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1.
Neurochirurgie ; 70(5): 101573, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38851138

ABSTRACT

BACKGROUND: Adult intracranial capillary hemangioma (ICH) is an extremely rare disease with very few cases reported in the literature. Natural history is poorly understood and therapeutic management has not been clearly defined. METHODS: Using PRISMA guidelines, we systematically reviewed all published adult cases of ICH, to which we added our own case. CASE PRESENTATION: A 24-year-old patient with intracranial hypertension underwent stenting for left transverse sinus ICH. Recurrence was managed by subtotal resection, and radiotherapy was undertaken after a second relapse. Radiotherapy achieved complete response at last follow-up. RESULTS: Among cases of ICH found in the literature, 36 concerned adults (55.3%), with clear female predominance, and only 2 cases affecting the transverse sinus (8.1%). Adult ICHs grew over time, and pregnancy seemed to accelerate natural progression. Complete resection was achieved in most cases, and radiotherapy was used in case of relapse, with high rates of tumor control. CONCLUSION: Transverse sinus ICH is uncommon, and venous stenting is a suitable option in case of tumor invasion to treat intracranial hypertension. Surgery is the gold-standard treatment, and radiotherapy is a very effective alternative, with high rates of tumor control. Natural history is not benign, particularly in case of pregnancy.

2.
Acta Neurochir (Wien) ; 166(1): 214, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38740641

ABSTRACT

BACKGROUND AND OBJECTIVES: Meningioma is one of the most common neoplasm of the central nervous system. To describe the epidemiology of meningioma operated in France and, to assess grading and histopathological variability among the different neurosurgical centres. METHODS: We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed meningiomas between 2006 and 2015. RESULTS: 30,223 meningiomas cases were operated on 28,424 patients, in 61 centres. The average number of meningioma operated per year in France was 3,022 (SD ± 122). Meningioma was 3 times more common in women (74.1% vs. 25.9%). The incidence of meningioma increased with age and, mean age at surgery was 58.5 ± 13.9 years. Grade 1, 2, and 3 meningiomas accounted for 83.9%, 13.91% and, 2.19% respectively. There was a significant variability of meningioma grading by institutions, especially for grade 2 which spanned from 5.1% up to 22.4% (p < 0.001). Moreover, the proportion of grade 2 significantly grew over the study period (p < 0.001). There was also a significant variation in grade 1 subtypes diagnosis among the institutions (p < 0.001). 89.05% of the patients had solely one meningioma surgery, 8.52% two and, 2.43% three or more. The number of surgeries was associated to the grade of malignancy (p < 0.001). CONCLUSION: The incidence of meningioma surgery increased with age and, peaked at 58.5 years. They were predominantly benign with meningothelial subtype being the most common. However, there was a significant variation of grade 1 subtypes diagnosis among the centres involved. The proportion of grade 2 meningioma significantly grew over the study time, on contrary to malignant meningioma proportion, which remained rare and, stable over time around 2%. Likewise, there was a significant variability of grade 2 meningioma rate among the institutions.


Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Meningioma/epidemiology , Meningioma/pathology , Meningioma/surgery , France/epidemiology , Female , Male , Middle Aged , Meningeal Neoplasms/epidemiology , Meningeal Neoplasms/pathology , Meningeal Neoplasms/surgery , Aged , Adult , Incidence , Aged, 80 and over , Neoplasm Grading , Young Adult , Adolescent , Databases, Factual
3.
J Neurosurg ; : 1-11, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38241682

