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Background Enhanced recovery after surgery (ERAS) programs are a model of care that aim to improve patient outcomes, reduce complications, and facilitate recovery while reducing healthcare-associated costs and admission length. While such programs have been developed in other surgical subspecialties, there have yet to be guidelines published specifically for laser interstitial thermal therapy (LITT). Here we describe the first multidisciplinary ERAS preliminary protocol for LITT for the treatment of brain tumors. Methods Between the years 2013 and 2021, 184 adult patients consecutively treated with LITT at our single institution were retrospectively analyzed. During this time, a series of pre, intra, and postoperative adjustments were made to the admission course and surgical/anesthesia workflow with the goal of improving recovery and admission length. Results The mean age at surgery was 60.7 years with a median preoperative Karnofsky performance score of 90 ± 13. Lesions were most commonly metastases (50%) and high-grade gliomas (37%). The mean length of stay was 2.4 days, with the average patient being discharged 1.2 days after surgery. There was an overall readmission rate of 8.7% with a LITT-specific readmission rate of 2.2%. Three of 184 patients required repeat intervention in the perioperative period, and there was one perioperative mortality. Conclusions This preliminary study shows the proposed LITT ERAS protocol to be a safe means of discharging patients on postoperative day 1 while preserving outcomes. Although future prospective work is needed to validate this protocol, results show the ERAS approach to be promising for LITT.

OBJECTIVE Supramaximal resection (SMR) has arisen as a possible surrogate to gross-total resection (GTR) to improve survival in newly diagnosed glioblastoma (nGBM). However, SMR has traditionally been limited to noneloquent regions and its feasibility in eloquent nGBM remains unclear. The authors conducted a retrospective multivariate propensity-matched analysis comparing survival outcomes for patients with left-sided eloquent nGBM undergoing SMR versus GTR. METHODS A retrospective review was performed of all patients at our institution who underwent SMR or GTR of a left-sided eloquent nGBM during the period from 2011 to 2020. All patients underwent some form of preoperative or intraoperative functional mapping and underwent awake or asleep craniotomy (craniotomy under general anesthesia); however, awake craniotomy was performed in the majority of patients and the focus of the study was SMR achieved via awake craniotomy and functional mapping with lesionectomy and additional peritumoral fluid attenuated inversion recovery (FLAIR) resection. Propensity scores were generated controlling for age, tumor location, and preoperative Karnofsky Performance Status (KPS) score with the nearest-neighbor algorithm. RESULTS A total of 102 patients (48 SMR, 54 GTR) were included in this study. The median overall survival (OS) and progression-free survival (PFS) for patients receiving SMR were 22.9 and 5.1 months, respectively. Propensity matching resulted in a final cohort of 27 SMR versus 27 GTR patients. SMR conferred improved OS (21.55 vs 15.49 months, p = 0.0098) and PFS (4.51 vs 3.59 months, p = 0.041) compared to GTR. There was no significant difference in postoperative complication rates or KPS score in SMR compared with GTR patients (p = 0.236 and p = 0.736, respectively). In patients receiving SMR, improved OS and PFS showed a dose-dependent relationship with extent of FLAIR resection (EOFR) on log-rank test for trend (p < 0.001). CONCLUSIONS SMR by means of awake craniotomy with functional mapping for left-sided eloquent nGBM is safe and confers a survival benefit compared to GTR obtained with lesionectomy alone while preserving postoperative neurological integrity. When tolerated, greater EOFR with SMR may be associated with improved survival.

Background and ObjectivesSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause a wide range of neurologic complications; however, its neuropenetrance during the acute phase of the illness is unknown.MethodsExtracellular vesicles were isolated from brain biopsy tissue from a patient undergoing epilepsy surgery using ultracentrifugation and analyzed by Western blot and qPCR for the presence of virus protein and RNA, respectively. Biopsy tissue was assessed by immunohistochemistry for the presence of microvascular damage and compared with 3 other non-COVID surgical epilepsy brain tissues.ResultsWe demonstrate the presence of viral nucleocapsid protein in extracellular vesicles and microvascular disease in the brain of a patient undergoing epilepsy surgery shortly after SARS-CoV-2 infection. Endothelial cell activation was indicated by increased levels of platelet endothelial cell adhesion molecule-1 and was associated with fibrinogen leakage and immune cell infiltration in the biopsy tissue as compared with control non-COVID surgical epilepsy brain tissues.DiscussionDespite the lack of evidence of viral replication within the brain, the presence of the nucleocapsid protein was associated with disease-specific endothelial cell activation, fibrinogen leakage, and immune cell infiltration.

