Evaluation of KIAA1549::BRAF fusions and clinicopathological insights of pilocytic astrocytomas.

BACKGROUND: Pilocytic astrocytoma (PAs) represents a significant portion of childhood primary brain tumors, with distinct histological and radiological features. The prevalence of KIAA1549::BRAF fusion in PAs has been well-established, this study aims to assess the prevalence of KIAA1549::BRAF fusions and explore their associations with tumor characteristics, radiological findings, and patient outcomes in PAs. METHODS: Histologically confirmed cases of PAs from a 5-year period were included in the study. Demographic, histopathological, and radiological data were collected, and immunohistochemistry was performed to characterize tumor markers. FISH and qRT-PCR assays were employed to detect KIAA1549::BRAF fusions. Statistical analyses were conducted to examine associations between fusion status and various other parameters. RESULTS: Histological analysis revealed no significant differences in tumor features based on fusion status. However, younger age groups showed higher fusion prevalence. Radiologically, fusion-positive cases were distributed across different tumor subtypes SE, CWE and NCWE. Survival analysis did not demonstrate a significant impact of fusion status on overall survival, however most cases with recurrence and death harboured KIAA1549::BRAF fusion. Of 200 PAs, KIAA1549::BRAF fusions were detected in 64 % and 74 % of cases via qRT-PCR and FISH, respectively. Concordance between the two platforms was substantial (86 %). CONCLUSION: KIAA1549::BRAF fusions are prevalent in PAs and can be reliably detected using both FISH and qRT-PCR assays. Cost considerations suggest qRT-PCR as a more economical option for fusion detection in routine clinical practice.

Clinico-radiological parameters, biochemical and molecular alterations predicting remission and recurrence after surgical treatment of corticotroph adenomas - Cushing's disease.

OBJECTIVES: Endonasal endoscopic transsphenoidal surgery (TSS) and resection of pituitary adenomas is considered to be the gold standard treatment for Cushing's Disease (CD). Even with various recent advances in management, disease persistence and recurrences are common in these patients. The remission rate in the global population after surgery has been reported to vary widely from 64 to 93%. This study aims to determine various clinical, biochemical, radiological and histological factors that correlate with persistence and recurrence in patients with CD. This study also aims to understand the clinicopathological significance of EGFR-MAPK, NF-kB and SHH pathway activation and to study the protein expression levels of activation markers of these pathways viz. c-Fos , c-Jun, GLI-1 , pMEK, NR4A1 and p44 in functioning corticotroph pituitary adenomas. METHODS: From January 2009 to September 2022, the clinical data of 167 patients who underwent surgical treatment (n=174 surgeries) for Cushing's disease was ambispectively analysed with a median follow up of 8.1 years (1-13.29 years). The preoperative clinical, biochemical, radiological features, operative findings, postoperative clinical and biochemical data, histopathological and molecular profile, were retrieved from electronic records. The patients were followed up to assess the remission status. RESULTS: Among the 174 surgeries performed, 140 were primary surgeries, 22 were revision surgeries, 24 surgeries were for paediatric patients and 12 surgeries were performed in patients with Nelson syndrome. In the primary surgery cohort, 74.3% were females and the average age was 28.73 years (SD 10.15). 75% of the patients experienced remission after primary surgery compared to 47.4% in revision surgery. The remission rate in paediatric patients was 55.5%. Post-operative day 1 plasma cortisol (p<0.001; AUC 0.8894 [0.8087-0.9701]) and ACTH (p<0.001; AUC 0.9 [0.7386-1]) levels were seen to be strong independent predictors of remission in the primary surgery cohort. Remission rates after Endoscopic TSS were more than that after microscopic TSS, in patients undergoing primary surgery (81.08% vs 57.14%; p=0.008). Presence of adenoma on histopathological examination (HPE) was also a strong predictor of disease remission (p=0.020). On categorising based on surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of non-remission (OR 38.1 95% CI 4.2-348.3) compared to endoscopically operated patients with adenoma on HPE. Lower immune reactivity score (IRS) of NR4A1 was found to correlate with higher remission rates (p=0.074). However, none of the molecular markers studied viz. c-Fos , c-Jun, GLI-1, pMEK and p44 showed a significant correlation with the preoperative cortisol values. CONCLUSION: Remission rate after primary surgery is higher as compared to that after revision surgery, and that in paediatric patients is lower as compared to adults. Post-operative day 1 plasma cortisol and ACTH levels are strong independent predictors of remission in the primary surgery cohort. Endoscopic approach with histopathological evidence of adenoma is associated with a higher remission rate and thus endoscopy should be the approach of choice in these patients with the goal of identification of an adenoma on histopathological analysis.