ABSTRACT

OBJECTIVE: Systemic therapeutic advancements have improved the prognosis of cancer patients, leading to surgery more frequently being carried out for patients with multiple brain metastases (BM). The underlying evidence for the strategy is currently lacking. This study aimed to evaluate the prognostic significance of the number of BM and total tumor burden (TTB) on the overall survival (OS) of patients with resected BM of non-small cell lung cancer (NSCLC) in a modern series. METHODS: In this monocentric retrospective series, patients who underwent resection of BM of NSCLC between 2015 and 2021 were included. Demographic, clinical, and histological parameters were collected, and formal radiological volumetric analyses were performed. Prognostic biomarkers for cerebral progression-free survival (C-PFS) and OS were analyzed with univariate and multivariate Cox proportional hazards analysis. RESULTS: One hundred eighty-four patients were included in the study. Among these, 108 patients (58.7%) presented with a single brain metastasis, 36 patients (19.6%) with 2 BM, 22 patients (11.9%) with 3 BM, and 18 patients (9.8%) with more than 3 BM (maximum 15 BM). The mean ± SD (range) preoperative tumor burden was 23.1 ± 25.3 (1.1-145.3) cm3. The mean residual tumor burden after surgery was 0.3 ± 0.8 (0.0-6.3) cm3. By the time of the analysis, 128 patients (69.6%) had died. The median follow-up duration was 49.0 months (95% CI 39.6-63.6). The median OS was 19.2 months (95% CI 13.2-24.0), and the survival rates at 6 months, 1 year, and 2 years were 76% (95% CI 69%-82%), 61% (95% CI 53%-67%), and 43% (95% CI 35%-50%), respectively. The median C-PFS was 8.4 months (95% CI 7.2-12.0). In the Cox multivariate regression model, younger age (< 65 years), single brain metastasis, adjuvant brain radiation therapy, adjuvant use of targeted therapy, and TTB < 7 cm3 were all independent predictors of longer OS. CONCLUSIONS: In this era of modern systemic treatments for cancer, the number of BM and total cerebral tumor burden remain significant prognostic factors of OS. However, resection should be considered as an option even in those patients with multiple BM in order to enhance patient clinical status, enable further local and systemic treatment delivery, and improve their survival and quality of life.

4.
Nat Commun ; 14(1): 6279, 2023 10 07.
Article in English | MEDLINE | ID: mdl-37805627

ABSTRACT

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway  in neoplasia.


Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Meningioma/genetics , Ligands , Signal Transduction , Meningeal Neoplasms/genetics
6.
Cancer Gene Ther ; 30(8): 1114-1123, 2023 08.
Article in English | MEDLINE | ID: mdl-37188724

ABSTRACT

Despite their rarity, PIK3CA mutations in meningiomas have raised interest as potentially targetable, ubiquitous mutations owing to their presence in sporadic benign and malignant tumors but also in hormone-related cases. Using new genetically engineered mouse models, we here demonstrate that Pik3ca mutations in postnatal meningeal cells are sufficient to promote meningioma formation but also tumor progression in mice. Conversely, hormone impregnation, whether alone or in association with Pik3ca and Nf2 mutations, fails to induce meningioma tumorigenesis while promoting breast tumor formation. We then confirm in vitro the effect of Pik3ca mutations but not hormone impregnation on the proliferation of primary cultures of mouse meningeal cells. Finally, we show by exome analysis of breast tumors and meninges that hormone impregnation promotes breast tumor formation without additional somatic oncogenic mutation but is associated with an increased mutational burden on Pik3ca-mutant background. Taken together, these results tend to suggest a prominent role of Pik3ca mutations over hormone impregnation in meningioma tumorigenesis, the exact effect of the latter is still to be discovered.


Subject(s)
Breast Neoplasms , Meningeal Neoplasms , Meningioma , Mice , Animals , Humans , Female , Meningioma/genetics , Meningioma/pathology , Meningeal Neoplasms/genetics , Meningeal Neoplasms/pathology , Cyproterone Acetate , Mutation , Cell Transformation, Neoplastic , Class I Phosphatidylinositol 3-Kinases/genetics
7.
J Neurosurg ; 139(4): 934-943, 2023 10 01.
Article in English | MEDLINE | ID: mdl-36964732