Permanent pacemaker (PPM) implantation may be indicated post-transcatheter aortic valve implantation (TAVI). The Emory Risk Score (ERS) is a validated predictive risk score of the need for a PPM post-TAVI using a balloon-expandable valve. Our objectives were to determine the validity of the ERS in our local TAVI population with both balloon-expandable and self-expanding valves and to identify additional electrocardiographic (ECG) parameters predictive of the need for a PPM post-TAVI.Retrospective chart and electronic database reviews were performed to collect demographic and procedural information. Two expert readers reviewed all ECGs. Independent factors associated with PPM implantation were examined with multivariable logistic regression via a stepwise selection process with calculation of the area under the receiver operating characteristic curve to assess model discrimination.The overall PPM implantation rate was 11.7%; rates were 9% for the Sapien 3 valves, 10% for the Evolut Pro valves, and 17% for the Evolut R valves. The ERS was found to not be predictive of need for PPM post-TAVI for the entire cohort. Right bundle branch block was the only ERS parameter independently associated with new PPM implant (8.5% vs 25%, odds ratio = 3.59,The poor predictive value of the ERS in determining the need for a PPM post-TAVI in our patient population suggests that further refinement of a formula (or risk-calculator) is warranted. Identification of a precise risk-calculator is likely to facilitate patient mobilization and reduce inpatient healthcare resource utilization.L’implantation d’un stimulateur cardiaque permanent (SCP) peut être indiquée après l’implantation valvulaire aortique par cathéter (post-IVAC). L’Emory Risk Score (ERS) est un score de prédiction du risque validé de la nécessité d’un SCP post-IVAC au moyen d’une valve expansible par ballonnet. Nous avions pour objectif de déterminer la validité de l’ERS auprès de notre population ayant eu une IVAC soit par valve expansible par ballonnet ou valve auto-expansible, et de déterminer d’autres paramètres électrocardiographiques (ECG) prédictifs de la nécessité d’un SCP post-IVAC.Nous avons réalisé des revues rétrospectives de dossiers et de bases de données électroniques pour collecter les données démographiques et interventionnelles. Deux experts ont lu et interprété tous les ECG. Les facteurs indépendants associés à l’implantation du SCP ont été examinés en effectuant la régression logistique multivariée par processus de sélection pas-à-pas au moyen du calcul de la surface sous la courbe caractéristique d’efficacité du récepteur afin d’évaluer la discrimination du modèle.Le taux global d’implantation d’un SCP était de 11,7 % ; les taux étaient de 9 % pour les valves Sapien 3, de 10 % pour les valves Evolut Pro et de 17 % pour les valves Evolut R. Nous avons observé que l’ERS ne permettait pas de prédire si l’implantation d’un SCP post-IVAC était nécessaire pour la cohorte entière. Le bloc de branche droit était le seul paramètre de l’ERS indépendamment associé à la nouvelle implantation d’un SCP (8,5 %La faible valeur prédictive de l’ERS à déterminer la nécessité d’un SCP post-IVAC au sein de notre population de patients montre que des améliorations de la formule (ou calculateur de risques) sont justifiées. L’identification d’un calculateur de risques précis devrait favoriser l’adhésion des patients et réduire l’utilisation des ressources en soins de santé en milieu hospitalier.

To systematically review existing literature on the neurosurgical management and outcomes of brain metastasis from pancreatic cancer in comparison with our institutional experience of this patient cohort.Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed using PubMed, Ovid Embase, Scopus, and Web of Science databases from date of database inception to March 2022. Studies were selected based on predetermined inclusion and exclusion criteria. Simultaneously, a retrospective analysis was conducted of patients who underwent neurosurgical evaluation and treatment for intracranial metastatic lesions from pancreatic origin at a single institution.The original literature search yielded 292 articles, of which 17 studies comprising 23 patients with brain metastases of pancreatic origin were ultimately selected. Median overall survival from primary diagnosis of pancreatic cancer was 22 months (interquartile range: 3-84) and 3 months (interquartile range: 1-36) after diagnosis of brain metastasis. In our institutional cohort, 4 patients were identified with a median overall survival of 30.5 months (interquartile range: 2-108). Our institutional cohort experienced a prolonged median overall survival (3 months vs. 30.5 months, P = 0.03) compared with the literature.Brain metastasis from pancreatic cancer is rare and associated with a fatal outcome. However, based on the data presented in this review, patient-specific and treatment-related factors could signal better prognosis. Further studies are needed to elucidate multimodal therapy and survival to suggest a more personalized decision-making process.

Background There is a need to evaluate the outcomes of patients who underwent brain tumor surgery with subsequent telemedicine or in-person follow-up during the COVID-19 pandemic. Methods We retrospectively included all patients who underwent surgery for brain tumor resection by a single neurosurgeon at our Institution from the beginning of the COVID-19 pandemic restrictions (March 2020) to August 2021. Outcomes were assessed by stratifying the patients using their preference for follow-up method (telemedicine or in-person). Results Three-hundred and eighteen (318) brain tumor patients who were included. The follow-up method of choice was telemedicine (TM) in 185 patients (58.17%), and in-person (IP) consults in 133 patients. We found that patients followed by TM lived significantly farther, with a median of 36.34 miles, compared to a median of 22.23 miles in the IP cohort (P = .0025). We found no statistical difference between the TM and the IP group, when comparing visits to the emergency department (ED) within 30 days after surgery (7.3% vs 6.01%, P = .72). Readmission rates, wound infections, and 30-day mortality were similar in both cohorts. These findings were also consistent after matching cohorts using a propensity score. The percentage of telemedicine follow-up consults was higher in the first semester (73.17%) of the COVID-19 pandemic, compared to the second (46.21%), and third semesters (47.86%). Conclusions Telehealth follow-up alternatives may be safely offered to patients after brain tumor surgery, thereby reducing patient burden in those with longer distances to the hospital or special situations as the COVID-19 pandemic.

Purpose The postoperative period after laser interstitial thermal therapy (LITT) is marked by a temporary increase in volume, which can impact the accuracy of radiographic assessment. The current criteria for progressive disease (PD) suggests that a 20% increase in size of brain metastasis (BM) assessed in 6–12 weeks intervals should be considered as local progression (LP). However, there is no agreement on how LP should be defined in this context. In this study, we aimed to statistically analyzed which variations in tumor volume were associated with LP. Methods We analyzed 42 BM that underwent LITT between 2013–2022. For this study, LP was defined following radiographic features, while PD with a combined clinical and radiographic criterion. A ROC curve was generated to evaluate volume change as a predictor of LP and find the optimal cutoff point. A logistic regression analysis and Kaplan Meier curves were performed to assess the impact of various clinical variables on LP. Results Out of 42 lesions, 12 (26.7%) had LP. An increase in volume of 25.6% from baseline within 120–180 days after LITT presented a 70% sensitivity and 88.9% specificity for predicting LP (AUC: 0.78, p = 0.0412). The multivariate analysis showed a 25% increase in volume between 120–180 days as a negative predictive factor (p = 0.007). Volumetric changes within 60–90 days after LITT did not predict LP (AUC: 0.57; p = 0.612). Conclusion Volume changes within the first 120 days after the procedure are not independent indicators of LP of metastatic brain lesions treated with LITT.

