Outcomes of Fluorescence-Guided vs White Light Resection of Glioblastoma in a Single Institution.

Background Glioblastoma (GBM) is the most common malignant primary brain tumour and confers a very poor prognosis. Maximal safe resection of tumour is the goal of neurosurgical intervention and may be more easily achieved through the use of surgical adjuncts such as fluorescence-guided surgery (FGS). 5-Aminolevulinic acid (5-ALA) accumulates in GBM tissue and fluoresce red, distinguishing tumour cells from the surrounding tissue and therefore making resection easier. 5-ALA-guided resection in GBM has been shown to increase resection rates and prolong progression-free survival without impacting post-operative morbidity. Radiotherapy and concomitant chemotherapy also improve survival in GBM. Other factors such as patient age and molecular status of the tumour also impact prognosis. Aims The aim of this study was to compare the outcomes of 5-ALA vs white light-guided resection for glioblastoma in the west of Scotland. Methods  This was a retrospective analysis of baseline characteristics (age, sex, tumour molecular markers, radiotherapy, chemotherapy, anatomical location of tumour and treatment group) and outcomes (mortality, survival, degree of resection and performance status) of 239 patients who underwent primary resection of glioblastoma over a four-year period (2017-2020). A variety of statistical methods were used to analyse the relationship between each variable and surgical technique; multivariate Cox regression and the Kaplan-Meier method were used in survival analysis. Results  5-ALA-guided resection substantially improved resection rates (74.0% vs 40.2%). Mortality at 15 months was 5.1% lower in the 5-ALA group (52.0% vs 57.1%, p = 0.53), and patients lived an average of 68 days longer compared to the white light group (444 days vs 376 days, p = 0.21). There were negligible differences between treatment groups in terms of post-operative performance status (PS) and post-operative complications. In our multivariate Cox regression model, six factors were statistically significant at a level of p ≤ 0.05: age, radiotherapy, chemotherapy, O(6)-methylguanine-DNA methyltransferase (MGMT) methylation, anatomical location and >90% resection. Receiving chemotherapy and radiotherapy, MGMT methylation and undergoing >90% resection conferred a survival benefit at 15 months. Older age and multi-focal disease were related to a worsened mortality rate. Undergoing radiotherapy and maximal resection were the two greatest predictors of improved survival, reducing mortality risk by 58% and 51%, respectively. Conclusion 5-ALA-guided resection improved resection rates without impacting post-operative morbidity. 5-ALA-guided resection was associated with improved survival and lower mortality rate, but this was not statistically significant. Receiving chemoradiotherapy, MGMT methylation and undergoing maximal resection conferred a survival benefit, whilst older age and multi-focal disease were associated with a poorer prognosis.

Two cases of SMA syndrome after neurosurgical injury to the frontal aslant tract.

Supplementary motor area (SMA) syndrome is characterised by transient disturbance in volitional movement and speech production which classically occurs after injury to the medial premotor area. We present two cases of SMA syndrome following isolated surgical injury to the frontal aslant tract (FAT) with the SMA intact. The first case occurred after resection of a left frontal operculum tumour. The second case occurred after a transcortical approach to a ventricular neurocytoma. The clinical picture and fMRI activation patterns during recovery were typical for SMA syndrome and support the theory that the FAT is a critical bundle in the SMA complex function.

Relationship between molecular characteristics of glioblastoma multiforme and the subventricular zone.

OBJECTIVE: This study aims to assess the relationship between the molecular characteristics of glioblastoma multiforme (GBM) and the subventricular zone (SVZ). MATERIAL AND METHODS: Eligible patients had their data anonymously collected from an institutional database, including age, sex, preoperative performance status, the extent of tumour resection, anatomical location, IDH mutation and MGMT methylation status. An Institutional picture archiving and communications system was used for volumetric and morphometric analysis. All measurements were made on T1-weighted magnetic resonance images with gadolinium contrast enhancement. IDH wild-type and mutant GBMs were stratified by MGMT methylation status. The relationship between tumour volume, distance from the tumour's enhancing edge and the tumour's geometric centre to the SVZ and their molecular characteristics were assessed. RESULTS: Fifty IDH wild-type GBMs were studied. Twenty-three were MGMT methylated, Twenty-seven were unmethylated. IDH wild-type MGMT methylated GBMs were significantly associated with a tumour's enhancing boundary being contiguous to the SVZ (P < 0.001). Ninety percent of tumours contiguous to the SVZ were wild-type methylated (n = 18) and 10% were unmethylated (n = 2). Mean GBM geometric centre distance to SVZ was significantly less for methylated wild-type GBMs compared to unmethylated (P = 0.025) and median GBM distance from the tumour's edge of enhancement to the SVZ was significantly shorter in methylated tumours compared to unmethylated (P < 0.001). Mean and median distances to SVZ from the edge of enhancement was 3.8 millimetres (mm) and 0 mm, respectively, for wild-type methylated GBMs, while for unmethylated wild-types, 14.6 mm, and 12.5 mm. There was no anatomical localisation of IDH wild-type GBMs by MGMT methylation status to a cerebral hemisphere or lobe. CONCLUSION: IDH wild-type GBMs contiguous to the SVZ are highly likely to be MGMT methylated. Replication by further studies is required to affirm our results and conclusion.