ABSTRACT

OBJECTIVE: Surgery for giant diffuse lower-grade gliomas (LGGs) is challenging, and very few data have been reported on this topic in the literature. In this article, the authors investigated surgical, functional, and oncological aspects in patients who underwent awake resection for large LGGs with a volume > 100 cm3. METHODS: The authors retrospectively reviewed a consecutive cohort of patients who underwent surgery in an awake condition for an LGG (WHO grade 2 with possible foci of grade 3 transformation) with a volume > 100 cm3. RESULTS: A total of 108 patients were included, with a mean age of 36.1 ± 8.5 years. The mean presurgical LGG volume was 136.7 ± 34.5 cm3. In all but 2 patients a disconnection resective surgery up to functional boundaries was possible thanks to active patient collaboration during the awake period. At 3 months of follow-up, all but 1 patient had a normal neurological examination, with a mean Karnofsky Performance Status (KPS) score of 89.8 ± 10.36. In all patients with preoperative epilepsy, there was postoperative control or significant reduction of seizure events. Moreover, 85.1% of patients returned to work. The mean extent of resection (EOR) was 88.9% ± 7.0%, with a mean residual tumor volume (RTV) of 16.3 ± 12.0 cm3 (median RTV 15 cm3). Pathological examination revealed 73 grade 2 gliomas (67.6%; 26 oligodendrogliomas and 47 astrocytomas) and 35 gliomas with foci of grade 3 (32.4%; 19 oligodendrogliomas and 16 astrocytomas). During the postoperative period, 93.6% of patients underwent adjuvant chemotherapy with a median interval between surgery and first chemotherapy of 14 months (IQR 2-26 months), and 55% of patients had radiotherapy with a median interval of 38.5 months (IQR 18-59.8 months). At the last follow-up, 69.7% of patients were still alive with a median follow-up of 62 months (IQR 36-99 months). Overall survival (OS) rates at 1, 5, and 10 years were 100% (95% CI 0.99-1), 80% (95% CI 0.72-0.9), and 58% (95% CI 0.45-0.73), respectively. The median OS was 138 months. In multivariable Cox regression analysis, RTV was established as the only independent prognostic factor for survival. CONCLUSIONS: With the application of rigorous surgical methodology based on functional-guided resection, resection of giant LGGs (volume > 100 cm3) can be reproducibly achieved during surgery with patients under awake mapping with both favorable functional results (< 1% permanent neurological worsening) and favorable long-term oncological outcomes (median OS > 11 years, with a more significant benefit when the RTV is < 15 cm3).


Subject(s)
Astrocytoma , Brain Neoplasms , Glioma , Oligodendroglioma , Humans , Adult , Brain Neoplasms/surgery , Retrospective Studies , Wakefulness , Treatment Outcome , Glioma/surgery , Magnetic Resonance Imaging
8.
Neurosurgery ; 92(2): 391-397, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36637273

ABSTRACT

BACKGROUND: About one-third of anterior skull base meningiomas show Hedgehog pathway activation. We have recently identified GAB1 as a surrogate marker for Hedgehog pathway-activated meningiomas. OBJECTIVE: To determine the reproducibility and prognostic value of GAB1 marker in anterior skull base meningiomas. METHODS: A retrospective bicentric cohort of anterior skull base meningiomas, operated from 2005 to 2015, was constituted. GAB1 immunohistochemistry was performed in 2 centers, and the GAB1 score was assessed. Clinical and pathological data were reviewed to determine the prognostic value of the GAB1 score, along with classical factors of recurrence. RESULTS: One hundred forty-eight patients were included (median follow-up of 72 ± 46 months). 78% of patients had gross total resection. Eighty-four percentage of patients harbored grade 1 meningiomas. GAB1 immunohistochemistry was positive (ie, GAB1 staining score was >250) in 53 cases (35%). GAB1-positive cases were mainly at olfactory groove, of meningothelial grade 1 subtype, and showed greater recurrence (36% vs 14%, P = .002), greater requirement for multiple surgeries (17% vs 4.2%, P = .014), and more likely evolution toward diffuse skull base infiltration (15% vs 3%, P = .0017). By multivariable Cox regression analysis, incomplete surgical resection (hazard ratios [HR] = 8.3, 95% IC [3.7-18.2], P < .001), male sex (HR = 5.4, 95% IC [2.2-13.5], P < .001), GAB1 positivity (HR = 3.2, 95% CI [1.5-6.9], P = .004), and Ki67 index >4 (HR = 2.2, 95% IC [1.2-4.6], P = .035) were independent prognostic factors for recurrence. CONCLUSION: GAB1 marker is an independent prognostic factor for anterior skull base meningioma and could be useful for both prognostic evaluation and identification of Hedgehog-activated meningiomas.