BACKGROUND The diagnosis of glioblastoma (GBM) in infants aged ≤ 1 year is extremely rare, and its comparability to the more common adult diagnosis is underexplored. Correspondingly, the objective of this study was to interrogate a national cancer database to elucidate the typical survival and clinical profile of this demographic. METHODS All GBM patients aged ≤ 1 year in the U.S. National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized, and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses. RESULTS A total of 86 patients satisfied criteria for entry into study, making up 0.08% of all GBM diagnoses in the database. There were 32 (37%) females and 54 (63%) males. Irrespective of treatment, median OS was 67.3 months (95% CI, 46-91), which was distinct from all other ages and pediatric age groups. There were 74 (86%) treated by surgery, 51 (59%) treated by chemotherapy, and 17 (20%) treated by radiation therapy. Multivariable analysis demonstrated that Hispanic status (HR = 3.41, P = 0.02) and the presence of comorbidity (HR = 3.24, P = 0.01) independently predicted shorter OS, whereas treatment with chemotherapy (HR = 0.18, P

Pineal parenchymal tumors of intermediate differentiation (PPTID) are a rare group of pineal parenchymal tumors classified by histology as either World Health Organization (WHO) Grades 2 or 3. The rarity of these tumors in adults has left a number of clinical management questions open. Correspondingly, the aim of this study was to aggregate a large PPTID cohort with sufficient statistical power from a large national cancer database to analyze prognostic parameters. All PPTID patients aged over 18 years in the U.S. National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized and survival was modeled using Kaplan–Meier and Cox regression analyses. A total of 103 adult PPTID patients were identified in the NCDB with 63 (61%) WHO Grade 2 and 40 (39%) WHO Grade 3 tumors. Overall, mean age was 53 ± 18 years with even gender distribution. A total of 75 (73%) patients underwent surgical resection for diagnosis, with gross total resection (GTR) was the most common resection outcome in 50/75 (67%). Chemotherapy was utilized in 18 (17%) patients, and radiation therapy in 37 (36%) patients. Overall, 5-year survival rate was estimated to be 54% (95% CI 42–64%), with mean survival was 84 (95% CI 69–99) months. Patients with Grade 2 tumors survived statistically longer than Grade 3 tumor counterparts (P

Adult thalamic gliomas (ATGs) present a surgical challenge given their depth and proximity to eloquent brain regions. Choosing a surgical approach relies on different clinical variables such as anatomical location and size of the tumor. However, conclusive data regarding how these variables influence the balance between extent of resection and complications are lacking. We aim to systematically review the literature to describe the current surgical outcomes of ATG and to provide tools that may improve the decision-making process.Literature regarding the surgical management of ATG patients was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases were queried and a description of clinical characteristics and survival analysis were performed. An individual patient data analysis was conducted when feasible.A total of 462 patients were included from 13 studies. The mean age was 39.8 years with a median preoperative Karnofsky performance scale of 70. The lateral approaches were most frequently used (74.9%), followed by the interhemispheric (24.2%). Gross total and subtotal/partial resections were achieved in 81%, and 19% of all cases, respectively. New permanent neurological deficits were observed in 51/433 patients (11.8%). individual patient data was pooled from 5 studies (n = 71). In the multivariate analysis, tumors located within the posterior thalamus had worse median overall survival compared to anterior gliomas (14.5 vs. 27 months, P = 0.003).Surgical resection of ATGs can increase survival but at the risk of operative morbidity. Knowing which factors impact survival may allow neurosurgeons to propose a more evidence-based treatment to their patients.

Cardiac output (CO) and other hemodynamic parameter measurements play an important role in the management of cardiovascular conditions; however, due to limitations of current day technologies, such measurements are either not routinely performed or incorporated into clinical practice. Moreover, measurement of these hemodynamic parameters in the outpatient setting at different time points to assess interval change is currently not feasible. We attempted to validate total-body impedance cardiography-based Non-Invasive Cardiac System (NICaS) derived stroke volume (SV) with that from cardiac magnetic resonance (CMR), a current day gold standard method of assessment. We compared SV, as it is the primary unit of measurement utilized by both technologies. Forty-one consecutive patients undergoing CMR were also investigated by NICaS following CMR. The consistency of non-invasive technology-derived SV measurement was validated by NICaS measurement in 10 subjects, both before and after CMR. Of the 41 enrolled patients; data from 38 patients was adequate for comparison (motion artifact prevented CMR measures in 3 patients). Fourteen patients (37%) were female; mean age was 55 ± 15 years (28-87 years) and body-mass index was 28.7 ± 5.5 kg/m

Cavernous sinus cavernous malformations (CSCMs) is a vascular malformation of the cavernous sinus. Nowadays, there is an increasing preference to withhold using the terms cavernoma or cavernous hemangioma in order to stop considering these lesions as vascular neoplasms. These lesions are highly vascularized making surgical resection a challenge, mainly in endoscopic approaches. We present a case of this tumor treated in our institution with an endoscopic endonasal approach and incomplete resection. Because of the strenuous resection through this approach, we systematically reviewed the reported endoscopic cases of CSCMs to determine their intraoperative complications, results and tumor features.Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, one database (PubMed) and crossed references were queried for CSCMs from 1948 to 2020. Data regarding demographic features, clinical presentation, MRI features, surgical results and overall pathology features extracted.Eighteen patients were selected (including our case). The mean age was 50.4 ± 14 years. Pituitary dysfunction and cavernous sinus nerve compression were the most reported symptoms. Only five cases (27%) reported a gross total resection (GTR) through endoscopic endonasal approach. Intraoperative bleeding was the most frequent intraoperative complication.We present a comprehensive analysis of every reported CSCM treated through endoscopic approach. Partial or subtotal resection are the most used techniques because of the intraoperative bleeding and the adherence to surrounding structures. Radiotherapy is a very good option for patients with incomplete resections.

