both the bone and the arachnoid trabeculae are composed of type 1 collagen. We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation treatment in patients with meningioma. METHODS: A receiver operating characteristic curve analysis was used to identify the optimal cut-off values of mean skull Hounsfield unit for predicting osteopenia and osteoporosis in patients from our registry. Multivariate Cox regression analysis was used to determine whether possible osteoporosis independently predicted PTBE development in patients with meningioma after radiation. RESULTS: A total of 106 intracranial meningiomas were included for the study. All patients received linear accelerator-based radiation therapy in our hospital over an approximate 6-year period. Multivariate Cox regression analysis identified that hypothetical osteoporosis was an independent predictive factor for the development of PTBE in patients with meningioma after linear accelerator-based radiation treatment (hazard ratio 5.20; 95% confidence interval 1.11-24.46; p = 0.037). CONCLUSIONS: Our study suggests that possible osteoporotic conditions may affect PTBE development after linear accelerator-based radiation treatment for intracranial meningioma. However, due to the study's small number of patients, these findings need to be validated in future studies with larger cohorts, before firm recommendations can be made.

The positive effects of surgery on symptomatic stereotactic radiation-induced peritumoral brain edema: A report of three cases.

BACKGROUND: Peritumoral brain edema is an uncommon but life-threatening side effect of brain tumors radiosurgery. Medical therapy usually alleviates symptoms until edema spontaneously disappears. However, when peritumoral brain edema endangers the patient's life or medical therapy fails to guarantee an acceptable quality of life, surgery might be considered. CASE DESCRIPTION: Our report focuses on three patients who developed extensive peritumoral brain edema after radiosurgery. Two were affected by vestibular schwannomas and one by a skull-base meningioma. Peritumoral brain edema worsened despite maximal medical therapy in all cases; therefore, surgical removal of the radiated lesion was carried out. In the first patient, surgery was overdue and resulted in a fatal outcome. On the other hand, in the latter two cases surgery was quickly effective. In all three cases, an unmanageable brain swelling was not found at surgery. CONCLUSION: Surgical removal of brain tumors previously treated with radiosurgery was safe and effective in resolving shortly peritumoral brain edema. This solution should be considered in patients who do not respond to medical therapy and before worsening of clinical conditions. Interestingly, the expected brain swelling was not confirmed intraoperatively. In our experience, this magnetic resonance finding should not be considered a criterion to delay surgery.

Evaluation of AQP4/TRPV4 Channel Co-expression, Microvessel Density, and its Association with Peritumoral Brain Edema in Intracranial Meningiomas.

Apart from VEGF-A pathway activation, the existence of peritumoral edema (PTBE) in meningiomas has been correlated with the expression levels of water transporter aquaporin 4 (AQP4). A novel cooperation of AQP4 with the transient receptor potential isoform 4 (TRPV4), a polymodal swelling-sensitive cation channel, has been proposed for regulating cell volume in glial cells. We investigated AQP4/TRPV4 channel co-expression in meningiomas along with the neovascularization of tumors and associate with PTBE. Immunohistochemical staining for AQP4 and TRPV4 expression was quantitatively analyzed in semi-serial sections of archival tissue from 174 patients. Microvessel density was expressed as microvessel count (MVC). PTBE was measured and edema index (EI) was assessed in 23 patients, based on magnetic resonance images (MRI) whereas mRNA levels of AQP4 and TRPV4 were evaluated in these patients using quantitative real-time PCR. High AQP4 was associated with lower-tumor grade (p < 0.05). AQP4 and TRPV4 were correlated in benign (WHO, grade I) (p < 0.0001) but not in high-grade (WHO, grades II and III) meningiomas (p > 0.05). AQP4/TRPV4 levels were independent of EI and MVC (p > 0.05). In contrast, EI was correlated to MVC (p = 0.02). AQP4/TRPV4 co-expression was detected in both edematous and non-edematous meningiomas. However, most of tumors with larger edema (EI ≥ 2) demonstrated increased levels of AQP4 and TRPV4. Importantly, peri-meningioma tissue of edematous meningiomas demonstrated significantly increased expression for AQP4 (p = 0.007) but not for TRPV4 (p > 0.05) compared with the main tumor. AQP4 and TRPV4 expression is rather associated with a response to vasogenic edema of meningiomas than with edema formation.

The Relationship Between Peritumoral Brain Edema and the Expression of Vascular Endothelial Growth Factor in Vestibular Schwannoma.

Objective: This study aimed to explore the potential mechanism of peritumoral brain edema (PTBE) formation in vestibular schwannoma (VS) by detecting intra-tumoral vascular endothelial growth factor (VEGF) expression. Methods: Between January 2018 and May 2021, 15 patients with PTBE and 25 patients without PTBE were included in the analysis. All patients enrolled in our study underwent surgery in our institution. Expression level of VEGF and microvessel density (MVD) between the two groups were analyzed. Edema index (EI) of each patient with PTBE was calculated. Results: In the PTBE group, the average of EI was 1.53 ± 0.22. VEGF expression levels were significantly enhanced in the PTBE group compared with the non-PTBE group (p < 0.001). The expression level of VEGF in the PTBE group and non-PTBE group was 1.14 ± 0.21 and 0.52 ± 0.09, respectively. Similarly, there were significantly different amounts of MVD in the two groups (p < 0.001). The amount of MVD in the PTBE group and non-PTBE group was 11.33 ± 1.59 and 6.28 ± 1.77, respectively. Correlation analysis showed a highly significant positive correlation between VEGF and MVD (r = 0.883, p < 0.001) and VEGF and EI (r = 0.876, p < 0.001). Conclusion: Our study confirmed the close relationship among VEGF expression, tumor angiogenesis, and formation of PTBE in VS patients. It may be possible to develop new effective therapies to attenuate PTBE in VS for alleviation of symptoms and reduction of postoperative complication.