Androgen loss weakens anti-tumor immunity and accelerates brain tumor growth.

Many cancers, including glioblastoma (GBM), have a male-biased sex difference in incidence and outcome. The underlying reasons for this sex bias are unclear but likely involve differences in tumor cell state and immune response. This effect is further amplified by sex hormones, including androgens, which have been shown to inhibit anti-tumor T cell immunity. Here, we show that androgens drive anti-tumor immunity in brain tumors, in contrast to its effect in other tumor types. Upon castration, tumor growth was accelerated with attenuated T cell function in GBM and brain tumor models, but the opposite was observed when tumors were located outside the brain. Activity of the hypothalamus-pituitary-adrenal gland (HPA) axis was increased in castrated mice, particularly in those with brain tumors. Blockade of glucocorticoid receptors reversed the accelerated tumor growth in castrated mice, indicating that the effect of castration was mediated by elevated glucocorticoid signaling. Furthermore, this mechanism was not GBM specific, but brain specific, as hyperactivation of the HPA axis was observed with intracranial implantation of non-GBM tumors in the brain. Together, our findings establish that brain tumors drive distinct endocrine-mediated mechanisms in the androgen-deprived setting and highlight the importance of organ-specific effects on anti-tumor immunity.

Emergency department visits following endoscopic skull base surgery: An opportunity for improvement.

BACKGROUND: Readmissions are major healthcare expenditures, key hospital metrics, and are often preceded by an evaluation in the emergency department (ED). The purpose of this study was to analyze ED visits within 30 days of endoscopic skull base surgery (ESBS), risk factors for readmission once in the ED, and ED-related evaluation and outcomes. METHODS: Retrospective review from January 2017 to December 2022 at a high-volume center of all ESBS patients who presented to the ED within 30 days of surgery. RESULTS: Of 593 ESBS cases, 104 patients (17.5%) presented to the ED following surgery within 30 days, with a median presentation of 6 days post-discharge (IQR 5-14); 54 (51.9%) patients were discharged while 50 (48.1%) were readmitted. Readmitted patients were significantly older than discharged patients (median 60 years, IQR 50-68 vs. 48 years, 33-56; p < 0.01). Extent of ESBS was not associated with readmission or discharge from the ED. The most common discharge diagnoses were headache (n = 13, 24.1%) and epistaxis (n = 10, 18.5%); the most common readmitting diagnoses were serum abnormality (n = 15, 30.0%) and altered mental status (n = 5, 10.0%). Readmitted patients underwent significantly more laboratory testing than discharged patients (median 6, IQR 3-9 vs. 4, 1-6; p < 0.01). CONCLUSIONS: Approximately half of patients who presented to the ED following ESBS were discharged home but underwent significant workup. Follow-up within 7 days of discharge, risk-stratified endocrine care pathways, and efforts to address the social determinants of health may be considered to optimize postoperative ESBS care.

Percutaneous Rhizotomy of the Gasserian Ganglion in Patients With Mass Lesion-Associated Trigeminal Neuralgia: A Case Series.

BACKGROUND: Patients with trigeminal neuralgia (TN) secondary to mass lesions are typically treated by directly addressing the underlying pathology. In cases of TN not alleviated by treatment of the pathology, percutaneous balloon compression (PBC) and glycerol rhizotomy (Gly) are simple and effective ways to alleviate pain. However, there is limited literature on the use of these techniques for patients with TN caused by mass lesions. OBJECTIVE: To describe the use of PBC/Gly to treat mass lesion-related TN. METHODS: We report a retrospective, single-institution, descriptive case series of patients who presented with TN secondary to tumor or mass-like inflammatory lesion from 1999 to 2021. Patients with primary, idiopathic, or multiple sclerosis-related TN were excluded. Outcomes included Barrow Neurological Institute (BNI) pain intensity and hypesthesia scores, pain persistence, and postoperative complications. RESULTS: A total of 459 procedures were identified, of which 16 patients met the inclusion criterion (14 PBC and 2 Gly). Of the 15 patients with tumors, 12 had TN pain despite prior tumor-targeted radiation. Short-term (<3 months) BNI pain intensity improvement occurred in 15 (93.8%) patients. The mean follow-up was 54.4 months. Thirteen (81.3%) patients were pain-free (Barrow Neurological Institute pain intensity scale: IIIa-50%; I-25.0%; II-6.3%) for a mean of 23.8 (range 1-137) months. Ten patients (62.5%) had pain relief for ≥6 months from first procedure. New facial numbness developed immediately postprocedure in 8 (50%) patients. Transient, partial abducens nerve palsy occurred in 1 patient. CONCLUSION: PBC/Gly is an effective option for medically refractory TN in patients with mass-associated TN and is a viable option for repeat treatment.

Metastatic Breast Cancer to the Spine: Incidence of Somatic Gene Alterations and Association of Targeted Therapies With Overall Survival.