Middle third falcine meningiomas-surgical nuances for cortical venous preservation.

PURPOSE: To improve postoperative outcome in middle third falcine meningiomas by cortical venous preservation. BACKGROUND: Falcine meningiomas arise from the falx and do not involve the superior sagittal sinus (SSS). Their complete resection is often associated with the risk of venous infarction in the eloquent cortex due to overlying superficial cortical veins on the tumors. METHOD: We report one case of middle third falcine meningioma, where we used the posterior interhemispheric corridor for tumor approach. CONCLUSION: Use of the posterior interhemispheric approach, carefully raised bone flap, along with sharp dissection and vein reinforcement using fibrin glue can help to preserve the cortical veins while resecting the falcine meningiomas.

STAT1 mediated downregulation of the tumor suppressor gene PDCD4, is driven by the atypical cadherin FAT1, in glioblastoma.

STAT1 (Signal Transducer and Activator of Transcription 1), belongs to the STAT protein family, essential for cytokine signaling. It has been reported to have either context dependent oncogenic or tumor suppressor roles in different tumors. Earlier, we demonstrated that Glioblastoma multiforme (GBMs) overexpressing FAT1, an atypical cadherin, had poorer outcomes. Overexpressed FAT1 promotes pro-tumorigenic inflammation, migration/invasion by downregulating tumor suppressor gene, PDCD4. Here, we demonstrate that STAT1 is a novel mediator downstream to FAT1, in downregulating PDCD4 in GBMs. In-silico analysis of GBM databases as well as q-PCR analysis in resected GBM tumors showed positive correlation between STAT1 and FAT1 mRNA levels. Kaplan-Meier analysis showed poorer survival of GBM patients having high FAT1 and STAT1 expression. SiRNA-mediated knockdown of FAT1 decreased STAT1 and increased PDCD4 expression in glioblastoma cells (LN229 and U87MG). Knockdown of STAT1 alone resulted in increased PDCD4 expression. In silico analysis of the PDCD4 promoter revealed four putative STAT1 binding sites (Site1-Site4). ChIP assay confirmed the binding of STAT1 to site1. ChIP-PCR revealed decrease in the binding of STAT1 on the PDCD4 promoter after FAT1 knockdown. Site directed mutagenesis of Site1 resulted in increased PDCD4 luciferase activity, substantiating STAT1 mediated PDCD4 inhibition. EMSA confirmed STAT1 binding to the Site 1 sequence. STAT1 knockdown led to decreased expression of pro-inflammatory cytokines and EMT markers, and reduced migration/invasion of GBM cells. This study therefore identifies STAT1 as a novel downstream mediator of FAT1, promoting pro-tumorigenic activity in GBM, by suppressing PDCD4 expression.

A Narrative Review on 3-Dimensional Visualization Techniques in Neurosurgical Education, Simulation, and Planning.

BACKGROUND: High-fidelity visualization of anatomical organs is crucial for neurosurgical education, simulation, and planning. This becomes much more important for minimally invasive neurosurgical procedures. Realistic anatomical visualization can allow resident surgeons to learn visual cues and orient themselves with the complex 3-dimensional (3D) anatomy. Achieving full fidelity in 3D medical visualization is an active area of research; however, the prior reviews focus on the application area and lack the underlying technical principles. Accordingly, the present study attempts to bridge this gap by providing a narrative review of the techniques used for 3D visualization. METHODS: We conducted a literature review on 3D medical visualization technology from 2018 to 2023 using the PubMed and Google Scholar search engines. The cross-referenced manuscripts were extensively studied to find literature that discusses technology relevant to 3D medical visualization. We also compiled and ran software applications that were accessible to us in order to better understand them. RESULTS: We present the underlying fundamental technology used in 3D medical visualization in the context of neurosurgical education, simulation, and planning. Further, we discuss and categorize a few important applications based on the 3D visualization techniques they use. CONCLUSIONS: The visualization of virtual human organs has not yet achieved a level of realism close to reality. This gap is largely due to the interdisciplinary nature of this research, population diversity, and validation complexities. With the advancements in computational resources and automation of 3D visualization pipelines, next-gen applications may offer enhanced medical 3D visualization fidelity.

