Follow-up care compliance among patients diagnosed with unruptured intracranial aneurysms.

OBJECTIVES: Periodic imaging follow-up for patients with unruptured intracranial aneurysms (UIA) is crucial, as studies indicate higher rupture risk with aneurysm growth. However, few studies address patient adherence to follow-up recommendations. This study aims to identify compliance rates and factors influencing follow-up adherence. METHODS: Patients with a UIA were identified from our institution's database from 2011-2021. Follow-up imaging (CT/MR Angiogram) was advised at specific intervals. Patients were categorized into compliant and non-compliant groups based on first-year compliance. Factors contributing to compliance were assessed through multivariate logistic regression. Phone interviews were conducted with non-compliant patients to understand reasons for non-adherence. RESULTS: Among 923 UIA diagnosed patients, 337 were randomly selected for analysis. The median follow-up period was 1.4 years, with a 42% first-year compliance rate. The mean aneurysm size was 3.3 mm. Five patients had a rupture during follow-up, of which 4 died. Compared with patients consulting specialists at the initial diagnosis, those seen by non-specialists exhibited lower compliance (OR 0.25, p < 0.001). Loss to follow-up was greatest during transition from emergency service to specialist appointments. Patients who spoke languages other than English exhibited poorer compliance than those speaking English (OR 0.20, p = 0.01). CONCLUSIONS: Significant amounts of UIA patients at low rupture risk were lost to follow-up before seeing UIA specialists. Main non-compliance factors include inadequate comprehension of follow-up instructions, poor care transfer from non-specialists to specialist, and insurance barriers.

Multimodal diagnosis of cerebrospinal fluid rhinorrhea: State of the art review and emerging concepts.

Objective: Currently, diagnosis of cerebrospinal fluid (CSF) rhinorrhea relies on a multimodal approach, increasing costs and ultimately delaying diagnosis. In the United States and internationally, the crux of such a diagnosis relies on confirmation testing (via biomarkers) and localization (e.g., imaging). Biomarker testing may require analysis at an outside facility, resulting in delays diagnosis and treatment. In addition, specialized imaging may be nonspecific and often requires an active leak for diagnosis. There remains a clear need for innovative new technology. Methods: A comprehensive review was conducted on both foundational and innovative scholarly articles regarding current and emerging diagnosis modalities for CSF. Results: Current modalities in CSF rhinorrhea diagnosis and localization include laboratory tests (namely, B2T immunofixation), imaging (CT and/or MRI) with or without intrathecal administration, and surgical exploration. Each of these modalities carry flaws, risks, and benefits, ultimately contributing to delays in diagnosis and morbidity. Promising emerging technologies include lateral flow immunoassays (LFI) and biologically functionalized field-effect transistors (BioFET). Nevertheless, these carry some drawbacks of their own, and require further validation. Conclusion: CSF rhinorrhea remains a challenging diagnosis, requiring a multimodal approach to differentiate from nonpathologic causes of rhinorrhea. Current methods in diagnosis are imperfect, as the ideal test would be a readily accessible, inexpensive, rapid, highly accurate point-of-care test without the need for excess fluid or specialized processing. Critical work is being done to develop promising, new, improved tests, though a clear successor has not yet emerged. Level of Evidence: N/A.

Conventional clinical signs and symptoms are poor predictors of postoperative cerebrospinal fluid leak: A single-centre cohort perspective.

