Background: High-grade glioma (HGG) is associated with a dismal prognosis despite significant advances in adjuvant therapies, including chemotherapy, immunotherapy, and radiotherapy. Extent of resection continues to be the most important independent prognosticator of survival. This underlines the significance of increasing gross total resection (GTR) rates by using adjunctive intraoperative modalities to maximize resection with minimal neurological morbidity. 5-aminolevulinic acid (5-ALA) is the only US Food and Drug Administration–approved intraoperative optical agent used for fluorescence-guided surgical resection of gliomas. Despite several studies on the impact of intra-operative 5-ALA use on the extent of HGG resection, a clear picture of how such usage affects patient survival is still unavailable. Methods: A systematic review was conducted of all relevant studies assessing the GTR rate and survival outcomes [overall survival (OS) and progression-free survival (PFS)] in HGG. A meta-analysis of eligible studies was performed to assess the influence of 5-ALA-guided resection on improving GTR, OS, and PFS. GTR was defined as >95% resection. Results: Of 23 eligible studies, 19 reporting GTR rates were included in the meta-analysis. The pooled cohort had 998 patients with HGG, including 796 with newly diagnosed cases. The pooled GTR rate among patients with 5-ALA–guided resection was 76.8% (95% confidence interval, 69.1–82.9%). A comparative subgroup analysis of 5-ALA–guided vs. conventional surgery (controlling for within-study covariates) showed a 26% higher GTR rate in the 5-ALA subgroup (odds ratio, 3.8; P < 0.001). There were 11 studies eligible for survival outcome analysis, 4 of which reported PFS. The pooled mean difference in OS and PFS was 3 and 1 months, respectively, favoring 5-ALA vs. control ( P < 0.001). Conclusions: This meta-analysis shows a significant increase in GTR rate with 5-ALA–guided surgical resection, with a higher weighted GTR rate (~76%) than the pivotal phase III study (~65%). Pooled analysis showed a small yet significant increase in survival measures associated with the use of 5-ALA. Despite the statistically significant results, the low level of evidence and heterogeneity across these studies make it difficult to conclusively report an independent association between 5-ALA use and survival outcomes in HGG. Additional randomized control studies are required to delineate the role of 5-ALA in survival outcomes in HGG.
OBJECTIVEMeningiomas at the falcotentorial junction represent a rare subgroup of complex meningiomas. Debate remains regarding the appropriate treatment strategy for and optimal surgical approach to these tumors, and surgical outcomes have not been well described in the literature. The authors reviewed their single-institution experience in the management, approach selection, and outcomes for patients with falcotentorial meningiomas.METHODSFrom the medical records, the authors identified all patients with falcotentorial meningiomas treated with resection at the Barrow Neurological Institute between January 2007 and October 2017. Perioperative clinical, surgical, and radiographic data were retrospectively collected. For patients who underwent the supracerebellar infratentorial approach, the tentorial angle was defined as the angle between the line joining the nasion with the tuberculum sellae and the tentorium in the midsagittal plane.RESULTSFalcotentorial meningiomas occurred in 0.97% (14/1441) of the patients with meningiomas. Most of the patients (13/14) were female, and the mean patient age was 59.8 ± 11.3 years. Of 17 total surgeries (20 procedures), 11 were single-stage primary surgeries, 3 were two-stage primary surgeries (6 procedures), 2 were reoperations for recurrence, and 1 was a reoperation after surgery had been aborted because of brain edema. Hydrocephalus was present in 5 of 17 cases, 4 of which required additional treatment. Various approaches were used, including the supracerebellar infratentorial (4/17), occipital transtentorial/transfalcine (4/17), anterior interhemispheric transsplenial (3/17), parietal transventricular (1/17), torcular (2/17), and staged supracerebellar infratentorial and occipital transtentorial/transfalcine (3/17) approaches. Of the 17 surgeries, 9 resulted in Simpson grade IV resection, and 3, 1, and 4 surgeries resulted in Simpson grades III, II, and I resection, respectively. The tentorial angle in cases with Simpson grade I resection was significantly smaller than in those with an unfavorable resection grade (43.3° ± 4.67° vs 54.0° ± 3.67°, p = 0.04). Complications occurred in 10 of 22 approaches (17 surgeries) and included visual field defects (6 cases, 2 permanent and 4 transient), hemiparesis (2 cases), hemidysesthesia (1 case), and cerebellar hematoma (1 case).CONCLUSIONSFalcotentorial meningiomas are challenging lesions. A steep tentorial angle is an unfavorable preoperative radiographic factor for achieving maximal resection with the supracerebellar infratentorial approach. Collectively, the study findings show that versatility is required to treat patients with falcotentorial meningiomas and that treatment goals and surgical approach must be individualized to obtain optimal surgical results.
Confocal Laser Endomicroscopy (CLE) is novel handheld fluorescence imaging technology that has shown promise for rapid intraoperative diagnosis of brain tumor tissue. Currently CLE is capable of image display only and lacks an automatic system to aid the surgeon in diagnostically analyzing the images. The goal of this project was to develop a computer-aided diagnostic approach for CLE imaging of human glioma with feature localization function. Despite the tremendous progress in object detection and image segmentation methods in recent years, most of such methods require large annotated datasets for training. However, manual annotation of thousands of histopathology images by physicians is costly and time consuming. To overcome this problem, we constructed a Weakly-Supervised Learning (WSL)-based model for feature localization that trains on image-level annotations, and then localizes incidences of a class-of-interest in the test image. We developed a novel convolutional neural network for diagnostic features localization from CLE images by employing a novel multiscale activation map that is laterally inhibited and collaterally integrated. To validate our method, we compared the model output to the manual annotation performed by four neurosurgeons on test images. The model achieved 88% mean accuracy and 86% mean intersection over union on intermediate features and 87% mean accuracy and 88% mean intersection over union on restrictive fine features, while outperforming other state of the art methods tested. This system can improve accuracy and efficiency in characterization of CLE images of glioma tissue during surgery, and may augment intraoperative decision-making regarding the tumor margin and improve brain tumor resection.
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