Current Trends in Neurosurgical Management of Adult Diffuse Low-Grade Gliomas in Canada.

There is considerable variability in the management of diffuse low-grade gliomas (LGGs). To characterize treatment paradigms, a survey of Canadian neurosurgeons was performed with forty neurosurgeons responding. Their responses show that the management of patients with LGGs has evolved in the past decade and findings from the RTOG9802 trial have been integrated into the practice of Canadian neurosurgeons. Most respondents stated that the patient selection and treatment strategy advocated by the RTOG9802 trial needs further evaluation. Overall, there is a trend toward more aggressive surgical resections, and future investigations will have to more accurately stratify patient risk profiles.

A 3D bioprinted hydrogel mesh loaded with all-trans retinoic acid for treatment of glioblastoma.

Treatment of glioblastoma (GBM), as the most lethal type of brain tumor, still remains a major challenge despite the various therapeutic approaches developed over the recent decades. GBM is considered as one of the most therapy-resistant human tumors. Treatment with temozolomide (TMZ) chemotherapy and radiotherapy in GBM patients has led to 30% of two-year survival rate (American Brain Tumor Association), representing a demanding field to develop more effective therapeutic strategies. This study presents a novel method for local delivery of all-trans retinoic acid (ATRA) for targeting GBM cells as a possible adjuvant therapeutic strategy for this disease. We have used 3D bioprinting to fabricate hydrogel meshes laden with ATRA-loaded polymeric particles. The ATRA-loaded meshes have been shown to facilitate a sustained release of ATRA with tunable release rate. Cell viability assay was used to demonstrate the ability of fabricated meshes in reducing cell growth in U-87 MG cell line. We later showed that the developed meshes induced apoptotic cell death in U-87 MG. Furthermore, the use of hydrogel for embedding the ATRA-loaded particles can facilitate the immobilization of the drug next to the tumor site. Our current innovative approach has shown the potential to open up new avenues for treatment of GBM, benefiting patients who suffer from this debilitating disease.

Recent Trends in Neurosurgery Career Outcomes in Canada.

BACKGROUND: As with other specialties, Royal College of Physicians and Surgeons of Canada (RCPSC) trainees in Neurosurgery have anecdotally had challenges securing full-time employment. This study presents the employment status, research pursuits, and fellowship choices of neurosurgery trainees in Canadian programs. METHODS: RCPSC neurosurgery trainees (n = 143) who began their residency training between 1998 and 2008 were included in this study. Associations between year of residency completion, research pursuits, and fellowship choice with career outcomes were determined by Fisher's exact test (p < 0.05, statistical significance). RESULTS: In 2015, 60% and 26% of neurosurgery trainees had permanent positions in Canada and the USA, respectively. Underemployment, defined as locum and clinical associate positions, pursuit of multiple unrelated fellowships, unemployment, and career change to non-surgical career, was 12% in 2015. The proportion of neurosurgery trainees who had been underemployed at some point within 5 years since residency completion was 20%. Pursuit of in-folded research (MSc, PhD, or non-degree research greater than 1 year) was significantly associated with obtaining full employment (94% vs. 73%, p = 0.011). However, fellowship training was not significantly associated with obtaining full employment (78% vs. 75%, p = 1.000). CONCLUSIONS: Underemployment in neurosurgery has become a significant issue in Canada for various reasons. Pursuit of in-folded research, but not fellowship training, was associated with obtaining full employment.

