Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly.

OBJECTIVE: Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. METHODS: The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. RESULTS: The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. CONCLUSIONS: Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.

Sporadic and Von-Hippel Lindau disease-associated spinal hemangioblastomas: institutional experience on their similarities and differences.

INTRODUCTION: Hemangioblastomas are uncommon tumors of the central nervous system that can be seen in Von Hippel-Lindau (VHL) disease. Despite their benign histology, hemangioblastomas can cause substantial morbidity due to involvement of critical structures. In order to better understand the clinical behavior of spinal cord hemangioblastomas, we have analyzed the clinical, pathologic, radiologic characteristics and management of sporadic and VHL-associated cases at our institution. METHODS: We performed a database search to identify all spinal hemangioblastomas at our institution between 1997 and 2016. Tumor characteristics were analyzed for sporadic and VHL-associated tumors separately in order to understand the differences in groups. RESULTS: We included 20 patients with VHL-associated spinal hemangioblastomas, and 22 patients with sporadic spinal hemangioblastomas. VHL-associated patients were significantly younger at time of presentation compared to sporadic patients (p < 0.0025). Thirty-two patients (76.2%) presented with focal weakness, 34 (81.0%) with sensory loss, and 22 (52.4%) with pain. VHL patients were more likely to present with multiple symptoms (p < 0.001). Median follow-up time was 20.9 months, during which 17 tumors recurred. The median recurrence free interval was 44 months. There were no differences in gross total resection rates between sporadic and VHL-associated cases (p = 0.197). VHL-associated cases had a higher rate of repeat surgery for recurrence (14 patients-73.6%) compared to sporadic cases (3 patients-13.6%; p < 0.001). CONCLUSION: VHL-associated spinal hemangioblastomas differ from sporadic tumors in terms of age, presenting symptoms, multifocality, and rate of recurrence. Recurrences seem to be unrelated to the extent of resection, indicating the need for life-long follow up for VHL patients.

Approach to the postoperative patient with Cushing's disease.

INTRODUCTION: Cushing's disease is a neuroendocrine disorder marked by hypercortisolemia secondary to overproduction of ACTH by a corticotropic pituitary adenoma. Due to the diverse and deleterious effects of hypercortisolemia including diabetes mellitus, hypertension, and cardiovascular disease, prompt and accurate diagnosis followed by surgical resection of the responsible corticotropic adenoma is critical. METHODS: In the following review, we present a focused synopsis of recently published data and management strategies for the post-operative Cushing's disease patient with a particular focus on studies examining perioperative complications, establishment of biochemical remission, factors associated with disease remission, and predictors of recurrence. CONCLUSIONS: Although no standard definition of remission exists, we suggest measurement of serum cortisol level on the morning of postoperative day 1 given the preponderance of evidence in the published literature suggesting its association with long-term remission and relatively low rates of recurrence. Nevertheless, all patients should be counseled that recurrence can occur in a delayed fashion and that annual endocrine testing should be utilized to track and confirm disease status.

Update on the management of recurrent Cushing's disease.

After transsphenoidal surgery, Cushing's disease (CD) shows excellent long-term remission rates, but it may recur and pose a therapeutic challenge. Findings in recent published reports on the treatment of recurrent adrenocorticotropic hormone (ACTH)-secreting tumors suggest that repeat resection, radiation-based therapies such as Gamma Knife surgery and proton-beam radiosurgery, pharmacotherapy, and bilateral adrenalectomy all have important roles in the treatment of recurrent CD. Each of these interventions has inherent risks and benefits that should be presented to the patient during counseling on retreatment options. Radiation-based therapies increasingly appear to have efficacies similar to those of repeat resection in achieving biochemical remission and tumor control. In addition, an expanding retinue of medication-based therapies, several of which are currently being evaluated in clinical trials, has shown some promise as tertiary adjunctive therapies. Lastly, bilateral adrenalectomy may offer durable control of refractory recurrent CD. An increasing number of published studies with long-term patient outcomes highlight the evolving treatment patterns in the management of recurrent CD.

Altering biomolecular condensates as a potential mechanism that mediates cannabidiol effect on glioblastoma.