While laser ablation has become an increasingly important tool in the neurosurgical oncologist’s armamentarium, deep seated lesions, and those located near critical structures require utmost accuracy during stereotactic laser catheter placement. Robotic devices have evolved significantly over the past two decades becoming an accurate and safe tool for stereotactic neurosurgery. Here, we present our single center experience with the MedTech ROSA ONE Brain robot for robotic guidance in laser interstitial thermal therapy (LITT) and stereotactic biopsies. We retrospectively analyzed the first 70 consecutive patients treated with ROSA device at a single academic medical center. Forty-three patients received needle biopsy immediately followed by LITT with the catheter placed with robotic guidance and 27 received stereotactic needle biopsy alone. All the procedures were performed frameless with skull bone fiducials for registration. We report data regarding intraoperative details, mortality and morbidity, diagnostic yield and lesion characteristics on MRI. Also, we describe the surgical workflow for both procedures. The mean age was 60.3 ± 15 years. The diagnostic yield was positive in 98.5% (n = 69). Sixty-three biopsies (90%) were supratentorial and seven (10%) were infratentorial. Gliomas represented 54.3% of the patients (n = 38). There were two postoperative deaths (2.8%). No permanent morbidity related to surgery were observed. We did not find intraoperative technical problems with the device. There was no need to reposition the needle after the initial placement. Stereotactic robotic guided placement of laser ablation catheters and biopsy needles is safe, accurate, and can be implemented into a neurosurgical workflow.

Papaverine, a vasodilator approved for use by the U.S. Food and Drug Administration, has shown efficacy in treating vasospasm in cardiology, urology, and nephrology. The vasodilatory effect of papaverine is also hoped to protect the facial nerve from ischemic damage and nerve manipulation during vestibular schwannoma surgery. Our institution uses intracisternal papaverine irrigation during vestibular schwannoma resection to protect the facial nerve in patients with neuromonitoring changes. Our objective was to investigate the safety and facial nerve outcomes of intracisternal papaverine irrigation during vestibular schwannoma resection.We retrospectively reviewed patients who underwent resection of vestibular schwannoma at our institution between 2008 and 2021. Patients received papaverine if the intraoperative facial nerve stimulation threshold increased above 0.05 mA. Postoperative outcomes were compared with control patients who did not receive papaverine.A total of 283 cases were included in our analysis. Patients who received papaverine (n = 60) had lower immediate postoperative House-Brackmann (HB) grades than did control individuals (mean, 1.54 vs. 1.95; P = 0.029) and a lower likelihood of immediate postoperative HB grade1 (odds ratio, 0.514; P = 0.039). At long-term follow-up, there was no significant difference in HB grade. Papaverine use was not associated with increased rates of perioperative complications (P = 0.24).The off-label use of intracisternal papaverine irrigation during vestibular schwannoma resection can certainly be used safely for select cases. It is associated with improved immediate postoperative facial nerve outcomes, similar long-term facial nerve outcomes, and no significant increase in complications.

Background The prognosis of glioblastoma (GBM) remains dismal because therapeutic approaches have limited effectiveness. A new targeted treatment using MEK inhibitors, including trametinib, has been proposed to improve GBM therapy. Trametinib had a promising preclinical effect against several cancers, but its adaptive treatment resistance precluded its clinical translation in GBM. Previously, we have demonstrated that protein arginine methyltransferase 5 (PRMT5) is upregulated in GBM and its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. We tested whether inhibition of PRMT5 can enhance the efficacy of trametinib against GBM. Methods Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot were analyzed. In vivo, NSG mice were intracranially implanted with PRMT5-intact and -depleted GBMNS, treated with trametinib by daily oral gavage, and observed for tumor progression and mice survival rate. Results PRMT5 depletion enhanced trametinib-induced cytotoxicity in GBMNS. PRMT5 knockdown significantly decreased trametinib-induced AKT and ERBB3 escape pathways. However, ERBB3 inhibition alone failed to block trametinib-induced AKT activity suggesting that the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib-treated GBMNS resulted from AKT inhibition and not ERBB3 inhibition. In orthotopic murine xenograft models, PRMT5-depletion extended the survival of tumor-bearing mice, and combination with trametinib further increased survival. Conclusion Combined PRMT5/MEK inhibition synergistically inhibited GBM in animal models and is a promising strategy for GBM therapy.

Intraoperative pathologic diagnosis traditionally involves frozen section histopathology, which may be labor and time intensive. Indeed, a technique that streamlines the acquisition and evaluation of intraoperative histologic data may expedite surgical decision-making and shorten operative time. Stimulated Raman histology (SRH) is an emerging technology that allows for more rapid acquisition and interpretation of intraoperative histopathologic data.A blinded, prospective cohort study was performed for 82 patients undergoing resection for a central nervous system tumor. Of these, 21 patients were diagnosed with glioma either intraoperatively or postoperatively on permanent section histology and included in this study. Time to diagnosis (TTD) and diagnostic accuracy relative to permanent section (the gold standard) were compared between SRH-based diagnosis and conventional frozen section histology. Diagnostic concordance with permanent section was also compared between frozen histopathology and SRH diagnosis.Diagnostic accuracy was not significantly different between methods (P = 1.00). Diagnostic concordance was not significantly different between methods when comparing 95% confidence intervals for kappa values (κ = 0.215; κ = 0.297; κ = 0.369). Lastly, mean TTD was significantly shorter with SRH-based diagnosis compared with frozen section (43 vs. 9.7 minutes, P0.0001). SRH was able to identify key features associated with varying glioma types.SRH allows for rapid intraoperative diagnosis without sacrificing diagnostic accuracy. SRH may serve as a promising adjuvant to conventional histopathology to expedite intraoperative pathology consultation and surgical decision-making.

Introduction The use of tumor-selectively replicating viruses is a rapidly expanding field that is showing considerable promise for cancer treatment. Retroviral replicating vectors (RRV) are unique among the various replication-competent viruses currently being investigated for potential clinical utility, because they permanently integrate into the cancer cell genome, and are capable of long-term persistence within tumors. RRV can mediate efficient tumor-specific delivery of prodrug activator genes, and subsequent prodrug treatment leads to synchronized cell killing of infected cancer cells, as well as activation of anti-tumor immune responses. Areas covered Here we review preclinical studies supporting bench-to-bedside translation of Toca 511, an optimized RRV for prodrug activator gene therapy, the results from Phase I through III clinical trials to date, and potential future directions for this therapy as well as other clinical candidate RRVs. Expert opinion Toca 511 has shown highly promising results in early-stage clinical trials. This vector progressed to a registrational Phase III trial, but the results announced in late 2019 appeared negative overall. However, the median prodrug dosing schedule was not optimal, and promising possible efficacy was observed in some prespecified subgroups. Further clinical investigation, as well as development of RRV with other transgene payloads, is merited.

Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Given their relatively high recurrence rate after surgical resection and radiotherapy, there has been a recent push to explore other adjuvant treatment options for these treatment-refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets which are currently being studied. This article provides a thorough overview of novel investigational therapeutics including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas. We performed a comprehensive review of the available literature regarding preclinical and clinical evidence for emerging treatments for high grade meningiomas from 1980 to 2020 including contemporaneous clinical trials. There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this article. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for meningiomas. Several clinical studies have suggested a clinical benefit of combinatorial treatment for these treatment-refractory tumors. With numerous active clinical trials for high grade meningiomas, a meaningful improvement in the outcomes for these tumors may be on the horizon.

Background: Health care resource utilization for patients with adult congenital heart disease (ACHD) has not been well characterized outside of large Canadian specialized regional centres. We sought to describe the ACHD population and resource utilization patterns seen in a medium regional Canadian centre providing specialized ACHD care. Methods: A cross-sectional retrospective study was done from a sample of patients seen in 2018 at the ACHD clinic in Manitoba, Canada. Demographic data were collected along with cardiac anatomy and repair type. Health care resource utilization, clinic visits, hospital admissions, unexpected hospital presentations, and cardiac interventions were measured over a 5-year period. Results: A random sample of 262 patients was selected from our specialized ACHD clinic. Mean age was 33.5 (±13.7) years; 48% of the population was female, and >50% resided within the major city limits. A total of 21% of the population had simple anatomy, 44% had moderate anatomy, and 35% had complex anatomy. The most commonly used imaging modality was echocardiography, followed by cardiac magnetic resonance imaging, with more frequent imaging done in patients with complex anatomy. Unexpected hospital encounters occurred at a rate of 16 per 100 person-years. Total inpatient hospital days occurred at a rate of 33 per 100 person-years, and visits to the congenital clinic occurred at a rate of 90 per 100 person-years. Conclusions: Health care resource utilization appears to be highest in older adults and those with more complex ACHD anatomy. As the overall cohort of adults with ACHD continues to age, resource needs are likely to increase. Résumé: Contexte: L'utilisation des ressources de santé à l'extérieur des grands centres spécialisés régionaux au Canada n'a pas été bien caractérisée pour les patients atteints de cardiopathie congénitale de l'adulte (CCA). Nous avons cherché à décrire la population atteinte de CCA et les schémas d'utilisation des ressources observés dans un centre régional canadien de taille moyenne fournissant des soins spécialisés en CCA. Méthodologie: Une étude transversale rétrospective a été réalisée à partir d'un échantillon de patients rencontrés en 2018 dans une clinique spécialisée en CCA du Manitoba, au Canada. Des données démographiques ont été recueillies de même que des données sur l'anatomie cardiaque et le type de réparation. L'utilisation des ressources de soins de santé, les visites à la clinique, les admissions à l'hôpital, les consultions hospitalières imprévues et les interventions cardiaques ont été mesurées sur une période de cinq ans. Résultats: Un échantillon aléatoire de 262 patients a été sélectionné dans notre clinique spécialisée en CCA. L’âge moyen des patients était de 33,5 (±13,7) ans; 48 % de la population était de sexe féminin et plus de 50 % résidait dans les limites d'une grande ville. Au total, 21 % de la population présentait une anatomie cardiaque simple, 44 % une anatomie modérément complexe et 35 % une anatomie complexe. La technique d'imagerie la plus utilisée était l’échocardiographie, suivie de l'imagerie par résonance magnétique cardiaque, l'imagerie étant plus fréquente chez les patients présentant une anatomie cardiaque complexe. Le taux de consultations hospitalières imprévues était de 16 pour 100 années-patient. Le nombre total de jours d'hospitalisation était de 33 pour 100 années-patient, et le nombre de visites à la clinique spécialisée en CCA était de 90 pour 100 années-patient. Conclusions: L'utilisation des ressources de soins de santé semble être plus élevée chez les adultes plus âgés et chez ceux qui présentent une anatomie plus complexe liée à la CCA. Puisque l'ensemble de la cohorte d'adultes atteints de CCA continue de vieillir, les besoins en ressources sont susceptibles d'augmenter.

Originally approved in 1979, a specific grading classification for central nervous system (CNS) tumors was devised by the World Health Organization (WHO) in an effort to guide cancer treatment and better understand prognosis. These “blue books” have since undergone several iterations based on tumor location, advancements in histopathology, and most recently, diagnostic molecular pathology in its fifth edition. As new research methods have evolved to elucidate complex molecular mechanisms of tumorigenesis, a need to update and integrate these findings into the WHO grading scheme has become apparent. Epigenetic tools represent an area of burgeoning interest that encompasses all non-Mendelian inherited genetic features affecting gene expression, including but not limited to chromatin remodeling complexes, DNA methylation, and histone regulating enzymes. The SWItch/Sucrose non-fermenting (SWI/SNF) chromatin remodeling complex is the largest mammalian family of chromatin remodeling proteins and is estimated to be altered in 20–25% of all human malignancies; however, the ways in which it contributes to tumorigenesis are not fully understood. We recently discovered that CNS tumors with SWI/SNF mutations have revealed an oncogenic role for endogenous retroviruses (ERVs), remnants of exogenous retroviruses that integrated into the germline and are inherited like Mendelian genes, several of which retain open reading frames for proteins whose expression putatively contributes to tumor formation. Herein, we analyzed the latest WHO classification scheme for all CNS tumors with documented SWI/SNF mutations and/or aberrant ERV expression, and we summarize this information to highlight potential research opportunities that could be integrated into the grading scheme to better delineate diagnostic criteria and therapeutic targets.