BACKGROUND: Postoperative cerebrospinal fluid (CSF) leak remains a concerning complication of the endoscopic endonasal approach (EEA) for skull base pathology. Signs and symptoms suggesting CSF leak often trigger additional workup during the postoperative course. We systematically evaluate associations between subjectively reported clinical signs/symptoms noted during the immediate postoperative period and incidence of postoperative CSF leaks. METHODS: Retrospective chart review was conducted at a tertiary academic medical centre including 137 consecutive patients with intraoperative CSF leak during EEA with primary repair between July 2018 and August 2022. Postoperative CSF leak associations with clinical signs and symptoms were evaluated using positive (PPV) and negative predictive values (NPV), sensitivity, specificity and odds ratio (OR) via univariate logistic regression. RESULTS: Seventy-nine patients (57.7%) had high-flow leaks repaired and 5 (3.6%) developed CSF leaks postoperatively. Of reported symptoms, rhinorrhea was most common (n = 52, 38.0%; PPV [95% CI] = 7.6% [4.8%, 11.9%]), followed by severe headache (n = 47, 34.3%; 6.3% [3.1%, 12.5%]), dizziness (n = 43, 31.4%; 2.3% [0.4%, 12.1%]), salty or metallic taste (n = 20, 14.6%; 9.9% [3.3%, 25.8%]), and throat drainage (n = 10, 7.3%; 9.9% [1.7%, 41.4%]). Nausea or vomiting constituted the most reported sign concerning for CSF leak (n = 73, 53.3%; PPV [95% CI] = 4.1% [2.0%, 8.1%]). On univariate regression, no sign or symptom, including rhinorrhea (OR [95% CI] = 7.00 [0.76-64.44]), throat drainage (3.42 [0.35-33.86]), salty/metallic taste (4.22 [0.66-27.04]), severe headache (3.00 [0.48-18.62]), dizziness (0.54 [0.06-4.94]), fever (3.16 [0.50-19.99]), and nausea/vomiting (1.33 [0.22-8.21]), associated with postoperative CSF leak. CONCLUSIONS: A range of subjectively reported symptoms and signs failed to predict postoperative CSF leak. Further investigation is warranted to inform appropriate attention and response.

Comparison of patient-reported outcomes and clinical characteristics among patients with pituitary macroadenomas and giant adenomas.

KEY POINTS: Patients with giant adenomas are more likely to have tumor extension into the paranasal sinuses. Compared to macroadenomas, giant adenomas are not associated with worse preoperative SNOT-22 scores.

What is the Philosophy of Neurosurgery? Systematic Review and Defining the Discipline.

INTRODUCTION: Despite centuries of joint investigation of philosophy and neurological interventions, a founding account for the philosophy of neurosurgery has yet to be rigorously constructed or defended. This paper reviews recent work on the philosophy of neurosurgery, spanning metaphysics, epistemology, and value theory, to establish a framework and clinical relevance for study in the philosophy of neurosurgery. METHODS: A systematic review of an online database was conducted using the broad search terms, "Philosophy AND (Neurosurgery OR Neurological Surgery)." Records were included if they demonstrated relevance to the philosophy of neurosurgery and analytical rigor, but were excluded if solely legal, clinical, or ethical principles were considered without substantive discussion of underlying ethical frameworks and philosophical principles. RESULTS: Of 8025 candidates from online and print records, 16 records (14 from online sources and 2 from an edited volume) met inclusion criteria for the systematic review. Three dealt with metaphysics, 3 dealt with epistemology, 4 dealt with value theory, 5 dealt with metaphysics/epistemology, and 1 dealt with value theory/metaphysics. Questions of free will, consciousness, personal identity, neurosurgical knowledge, ascription of other minds, deontology, and minimalism, among others, were considered. DISCUSSION: Based on identified studies, the philosophy of neurosurgery is defined as the discipline of rigorously and methodically addressing metaphysical, epistemological, and value-theoretic questions arising from physically intervening in the nervous system. We discuss future directions for questions within the philosophy of neurosurgery and consider their relevance for patient care and the practice of neurosurgery.

Staged Resection of Difficult-to-Treat Intracranial Meningiomas: A Systematic Review of the Indications, Surgical Approaches, and Postoperative Outcomes.

Introduction Meningiomas-the most common extra-axial tumors-are benign, slow-growing dural-based lesions that can involve multiple cranial fossae and can progress insidiously for years until coming to clinical attention secondary to compression of adjacent neurovascular structures. For complex, multicompartmental lesions, multistaged surgeries have been increasingly shown to enhance maximal safe resection while minimizing adverse sequela. Here, we systematically review the extant literature to highlight the merits of staged resection. Methods PubMed, Scopus, and Web of Science databases were queried to identify articles reporting resections of intracranial meningiomas using a multistaged approach, and articles were screened for possible inclusion in a systematic process performed by two authors. Results Of 118 identified studies, 36 describing 169 patients (mean age 42.6 ± 21.3 years) met inclusion/exclusion criteria. Petroclival lesions comprised 57% of cases, with the most common indications for a multistaged approach being large size, close approximation of critical neurovascular structures, minimization of brain retraction, identification and ligation of deep vessels feeding the tumor, and resection of residual tumor found on postoperative imaging. Most second-stage surgeries occurred within 3 months of the index surgery. Few complications were reported and multistaged resections appeared to be well tolerated overall. Conclusions Current literature suggests multistaged approaches for meningioma resection are well-tolerated. However, there is insufficient comparative evidence to draw definitive conclusions about its advantages over an unstaged approach. There are similarly insufficient data to generate an evidence-based decision-making framework for when a staged approach should be employed. This highlights the need for collaborative efforts among skull base surgeons to establish an evidentiary to support the use of staged approaches and to outline those indications that merit such an approach.

