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.

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.

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.

Mutational landscape and predictors of survival in head and neck mucosal melanoma.

KEY POINTS: Head and neck mucosal melanomas have a diverse mutational landscape with low mutational burden. A molecular subset (∼13%) has ROS1 mutations, which is an actionable driver mutation. ROS1-mutated patients have improved overall survival likely due to high mutational burden.

Changes in beat-to-beat blood pressure and pulse rate variability following stroke.

Associations between cerebrovascular disease and impaired autonomic function and cerebrovascular reactivity have led to increased interest in variability of heart rate (HRV) and blood pressure (BPV) following stroke. In this study, beat-to-beat pulse rate variability (PRV) and BPV were measured in clinically stable stroke patients (6 ischemic, 2 hemorrhagic) at least one year after their last cerebrovascular event. Beat-to-beat blood pressure (BP) measurements were collected from subjects while resting in the sitting position for one hour. Compared with healthy controls, stroke patients exhibited significantly greater time-domain (standard deviation, coefficient of variation, average real variability) and normalized high-frequency BPV (all p < 0.05). Stroke patients also exhibited lower LF:HF ratios than control subjects (p = 0.003). No significant differences were observed in PRV between the two groups, suggesting that BPV may be a more sensitive biomarker of cerebrovascular function in long-term post-stroke patients. Given a paucity of existing literature investigating beat-to-beat BPV in clinically stable post-stroke patients long (> 1 year) after their cerebrovascular events, this pilot study can help inform future studies investigating the mechanisms and effects of BPV in stroke. Elucidating this physiology may facilitate long-term patient monitoring and pharmacological management to mitigate the risk for recurrent stroke.

Recurrence patterns among patients with sinonasal mucosal melanoma: A multi-institutional study.

OBJECTIVE: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM). METHODS: This was a multi-institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan-Meier tests were used to evaluate disease-free survival (DFS), overall survival (OS), and post-recurrence survival (PRS) reported with standard errors (SE) and log-rank testing used for comparison. Cox-regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported. RESULTS: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60-month DFS (SE) was 15.5% (2.9%), 60-month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60-month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60-month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12-month PRS (HR = 0.32, 95% CI = 0.11-0.92, p = 0.034), and no treatment group was associated with improved 24- or 60-month PRS (p > 0.05). CONCLUSION: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12-month PRS.

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.

Development of a Machine Learning Model to Predict Recurrence of Oral Tongue Squamous Cell Carcinoma.

Despite diagnostic advancements, the development of reliable prognostic systems for assessing the risk of cancer recurrence still remains a challenge. In this study, we developed a novel framework to generate highly representative machine-learning prediction models for oral tongue squamous cell carcinoma (OTSCC) cancer recurrence. We identified cases of 5- and 10-year OTSCC recurrence from the SEER database. Four classification models were trained using the H2O ai platform, whose performances were assessed according to their accuracy, recall, precision, and the area under the curve (AUC) of their receiver operating characteristic (ROC) curves. By evaluating Shapley additive explanation contribution plots, feature importance was studied. Of the 130,979 patients studied, 36,042 (27.5%) were female, and the mean (SD) age was 58.2 (13.7) years. The Gradient Boosting Machine model performed the best, achieving 81.8% accuracy and 97.7% precision for 5-year prediction. Moreover, 10-year predictions demonstrated 80.0% accuracy and 94.0% precision. The number of prior tumors, patient age, the site of cancer recurrence, and tumor histology were the most significant predictors. The implementation of our novel SEER framework enabled the successful identification of patients with OTSCC recurrence, with which highly accurate and sensitive prediction models were generated. Thus, we demonstrate our framework's potential for application in various cancers to build generalizable screening tools to predict tumor recurrence.

Head and neck solitary fibrous tumors: A review of the National Cancer Database.

BACKGROUND: Head and neck solitary fibrous tumors (SFTs) are rare neoplasms, with few large-scale studies describing this entity. We evaluated the demographics and correlates of survival in a large series of SFT patients. METHODS: The 2004-2017 National Cancer Database was queried for head and neck SFT patients receiving definitive surgery. Cox proportional-hazards and Kaplan-Meier analyses assessed overall survival (OS). RESULTS: Of 135 patients, sinonasal (33.1%) and orbital (25.9%) SFTs were most common. Approximately 93% of SFTs were invasive and 64% were classified as hemangiopericytomas. The 5-year OS of skull base SFTs (84.5%) was lower than sinonasal (98.7%) and orbital (90.7%) SFTs (all p < 0.05). Government insurance exhibited higher mortality (HR 5.116; p < 0.001) and lower OS (p = 0.001). CONCLUSION: Head and neck SFTs presented with distinct prognoses based on anatomical origin. Overall survival was particularly worse in patients with skull base SFTs or government insurance. Prognostically, hemangiopericytomas were indistinct from other SFTs.