Background During the coronavirus 19 (COVID-19) pandemic, physicians have begun adapting their daily practices to prevent transmissions. In this study we aimed to provide surgical neuro-oncologists with practice guidelines during the COVID-19 pandemic based on objective data from a high-volume brain tumor surgeon at the current COVID-19 epicenter. Methods All outpatient visits and surgeries performed by the senior author during the COVID-19 pandemic were compared between the initial quarantine (3/23/20–5/4/20), the plateau period following quarantine (5/5/20–6/27/20), and the second peak (6/28/20–7/20/20). In-person and telemedicine visits were evaluated for crossovers. Surgeries were subdivided based on lesion type and evaluated across the same time period. Results From 3/23/20–7/20/20, 469 clinic visits and 196 surgeries were identified. After quarantine was lifted, face-to-face visits increased (P

Human endogenous retrovirus-K (HERV-K) is the most recently integrated retrovirus in the human genome, with implications for multiple disorders, including cancer. Although typically transcriptionally silenced in normal adult cells, dysregulation of HERV-K (HML-2) elements has been observed in cancer, including breast, germ cell tumors, pancreatic, melanoma, and brain cancer. While multiple methods of carcinogenesis have been proposed, here we discuss the role of HERV-K (HML-2) in the promotion and maintenance of the stem-cell in cancer. Aberrant expression of HERV-K has been shown to promote expression of stem cell markers and promote dedifferentiation. In this review, we discuss HERV-K (HML-2) as a potential therapeutic target based on evidence that some tumors depend on the expression of its proteins for survival.

As lifespans for persons living with HIV (PLWH) have improved over the last decade, there has been a simultaneous increase in non-AIDS-related cancer in that group. However, there is a paucity of data regarding the incidence of glioblastoma multiforme (GBM) in PLWH. Better understanding of the oncogenesis, natural history, and treatment outcomes of GBM in PLWH should lead to improved treatment strategies.We performed a comprehensive literature search of six electronic databases to identify eligible cases of GBM among PLWH. Kaplan-Meier estimates, Fisher's exact test, and logistic regression were used to interrogate the data. Epidemiologic data on global HIV prevalence was obtained from the 2016 UNAIDS incidence report, and CNS cancer incidence was obtained from the GDB 2016 Brain and Other CNS Cancer Collaborators.There is an inverse relationship between the incidence of HIV and CNS cancer globally. Median overall survival (OS) from GBM diagnosis was 8 months. Estimates for survival at 1 and 2 years were 28 and 5%, respectively. There were no statistically significant predictors of OS in this setting. There was a significant difference (p 0.01) in OS in PLWH and GBM when compared to TCGA age matched cohorts.The diagnosis of GBM in PLWH is severely underreported in the literature. Despite maximal treatment, OS in this patient population is significantly less than in HIV-negative people. There was a poor prognosis of GBM in PLWH, which is inconsistent with previous reports. Further investigation is required for PLWH and concomitant GBM. Analyses must consider if HAART is maintained in PLWH during GBM treatment.

Background Lung carcinoma metastasizing to a skull base meningioma remains an extremely rare phenomenon, with only 3 studies reported. Furthermore, no documented cases have been reported in the petroclival region. Thus, we have presented the first 2 cases of tumor-to-tumor metastasis (TTM) in which a petroclival lesion, initially thought to be purely meningioma, was also found to contain metastatic lung adenocarcinoma. Case Description We present the cases of 2 patients with a known history of lung adenocarcinoma and stable petroclival meningioma who had presented with new-onset neurologic deficits. Repeat imaging studies for both patients found an increased lesion size and peritumoral enhancement; thus, both patients underwent emergent craniotomy for complete lesion resection. Intraoperatively, both lesions had zones of markedly different tumoral texture. On histologic analysis, both lesions showed metastatic lung adenocarcinoma contained within the primary petroclival meningioma. Conclusion Skull base TTM is a rare entity for which no specific management guidelines have been created. Therefore, even if the imaging characteristics suggest a more benign process, skull base TTM should remain high on the differential diagnosis for patients with a known primary cancer and new-onset, rapidly progressive, neurologic deficits. Close clinical follow-up with short-interval repeat imaging in this subset of patients might prevent misdiagnosis and facilitate prompt treatment.

Background To our knowledge, we report the first case of a cholangiocarcinoma brain metastasis successfully treated with magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy. Case Description In 2017, a 71-year-old man was diagnosed with unresectable intrahepatic cholangiocarcinoma. In August 2018, a brain MRI scan was performed after a transient episode of altered mental status and revealed a subcentimeter enhancing lesion in the deep white matter of the right cerebellum. Due to lack of symptoms and the small size of the lesion, it was initially observed. However, a follow-up MRI scan at 2.5 months demonstrated increased lesion size with worsening perilesional edema. Given the rarity of cholangiocarcinoma brain metastases and the deep location, the patient underwent stereotactic needle biopsy to confirm the diagnosis followed by laser ablation as a primary treatment for the metastasis. The patient tolerated the surgery well with no complications, and the postoperative course was uneventful. At 16 months postablation, there has been no recurrence or disease progression. Conclusions Although prognosis for these tumors is poor, our result suggests that laser ablation can be an effective treatment for this rare entity and is a representative example of the expanding indications for laser interstitial thermal therapy.