Tissue Sealant Impact on Skull Base Reconstruction Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVE: Despite significant advances in understanding of skull base reconstruction principles, the role of tissue sealants in modifying postoperative cerebrospinal fluid (CSF) leak outcomes remains controversial. We evaluate postoperative CSF leak incidence associated with tissue sealant use in skull base defect repair during endoscopic skull base surgery (ESBS). DATA SOURCES: Web of Science, PubMed/MEDLINE, Scopus, and Cochrane Library. REVIEW METHODS: Systematic review and meta-analysis of risk differences (RD). A search strategy identified original studies reporting CSF leakage following ESBS with disaggregation by tissue sealant use and/or type. RESULTS: 27 non-randomized studies (n = 2,403) were included for qualitative and meta-analysis. Reconstruction with a tissue sealant did not significantly reduce postoperative CSF leak risk compared with reconstruction without sealant (RD[95% CI] = 0.02[-0.01, 0.05]). Sub-analyses of dural sealant (-0.02[-0.11, 0.07]) and fibrin glue (0.00[-0.07, 0.07]) compared with no sealant were similarly unremarkable. Postoperative CSF leakage was not significantly modulated in further sub-analyses of DuraSeal (0.02[-0.02, 0.05]), Adherus (-0.03[-0.08, 0.03]), or Bioglue (-0.06[-0.23, 0.12]) versus no dural sealant use, or Tisseel/Tissucol versus fibrin glue nonuse (0.00[-0.05, 0.05]). No significant association was seen comparing dural sealant use versus fibrin glue use on pairwise (0.01[-0.03, 0.05]) or network meta-analysis (-0.01[-0.05, 0.04]). Limitations in source literature prevented sub-analyses stratified by leak characteristics, defect size and location, and accompanying reconstruction materials. CONCLUSION: Tissue sealant use did not appear to impact postoperative CSF leak incidence when compared with nonuse. Higher quality studies are warranted to thoroughly elucidate the clinical value of adjunct sealant use in endoscopic skull base reconstruction. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Neoadjuvant CD40 Agonism Remodels the Tumor Immune Microenvironment in Locally Advanced Esophageal/Gastroesophageal Junction Cancer.

Sotigalimab is an agonistic anti-CD40 mAb that can modulate antitumor immune responses. In a phase II clinical trial of sotigalimab combined with neoadjuvant chemoradiation (CRT) in locally advanced esophageal/gastroesophageal junction (E/GEJ) cancer with the primary outcome of efficacy as measured by pathologic complete response (pCR) rate, the combination induced pCR in 38% of treated patients. We investigated the mechanism of action of sotigalimab in samples obtained from this clinical trial. Tumor biopsies and peripheral blood samples were collected at baseline, following an initial dose of sotigalimab, and at the time of surgery after CRT completion from six patients. High dimensional single-cell techniques were used, including combined single-cell RNA-sequencing and proteomics (CITEseq) and multiplexed ion beam imaging, to analyze immune responses. Sotigalimab dramatically remodeled the immune compartment in the periphery and within the tumor microenvironment (TME), increasing expression of molecules related to antigen processing and presentation and altering metabolic pathways in myeloid cells. Concomitant with these changes in myeloid cells, sotigalimab treatment primed new T cell clonotypes and increased the density and activation of T cells with enhanced cytotoxic function. Sotigalimab treatment also induced a decrease in the frequency of Tregs in the TME. These findings indicate that a single dose of sotigalimab leads to enhanced antigen presentation that can activate T cells and induce new T cell clones. This restructuring of the TME provides elements which are critical to the development of effective antitumor immune responses and improved clinical outcomes.

The impact of nasal packing on skull base reconstruction and quality-of-life outcomes following endoscopic skull base surgery.

KEY POINTS: Nasal packing type was not associated with postoperative cerebrospinal fluid leaks Nondissolvable packing conferred an increased risk for postoperative sinonasal infections Nasal packing type did not influence short- and long-term quality-of-life scores.