Skull Base Reconstruction following Surgical Treatment of Sinonasal Malignancies.

Skull base defects following resection of anterior cranial fossa and sinonasal tumors are not uncommon. Advances in endoscopic techniques have allowed for entirely endonasal resection and reconstruction of these tumors. This article discusses techniques in the evaluation and management of anterior skull base defects.

A comparative analysis of treatment efficacy in intermediate-risk thyroid cancer.

PURPOSE: This study aimed to evaluate the efficacy of different treatment combinations on patient survival in intermediate-risk differentiated thyroid cancer (DTC). METHODS: The 2004-2017 National Cancer Database was queried for intermediate-risk papillary (PTC), follicular (FTC), or Hurthle cell (HTC) thyroid cancer patients. Four treatments were analyzed using Kaplan Meier and multivariable Cox regression: surgery, surgery with adjuvant radioiodine ablation (S + RAI), surgery with adjuvant thyroid-stimulating hormone suppression therapy (S + THST), and S + RAI + THST. Kaplan-Meier and multivariable Cox proportional-hazards analyses evaluated treatment-associated overall survival (OS). RESULTS: Of 65,736 patients, 72.2% were female and the average age was 45.4 ± 15.4 years. The 10-year OS rates for PTC, FTC, and HTC were 93.2%, 85.2%, and 78.5%, respectively. S + RAI + THST exhibited higher OS than surgery alone and S + RAI (all p < 0.05). Compared to surgery alone, S + RAI + THST demonstrated reduced mortality in PTC (Hazard Ratio [HR]: 0.628, p < 0.001), FTC (HR: 0.490, p < 0.001), and HTC (HR: 0.520, p = 0.006). Similarly, adjuvant RAI + THST reduced mortality regardless of lymphovascular invasion (HR: 0.490, p < 0.001), N1a (HR: 0.570, p < 0.001) or N1b metastasis (HR: 0.621, p < 0.001), or positive margin status (HR: 0.572, p < 0.001). CONCLUSIONS: Treatment combinations demonstrated varying efficacies in intermediate-risk DTC depending on histology and tumor characteristics, with S + RAI + THST exhibiting the greatest treatment response.

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.

Facility Volume as a Prognosticator of Survival in Locally Advanced Papillary Thyroid Cancer.

OBJECTIVES: To evaluate the influence of facility case-volume on survival in patients with locally advanced papillary thyroid cancer (PTC), and to identify prognostic case-volume thresholds for facilities managing this patient population. STUDY DESIGN: Retrospective database study. METHODS: The 2004-2017 National Cancer Database was queried for patients receiving definitive surgery for locally advanced PTC. Using K-means clustering and multivariable Cox proportional-hazards (CPH) regression, two groups with distinct spectrums of facility case-volumes were generated. Multivariable CPH regression and Kaplan-Meier analysis assessed for the influence of facility case-volume and the prognostic value of its stratification on overall survival (OS). RESULTS: Of 48,899 patients treated at 1304 facilities, there were 34,312 (70.2%) females and the mean age was 48.0 ± 16.0 years. Increased facility volume was significantly associated with reduced all-cause mortality (HR 0.996; 95% CI, 0.992-0.999; p = 0.008). Five facility clusters were generated, from which two distinct cohorts were identified: low (LVF; <27 cases/year) and high (HVF; ≥27 cases/year) facility case-volume. Patients at HVFs were associated with reduced mortality compared to those at LVFs (HR 0.791; 95% CI, 0.678-0.923, p = 0.003). Kaplan-Meier analysis of propensity score-matched N0 and N1 patients demonstrated higher OS in HVF cohorts (all p < 0.001). CONCLUSIONS: Facility case-volume was an independent predictor of improved OS in locally advanced PTC, indicating a possible survival benefit at high-volume medical centers. Specifically, independent of a number of sociodemographic and clinical factors, facilities that treated ≥27 cases per year were associated with increased OS. Patients with locally advanced PTC may, therefore, benefit from referrals to higher-volume facilities. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:443-450, 2023.

Postoperative protocols following endoscopic skull base surgery: An evidence-based review with recommendations.