Functional and Neuropsychological Outcome After Surgical Treatment of Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the supraclinoid internal carotid artery. As a result of chronically decreased brain perfusion, eloquent areas of the brain become hypoperfused, leading to cognitive changes in patients. Repeated infarcts and bleeds produce clinically apparent neurologic deficits. OBJECTIVES: 1) To study the functional and neuropsychological outcome in MMD after revascularization surgery. 2) To find postrevascularization correlation between functional and neuropsychological improvement and radiologic improvement. METHODS: A single-center prospective and analytic study was carried out including 21 patients with MMD during the study period from March 2021 to December 2022. Patients were evaluated and compared before and after revascularization for functional, neuropsychological, and radiologic status. RESULTS: Postoperative functional outcome in terms of modified Rankin Scale score showed improvement in 33.33% of cases (P = 0.0769). An overall improving trend was observed in different neuropsychological domains in both adult and pediatric age groups. However, the trend of neuropsychological improvement was better in adults compared with pediatric patients. Radiologic outcome in the form of the Angiographic Outcome Score (AOS) significantly improved after revascularization (P = 0.0001). There was a trend toward improvement in magnetic resonance imaging (MRI) perfusion in the middle cerebral artery and anterior cerebral artery territories, 4.7% (P = 0.075) and 9.33% (P = 0.058) respectively, compared with preoperative MRI perfusion. CONCLUSIONS: After revascularization, significant improvement occurred in functional and neuropsychological status. This result was also shown radiologically as evidenced by improvement in MRI perfusion and cerebral angiography.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Neurosurgery residency match for international medical graduates in the United States.

OBJECTIVE: Training of international medical graduates (IMGs) offers opportunities for the US neurosurgery community to engage the global talent pool and impact national and international healthcare. Here, the authors analyzed the time trend of IMGs matching into US neurosurgery programs and identified potential opportunities for enhancing IMG engagement. METHODS: The authors analyzed the National Resident Matching Program (NRMP) match results, NRMP program director (PD) surveys, and applicant surveys from 2013 to 2022. Regression methods were used to analyze time trends. RESULTS: Between 2013 and 2022, the number of US neurosurgery residency positions increased by 17.6% (from 204 to 240). During this period, the percentage of IMGs matching into neurosurgery increased from 3.5% to 7%, translating into a 6.8% increase in the likelihood of a successful IMG match per year (95% CI 0.3%-13.8%, p = 0.042). The likelihoods of a successful match for US MDs and IMGs scoring > 260 on the USMLE Step 1 were > 90% and approximately 55%, respectively. In PD surveys, approximately 90% of PDs indicated that they seldom/never interview or rank IMGs. In terms of factors that influenced the PD decision for interviewing/ranking, IMGs are disadvantaged in several categories, including the ability to secure an audition elective/rotation, and proper letters of recommendation, as well as the influence of the culture on the preconceived perception of poor interpersonal skills. CONCLUSIONS: The number of IMGs matching successfully in neurosurgery has increased marginally during the past decade. The authors outline the challenges that IMGs encounter in this process and suggest strategies for considerations of IMG training in NRMP-associated institutions.

Non-chordomatous clival bony tumors: A rare experience and systematic literature review.

BACKGROUND: Non-chordomatous bony tumors of the clivus are extremely rare. Site, extent, and aggressiveness of tumor limits the extent of resection. It poses challenge to the neurosurgeons due to the complexity of anatomy. There is paucity of literature exclusively on non-chordomatous bone tumors of the clivus in young adults. OBJECTIVES: To analyze the clinical presentation, imaging findings, surgical approach, complications, and outcome of primary clival bony tumors in young adults. METHODS: We retrospectively reviewed children and young adults with primary clival bony tumors excluding chordoma who underwent surgical resection between years 2010 and 2023 in our center. We analyzed the demographic details, imaging findings, operative variables, perioperative complications, length of stay, complications, and outcome at latest follow-up. RESULTS: The mean age was 17.5 ± 1.73 years (range 16 to 19 years). Headache was the presenting complaint in all four patients (100%). The mean duration of symptom was 7.25 ± 3.2 months (range 5 to 12 months). The tumor was localized in clivus in all four patients (100%). The mean length of stay in hospital was 30.5 ± 13.48 days (range 11 to 40 days). All patients underwent surgical treatment. Surgical approaches used were anterior approach in four patients (100%). Gross total excision was performed in one patient (25%), sub-total excision was performed in two patients (50%), and tumor decompression was performed in one patient (25%). Of these, three were designated as having benign tumors and one had a malignant tumor. There was no perioperative mortality. There was one mortality (25%) on 2 months follow-up due to tumor progression. Three patients (75%) had improved symptomatically at latest follow-up. Two patients (50%) received adjuvant chemoradiotherapy. The mean follow-up was 38 ± 39.29 months (range 2 to 72 months). CONCLUSION: Non-chordomatous bony tumors of the clivus are rare and often underestimated. Surgery is the treatment of choice. Tumor consistency and adhesion to critical neurovascular structures precludes gross total resection. Various approaches are in the armamentarium. Approach to be decided based on the expertise of the neurosurgeon to achieve safe maximal resection. Multidisciplinary approach is mandatory for streamlined management. Adjuvant therapy is decided based on the residual tumor following surgery.