Tendances récentes au Canada en ce qui regarde les possibilités d'emploi en neurochirurgie.Contexte: À l'instar d'autres stagiaires de la médecine spécialisée, des stagiaires en neurochirurgie membres du Collège royal des médecins et des chirurgiens du Canada (CRMCC) ont dit éprouver, selon des données empiriques, des difficultés à obtenir un emploi à plein temps. Cette étude entend présenter la situation professionnelle des stagiaires inscrits dans des programmes canadiens en neurochirurgie ainsi que leurs activités de recherche et leurs choix en matière de bourses de recherche postdoctorale. Méthodes : Des stagiaires membres du CRMCC ayant entrepris leur résidence entre 1998 et 2008 (n = 143) ont été inclus dans cette étude. Les liens pouvant exister entre l'année de résidence complétée, les activités de recherche, les choix en matière de bourses de recherche postdoctorale et les possibilités d'emploi ont été déterminés au moyen du test exact de Fisher (p < 0,05 ; signification statistique). Résultats : En 2015, 60 % des stagiaires en neurochirurgie du Canada disaient compter sur un poste permanent alors qu'ils étaient 26 % à affirmer la même chose aux États-Unis. Le sous-emploi, défini comme par des postes de suppléant (locum) et de clinicien adjoint, par l'obtention de plusieurs bourses de recherche postdoctorale sans liens apparents, par le chômage et par un changement d'orientation excluant la chirurgie, atteignait 12 % la même année. La proportion de stagiaires disant avoir été sous-employés à un moment ou un autre au cours des 5 années de leur résidence était par ailleurs de 20 %. Le fait de mener un projet de recherche dans le cadre de sa résidence (M.Sc., Ph.D. ou en dehors des cycles supérieurs pendant au moins 12 mois) était clairement associé à l'obtention d'un emploi à temps plein (94 % contre 73 % ; p = 0,011). Cela dit, une formation offerte à la suite de l'obtention d'une bourse de recherche postdoctorale n'a pas été associée de manière notable à l'obtention d'un emploi à temps plein (78 % contre 75 % ; p = 1,000). Conclusions : Le sous-emploi en neurochirurgie est désormais un enjeu important au Canada, et ce, pour toutes sortes de raisons. Contrairement aux formations liées à l'obtention d'une bourse de recherche postdoctorale, le fait de mener un projet de recherche régulier a été associé à l'obtention d'un emploi à temps plein.

Impact of work hours and sleep on well-being and burnout for physicians-in-training: the Resident Activity Tracker Evaluation Study.

OBJECTIVE: The Resident Activity Tracker Evaluation (RATE) is a prospective observational study evaluating the impact of work hours, sleep and physical activity on resident well-being, burnout and job satisfaction. BACKGROUND: Physician burnout is common and its incidence is increasing. The impact of work hours and sleep on resident well-being and burnout remains elusive. Activity trackers are an innovative tool for measuring sleep and physical activity. METHODS: Residents were recruited from (i) general surgery and orthopaedics (SURG), (ii) internal medicine and neurology (MED) and (iii) anaesthesia and radiology (RCD). Groups 1 and 2 do not enforce restrictions on the duration of being on-call, and group 3 had restricted the duration of being on-call to 12 hours. Participants wore FitBit trackers for 14 days. Total hours worked, daily sleep, sleep on-call and daily steps were recorded. Participants completed validated surveys assessing self-reported well-being (Short-Form Health Survey), burnout (Maslach Burnout Inventory), and satisfaction with medicine. RESULTS: Surgical residents worked the most hours per week, followed by medical and RCD residents (SURG, 84.3 hours, 95% CI, 80.2-88.5; MED, 69.2 hours, 95% CI, 65.3-73.2; RCD, 52.2 hours, 95% CI, 48.2-56.1; p < 0.001). Surgical residents obtained fewer hours of sleep per day (SURG, 5.9 hours, 95% CI, 5.5-6.3; MED, 6.9 hours, 95% CI, 6.5-7.3; RCD, 6.8 hours, 95% CI, 5.6-7.2; p < 0.001). Nearly two-thirds of participants (61%) scored high burnout on the Maslach depersonalisation subscore. Total steps per day and well-being, burnout and job satisfaction were comparable between groups. Total hours worked, daily sleep and steps per day did not predict burnout or well-being. CONCLUSIONS: Work hours and average daily sleep did not affect burnout. Physical activity did not prevent burnout. Work hour restrictions may lead to increased sleep but may not affect resident burnout or well-being.

Persistent Disparities in Survival for Patients with Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain cancer in adults. Recent efforts have elucidated genetic features of tumor cells and thus enhanced our knowledge of GBM pathophysiology. The most recent clinical trials report median overall survival between 14 and 20 months. However, population level outcomes are quite variable and there is a paucity of such data within the literature. METHODS: Three hundred seventy-two patients with GBM were diagnosed in the Canadian province of British Columbia between January 2013 and January 2015 and 278 patients had surgery. Of these, 268 had surgery in British Columbia and we have performed a retrospective review of their survival outcomes. RESULTS: Our results indicate a median age of 61.8 years at time of diagnosis, with a slight preponderance of male patients. The median overall survival was 10 months for patients in our cohort. As expected, patients older than the age of 65 and those with worse initial Karnofsky Performance Status scores had a poorer prognosis. Moreover, we have found extent of resection, treatment strategies, and treatment location affect overall survival. CONCLUSIONS: The present study highlights factors that affect patient survival after surgery in British Columbia. Our data are gathered within a single-payer, high-resource setting which removes possible confounders in outcome analysis. We find persistent differences in overall survival when compared with clinical trials and the Surveillance, Epidemiology, and End Results database. Further efforts should ensure access to the gold standard of care. All neuro-oncology centers should analyze the real-world outcomes of their local glioblastoma treatment strategies. Knowledge of the variance from expected and comparative results are fundamental for appropriate patient care.

Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response.

Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB.

Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor.

Glioneuronal tumors constitute a histologically diverse group of primary central nervous system neoplasms that are typically slow-growing and managed conservatively. Genetic alterations associated with glioneuronal tumors include BRAF mutations and oncogenic fusions. To further characterize this group of tumors, we collected a cohort of 26 glioneuronal tumors and performed in-depth genomic analysis. We identified mutations in BRAF (34%) and oncogenic fusions (30%), consistent with previously published reports. In addition, we discovered novel oncogenic fusions involving members of the NTRK gene family in a subset of our cohort. One-patient with BCAN exon 13 fused to NTRK1 exon 11 initially underwent a subtotal resection for a 4th ventricular glioneuronal tumor but ultimately required additional therapy due to progressive, symptomatic disease. Given the patient's targetable fusion, the patient was enrolled on a clinical trial with entrectinib, a pan-Trk, ROS1, and ALK (anaplastic lymphoma kinase) inhibitor. The patient was treated for 11 months and during this time volumetric analysis of the lesion demonstrated a maximum reduction of 60% in the contrast-enhancing tumor compared to his pre-treatment magnetic resonance imaging study. The radiologic response was associated with resolution of his clinical symptoms and was maintained for 11 months on treatment. This report of a BCAN-NTRK1 fusion in glioneuronal tumors highlights its clinical importance as a novel, targetable alteration.

The impact of subspecialization on postgraduate medical education in neurosurgery.

Medical subspecialization is a response to rapidly expanding technology and knowledge. Although beneficial to patient care, it poses a challenge to the current infrastructure of resident education. This article analyzes the advent of subspecialization, the current template of postgraduate neurosurgical education, the impact of subspecialization on postgraduate neurosurgical education, and, finally, suggests strategies to optimize professional education in the face of an increasingly subspecialized field.

Spinal subspecialization in post-graduate neurosurgical education.

BACKGROUND: The growing science and technology of various neurosurgical areas fosters subspecialization. The transmission of this expanding knowledge base to the neurosurgical resident becomes an increasing challenge. A survey of neurosurgical residency program directors was undertaken to evaluate their response to the budding subspecialization of spine surgery within general neurosurgery. METHODS: A survey requesting background data, educational infrastructure and prevailing opinion was distributed to all 13 neurosurgical program directors in Canada. The responses were tabulated and results recorded. It is upon these results that conclusions and proposed directions are based. RESULTS/CONCLUSIONS: The current practice of the overwhelming majority of Canadian academic neurosurgical centers is to have neurosurgical spinal subspecialists working under the umbrella of the general neurosurgical division. A large percentage of neurosurgical program directors in Canada believe that the management of spinal disease, including both intradural procedures and instrumentation, is and should remain an integral part of general neurosurgical training. A consensus statement regarding the requirements of neurosurgical training in spinal disorders is the expressed desire of almost all program directors. A proposed direction and resolution is discussed.

Jugular bulb oximetry for prediction of vasospasm following subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm adversely impacts the outcome of those suffering aneurysmal subarachnoid hemorrhage (SAH). Prediction of vasospasm could improve outcomes. We hypothesized that preclinical vasospasm would be heralded by an increase in cerebral oxygen extractions (AVDO2) which could be detected by jugular bulb oximetry. A pilot study was conducted to address this hypothesis. METHODS: Fourteen consenting patients with aneurysmal SAH, undergoing early surgery, were entered into the study. Four patients were withdrawn from the study secondary to failure of catheters or religious belief. At the time of craniotomy, a jugular bulb catheter was placed. Post-operatively, arterial and jugular bulb blood samples were taken every 12 hours to calculate AVDO2. As this was an observational study, no change in management occurred based on measurements. RESULTS: Four of 10 patients had clinical vasospasm. These patients had a significant rise in AVDO2 approximately one day prior to the onset of neurologic deficits (P<0.001). Symptoms resolved along with a significant improvement in AVDO2 on instituting hypertensive, hemo-dilutional, and hypervolemic therapy in these patients. The six patients who did not exhibit clinical vasospasm did not demonstrate significant rise in AVDO2. CONCLUSIONS: Jugular bulb oximetry is simple and cost effective. Increases in AVDO2 using this technique were predictive of clinically evident vasospasm in the subsequent hours to days. This investigation supports a larger study to assess the utility of jugular bulb oximetry in predicting vasospasm in aneurysmal SAH.