Glioblastoma (GBM) is an extremely aggressive primary brain tumor with poor prognosis, short survival time post-diagnosis and high recurrence. Currently, no cure for GBM exists. The identification of an effective therapeutic modality for GBM remains a high priority amongst medical professionals and researches. In recent studies, inhalant cannabidiol (CBD) has demonstrated promise in effectively inhibiting GBM tumor growth. However, exactly how CBD treatment affects the physiology of these tumor cells remains unclear. Stress granules (SG) (a sub-class of biomolecular condensates (BMC)) are dynamic, membrane-less intracellular microstructures which contain proteins and nucleic acids. The formation and signaling of SGs and BMCs plays a significant role in regulating malignancies. This study investigates whether inhaled CBD may play an intervening role towards SGs in GBM tumor cells. Integrated bioinformatics approaches were preformed to gain further insights. This includes use of Immunohistochemistry and flow cytometry to measure SGs, as well as expression and phosphorylation of eukaryotic initiation factor-2α (eIF2α). The findings of this study reveal that CBD receptors (and co-regulated genes) have the potential to play an important biological role in the formation of BMCs within GBM. In this experiment, CBD treatment significantly increased the volume of TIAR-1. This increase directly correlated with elevation in both eIF2α expression and p-eIF2α in CBD treated tissues in comparison to the placebo group (p < 0.05). These results suggest that inhalant CBD significantly up-regulated SGs in GBM, and thus support a theory of targeting BMCs as a potential therapeutic substrate for treating GBM.

Effects of temporal lobectomy on consciousness-impairing and consciousness-sparing seizures in children.

PURPOSE: Most children with medically refractory temporal lobe epilepsy (TLE) become seizure free after temporal lobectomy, but some individuals continue to seize. As studies of temporal lobectomy typically focus on seizure freedom, the effect of surgery on seizure type and frequency among children with persistent seizures is poorly understood. Seizures which impair consciousness are associated with increased morbidity compared to consciousness-sparing seizures. METHODS: A retrospective cohort study was performed to evaluate the effects of temporal lobectomy on seizure type and frequency in children with intractable TLE. RESULTS: Among 58 pediatric TLE patients with a mean (±SEM) age of 14.0 ± 0.7 years who received temporal lobectomy, 46 (79.3%) individuals achieved an Engel class I seizure outcome, including 38 (65.5%) children who became completely seizure free (Engel IA). Mean follow-up was 2.7 ± 0.4 years. While the number of patients experiencing simple partial seizures (SPSs) (consciousness sparing) decreased by only 23 % after surgery, the number of children having complex partial seizures and generalized tonic-clonic seizures (consciousness impairing) diminished by 87 and 83%, respectively (p < 0.01). SPS was the predominant seizure type in only 11.3% of patients before resection, but in 42.1% of patients with postoperative seizures (p < 0.01). Children with postoperative seizures experienced a 70% reduction in overall seizure frequency compared to baseline (p < 0.05), having consciousness-impairing seizures 94% less frequently (p < 0.05), but having consciousness-sparing seizures 35% more frequently (p = 0.73). CONCLUSIONS: Seizure type and frequency are important considerations in the medical and surgical treatment of children with epilepsy, although complete seizure freedom remains the ultimate goal.

Diploic Bone Channel Drilling Facilitates Dissection of the Midline Dura and Protects the Superior Sagittal Sinus in Hyperostosis Frontalis Interna.

Patients with space-occupying lesions adjacent to the superior sagittal sinus (SSS) present several technical considerations. For craniotomies crossing the SSS, a two-part method allows for dissection of the epidural space and dura under direct vision after removing a more lateral parasagittal bone flap. However, when the inner table surface of the medial component of the two-part bone flap is irregular, this can be difficult. We describe a method for channel drilling of the diploic bone, which allows for the piecemeal removal of the inner table using an upbiting rongeur. This article presents the case of meningioma with documented growth and provides a technical note of this technique to facilitate safe dissection of the midline dura. A patient presented with headaches and an anterior one-third parasagittal meningioma with documented growth. She selected surgical removal for treatment. A right frontal two-part parasagittal craniotomy was recommended. The preoperative imaging showed that the frontal bone was thick, with irregularity of the inner table. Intraoperatively, a channel was drilled in the diploic space of the bone, leaving the outer table intact. This provided a thin lip of the inner table that could be dissected over a short distance and then removed with a 2-mm upbiting rongeur. This allowed for further dissection of the dura crossing the midline under direct vision and safe secondary bone piece removal. The dura was opened to the edge of the SSS, allowing full exposure of the parasagittal region and interhemispheric fissure, thus limiting retraction of the medial right frontal lobe. The bone flap was removed in two pieces without a dural tear over the midline in spite of inner table irregularities. A Simpson grade 1 removal was accomplished, including excision of the affected falx, and the postoperative course was uncomplicated. In conclusion, diploic bone channel drilling is a technique that can be used to create a thin lip of the inner table, which can be removed piecemeal for safe dissection of the midline dura crossing the midline.