Subject(s)
Meningeal Neoplasms , Meningioma , Skull Base Neoplasms , Humans , Male , Meningioma/pathology , Meningeal Neoplasms/pathology , Retrospective Studies , Hedgehog Proteins/metabolism , Reproducibility of Results , Skull Base Neoplasms/surgery , Skull Base Neoplasms/pathology , Skull Base/surgery , Neoplasm Recurrence, Local/pathology , Adaptor Proteins, Signal Transducing/metabolism
9.
Front Surg ; 9: 959440, 2022.
Article in English | MEDLINE | ID: mdl-35983556

ABSTRACT

Background: To report the initial experience of surgery for non-functioning pituitary adenoma (NFPA) from a neurosurgeon in a dedicated residency training endoscopic transsphenoidal (ETS) program, and detail the surgical and clinical outcomes during this period. Methods: A prospective series of all patients operated for NFPA, using an ETS approach, during the three first years of experience of a newly board-certified neurosurgeon was analysed. Clinical, radiological and peri-operative data were collected. Extent of resection (EOR) was determined by formal volumetric analysis. Impact of the learning curve and predictive factors of gross total resection (GTR) were determined. Results: Fifty-three patients with NFPA were included in this prospective cohort which was divided in two periods of time ("First period": 30 first cases, and "second period": 23 following cases). Baseline characteristics of the patients in the two periods were similar. Overall occurrence of complication was 22% and was not significantly different in the two periods of time. No patient had severe neurological complication. Gross total resection was achieved in 70% of patients. Mean Extent of resection was 96%. In a multiple linear regression model, a higher EOR was positively correlated with experience (p = 0.018) and negatively correlated with Knosp Score equal to 4 (p < 0.001). Predictive factors for GTR were Higher Knosp grade (p = 0,01), higher pre-operative volume (p = 0.03), and second period of time (p = 0.01). Conclusion: NFPA surgery can be safe and efficient during the learning period. Dedicated intensive learning, careful patient selection and multidisciplinary work are key to shorten the learning curve and achieve satisfactory results.

10.
N Engl J Med ; 385(11): 996-1004, 2021 09 09.
Article in English | MEDLINE | ID: mdl-34496175

ABSTRACT

BACKGROUND: Cerebral cavernous malformations (CCMs) are common sporadic and inherited vascular malformations of the central nervous system. Although familial CCMs are linked to loss-of-function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3), the genetic cause of sporadic CCMs, representing 80% of cases, remains incompletely understood. METHODS: We developed two mouse models harboring mutations identified in human meningiomas with the use of the prostaglandin D2 synthase (PGDS) promoter. We performed targeted DNA sequencing of surgically resected CCMs from patients and confirmed our findings by droplet digital polymerase-chain-reaction analysis. RESULTS: We found that in mice expressing one of two common genetic drivers of meningioma - Pik3ca H1047R or AKT1 E17K - in PGDS-positive cells, a spectrum of typical CCMs develops (in 22% and 11% of the mice, respectively) instead of meningiomas, which prompted us to analyze tissue samples from sporadic CCMs from 88 patients. We detected somatic activating PIK3CA and AKT1 mutations in 39% and 1%, respectively, of lesion tissue from the patients. Only 10% of lesions harbored mutations in the CCM genes. We analyzed lesions induced by the activating mutations Pik3ca H1074R and AKT1 E17K in mice and identified the PGDS-expressing pericyte as the probable cell of origin. CONCLUSIONS: In tissue samples from sporadic CCMs, mutations in PIK3CA were represented to a greater extent than mutations in any other gene. The contribution of somatic mutations in the genes that cause familial CCMs was comparatively small. (Funded by the Fondation ARC pour la Recherche contre le Cancer and others.).