Analysis of Histomorphologic/Molecular Association and Immune Checkpoint Regulators in Epithelioid Glioblastoma and Pleomorphic Xanthoastrocytoma: Are These Tumors Potential Candidates for Immune Checkpoint Blockade?

Accurate diagnosis of Epithelioid glioblastoma (eGB) and pleomorphic xanthoastrocytoma (PXA) is sometimes challenging owing to overlapping histologic and genetic features. There are limited reports on the immune profile of these tumors. In this study, we assessed 21 PXA [15 PXA Grade 2 (PXAG2); 6 PXA Grade 3 (PXAG3)] and 14 eGB for their histopathological and molecular association. Further, their immune profile was compared with GB, IDH1 wild-type (wt) (n-18). Morphologically, PXAG2 mostly differed from eGB; however, it was occasionally difficult to differentiate PXAG3 from eGB due to their epithelioid pattern and less obvious degenerative features. PXAG2 showed predominantly diffuse, whereas variable positivity for epithelial and glial markers was seen in PXAG3 and eGB. All cases showed retained nuclear ATRX and INI-1 . H3K27M or IDH1 mutation was seen in none. P53 mutation was more common in eGB, followed by PXAG3, and least common in PXAG2. BRAF V600E mutation was observed in 66.67% PXAG2, 33.33% PXAG3, and 50% eGB, with 100% concordance between immunohistochemistry (IHC) and sequencing. Thirty-six percent eGB, 33% PXAG3, and 61% PXAG2 harbored CDKN2A homozygous deletion. EGFR amplification was observed in 14% eGB and 66% of GB, IDH wt. PDL1 and CTLA-4 expression was higher in eGB (71.4% and 57.1%), PXAG3 (66.6% and100%), and PXAG2 (60% & 66.7%) as compared with GB, IDH wt (38.8% and 16.7%). Tumor-infiltrating lymphocytes were also observed in a majority of eGB and PXA (90% to 100%) in contrast to GB, IDH wt (66%). This analysis highlights the homogenous molecular and immune profile of eGB and PXA, suggesting the possibility that histologically and molecularly, these two entities represent 2 ends of a continuous spectrum with PXAG3 lying in between. Higher upregulation of PDL1, CTLA-4, and increased tumor infiltrating lymphocytes in these tumors as compared with GB, IDH wt suggests potential candidature for immunotherapy.

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Comprehensive Outcome Assessment and Quality of Life Following Epilepsy Surgery.

BACKGROUND: Seizure freedom without deficits is the primary goal for epilepsy surgery. However, patients with medically refractory epilepsy commonly suffer from many co-morbidities related to mood, cognition, and sleep as well as social problems and resultant stigma. While epilepsy surgery literature does describe quality of life (QOL) and neuropsychological outcomes, there is a paucity of information on various common non-seizure outcomes, especially pertaining to mood, sleep, cognition, and social aspects. The objective of this study was to evaluate the role of various non-seizure parameters on post-epilepsy surgery QOL. METHODS: Consecutive adult patients operated for refractory epilepsy at least 1 year prior to initiation of this study were included and classified as seizure-free (group 1) or non-seizure-free (group 2). QOL was assessed using the QOLIE-31 instrument; patients with a T score less than 40 were categorized as "poor QOL." Non-seizure parameters assessed were cognition, mood disturbances, social improvement, social stigma, and sleep disturbances. Categorization into "good" and "poor" outcome subgroups on each item was carried out by dichotomization of scores. RESULTS: Thirty-seven patients (16 F) [mean age 23.5 ± 5.6 years] were evaluated; 26 were seizure-free (group 1). In this group, impaired memory, lower language scores, depression, not having been employed, not receiving education prior to surgery, and experiencing social stigma were factors significantly associated with poor QOL. In group 2, all patients had poor QOL scores. CONCLUSION: Non-seizure factors related to common epilepsy co-morbidities and social issues are highly prevalent among seizure-free patients reporting poor QOL after epilepsy surgery.