Endoscopic-Assisted Microsurgical Resection of a Recurrent Conus Medullaris Dermoid Tumor.

Surgery for intramedullary spinal cord tumors presents multiple unique challenges, including the need to operate through a very narrow myelotomy window. In this operative video, we demonstrate the use of the surgical endoscope in an operation performed on a 35-year-old woman. She has a history of conus medullaris dermoid tumor resection, and she presented to us with worsening lower extremity sensory and motor symptoms. Magnetic resonance imaging showed a 4-cm recurrence of her tumor. After consenting to surgery, she underwent reoperative posterior lumbar approach to resection of her tumor. In our video we demonstrate our use of a surgical endoscope, which allowed us to minimize the extent of our myelotomy and resect tumor rostral and caudal to our myelotomy, thus minimizing the risk of damage to normal spinal cord that is displaced by tumor (Video 1).

The Emotional Impact of Educational Productivity Videos on YouTube: A Global, Cross-Sectional Survey.

Introduction YouTube is the most popular video-sharing website, and many students use it as a resource to find educational content. One type of video category is "productivity," in which the creator teaches viewers how to lead a more productive lifestyle by sharing ways to maximize studying, reshape daily habits, or set achievable goals. Little research has been conducted on whether these videos actually promote positive or negative feelings among viewers. Methods A survey was created through Qualtrics and shared through YouTube and Instagram. The survey asked about exposure to productivity videos and also asked individuals to share their experiences with consuming productivity-related educational content on YouTube. Survey items asked students to rate the helpfulness of these videos and share their feelings about the content. Respondents were asked to share whether YouTube videos on productivity made them feel anxious, motivated, inspired, neutral/indifferent, or inadequate. Participants were also asked to rate how helpful they found productivity videos on YouTube (1-10, with 10 being most helpful). The survey included free response sections to assess viewers' perceptions and attitudes toward productivity videos. Results The cross-sectional survey amassed 595 responses across 60 countries, with 364 responses coming from individuals within the United States. Of the respondents, 397 of the respondents were female, 177 were male, and 21 preferred not to say or identified as non-binary. The average age of participants was 22 years; 79 were in high school, 174 were in college, 223 were in medical school, and the remainder identified as "other" (graduate school, gap year, etc.). Of the 595 completed responses, 494 reported watching videos on YouTube related to improving productivity; when asked how these videos made them feel, 127 participants answered "anxious," 357 answered "motivated," 308 answered "inspired," 95 answered "neutral/indifferent," and 97 answered "inadequate." When rating how helpful they found these videos (1-10), an average score of 6.8 was recorded. Conclusion Most viewers feel motivated or inspired by productivity videos on YouTube. Based on the free responses provided by survey participants, productivity videos can be made more effective by showing more relatable routines and demonstrating what viewers should do when goals are not met.

Inhalant Cannabidiol Inhibits Glioblastoma Progression Through Regulation of Tumor Microenvironment.

Introduction: Glioblastoma (GBM) is the most common invasive brain tumor composed of diverse cell types with poor prognosis. The highly complex tumor microenvironment (TME) and its interaction with tumor cells play important roles in the development, progression, and durability of GBM. Angiogenic and immune factors are two major components of TME of GBM; their interplay is a major determinant of tumor vascularization, immune profile, as well as immune unresponsiveness of GBM. Given the ineffectiveness of current standard therapies (surgery, radiotherapy, and concomitant chemotherapy) in managing patients with GBM, it is necessary to develop new ways of treating these lethal brain tumors. Targeting TME, altering tumor ecosystem may be a viable therapeutic strategy with beneficial effects for patients in their fight against GBM. Materials and Methods: Given the potential therapeutic effects of cannabidiol (CBD) in a wide spectrum of diseases, including malignancies, we tested, for the first time, whether inhalant CBD can inhibit GBM tumor growth using a well-established orthotopic murine model. Optical imaging, histology, immunohistochemistry, and flow cytometry were employed to describe the outcomes such as tumor progression, cancer cell signaling pathways, and the TME. Results: Our findings showed that inhalation of CBD was able to not only limit the tumor growth but also to alter the dynamics of TME by repressing P-selectin, apelin, and interleukin (IL)-8, as well as blocking a key immune checkpoint-indoleamine 2,3-dioxygenase (IDO). In addition, CBD enhanced the cluster of differentiation (CD) 103 expression, indicating improved antigen presentation, promoted CD8 immune responses, and reduced innate Lymphoid Cells within the tumor. Conclusion: Overall, our novel findings support the possible therapeutic role of inhaled CBD as an effective, relatively safe, and easy to administer treatment adjunct for GBM with significant impacts on the cellular and molecular signaling of TME, warranting further research.