Prognostic significance of IL-8-STAT-3 pathway in astrocytomas: correlation with IL-6, VEGF and microvessel morphometry.

Malignant astrocytomas are highly vascular neoplasms characterized by a potent angiogenic and immunosuppressive phenotype. Th2-cytokines (IL-6/IL-8) are implicated as major regulators of glioma cell growth and invasiveness. STAT-3, a downstream transducer of cytokine signaling is positively associated with tumor angiogenesis. The present study aimed to investigate the expression of IL-8 and p-STAT-3 in 97 diffusely infiltrating astrocytomas of various grades, in relation to IL-6, VEGF, clinicopathological features, microvascular characteristics and patients' survival. IL-8 expression was localized in neoplastic cells, being associated with p-STAT-3 (p = 0.0013), IL-6 (p = 0.0004) and VEGF (p < 0.0001) around areas of necrosis as well as in perivascular inflammatory and endothelial cells. All the molecules under study correlated with tumor grade and degree of necrosis (p < 0.05, respectively). p-STAT-3, IL-8 and VEGF expression was positively associated with microvessel density (p = 0.0491, p < 0.0001 and p = 0.0118, respectively). Univariate analysis indicated that overexpression of IL-8 and IL-6 adversely affected survival in the entire cohort whereas increased p-STAT-3 expression was predictive of improved survival in high grade (III/IV) astrocytomas (p = 0.0032). In multivariate analysis only IL-8 expression (p = 0.043) retained its significance. The prognostic significance of IL-8 expression and its correlation with p-STAT-3 and VEGF implicates this novel signaling pathway in astroglial tumors progression providing new targets for effective immunotherapy.

Surgical treatment for refractory temporal lobe epilepsy in the elderly: seizure outcome and neuropsychological sequels compared with a younger cohort.

PURPOSE: Surgical treatment of refractory temporal lobe epilepsy (TLE) is promising for selected patients, but only little experience has been acquired in operating on older patients, especially with limited resections. We intend to delineate clinical and surgical factors influencing outcome in patients older than 50 years at operation and to compare the results with those of a younger patient cohort. METHODS: Fifty-two patients older than 50 years were operated on for intractable mesial or combined mesiolateral TLE between 1991 and 2002. The mean age at operation was 55 years, and the mean duration of epilepsy was 33 years. Forty selective amygdalohippocampectomies (33 for hippocampal sclerosis, seven for removal of a mesiotemporal lesion), five lateral temporal lesionectomies plus amygdalohippocampectomy, and seven anterior temporal lobectomies were performed. Eleven (21%) patients had undergone invasive presurgical video-EEG monitoring. The mean follow-up period was 33 months. We compared the results with those of a younger cohort operated on in the same time period. RESULTS: Thirty-seven older patients attained complete seizure control (71% class I), and 10 patients had only rare postoperative seizures (19% class II). Four patients improved >75% (8% class III), and one patient did not improve (2% class IV). The same rate of seizure control was attained by 11 patients older than 60 years at surgery. These results were not significantly different from those in a younger patient group. A trend toward better seizure control was noted in 16 patients with an epilepsy duration of <30 years (all class I or II), and in 20 patients with a seizure frequency of fewer than five seizures per month (all class I or II). No mortality resulted from a total of 65 diagnostic and therapeutic procedures. A 3.8% permanent neurologic morbidity (dysphasia and hemiparesis) was noted. Hemianopia occurred in three (5.9%) patients. Neuropsychological testing revealed low preoperative performances and some gradual further deterioration after surgery. CONCLUSIONS: Results of surgery for TLE with mainly limited resections are promising in patients older than 50 years and older 60 years, despite the long seizure history. As expected, the risk of complications is somewhat higher compared with that in a younger control group. The impact of low neuropsychological performance is a concern.

Supraorbital eyebrow minicraniotomy for anterior circulation aneurysms.

BACKGROUND: We report our experience with the minimally invasive supraorbital approach to aneurysms of the ipsilateral anterior cerebral circulation. METHODS: A prospective review of all patients who underwent operations to clip aneurysms in Newcastle between 1993 and 2002. RESULTS: Fifty-six aneurysms were clipped via minicraniotomy in 47 patients. Six patients presented with acute subarachnoid hemorrhage (SAH), 40 patients were admitted for elective clipping, and 1 patient presented with an SAH, had the responsible aneurysm clipped and was readmitted later for elective clipping of a further aneurysm. Bilateral supraorbital craniotomies were performed in 3 patients. In 6 patients, multiple aneurysms were clipped via a single craniotomy. All aneurysms were well visualized with the microscope. Endoscopic assistance was not found necessary. All were successfully clipped. Two aneurysms ruptured while being clipped. There was no direct mortality from surgery. One patient died later from a separate posterior circulation aneurysm. One patient had a significant long-term deficit but remained independent, and 1 had 3 seizures over the 12 months after surgery. This represents a 4% morbidity at 1 year. CONCLUSION: Selected anterior cerebral circulation aneurysms can be clipped with low morbidity, using an ipsilateral minicraniotomy preserving the orbital rim, and without using an endoscope. The types of aneurysm selection criteria and operative equipment used are described.