A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy.

PURPOSE: Disease progression during or after anti-PD-1-based treatment is common in advanced melanoma. Sotigalimab is a CD40 agonist antibody with a unique epitope specificity and Fc receptor binding profile optimized for activation of CD40-expressing antigen-presenting cells. Preclinical data indicated that CD40 agonists combined with anti-PD1 could overcome resistance to anti-PD-1. PATIENTS AND METHODS: We conducted a multicenter, open-label, phase II trial to evaluate the combination of sotigalimab 0.3 mg/kg and nivolumab 360 mg every 3 weeks in patients with advanced melanoma following confirmed disease progression on a PD-1 inhibitor. The primary objective was to determine the objective response rate (ORR). RESULTS: Thirty-eight subjects were enrolled and evaluable for safety. Thirty-three were evaluable for activity. Five confirmed partial responses (PR) were observed for an ORR of 15%. Two PRs are ongoing at 45.9+ and 26+ months, whereas the other three responders relapsed at 41.1, 18.7, and 18.4 months. The median duration of response was at least 26 months. Two additional patients had stable disease for >6 months. Thirty-four patients (89%) experienced at least one adverse event (AE), and 13% experienced a grade 3 AE related to sotigalimab. The most common AEs were pyrexia, chills, nausea, fatigue, pruritus, elevated liver function, rash, vomiting, headache, arthralgia, asthenia, myalgia, and diarrhea. There were no treatment-related SAEs, deaths, or discontinuation of sotigalimab due to AEs. CONCLUSIONS: Sotigalimab plus nivolumab had a favorable safety profile consistent with the toxicity profiles of each agent. The combination resulted in durable and prolonged responses in a subset of patients with anti-PD-1-resistant melanoma, warranting further evaluation in this setting. See related commentary by Wu and Luke, p. 9.

Deep Brain Stimulation as an Emerging Therapy for Cognitive Decline in Alzheimer Disease: Systematic Review of Evidence and Current Targets.

OBJECTIVE: With no cure for Alzheimer disease (AD), current efforts involve therapeutics that prevent further cognitive impairment. Deep brain stimulation (DBS) has been studied for its potential to mitigate AD symptoms. This systematic review investigates the efficacy of current and previous targets for their ability to slow cognitive decline in treating AD. METHODS: A systematic review of the literature was performed through a search of the PubMed, Scopus, and Web of Science databases. Human studies between 1994 and 2023 were included. Sample size, cognitive outcomes, and complications were recorded for each study. RESULTS: Fourteen human studies were included: 7 studies with 6 distinct cohorts (n = 56) targeted the fornix, 6 studies with 3 distinct cohorts (n = 17) targeted the nucleus basalis of Meynert (NBM), and 1 study (n = 3) investigated DBS of the ventral striatum (VS). The Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental State Examination, and Clinical Dementia Rating Scale Sum of Boxes were used as the primary outcomes. In 5 of 6 cohorts where DBS targeted the fornix, cognitive decline was slowed based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale or Mini-Mental State Examination scores. In 2 of 3 NBM cohorts, a similar reduction was reported. When DBS targeted the VS, the patients' Clinical Dementia Rating Scale Sum of Boxes scores indicated a slowed decline. CONCLUSIONS: This review summarizes current evidence and addresses variability in study designs regarding the therapeutic benefit of DBS of the fornix, NBM, and VS. Because of varying study parameters, varying outcome measures, varying study durations, and limited cohort sizes, definitive conclusions regarding the utility of DBS for AD cannot be made. Further investigation is needed to determine the safety and efficacy of DBS for AD.

A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better.