The long-term postsurgical prognosis of patients with pineoblastoma.

BACKGROUND: For this report, the authors comprehensively summarized the existing literature on patients with pineoblastoma and identified the variables and treatments that had an impact patient on outcomes. METHODS: A comprehensive search identified 109 studies that collectively described the outcomes of patients with pineoblastoma. Individual patient data were classified based on treatment and were subjected to univariate comparisons. Cox regression analysis included comparisons of survival outcomes controlling for age, extent of resection, and treatment group, and between-group survival comparisons were performed using the Kendall tau (rank correlation) statistic. RESULTS: Two hundred ninety-nine patients met inclusion criteria. The overall survival rate was 54% (175 of 299 patients) at a mean follow-up of 31 ± 1.9 months (range, 1-159 months). The analyses demonstrated a markedly worse prognosis for children aged ≤ 5 years compared with older patients (5-year survival rate: 15% for children aged ≤ 5 years vs 57% for children aged ≥ 5 years; log-rank P < .00001). In addition, a graded increase in survival was observed with increasing degrees of resection (5-year survival rate: 84% for patients who underwent gross total resection vs 53% for patients who underwent subtotal resection vs 29% for patients who underwent debulking; log-rank P < .0001). Multivariate analysis indicated that not achieving gross total resection markedly worsened patient survival (subtotal resection: hazard ratio, 6.47; 95% confidence interval, 2.3-19; P = .001. debulking: hazard ratio, 9.27; 95% confidence interval, 3.2-27; P < .0001). CONCLUSIONS: The current findings emphasize the importance of aggressive surgical resection in the treatment of pineoblastoma. In addition, the authors conclude that clinical trials should not mix young patients with older patients or patients who undergo subtotal resection with patients who undergo gross total resection, because such heterogeneity may alter the variability of responses to treatment and reduce the likelihood of success.

Intracranial hemangiopericytoma: clinical experience and treatment considerations in a modern series of 40 adult patients.

INTRODUCTION: Intracranial hemangiopericytoma (HPC) is a malignant meningothelial tumor. Because of its rarity, few guidelines exist for optimal management. METHODS: University of California at San Francisco patients managed for intracranial HPC were compiled into a single database based on a retrospective review of patient records. Univariate and multivariate regression was performed to determine factors that independently predicted treatment outcomes. RESULTS: A total of 40 patients with intracranial HPC were treated from 1989 to 2010. Treatment and follow-up information was available for analysis on 35 patients. The median survival for all patients was 16.2 years after date of diagnosis, with 1-year, 5-year, and 10-year survival rates of 100%, 92%, and 68%, respectively. Nineteen patients (54%) had HPC recurrence. The median time until recurrence was 5 years, with 1-year, 5-year, and 10-year progression-free survival rates of 96%, 49%, and 28%, respectively. Seven patients (20%) developed extracranial metastasis. Tumor characteristics associated with earlier recurrence included size ≥6 cm (log-rank, P < .05) and nonskull base location (log-rank, P < .05). Strategies combining adjuvant radiation with tumor resection appeared to hinder tumor progression, but had no effect on overall survival or the development of metastasis. Greater extent of resection was associated with increased overall survival (log-rank, P < .05). CONCLUSIONS: Adjuvant radiation may show promise in preventing tumor progression, but recurrence remains a common treatment outcome regardless of initial strategy. When safe and feasible, gross total resection should be pursued as an initial surgical strategy to maximize overall survival. The propensity of these tumors to metastasize makes detailed staging imaging necessary.