Atypical teratoid/rhabdoid tumor (ATRT) is a rare and largely pediatric diagnosis, with poor survival. Diagnosis below the age of 3 years is characteristically seen as a poor prognostic sign. However, elucidating if clinical differences exist within this niche age group has never been attempted before. Correspondingly, we sought to characterize clinical profile of ATRT diagnoses before the age of 3 years based on separate ages of diagnosis. All pediatric ATRT patients aged < 3 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Age groups were divided based on diagnoses at ages 0–1 years in group 1, 1–2 years in group 2, and 2–3 years in group 3. Data were summarized, and overall survival (OS) was modeled using Kaplan–Meier and Cox regression analyses. A total of 354 ATRT diagnoses were made before the age of 3 years, with surgery used in 316 (89%) cases, chemotherapy in 242 (68%) cases, and radiation therapy in 118 (33%) cases. In terms of diagnosis age, there were 153 (43%) in group 1, 137 (39%) in group 2, and 64 (18%) in group 3. With respect to OS, median value was 9.9 months in group 1, 28.4 months in group 2, and 15.9 months in group 3. Upon multivariate analysis, receiving radiation therapy was the only parameter shared amongst all three groups as independently prognostic of longer OS (HR 0.53, P = 0.01 in group 1; HR 0.34, P < 0.01 in group 2; HR 0.31, P < 0.01 in group 3). In group 1, surgery (HR 0.47, P < 0.01) and chemotherapy (HR 0.44, P < 0.01) were also independently prognostic of longer OS. In group 3, multiple socioeconomic parameters were identified to independently predict longer OS. There were no additional predictive parameters identified in group 2. Although ATRT diagnosed before the age of 3 is typically viewed a poor prognostic age category, our findings demonstrate that the clinical profile of this pediatric niche is highly heterogeneous based on age of diagnosis. Survival of only those diagnosed between 0 and 1 years is independently prognosticated by all three treatment modalities; patients diagnosed between 1 and 2 years trend towards longest survival, and socioeconomic parameters are most influential in those diagnosed between 2 and 3 years.

OBJECTIVEUncontrolled epilepsy is associated with serious deleterious effects on the neurological development of infants and has been described as “catastrophic epilepsy.” Recently, there has been increased emphasis on early surgical interventions to preserve or rescue neurodevelopmental outcomes in infants with early intractable epilepsy. The enthusiasm for early treatments is often tempered by concerns regarding the morbidity of neurosurgical procedures in very young patients. Here, the authors report outcomes following the surgical management of infants (younger than 1 year).METHODSThe authors performed a retrospective review of patients younger than 1 year of age who underwent surgery for epilepsy at Miami (Nicklaus) Children’s Hospital and Jackson Memorial Hospital between 1994 and 2018. Patient demographics, including the type of interventions, were recorded. Seizure outcomes (at last follow-up and at 1 year postoperatively) as well as complications are reported.RESULTSThirty-eight infants (median age 5.9 months) underwent a spectrum of surgical interventions, including hemispherectomy (n = 17), focal resection (n = 13), and multilobe resections (n = 8), with a mean follow-up duration of 9.1 years. Hemimegalencephaly and cortical dysplasia were the most commonly encountered pathologies. Surgery for catastrophic epilepsy resulted in complete resolution of seizures in 68% (n = 26) of patients, and 76% (n = 29) had a greater than 90% reduction in seizure frequency. Overall mortality and morbidity were 0% and 10%, respectively. The latter included infections (n = 2), infarct (n = 1), and immediate reoperation for seizures (n = 1).CONCLUSIONSSurgical intervention for catastrophic epilepsy in infants remains safe, efficacious, and durable. The authors’ work provides the longest follow-up of such a series on infants to date and compares favorably with previously published series.

ObjectivesAlthough a life-preserving surgery for children with single ventricle physiology, the Fontan palliation is associated with striking morbidity and mortality with advancing age. Our primary objective was to evaluate the impact of non-invasive, external, thoraco-abdominal ventilation on pulmonary blood flow (PBF) and cardiac output (CO) as measured by cardiovascular magnetic resonance (CMR) imaging in adult Fontan subjects.MethodsAdults with a dominant left ventricle post-Fontan palliation (lateral tunnel or extracardiac connections) and healthy controls matched by sex and age were studied. We evaluated vascular flows using phase-contrast CMR imaging during unassisted breathing, negative pressure ventilation (NPV) and biphasic ventilation (BPV). Measurements were made within target vessels (aorta, pulmonary arteries, vena cavae and Fontan circuit) at baseline and during each ventilation mode.ResultsTen Fontan subjects (50% male, 24.5 years (IQR 20.8–34.0)) and 10 matched controls were studied. Changes in PBF and CO, respectively, were greater following BPV as compared with NPV. In subjects during NPV, PBF increased by 8% (Δ0.20 L/min/m2 (0.10–0.53), p=0.011) while CO did not change significantly (Δ0.17 L/min/m2 (−0.11–0.23), p=0.432); during BPV, PBF increased by 25% (Δ0.61 L/min/m2 (0.20–0.84), p=0.002) and CO increased by 16% (Δ0.47 L/min/m2 (0.21–0.71), p=0.010). Following BPV, change in PBF and CO were both significantly higher in subjects versus controls (0.61 L/min/m2 (0.2–0.84) vs −0.27 L/min/m2 (−0.55–0.13), p=0.001; and 0.47 L/min/m2 (0.21–0.71) vs 0.07 L/min/m2 (−0.47–0.33), p=0.034, respectively).ConclusionExternal ventilation acutely augments PBF and CO in adult Fontan subjects. Confirmation of these findings in larger populations with longer duration of ventilation and extended follow-up will be required to determine sustainability of haemodynamic effects.

Lesions located in subcortical areas are difficult to safely access. Tubular retractors have been increasingly used successfully with low complication profile to access lesions by minimizing brain retraction trauma and distributing pressure radially. Both binocular operative microscope and monocular exoscope are utilized for lesion visualization through tubular retractors. We present the largest multi-surgeon, multi-institutional series to determine the efficacy and safety profile of a transcortical-transtubular approach for intracranial lesion resections with both microscopic and exoscopic visualization. We reviewed a multi-surgeon, multi-institutional case series including transcortical-transtubular resection of intracranial lesions using either BrainPath (NICO, Indianapolis, Indiana) or ViewSite Brain Access System (VBAS, Vycor Medical, Boca Raton, Florida) tubular retractors (n = 113). One hundred thirteen transtubular resections for intracranial lesions were performed. Patients presented with a diverse number of pathologies including 25 cavernous hemangiomas (21.2%), 15 colloid cysts (13.3%), 26 GBM (23.0%), two meningiomas (1.8%), 27 metastases (23.9%), 9 gliomas (7.9%) and 9 other lesions (7.9%). Mean lesion depth below the cortical surface was 4.4 cm, and mean lesion size was 2.7 cm. A gross total resection was achieved in 81 (71.7%) cases. Permanent complication rate was 4.4%. One patient (0.8%) experienced one early postoperative seizure ( 1 week follow-up). Mean post-operative hospitalization length was 4.1 days. Tubular retractors provide a minimally invasive operative corridor for resection of intracranial lesions. They provide an effective tool in the neurosurgical armamentarium to resect subcortical lesions with a low complication profile.