BACKGROUND: Postoperative management strategies for endoscopic skull base surgery (ESBS) vary widely because of limited evidence-based guidance. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from January 1990 through February 2022 to examine 18 postoperative considerations for ESBS. Nonhuman studies, articles written in a language other than English, and case reports were excluded. Studies were assessed for levels of evidence, and each topic's aggregate grade of evidence was evaluated. RESULTS: A total of 74 studies reporting on 18 postoperative practices were reviewed. Postoperative pain management, prophylactic antibiotics, and lumbar drain use had the highest grades of evidence (B). The literature currently lacks high quality evidence for a majority of the reviewed ESBS precautions. There were no relevant studies to address postoperative urinary catheter use and medical intracranial pressure reduction. CONCLUSION: The evidence for postoperative ESBS precautions is heterogeneous, scarce, and generally of low quality. Although this review identified the best evidence available in the literature, it suggests the urgent need for more robust evidence. Therefore, additional high-quality studies are needed in order to devise optimal postoperative ESBS protocols.

Stage-Specific Survival in Young Patients With Oral Tongue Squamous Cell Carcinoma.

OBJECTIVE: To determine demographic factors and clinicopathologic characteristics associated with survival in young patients (age <45 years) with early- (I-II) or late-stage (III-IV) oral tongue squamous cell carcinoma (OTSCC). STUDY DESIGN: Retrospective database review. SETTING: National Cancer Database. METHODS: A retrospective review of 3262 OTSCC cases in young patients between 2005 and 2014 was performed by using data from the National Cancer Database. Factors affecting 2-year survival in patients with early- and late-stage disease were evaluated via univariate and multivariate analyses. RESULTS: Overall, 1899 patients with early-stage OTSCC and 1363 with late-stage OTSCC were analyzed. In multivariate analysis of early-stage OTSCC, high tumor grade (hazard ratio, 2.08 [95% CI, 1.45-2.99]), local metastasis (2.85 [1.37-5.95]), and tumor size (1.04 [1.02-1.07]) were predictors of mortality. In late-stage OTSCC, African American race (2.79 [1.40-5.56]), positive surgical margins (1.77 [1.07-2.93]), local metastasis (2.20 [1.03-4.72]), distant metastasis (11.66 [2.10-64.73]), depth of invasion (1.03 [1.01-1.05]), and tumor size (1.01 [1.003-1.01]) were predictors of mortality. Subset analysis of clinical N0-stage tumors revealed that treatment with surgery alone was associated with improved survival (P < .001). CONCLUSION: Positive lymph nodes, high tumor grade, and larger tumor size were associated with increased mortality risk in early- and late-stage young OTSCC. More aggressive up-front treatment, including extirpative surgery and elective neck dissection, may be associated with improved outcomes and should be considered in early-stage cases with high-risk features.

Prognostic Utility of Tumor Stage versus American Thyroid Association Risk Class in Thyroid Cancer.

OBJECTIVE: To evaluate the prognostic strengths of American Joint Committee on Cancer (AJCC) staging and American Thyroid Association (ATA) risk classification in well-differentiated thyroid cancer (DTC), and their implications in guiding medical decision-making and epidemiological study designs. METHODS: The 2004-2017 National Cancer Database was queried for DTC patients. Cox proportional hazards (CPH) and Kaplan-Meier analyses modeled patient mortality and overall survival, respectively. Each CPH model was evaluated by its concordance index, measure of explained randomness (MER), Akaike information criterion (AIC), and area under receiver operating characteristic curve (AUC). RESULTS: Overall, 134,226 patients were analyzed, with an average age of 48.1 ± 15.1 years (76.9% female). Univariate CPH models using AJCC staging demonstrated higher concordance indices, MERs, and AUCs than those using ATA risk classification (all p < 0.001). Multivariable CPH models using AJCC staging demonstrated higher concordance indices (p = 0.049), MERs (p = 0.046), and AUCs (p = 0.002) than those using ATA risk classification. The AICs of multivariable AJCC staging and ATA risk models were 7.564 × 104 and 7.603 × 104 , respectively. AJCC stage I tumors were associated with greater overall survival than those classified as ATA low risk, whereas AJCC stages II-III and stage IV tumors demonstrated worse survival than ATA intermediate- and high-risk tumors, respectively (all p < 0.001). CONCLUSION: AJCC staging may be a more predictive system for patient survival than ATA risk. The prognostic utility of these two systems converges when additional demographic and clinical factors are considered. AJCC staging was found to classify patients across a wider range of survival patterns than the ATA risk stratification system. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:205-211, 2023.