Pretemporal Transcavernous Approach for Resection of an Orbito-Cavernous Oculomotor Schwannoma.

The following operative video demonstrates surgical tenets and nuances of the pretemporal transcavernous approach in an unusual case of a 33-year-old patient suffering new onset diplopia and a third nerve palsy due to an orbito-cavernous oculomotor schwannoma. Near total resection was accomplished through an extended pterional craniotomy with pretemporal transcavernous exposure of her lesion, resulting in resolution of her preoperative oculomotor palsy and visual dysfunction. When combined with extended pterional and modified frontotemporal orbitozygomatic approaches, the pretemporal transcavernous approach provides excellent surgical access to the parasellar region including the superior orbital fissure and cavernous sinus. Meticulous dissection and early identification of tissue planes, including cranial nerve and vascular anatomy, allows for safe removal of tumors arising in this region. The link to the video can be found at: https://youtu.be/EuIRTP7wWBQ .

Endoscope-assisted far lateral craniotomy for resection of posterior fossa neurocysticercosis: illustrative case.

BACKGROUND: Neurocysticercosis is a parasitic infection that commonly affects the ventricles, subarachnoid spaces, and spinal cord of the central nervous system. The authors report an unusual manifestation of purely posterior fossa neurocysticercosis treated with endoscope-assisted open craniotomy for resection. OBSERVATIONS: A 67-year-old male presented with 2 months of progressive dizziness, gait ataxia, headaches, decreased hearing, and memory impairment. Imaging revealed an extra-axial cystic lesion occupying the foramen magnum and left cerebellopontine angle with significant mass effect and evidence of early hydrocephalus. Gross-total resection was accomplished via a left far lateral craniotomy with open endoscopic assistance, and pathological findings were consistent with neurocysticercosis. Postoperatively, he was noted to have a sixth nerve palsy, and adjuvant therapy included albendazole. By 9 months postoperatively, he exhibited complete resolution of an immediate postoperative sixth nerve palsy in addition to all preoperative symptoms. His hydrocephalus resolved and did not require permanent cerebrospinal fluid (CSF) diversion. LESSONS: When combined with traditional skull base approaches, open endoscopic techniques allow for enhanced visualization and resection of complex lesions otherwise inaccessible under the microscope alone. Recognition and obliteration of central nervous system neurocysticercosis can facilitate excellent neurological recovery without the need for CSF diversion.

Expert surgeons and deep learning models can predict the outcome of surgical hemorrhage from 1 min of video.

Major vascular injury resulting in uncontrolled bleeding is a catastrophic and often fatal complication of minimally invasive surgery. At the outset of these events, surgeons do not know how much blood will be lost or whether they will successfully control the hemorrhage (achieve hemostasis). We evaluate the ability of a deep learning neural network (DNN) to predict hemostasis control ability using the first minute of surgical video and compare model performance with human experts viewing the same video. The publicly available SOCAL dataset contains 147 videos of attending and resident surgeons managing hemorrhage in a validated, high-fidelity cadaveric simulator. Videos are labeled with outcome and blood loss (mL). The first minute of 20 videos was shown to four, blinded, fellowship trained skull-base neurosurgery instructors, and to SOCALNet (a DNN trained on SOCAL videos). SOCALNet architecture included a convolutional network (ResNet) identifying spatial features and a recurrent network identifying temporal features (LSTM). Experts independently assessed surgeon skill, predicted outcome and blood loss (mL). Outcome and blood loss predictions were compared with SOCALNet. Expert inter-rater reliability was 0.95. Experts correctly predicted 14/20 trials (Sensitivity: 82%, Specificity: 55%, Positive Predictive Value (PPV): 69%, Negative Predictive Value (NPV): 71%). SOCALNet correctly predicted 17/20 trials (Sensitivity 100%, Specificity 66%, PPV 79%, NPV 100%) and correctly identified all successful attempts. Expert predictions of the highest and lowest skill surgeons and expert predictions reported with maximum confidence were more accurate. Experts systematically underestimated blood loss (mean error - 131 mL, RMSE 350 mL, R2 0.70) and fewer than half of expert predictions identified blood loss > 500 mL (47.5%, 19/40). SOCALNet had superior performance (mean error - 57 mL, RMSE 295 mL, R2 0.74) and detected most episodes of blood loss > 500 mL (80%, 8/10). In validation experiments, SOCALNet evaluation of a critical on-screen surgical maneuver and high/low-skill composite videos were concordant with expert evaluation. Using only the first minute of video, experts and SOCALNet can predict outcome and blood loss during surgical hemorrhage. Experts systematically underestimated blood loss, and SOCALNet had no false negatives. DNNs can provide accurate, meaningful assessments of surgical video. We call for the creation of datasets of surgical adverse events for quality improvement research.