BACKGROUND: Stimulating inflammatory tumor associated macrophages can overcome resistance to PD-(L)1 blockade. We previously conducted a phase I trial of cabiralizumab (anti-CSF1R), sotigalimab (CD40-agonist) and nivolumab. Our current purpose was to study the activity and cellular effects of this three-drug regimen in anti-PD-1-resistant melanoma. METHODS: We employed a Simon's two-stage design and analyzed circulating immune cells from patients treated with this regimen for treatment-related changes. We assessed various dose levels of anti-CSF1R in murine melanoma models and studied the cellular and molecular effects. RESULTS: Thirteen patients were enrolled in the first stage. We observed one (7.7%) confirmed and one (7.7%) unconfirmed partial response, 5 patients had stable disease (38.5%) and 6 disease progression (42.6%). We elected not to proceed to the second stage. CyTOF analysis revealed a reduction in non-classical monocytes. Patients with prolonged stable disease or partial response who remained on study for longer had increased markers of antigen presentation after treatment compared to patients whose disease progressed rapidly. In a murine model, higher anti-CSF1R doses resulted in increased tumor growth and worse survival. Using single-cell RNA-sequencing, we identified a suppressive monocyte/macrophage population in murine tumors exposed to higher doses. CONCLUSIONS: Higher anti-CSF1R doses are inferior to lower doses in a preclinical model, inducing a suppressive macrophage population, and potentially explaining the disappointing results observed in patients. While it is impossible to directly infer human doses from murine studies, careful intra-species evaluation can provide important insight. Cabiralizumab dose optimization is necessary for this patient population with limited treatment options. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03502330.

Toll-Like Receptor 4 Agonist Injection With Concurrent Radiotherapy in Patients With Metastatic Soft Tissue Sarcoma: A Phase 1 Nonrandomized Controlled Trial.

Importance: Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts. Objective: To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions. Design, Setting, and Participants: This phase 1 nonrandomized controlled trial of patients with STS was performed at a single academic sarcoma specialty center from November 17, 2014, to March 16, 2016. Data analysis was performed from August 2016 to September 2022. Interventions: Two doses of IT GLA-SE (5 µg and 10 µg for 8 weekly doses) were tested for safety in combination with concurrent radiotherapy of the injected lesion. Main Outcomes and Measures: Primary end points were safety and tolerability. Secondary and exploratory end points included local response rates as well as measurement of antitumor immunity with immunohistochemistry and T-cell receptor (TCR) sequencing of tumor-infiltrating and circulating lymphocytes. Results: Twelve patients (median [range] age, 65 [34-78] years; 8 [67%] female) were treated across the 2 dose cohorts. Intratumoral GLA-SE was well tolerated, with only 1 patient (8%) experiencing a grade 2 adverse event. All patients achieved local control of the injected lesion after 8 doses, with 1 patient having complete regression (mean regression, -25%; range, -100% to 4%). In patients with durable local response, there were detectable increases in tumor-infiltrating lymphocytes. In 1 patient (target lesion -39% at 259 days of follow-up), TCR sequencing revealed expansion of preexisting and de novo clonotypes, with convergence of numerous rearrangements coding for the same binding sequence (suggestive of clonal convergence to antitumor targets). Single-cell sequencing identified these same expanded TCR clones in peripheral blood after treatment; these T cells had markedly enhanced Tbet expression, suggesting TH1 phenotype. Conclusions and Relevance: In this nonrandomized controlled trial, IT GLA-SE with concurrent radiotherapy was well tolerated and provided more durable local control than radiotherapy alone. Patients with durable local response demonstrated enhanced IT T-cell clonal expansion, with matched expansion of these clonotypes in the circulation. Additional studies evaluating synergism of IT GLA-SE and radiotherapy with systemic immune modulation are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02180698.

The impact of facility type and volume on treatment and overall survival in craniopharyngioma.

BACKGROUND: Craniopharyngiomas are uncommon benign sellar and parasellar tumors with high overall survival (OS) and recurrence rates. Treatment is often surgical but may include adjuvant therapies. The impact of adjuvant therapy and surgical approach have been evaluated, however, facility volume and type have not. The purpose of this study is to analyze the influence of facility volume and type on treatment modalities, extent of surgery and survival of craniopharyngioma. METHODS: The 2004-2016 National Cancer Database (NCDB) was queried for patients diagnosed with craniopharyngioma. Facilities were classified by type (academic vs. non-academic) and low-volume center (LVC) (Treating < 8 patients over the timeline) versus high-volume center (HVC), (Treating ≥ 8 patients over the timeline). Differences in treatment course, outcomes, and OS by facility type were assessed. RESULTS: 3730 patients (51.3% female) with mean age 41.2 ± 22.0 were included with a 5-year estimated OS of 94.8% (94.0-95.5%). 2564 (68.7%) patients were treated at HVC, of which 2142 (83.5%) were treated at academic facilities. Patients treated at HVC's were more likely to undergo both surgery and radiation. Surgical approach at HVC was more likely to be endoscopic. Patients treated at HVC demonstrated significantly higher 5-year OS compared to patients treated at LVC (96% [95% CI 95.6-97.1% versus 91.2% [95% CI 89-92.7%] with lower risk of mortality (Hazard ratio [95% CI] = 0.69 [0.56-0.84]). CONCLUSION: Treatment of craniopharyngioma at HVC compared to LVC is associated with improved OS, lower 30- and 90-day postoperative mortality risk, and more common use of both radiotherapy and endoscopic surgical approach.