Role of Cavernous Sinus Extension and MRI T2 Hypointensity in the Extent of Resection following Trans-Sphenoidal Surgery for Giant Pituitary Adenomas.

Background: Giant pituitary adenomas (GPA) pose a significant neurosurgical challenge. In this study, we present an experience of 60 consecutive patients with GPA operated by trans-sphenoidal surgery (microscopic/endoscopic). Objective: The aim of this study was to elucidate preoperative factors predicting extent of resection (EOR) following transsphenoidal surgery for GPA. Materials and Methods: The study was a retrospective evaluation of 60 adult patients (>18 years) with GPA operated over a decade. The patients were analyzed for their clinical presentation, EOR, radiology, visual outcome, endocrinological outcome, and complications. Results: The mean age of the cohort was 41.5 ± 13.3 years, mean tumor volume was 38.2 ± 19.1 cm3, and mean follow-up was 30.6 ± 21.7 months. Improvement in vision was seen in forty patients (66.7%), while another 16 (26.7%) had stable vision as prior to surgery. Duration of visual symptoms was found to be statistically significantly associated with postoperative improvement of vision (P = 0.001). Twenty-four patients (40.0%) underwent subtotal resection (STR), while the remaining 36 patients (60.0%) underwent either gross total or near-total resection. Factors associated with STR were retrosellar (P = 0.04), subfrontal (P = 0.02), Knosp 3,4 cavernous sinus extension (P = 0.03), and MRI T2 hypointensity (P = 0.02). During follow-up, eight patients (13.3%) had radiological evidence of growth of residual tumor. Conclusions: Most cases of GPA can be adequately handled by trans-sphenoidal surgery. The presence of retrosellar, subfrontal, cavernous sinus extensions, and T2 hypointensity should alert the surgeon for likelihood of STR, postoperative residual tumor hemorrhage and need for second-stage endonasal or transcranial surgery. However, utilization of extended endoscopic route has allowed good debulking of tumors having subfrontal and parasellar extensions, which was not possible previously using traditional microscopic transsphenoidal surgery.

Personalized 3D Printed Eye Gear for Microscopic Surgeons Amidst and beyond COVID-19.

The COVID-19 pandemic underscored the need for enhanced protective measures for healthcare workers, particularly surgeons, who face a heightened risk of exposure to infectious aerosols. However, conventional eye protection equipment such as face shields, goggles, or glasses often leads to ergonomic discomfort and a reduced field of view (FOV), impeding surgeons' ability to perform microsurgical procedures with precision and ease. To address these limitations, this study aimed to develop personalized 3D-printed eye gear for microscopic surgeons based on facial anthropometry data. 3D scanning was employed to obtain facial data from ten neurosurgery residents. Utilizing computer-aided designing, eye gears tailored to the unique facial features of each participant were developed. Finite element analysis-based contact simulation was used to assess the pressure exerted by the eye gear. Multi-material 3D printing was employed to fabricate the personalized eye gear. Participants, while donning the eye gear, engaged in simulation-based micro suturing tasks at various magnifications of the operating microscope, and marked the FOV range. They provided feedback scores (1-10) on the effectiveness of the eye gear through a Likert scale questionnaire (Q1-Q8). Finite element analysis demonstrated uniform strain distribution on the face, indicating that the edges of the customized eye gear fit exactly to the user's face. The average scores for the questionnaire Q1 to Q8 ranged from 6.8 to 8.5, with an overall mean score of 7.6. This indicates that the developed eye gear was simple to use and did not cause any discomfort. Additionally, the average reduction in the FOV was only 10.93% across the different operating microscope magnifications. These findings highlight eye gear's potential to alleviate discomfort and enhance precision in microscopic surgeries. Consequently, personalized 3D-printed eye gear offers a promising solution for providing surgeons with a safe environment while preserving the benefits of the operating microscope.