Treatment strategies for giant pituitary adenomas in the era of endoscopic transsphenoidal surgery: a multicenter series.

OBJECTIVE: Given the anatomical complexity and frequently invasive growth of giant pituitary adenomas (GPAs), individually tailored approaches are required. The aim of this study was to assess the treatment strategies and outcomes in a large multicenter series of GPAs in the era of endoscopic transsphenoidal surgery (ETS). METHODS: This was a retrospective case-control series of 64 patients with GPAs treated at two tertiary care centers by surgeons with experience in ETS. GPAs were defined by a maximum diameter of ≥ 4 cm and a volume of ≥ 10 cm3 on preoperative isovoxel contrast-enhanced MRI. RESULTS: The primary operation was ETS in all cases. Overall gross-total resection rates were 64% in round GPAs, 46% in dumbbell-shaped GPAs, and 8% in multilobular GPAs (p < 0.001). Postoperative outcomes were further stratified into two groups based on extent of resection: group A (gross-total resection or partial resection with intracavernous remnant; 21/64, 33%) and group B (partial resection with intracranial remnant; 43/64, 67%). Growth patterns of GPAs were mostly round (11/14, 79%) in group A and multilobular (33/37, 89%) in group B. In group A, no patients required a second operation, and 2/21 (9%) were treated with adjuvant radiosurgery. In group B, early transcranial reoperation was required in 6/43 (14%) cases due to hemorrhagic transformation of remnants. For the remaining group B patients with remnants, 5/43 (12%) underwent transcranial surgery and 12/43 (28%) underwent delayed second ETS. There were no deaths in this series. Severe complications included stroke (6%), meningitis (6%), hydrocephalus requiring shunting (6%), and loss or distinct worsening of vision (3%). At follow-up (mean 3 years, range 0.5-16 years), stable disease was achieved in 91% of cases. CONCLUSIONS: ETS as a primary treatment modality to relieve mass effect in GPAs and extent of resection are dependent on GPA morphology. The pattern of residual pituitary adenoma guides further treatment strategies, including early transcranial reoperation, delayed endoscopic transsphenoidal/transcranial reoperation, and adjuvant radiosurgery.

Epidermal growth factor module-containing mucin-like receptor 2 is a newly identified adhesion G protein-coupled receptor associated with poor overall survival and an invasive phenotype in glioblastoma.

Epidermal growth factor (EGF) module-containing mucin-like receptor 2 (EMR2) is a member of the seven span transmembrane (TM7) adhesion G-protein coupled receptor subclass. It is abundantly expressed in immune cells of myeloid origin and appears to mediate cellular adhesion, migration, and signaling. Based on an analysis showing earlier mortality among glioblastoma patients whose tumors highly express EMR2, we studied its expression patterns in glioblastoma and potential to mediate cellular proliferation and invasion. We performed univariate analysis of overall survival in GBM patients expressing low, moderate, and high amounts of EMR2 based on publicly available microarray data in the Cancer Genome Atlas (TCGA). Using RT-PCR and western blotting, we studied mRNA and protein expression patterns of EMR2, respectively. We then employed siRNA knockdown of EMR2 in two human glioblastoma cell lines expressing high levels of EMR2 to assess functional effects on cellular proliferation and invasion, in vitro. Kaplan-Meier analysis of TCGA survival data for GBM demonstrated that EMR2 levels are inversely correlated with overall time until mortality (log rank, P < 0.01). EMR2 mRNA and protein is variably expressed in primary glioblastoma samples and human glioblastoma cell lines. When comparing cells transfected with siRNA targeting EMR2 to those transfected with a negative, scramble control, there was no difference in proliferation over 72 h in the SF767 and G55 glioblastoma cell lines. However, EMR2 knockout cells demonstrated an almost 3-fold reduction in migration compared to their negative controls (P < 0.05) in the SF767 cell line, and an almost 2-fold reduction (P < 0.05) in migration in the G55 cell line. We provide evidence that EMR2 is expressed in glioblastoma and has significant functional consequences on cellular invasion, but not proliferation. In light of its ability to promote adhesion and migration in immune cells, our data suggest that EMR2 may mediate similar phenomena in glioblastoma. The invasive phenotype conferred by EMR2 correlates with clinical data demonstrating poor survival in glioblastoma patients who express high levels of EMR2 in their tumor.