Subject(s)
Class I Phosphatidylinositol 3-Kinases/genetics , Intracranial Arteriovenous Malformations/genetics , Mutation , Proto-Oncogene Proteins c-akt/genetics , Animals , Disease Models, Animal , Female , Humans , Intracranial Arteriovenous Malformations/pathology , KRIT1 Protein/genetics , Male , Meningioma/genetics , Mice , Mice, Inbred Strains
11.
Cancers (Basel) ; 13(15)2021 Jul 26.
Article in English | MEDLINE | ID: mdl-34359639

ABSTRACT

Meningiomas are the most frequent primitive central nervous system tumors found in adults. Mouse models of cancer have been instrumental in understanding disease mechanisms and establishing preclinical drug testing. Various mouse models of meningioma have been developed over time, evolving in light of new discoveries in our comprehension of meningioma biology and with improvements in genetic engineering techniques. We reviewed all mouse models of meningioma described in the literature, including xenograft models (orthotopic or heterotopic) with human cell lines or patient derived tumors, and genetically engineered mouse models (GEMMs). Xenograft models provided useful tools for preclinical testing of a huge range of innovative drugs and therapeutic options, which are summarized in this review. GEMMs offer the possibility of mimicking human meningiomas at the histological, anatomical, and genetic level and have been invaluable in enabling tumorigenesis mechanisms, including initiation and progression, to be dissected. Currently, researchers have a range of different mouse models that can be used depending on the scientific question to be answered.

12.
Neuropathol Appl Neurobiol ; 47(6): 748-755, 2021 10.
Article in English | MEDLINE | ID: mdl-34056767

ABSTRACT

AIMS: Mutations activating the hedgehog (Hh) signalling pathway have been described in anterior skull base meningiomas, raising hope for the use of targeted therapies. However, identification of Hh-activated tumours is hampered by the lack of a reliable immunohistochemical marker. We report the evaluation of GAB1, an immunohistochemical marker used to detect Hh pathway activation in medulloblastoma, as a potential marker of Hh-activated meningiomas. METHODS: GAB1 staining was compared to SMO mutation detection with Sanger and NGS techniques as well as Hh pathway activation study through mRNA expression level analyses in a discovery set of 110 anterior skull base meningiomas and in a prospective validation set of 21 meningiomas. RESULTS: Using an expression score ranging from 0 to 400, we show that a cut-off score of 250 lead to excellent detection of Hh pathway mutations (sensitivity 100%, specificity 86%). The prospective validation set confirmed the excellent negative predictive value of GAB1 to exclude Hh-independent meningiomas. We describe a large series of 32 SMO-mutant meningiomas and define multiple ways of Hh activation, either through somatic mutations or associated with mutually co-exclusive sonic hedgehog (SHH) or Indian hedgehog (IHH) overexpression independent of the mutations. CONCLUSION: The assessment of GAB1 expression by an immunohistochemical score is a fast and cost-efficient tool to screen anterior skull base meningiomas for activation of the Hh pathway. It could facilitate the identification of selected cases amenable to sequencing for Hh pathway genes as predictive markers for targeted therapy.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Hedgehog Proteins/metabolism , Meningioma/metabolism , Skull Base/metabolism , Adaptor Proteins, Signal Transducing/genetics , Cerebellar Neoplasms , Hedgehog Proteins/genetics , Humans , Medulloblastoma/metabolism , Medulloblastoma/pathology , Meningeal Neoplasms/genetics , Meningioma/genetics , Meningioma/pathology , Mutation/genetics , Skull Base/pathology
13.
J Neurooncol ; 153(1): 55-64, 2021 May.
Article in English | MEDLINE | ID: mdl-33778930

ABSTRACT

PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.