BACKGROUND: The increase in use of targeted systemic therapies in cancer treatments has catalyzed the importance of identifying patient- and tumor-specific somatic mutations, especially regarding metastatic disease. Mutations found to be most prevalent in patients with metastatic breast cancer include TP53, PI3K, and CDH1. OBJECTIVE: To determine the incidence of somatic mutations in patients with metastatic breast cancer to the spine (MBCS). To determine if a difference exists in overall survival (OS), progression-free survival, and progression of motor symptoms between patients who do or do not undergo targeted systemic therapy after treatment for MBCS. METHODS: This is a retrospective study of patients with MBCS. Review of gene sequencing reports was conducted to calculate the prevalence of various somatic gene mutations within this population. Those patients who then underwent treatment (surgery/radiation) for their diagnosis of MBCS between 2010 and 2020 were subcategorized. The use of targeted systemic therapy in the post-treatment period was identified, and post-treatment OS, progression-free survival, and progression of motor deficits were calculated for this subpopulation. RESULTS: A total of 131 patients were included in the final analysis with 56% of patients found to have a PI3K mutation. Patients who received targeted systemic therapies were found to have a significantly longer OS compared with those who did not receive targeted systemic therapies. CONCLUSION: The results of this study demonstrate that there is an increased prevalence of PI3K mutations in patients with MBCS and there are a significant survival benefit and delay in progression of motor symptoms associated with using targeted systemic therapies for adjuvant treatment.

Immediate Titanium Mesh Cranioplasty After Debridement and Craniectomy for Postcraniotomy Surgical Site Infections and Risk Factors for Reoperation.

BACKGROUND: We previously published a novel strategy for management of postcraniotomy bone flap infection consisting of single stage debridement, bone flap removal, and immediate titanium mesh cranioplasty. METHODS: Postcraniotomy patients with surgical site infections treated with surgical debridement, bone flap removal, and immediate titanium mesh cranioplasty were retrospectively reviewed. The primary outcome measure was reoperation due to persistent infection or wound healing complications from the titanium mesh. RESULTS: We included 48 patients, of which 15 (31.3%) were female. The most common primary diagnoses were glioblastoma (31.3%), meningioma (18.8%), and vascular/trauma (16.7%). Most patients had a history of same-site craniotomy prior to the surgery complicated by surgical site infection and 47.9% had prior cranial radiation. Thirty-six (75.0%) patients achieved resolution of their infection and did not require a second operation. Twelve (25.0%) patients required reoperation: 6 (12.5%) patients were found to have frank intraoperative purulence on reoperation, whereas 6 (12.5%) had reoperation for poor wound healing without any evidence of persistent infection. Cochran Armitage trend test revealed that patients with increasing number of wound healing risk factors had significantly higher risk of reoperation (P = 0.001). Prior intensity modulated radiotherapy alone was a significant risk factor for reoperation (6.5 [1.40-30.31], P = 0.002). Median follow-up time was 20.5 weeks. CONCLUSIONS: Immediate titanium mesh cranioplasty at the time of debridement and bone flap removal is an acceptable option in the management of post-craniotomy bone flap infection. Patients with multiple wound healing risk factors are at higher risk for reoperation.

Predictive Factors for Postoperative Opioid Use in Elective Endoscopic Endonasal Skull Base Surgery.

OBJECTIVE: In 2017, the United States opioid epidemic was declared a public health emergency. Increased efforts have been made to understand and reduce patient opioid use in neurosurgery. However, the factors associated with postoperative opioid use remain understudied in endoscopic endonasal skull base surgery (EESBS). We identified the demographic and surgical factors associated with postoperative opioid use in EESBS. METHODS: A retrospective review was conducted of patients who underwent elective EESBS between January 2015 and December 2020. Patient demographics, relevant clinical history, and operative data were collected and analyzed. Total opioid use was calculated 24, 48, and 72 hours postoperatively. Multivariable linear regression analyses were performed to identify factors associated with opioid use. RESULTS: There were 454 patients included. A history of anxiety/depression and younger patient age were associated with a significant increase in opioid use at 24 (28.2 MME, p < 0.001), 48 (53.4 MME, p < 0.001), and 72 (89.4 MME, p < 0.001) hours after surgery. Nasoseptal flap use was significantly associated with increased opioid use at 24 (12.8 MME, p < 0.49) and 48 (19.6 MME, p < 0.048) h postoperatively while controlling for intraoperative variables and surgical approach (trans-sellar vs. expanded). No significant association was observed for patient sex, history of migraines, preoperative opioid use, length of surgery, or surgical approach. CONCLUSION: In patients undergoing EESBS, patient history of anxiety/depression, younger patient age, and nasoseptal flap use are associated with increased postoperative opioid use. Knowledge of these risk factors may guide perioperative prescribing patterns to both adequately control postoperative pain and reduce opioid use. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:494-499, 2023.

The Current State of Visualization Techniques in Endoscopic Skull Base Surgery.

Skull base surgery has undergone significant progress following key technological developments. From early candle-lit devices to the modern endoscope, refinements in visualization techniques have made endoscopic skull base surgery (ESBS) a standard practice for treating a variety of conditions. The endoscope has also been integrated with other technologies to enhance visualization, including fluorescence agents, intraoperative neuronavigation with augmented reality, and the exoscope. Endoscopic approaches have allowed neurosurgeons to reevaluate skull base neuroanatomy from new perspectives. These advances now serve as the foundation for future developments in ESBS. In this narrative review, we discuss the history and development of ESBS, current visualization techniques, and future innovations.