Protumorigenic role of the atypical cadherin FAT1 by the suppression of PDCD10 via RelA/miR221-3p/222-3p axis in glioblastoma.

The atypical cadherin FAT1 function either as a pro or antitumorigenic in tumors of different tissue origins. Our group previously demonstrated the protumorigenic nature of FAT1 signaling in glioblastoma (GBM). In this study, we investigated how FAT1 influences the expression of clustered oncomiRs (miR-221-3p/miR-222-3p) and their downstream effects in GBM. Through several experiments involving the measurement of specific gene/microRNA expression, gene knockdowns, protein and cellular assays, we have demonstrated a novel oncogenic signaling pathway mediated by FAT1 in glioma. These results have been verified using antimiRs and miR-mimic assays. Initially, in glioma-derived cell lines (U87MG and LN229), we observed FAT1 as a novel up-regulator of the transcription factor NFκB-RelA. RelA then promotes the expression of the clustered-oncomiRs, miR-221-3p/miR-222-3p, which in turn suppresses the expression of the tumor suppressor gene (TSG), PDCD10 (Programmed cell death protein10). The suppression of PDCD10, and other known TSG targets (PTEN/PUMA), by miR-221-3p/miR-222-3p, leads to increased clonogenicity, migration, and invasion of glioma cells. Consistent with our in-vitro findings, we observed a positive expression correlation of FAT1 and miR-221-3p, and an inverse correlation of FAT1 and the miR-targets (PDCD10/PTEN/PUMA), in GBM tissue-samples. These findings were also supported by publicly available GBM databases (The Cancer Genome Atlas [TCGA] and The Repository of Molecular Brain Neoplasia Data [Rembrandt]). Patients with tumors displaying high levels of FAT1 and miR-221-3p expression (50% and 65% respectively) experienced shorter overall survival. Similar results were observed in the TCGA-GBM database. Thus, our findings show a novel FAT1/RelA/miR-221/miR-222 oncogenic-effector pathway that downregulates the TSG, PDCD10, in GBM, which could be targeted therapeutically in a specific manner.

Management protocol and surgical techniques for MRI-Negative Cushing's disease: a series of 6 cases.

Up to 40% of Cushing's disease (CD) patients show no evidence of an adenoma on dynamic contrast-enhanced MRI. Inferior petrosal sinus sampling (IPSS) remains the gold standard for diagnosis in these patients. Remission rates in MRI-Negative CD are far less at 50%-71%, compared with patients in whom an adenoma is identified on MRI. Endoscopic endonasal transsphenoidal surgery is the surgical approach of choice in these cases. Various adjuncts can be used to localize an adenoma. In this video, the authors highlight their additional usage of pituitary perfusion MRI for identification of the adenoma. They present their stepwise management algorithm and surgical techniques for sellar and suprasellar exploration in 6 cases of MRI-Negative CD operated on by the senior author (A.S.). The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2318.

Virtual Reality in Preoperative Planning of Complex Cranial Surgery.

OBJECTIVE: Changing paradigms of neurosurgical training and limited operative exposure during the residency period have made it necessary to evaluate newer technologies for training. Virtual reality (VR) technology provides three-dimensional reconstruction of routine imaging, along with the ability to see as well as interact. The application of VR technology in operative planning, which is an important part of neurosurgical training, has been incompletely studied so far. METHODS: Sixteen final-year residents, post-M.Ch. (magister chirurgiae) residents, and fellows were included as study participants. They were divided into 2 groups based on their seniority for further analysis. Five complex cranial cases were selected and a multiple-choice question-based test was prepared by the authors, with 5 questions for each of the cases. The pretest score was determined based on performance on the test after participants accessed routine preoperative imaging. The posttest score was calculated after use of the VR system (ImmersiveTouch VR System, ImmersiveTouch Inc.). Analysis was performed by the investigators, who were blinded to the identity of the participant. Subanalysis based on the type of case and type of question was performed. Feedback was obtained from each participant regarding VR use. RESULTS: There was an overall improvement in scores from pretest to posttest, which was also noted in the analysis based on the participants' seniority. This improvement was noted to be more for the vascular cases (15.89%) compared with the tumor cases (7.84%). Participants also fared better in questions related to surgical anatomy and surgical approach, compared with questions based on the diagnosis. There was overall positive feedback from participants regarding VR use, and most participants wanted VR to become a routine part of operative planning. CONCLUSIONS: Our study shows that there is improvement in understanding of surgical aspects after use of this VR system.