Racial and ethnic disparities in the presentation size and timing of pituitary adenomas resected via endoscopic endonasal approach.

KEY POINTS: In a single-center cohort of pituitary adenoma patients, non-White race independently predicted larger tumor size at initial presentation. Uninsured patients suffered a significantly higher rate of pituitary apoplexy at initial presentation. Geographically distant care appeared to present a greater barrier for non-White and Hispanic patients relative to their White and non-Hispanic counterparts.

Acute airway obstruction requiring nasotracheal intubation following hypoglossal neuromonitoring: a case report.

BACKGROUND: Intraoperative neurophysiological monitoring (IONM) is utilized for both the localization of critical structures and for real time detection and prevention of intraoperative neurological injury. Use of IONM to monitor the hypoglossal nerve is performed during neurosurgical, otolaryngological, and vascular procedures to improve surgical outcomes. There is a paucity of literature describing potential complications of IONM of the hypoglossal nerve, especially with respect to airway compromise. Here we present our findings regarding a case of acute airway obstruction following hypoglossal nerve monitoring. CASE PRESENTATION: A 54-year-old male was admitted for left far-lateral craniotomy and microsurgical clipping of a left posterior inferior cerebellar artery (PICA) aneurysm. Following induction and intubation but prior to the procedure start, the patient was placed in the ¾ prone position with the left side up and his neck was flexed approximately 10 degrees. He then underwent placement of subdermal needle electrodes into the facial muscles, trapezius muscles, soft palate, and tongue for IONM. The procedure lasted 523 minutes and was completed without complication. However, approximately one hour after emergence from general anesthesia, the patient experienced progressive difficulty breathing secondary to severe lingual swelling. He required emergent placement of a nasotracheal tube guided by a fiberoptic bronchoscope. He remained intubated for 3 days and was treated with dexamethasone, after which the swelling resolved, and the patient was successfully extubated. CONCLUSIONS: Acute lingual edema is a potentially life-threatening phenomenon that can lead to rapid airway compromise. Generally, causes of acute lingual swelling include hemorrhage, edema, infarction, and infection. In the case described above, we suspect traumatic injury to the tongue's vascular supply caused a deep tissue hematoma leading to postoperative acute lingual swelling and airway obstruction. With the widespread use of IONM, it becomes essential for providers to be aware that perioperative airway compromise is a potentially life-threatening complication, especially with respect to monitoring of the hypoglossal nerve. Awake fiberoptic nasotracheal intubation can successfully be employed to establish an emergency airway in such situations.

Impact of Treatment Modalities upon Survival Outcomes in Skull Base and Clival Chordoma: An NCDB Analysis.

Objectives Skull base chordomas are locally aggressive malignant tumors derived from the notochord remnant. There are limited large-scale studies examining the role and extent of surgery and radiation therapy. Design Analysis of the National Cancer Database (NCDB) was performed to evaluate the survival outcomes of various treatments, and to assess for predictors of overall survival (OS). Participants This is a retrospective, population-based cohort study of patients diagnosed with a clival/skull base chordoma between 2004 and 2015 in the NCDB. Main Outcome Measures The primary outcome was overall survival (OS). Results In all, 468 cases were identified. Forty-nine percent of patients received surgery and 20.7% had positive margins. Mean age at diagnosis was 48.4 years in the surgical cohort, and 55% were males. Of the surgical cohort, 33.8% had negative margins, 20.7% had positive margins, and 45.5% had unknown margin status. Age ≥ 65 (hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 1.63-5.76; p < 0.001), diagnosis between 2010 and 2015 (HR: 0.49; 95% CI: 0.26-0.90; p = 0.022), tumor size >5 cm (HR: 2.29; 95% CI: 1.26-4.15; p = 0.007), and government insurance (HR: 2.28; 95% CI: 1.24-4.2; p = 0.008) were independent predictors of OS. When comparing surgery with or without adjuvant radiation, no survival differences were found, regardless of margin status ( p = 0.66). Conclusion Surgery remains the mainstay of therapy. Advanced age (>65 years), large tumor size, and government insurance were predictors of worse OS. Whereas negative margins and the use of adjuvant radiation did not appear to impact OS, these may very well reduce local recurrences. A multidisciplinary approach is critical in achieving optimal outcomes in this challenging disease.