Subject(s)
Meningeal Neoplasms , Meningioma , Radiosurgery , Bevacizumab , Combined Modality Therapy , Everolimus , Follow-Up Studies , Humans , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/surgery , Meningioma/radiotherapy , Meningioma/surgery , Octreotide , Retrospective Studies , Treatment Outcome
14.
J Neurotrauma ; 38(11): 1484-1494, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33787345

ABSTRACT

Chronic subdural hematoma (CSDH) is a common condition necessitating surgery; however, recurrence occurs in 15-25% of cases despite surgical management. The HEMACORT trial was a prospective randomized, double-blind, placebo-controlled, multi-centric study (NCT01380028). The aim of this trial was to determine the effect of corticosteroids as an adjuvant treatment to surgery on CSDH recurrence at 6 months. After surgery, participants were assigned by block-randomization to receive either placebo or oral prednisone at a dose of 1 mg/kg/day followed by weekly stepwise tapering in steps of 10 mg/day. The primary outcome was CSDH recurrence, defined by the need for reoperation and/or radiological progression of CSDH. Secondary outcomes were one-year death, radiological changes, safety, neurological status, and quality of life. The trial was discontinued at midpoint of expected inclusions: 78 participants received prednisone and 77 received placebo controls. In an intention-to-treat analysis, CSDH clinicoradiological recurrence was not different between prednisone and placebo groups (21.8% vs. 35.1%, respectively; hazard ratio 0.56; 95% confidence interval 0.30-1.02; p = 0.06), although post hoc analyses concluded to statistical significance (p = 0.02). Earlier radiological resolution was observed after prednisone administration, but reoperation rates (reaching 5.8% overall) and functional outcomes were not different at 6 months. Among adverse events, sleep disorders occurred more often in the prednisone group (26.1% vs. 9.1%, p = 0.02). The HEMACORT trial data suggest that prednisone, as an adjuvant treatment to surgery, may reduce early radiological recurrence of CSDH, although clinical benefits are unclear. In view of these findings, the authors suggest that shorter treatment duration should be assessed for safety and efficacy in future trials.


Subject(s)
Glucocorticoids/therapeutic use , Hematoma, Subdural, Chronic/drug therapy , Hematoma, Subdural, Chronic/surgery , Prednisone/therapeutic use , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Double-Blind Method , Female , Hematoma, Subdural, Chronic/mortality , Humans , Length of Stay , Male , Middle Aged , Quality of Life , Treatment Outcome
15.
Neurosurgery ; 88(4): 797-803, 2021 03 15.
Article in English | MEDLINE | ID: mdl-33372205

ABSTRACT

BACKGROUND: Incidentally discovered suspected diffuse low-grade gliomas (LGGs) on brain imaging pose a challenge to neurosurgeons. Modern surgical series of LGGs favor early prophylactic surgery with a maximal extent of resection. However, some nonevolutive lesions may mimic LGGs on magnetic resonance imaging (MRI). OBJECTIVE: To determine objective criteria to advocate surgical resection of an incidentally discovered suspected LGG based upon MRI findings. METHODS: The prospective cohort of patients referred to our institution for an incidental finding suggestive of LGG was retrospectively reviewed. Stable lesions underwent systematic serial MRI follow-up, while evolutive lesions underwent prophylactic surgery under awake conditions. Initial clinico-radiological features were compared between stable and evolutive lesions in order to determine predictive criteria of further evolution. RESULTS: Among 101 patients referred for surgical resection of incidentally discovered suspected LGG in our center, 19 patients (18.8%) had nonevolutive MRI lesions after a mean follow-up of 46.9 ± 34.9 mo. Insular topography (P = .003), higher mean volume at discovery (19.2 vs 5.2 cm3, P < .001), and adjacent sulcal effacement (P = .001) were associated with evolutive lesions. Histopathological diagnosis of LGG was confirmed in all surgical cases. CONCLUSION: Increasing volume is an effective predictor of LGG diagnosis in incidental MRI findings, as all patients who subsequently underwent surgery had confirmed histopathological diagnosis of diffuse glioma. Approximately 18.8% of incidental findings were stable over time. Insular topography, adjacent sulcal effacement, and volume greater than 4.5 cm3 were predictive of further radiological progression. These significant elements will help neurosurgeons to define personalized strategies in this complex setting of incidental discovery.