Factors associated with preservation of facial nerve function after surgical resection of vestibular schwannoma.

Avoidance of facial nerve palsy is one of the major goals of vestibular schwannoma (VS) microsurgery. In this study, we examined the significance of previously implicated prognostic factors (age, tumor size, the extent of resection and the surgical approach) on post-operative facial nerve function. We selected all VS patients from prospectively collected database (1984-2009) who underwent microsurgical resection as their initial treatment for histopathologically confirmed VS. The effect of variables such as surgical approach, tumor size, patient age and extent of resection on rates facial nerve dysfunction after surgery, were analyzed using multivariate logistic regression. Patients with preoperative facial nerve dysfunction (House-Brackman [HB] score 3 or higher) were excluded, and HB grade of 1 or 2 at the last follow-up visit was defined as "facial nerve preservation." A total of 624 VS patients were included in this study. Multivariate logistic regression analysis found that only pre-operative tumor size significantly predicted poorer facial nerve outcome for patients followed-up for ≥6 and ≥12 months (OR 1.27, 95% CI 1.09-1.49, p < 0.01; OR 1.35, 95% CI 1.10-1.67, P < 0.01, respectively). We found no significant relationship between facial nerve function and age, extent of resection, surgical approach, or tumor size (when extent of resection and surgical approach were included in the regression analysis). Because facial nerve palsy is a debilitating and psychologically devastating condition for the patient, we suggest altering surgical aggressiveness in patients with unfavorable tumor anatomy, particularly in cases with large tumors where overaggressive resection might subject the patient to unwarranted risk. Residual disease can be followed and controlled with radiosurgery if interval growth is noted.

CSF Leak After COVID-19 Nasopharyngeal Swab: A Case Report.

The nasopharyngeal swab has been used with increased frequency since the beginning of the COVID-19 pandemic. Little has been written in the literature regarding the complications arising from this procedure, as it is generally accepted as safe. In this report, we describe a case in which a young woman sustained a traumatic skull base injury during a nasopharyngeal swab for COVID-19. We then discuss the subsequent treatment and outcome. This case demonstrates the potential for significant complications arising from this widespread procedure and the necessity for awareness of these potential complications. Laryngoscope, 131:1927-1929, 2021.

Complementary and Alternative Medicine for the Treatment of Gliomas: Scoping Review of Clinical Studies, Patient Outcomes, and Toxicity Profiles.

INTRODUCTION: Complementary and alternative medicine (CAM) are highly used among those diagnosed with glioma. Further research is warranted, however, as it remains important to clearly delineate CAM practices that are unproven, disproven, or promising for future research and implementation. METHODS: A systematic review was conducted to identify all articles that investigated the effect of any CAM therapy on survival of patients with newly diagnosed or recurrent glioma. RESULTS: Eighteen papers and 4 abstracts pertaining to the effects of ketogenic diet (4), antioxidants (3), hyperbaric oxygen (4), cannabinoids (2), carbogen and nicotinamide (3), mistletoe extract (2), hypocupremia and penicillamine (1), and overall CAM use (3) on overall and progression-free survival in patients with low- and high-grade glioma were identified (Levels of Evidence I-IV). Ketogenic diets, hyperbaric oxygen therapy, and cannabinoids appear to be safe and well tolerated by patients; preliminary studies demonstrate tumor response and increased progression-free survival and overall survival when combined with standard of care therapies. Antioxidant usage exhibit mixed results perhaps associated with glioma grade with greater effect on low-grade gliomas; vitamin D intake was associated with prolonged survival. Conversely, carbogen breathing and hypocupremia were found to have no effect on the survival of patients with glioma, with associated significant toxicity. Most modalities under the CAM umbrella have not been appropriately studied and require further investigation. CONCLUSIONS: Despite widespread use, Level I or II evidence for CAM for the treatment of glioma is lacking, representing future research directions to optimally counsel and treat glioma patients.