Characteristics and Outcomes in Pediatric Versus Adult Craniopharyngiomas: A Systematic Review and Meta-Analysis.

BACKGROUND: Craniopharyngiomas account for 1.2% to 4.6% of all intracranial tumors. Although age at presentation is distributed bimodally, with a pediatric peak occurring between 5 and 15 years and an adult peak between 50 and 70 years, presentation, treatment, and outcome differences between these two craniopharyngioma populations have not been thoroughly characterized. OBJECTIVE: To compare treatments and outcomes between adult and pediatric craniopharyngiomas. METHODS: This is a systematic review and meta-analysis. Web of Science, MEDLINE, and Scopus databases were searched for primary studies reporting postoperative complications, functional outcomes, recurrence, and overall survival in patients with craniopharyngioma undergoing surgery. RESULTS: The search yielded 1,202 unique articles, of which 106 (n=4,202 patients) met criteria for qualitative synthesis and 23 (n=735 patients) met criteria for meta-analysis. Compared with adult, pediatric craniopharyngiomas were less likely to present with visual defects (odds ratio [OR] 0.54, 95% CI 0.36-0.80) or cognitive impairment (OR 0.29, 95% CI 0.12-0.71) and more likely with headaches (OR 2.08, 95% CI 1.16-3.73). Children presented with significantly larger tumors compared with adults (standardized mean difference 0.68, 95% CI 0.38-0.97). Comparing functional outcomes, pediatric patients sustained higher rates of permanent diabetes insipidus (OR 1.70, 95% CI 1.13-2.56), obesity (OR 3.15, 95% CI 1.19-8.31), and cranial nerve and/or neurological defects (OR 4.87, 95% CI 1.78-13.31) than adults. No significant differences were found in rates of postoperative cerebrospinal fluid leak, overall or progression-free survival, or recurrence. CONCLUSION: Adult and pediatric craniopharyngiomas seem to have fundamental differences in clinical presentation and functional outcomes. These patients frequently require multimodality treatment and are best managed with a multidisciplinary team and an individualized approach.

Impact of esthesioneuroblastoma treatment delays on overall patient survival.

OBJECTIVES: To characterize clinical factors associated with esthesioneuroblastoma treatment delays and determine the impact of these delays on overall survival. STUDY DESIGN: Retrospective database analysis. METHODS: The 2004-2016 National Cancer Database was queried for patients with esthesioneuroblastoma managed by primary surgery and adjuvant radiation. Durations of diagnosis-to-treatment initiation (DTI), diagnosis-to-treatment end (DTE), surgery-to-RT initiation (SRT), radiotherapy treatment (RTD), and total treatment package (TTP) were analyzed. The cohort was split into two groups for each delay interval using the median time as the threshold. RESULTS: A total of 814 patients (39.6% female, 88.5% white) with mean ± SD age of 52.6 ± 15.1 years who underwent both esthesioneuroblastoma surgery and adjuvant radiotherapy were queried. Median DTI, DTE, SRT, RTD, and TTP were 34, 140, 55, 45, and 101 days, respectively. A significant association was identified between increased regional radiation dose above 66 Gy and decreased DTI (OR = 0.54, 95% CI 0.35-0.83, p = 0.01) and increased RTD (OR = 3.94, 95% CI 2.36-6.58, p < 0.001) durations. Chemotherapy administration was linked with decreased SRT (OR = 0.64, 95% CI 0.47-0.89, p = 0.01) and TTP (OR = 0.59, 95% CI 0.43-0.82, p = 0.001) durations. Cox proportional-hazards analysis revealed that increased RTD was associated with decreased survival (HR = 1.80, 95% CI 1.26-2.57, p < 0.005), independent of age, sex, race, regional radiation dose, facility volume, facility type, insurance status, modified Kadish stage, chemotherapy status, Charlson-Deyo comorbidity index, and surgical margins. CONCLUSIONS: Delays during, and prolongation of radiotherapy for esthesioneuroblastoma appears to be associated with decreased survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:764-772, 2023.