Subject(s)
Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Incidental Findings , Adult , Brain Neoplasms/surgery , Cohort Studies , Female , Glioma/surgery , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoplasm Grading/methods , Predictive Value of Tests , Prospective Studies , Retrospective Studies , Wakefulness
16.
Acta Neurochir (Wien) ; 163(1): 57-66, 2021 01.
Article in English | MEDLINE | ID: mdl-33216210

ABSTRACT

Meningiomas are tumors arising from the meninges and represent the most frequent central nervous system tumors in adults. Recent large-scale genetic studies and preclinical meningioma mouse modelling led to a better comprehension of meningioma development and suggested evidences of close relationships between meningeal embryology and tumorigenesis. In this non-systematic review, we summarize the current knowledge on meningeal embryology and developmental biology, and illustrate how meningioma tumorigenesis is deeply related to meningeal embryology, concerning the potential cell of origin, the role of reactivation of embryonic stem cells, the influence of the embryonic tissue of origin, and the parallelism between topography-dependant molecular pathways involved in normal meninges and in meningioma development. Our study emphasizes why future studies on meningeal embryology are mandatory to affine our comprehension of mechanisms underlying meningioma initiation and development.


Subject(s)
Carcinogenesis , Meningeal Neoplasms/pathology , Meninges/embryology , Meningioma/pathology , Animals , Cell Transformation, Neoplastic , Humans , Meningeal Neoplasms/etiology , Meningioma/etiology
17.
Neuro Oncol ; 23(5): 783-794, 2021 05 05.
Article in English | MEDLINE | ID: mdl-33068421

ABSTRACT

BACKGROUND: We and others have identified mutually exclusive molecular subgroups of meningiomas; however, the implications of this classification for clinical prognostication remain unclear. Integrated genomic and epigenomic analyses implicate unique oncogenic processes associated with each subgroup, suggesting the potential for divergent clinical courses. The aim of this study was to understand the associated clinical outcomes of each subgroup, as this could optimize treatment for patients. METHODS: We analyzed outcome data for 469 meningiomas of known molecular subgroup, including extent of resection, postoperative radiation, surveillance imaging, and time to recurrence, when applicable. Statistical relationships between outcome variables and subgroup were assessed. Features previously associated with recurrence were further investigated after stratification by subgroup. We used Kaplan-Meier analyses to compare progression-free survival, and identified factors significantly associated with recurrence using Cox proportional hazards modeling. RESULTS: Meningioma molecular subgroups exhibited divergent clinical courses at 2 years of follow-up, with several aggressive subgroups (NF2, PI3K, HH, tumor necrosis factor receptor-associated factor 7 [TRAF7]) recurring at an average rate of 22 times higher than others (KLF4, POLR2A, SMARCB1). PI3K-activated tumors recurred earlier than other subgroups but had intermediate long-term outcome. Among low-grade tumors, HH and TRAF7 meningiomas exhibited elevated recurrence compared with other subgroups. Recurrence of NF2 tumors was associated with male sex, high grade, and elevated Ki-67. Multivariate analysis identified molecular subgroup as an independent predictor of recurrence, along with grade and previous recurrence. CONCLUSION: We describe distinct clinical outcomes and recurrence rates associated with meningioma molecular subgroups. Our findings emphasize the importance of genomic characterization to guide postoperative management decisions for meningiomas.