The most recent cIMPACT-NOW update highlighted the homozygous deletion of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene as a clinically important molecular alteration in IDH-mutant glioma. Correspondingly, we systematically reviewed the contemporary literature to affirm the contemporary stance of the literature on the prognostic significance of this alteration in this setting based on the current World Health Organization (WHO) Grade classification. A systematic search of seven electronic databases from inception to February 2020 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria to include lower-grade glioma (LGG, WHO Grade II/III) and glioblastoma (GBM, WHO Grade IV) separately. Progression free survival (PFS) and overall survival (OS) from Kaplan–Meier and multivariable analyses were outcomes of interest. Nine institutional studies describing 2193 IDH-mutant gliomas satisfied criteria for evaluation, with 1756 (80%) LGG and 437 (20%) GBM. When reported, the proportion of CDKN2A homozygous deleted gliomas ranged from 9 to 43%, with a median incidence of 22%. For LGG, Kaplan–Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in three studies (median values, 31 versus 91 months), and shorter OS in five studies (median values, 61 versus 154 months). For GBM, Kaplan–Meier analyses demonstrated shorter PFS in the presence of CDKN2A homozygous deletion in two studies (median values, 16 versus 30 months), and shorter OS in four studies (median values, 38 versus 86 months). By multivariable analyses, CDKN2A homozygous deletion was a predictor of significantly shorter PFS and OS in both LGG and GBM across all included studies. The CDKN2A homozygous deletion is an important prognostic factor for survival outcomes of IDH-mutant glioma patients across multiple histologic WHO grades with specific molecular features likely dependent on IDH-mutant status. Greater understanding of how identifying this deletion can assist in the stratification of management for these tumors to optimize clinical course is required.

Background Central neurocytomas (CNCs) are rare intraventricular lesions comprising Objective Our goal was to update Rades et al.‘s 2006 systematic review to assess the outcome differences among 3 fundamental therapies for CNC: gross total resection with and without radiation therapy (RT) versus maximal safe resection with adjuvant RT. Methods Articles indexed on PubMed and Google Scholar and published between January 1, 2006 and December 31, 2019 were selected using the PRISMA criteria. Studies were excluded if they had fewer than 3 cases, did not categorize extent of resection, or were duplicate studies, technical reports, case reports, or studies without follow-up. Complication rates, recurrence rates, overall survival and progression-free survival were extracted where possible. χ2 proportionality tests were used for comparison (P values >0.05 suggested significance). Results On aggregation, 615 patients from 13 studies including ours were assessed. Although overall survival was not significantly different (χ2 = 1.56; P = 0.46), the recurrence rate differed significantly between GTR + RT (6.9%, 92.11 months), GTR–RT (23.9%, 96.8 months), and MSR + RT (16.8%, 85 months) (χ2 = 10.94; P = 0.004). Pooled complication rates for GTR and MSR + RT were 31.2% and 24% (P = 0.049), respectively. Conclusions RT remains an important adjuvant treatment that can improve patient survival in the presence of MSR to levels comparable to those of GTR or GTR + RT. Where total resection carries too much risk, MSR + RT can be considered as the next best alternative for tumor control.

OBJECTIVEUntreated hydrocephalus poses a significant health risk to children in the developing world. In response to this risk, global neurosurgical efforts have increasingly focused on endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) in the management of infantile hydrocephalus in low- and middle-income countries (LMICs). Here, the authors report their experience with ETV/CPC at the Hospital Bernard-Mevs/Project Medishare (HBMPM) in Port-au-Prince, Haiti.METHODSThe authors conducted a retrospective review of a series of consecutive children who had undergone ETV/CPC for hydrocephalus over a 1-year period at HBMPM. The primary outcome of interest was time to ETV/CPC failure. Univariate and multivariate analyses using a Cox proportional hazards regression were performed to identify preoperative factors that were associated with outcomes.RESULTSOf the 82 children who underwent ETV/CPC, 52.2% remained shunt free at the last follow-up (mean 6.4 months). On univariate analysis, the ETV success score (ETVSS; p = 0.002), success of the attempted ETV (p = 0.018), and bilateral CPC (p = 0.045) were associated with shunt freedom. In the multivariate models, a lower ETVSS was independently associated with a poor outcome (HR 0.072, 95% CI 0.016–0.32, p < 0.001). Two children (2.4%) died of postoperative seizures.CONCLUSIONSAs in other LMICs, ETV/CPC is an effective treatment for hydrocephalus in children in Haiti, with a low but significant risk profile. Larger multinational prospective databases may further elucidate the ideal candidate for ETV/CPC in resource-poor settings.

Access to treatment for glioblastoma (GBM) can be impacted by multiple demographic parameters. Barriers specific to the Hispanic population of the United States (US) are not fully understood. Therefore, the aim of this study was to elucidate geographic disparities for access to GBM treatment in the US Hispanic population. All GBM patients with known Hispanic ethnicity status (and Caucasian race) in the US National Cancer Database (NCDB) between the years 2005–2016 were retrospectively reviewed. Treatment statuses of surgical resection, chemotherapy, radiation therapy and triple therapy (resection, chemotherapy and radiation) were summarized, and analyzed by comparison and regression analyses over US Census regions. A total cohort size of 40,232 Caucasian GBM patients were included, with 3,111 (8%) identifying as Hispanic. The odds of treatment by chemotherapy (OR 0.78, P