Subject(s)
Meningeal Neoplasms , Meningioma , Epigenomics , Genomics , Humans , Kruppel-Like Factor 4 , Male , Meningeal Neoplasms/genetics , Meningioma/genetics , Neoplasm Recurrence, Local/genetics , Retrospective Studies
19.
Eur Arch Otorhinolaryngol ; 277(4): 1079-1087, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31960129

ABSTRACT

PURPOSE: To report the results of a series of patients undergoing the endoscopic subperichondrial transseptal (STRAS) approach for pituitary surgery and to evaluate the efficiency and the safety of this approach. METHODS: This is a single-centre retrospective study including all patients undergoing pituitary lesion resection through the STRAS approach from January 2002 to December 2017 by a multidisciplinary surgical team (ENT and neurosurgeon). Demographic data, tumour type, complication rate and pre- and post-operative visual, endocrine and tumour status were retrospectively analysed. RESULTS: 119 patients were included in the study, 80 (67%) presenting macroadenoma, 24 (20%) microadenoma (20%) and 6 (5%) giant adenoma. 61 (51%) patients had secreting adenoma and 51 (42%) patient had non-functioning adenoma. The STRAS approach allowed a good visualization of intrasphenoidal and intrasellar anatomical landmarks in all cases and no patient needed turbinate resection. No patient died or had neurological deficit. Endocrine remission or control was achieved in 90.5% of hormone-secreting microadenomas and in 84.2% of hormone-secreting macroadenomas. Gross-total resection was achieved for 39 patients (48.8%) of the 80 macroadenomas. Nasal complication rate was very low, with no septal perforation and two epistaxis (1.7%) medically treated. CONCLUSION: The STRAS approach is an elegant approach to the sphenoid sinus that enables a good exposure of the intrasphenoidal anatomical landmarks with a maximal preservation of the nasal mucosa. This approach allows an intrasellar work with great comfort and safety for the surgeon using a two-hand or a four-hand technique.


Subject(s)
Adenoma , Endoscopy , Pituitary Neoplasms , Adenoma/surgery , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Pituitary Neoplasms/surgery , Retrospective Studies , Sphenoid Sinus/surgery , Treatment Outcome , Young Adult
20.
J Neurointerv Surg ; 12(7): 695-699, 2020 Jul.
Article in English | MEDLINE | ID: mdl-31862830

ABSTRACT

BACKGROUND: Chronic subdural hematoma (CSDH) is a common condition requiring surgical treatment; however, recurrence occurs in 15% of cases at 1 year. Middle meningeal artery (MMA) embolization has recently emerged as a promising treatment to prevent CSDH recurrence. OBJECTIVE: To investigate the effect of MMA embolization on hematoma volume resorption (HVR) after surgery in symptomatic patients. METHODS: From April 2018 to October 2018, participants with CSDH requiring surgery were prospectively randomized in a pilot study, and received either surgical treatment alone (ST group) or surgery and adjuvant MMA embolization (ST+MMAE group). The primary outcome was HVR measured on the 3 month CT scan compared with the immediate pre-embolization CT scan. Secondary outcomes were clinical recurrence of CSDH and safety measures. RESULTS: 46 patients were randomized and 41 of these achieved a 3 month follow-up . Twenty-one patients received MMA embolization. At 3 months, the HVR from postsurgical level was higher in the ST+MMAE group (mean difference 17.5 mL, 95% CI 3.87 to 31.16 mL; p=0.015). Two participants presented a CSDH recurrence (one in each group). One patient died (ST group). No MMA embolization-related adverse events were reported. CONCLUSION: The addition of MMA embolization to surgery led to an increase in CSDH resorption at 3 months. One recurrence of CSDH was reported in each group, and there were no treatment-related complications.


Subject(s)
Embolization, Therapeutic/methods , Endovascular Procedures/methods , Hematoma, Subdural, Chronic/diagnostic imaging , Hematoma, Subdural, Chronic/therapy , Meningeal Arteries/diagnostic imaging , Meningeal Arteries/surgery , Aged , Aged, 80 and over , Combined Modality Therapy/methods , Female , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Tomography, X-Ray Computed/methods , Treatment Outcome
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