Topical Application of 5-Fluorouracil for the Treatment of Sinonasal Adenocarcinoma and Inverted Papilloma.

BACKGROUND: Sinonasal tumors represent a rare and heterogeneous group of rhinologic neoplasms. Even with advancements in surgical approaches, mortality rates of patients with sinonasal adenocarcinoma (SNAC) have not significantly improved and persistently high rates of recurrence in certain patients with inverted papilloma (IP) are seen. The use of 5-fluorouracil (5-FU) has been successfully described as an adjuvant treatment of SNAC and in the prevention of IP recurrence. OBJECTIVE: This review aims to present the current evidence on the management of SNAC and IP with topical 5-FU. METHODS: A three-author independent literature review was conducted to identify research involving the use of topical 5-FU for the treatment of SNAC and IP. A total of nine papers on the treatment of SNAC and IP were collected. RESULTS: The earliest study looking at the combination of adjuvant low-dose radiation and topical 5-FU for adenocarcinoma of the ethmoid sinus showed a 5-year survival rate of 100%. A follow-up study evaluating a similar protocol reported adjusted disease-free survival at 2, 5, and 10 years of 96%, 87%, and 74%, respectively. Similar results have been demonstrated for adjuvant 5-FU use following endoscopic resection and have even been described in the novel setting of transcutaneous 5-FU delivery following frontal trephination. Topical 5-FU has also been described in the treatment of aggressive IP. The largest case series described the use of 5-FU for eighteen cases and demonstrated only a single recurrence. CONCLUSION: The use of topical 5-FU currently represents an underutilized therapeutic modality within the treatment of rhinologic neoplasms. Available literature suggests that neoadjuvant use of topical 5-FU can improve survival and decrease recurrence for SNAC and IP. However, the small sample sizes prevent advocation for routine use in the general population and further research on 5-FU is necessary.

Evaluation of Rhinology Fellowship Program Websites.

Objectives: Applicants for rhinology fellowship often utilize program websites to make informed application decisions. Although the American Rhinologic Society (ARS), the professional organization of rhinologists in the United States, maintains a directory of rhinology fellowships that includes basic information for each program, the ARS discloses that the information is provided directly by program directors and may therefore be inconsistent, inaccurate, or outdated. Methods: Our study evaluates the content and comprehensiveness of rhinology fellowship program websites in 31 areas related to either clinical training, research, application process, incentives, or administrative communications. Results: Of 32 unique rhinology fellowship programs, 29 of 32 (90.6%) had websites. On average program websites included 12.1 of the 31 items analyzed (39.0%). Information related to clinical training (mean 54.2%) and research (mean 60.9%) was included more often than information related to application process (mean 50.6%), and incentives (mean 14.9%). Programs with [Formula: see text] 5 dedicated physician faculty included more items than smaller programs (15.3 vs. 11.7 items, P = 0.015). Conclusion: Websites included information on clinical training and research more often than on incentives, even though these factors are important to many applicants. Few programs detailed past or ongoing research opportunities, which if included could help applicants identify mentors with similar research interests. Most websites had less than half of factors analyzed, emphasizing need for continued improvement.

Facility Volume and Changing Facilities for Postoperative Radiotherapy in Salivary Gland Cancer.

OBJECTIVES: Changing location of postoperative radiotherapy (PORT) after treatment at a high-volume facility (HVF) is associated with worse survival in various head and neck cancers. Our study investigates this relationship in salivary gland cancer (SGC). METHODS: The 2004-2016 National Cancer Database was queried for all cases of adult SGC treated with surgery and PORT with or without adjuvant chemotherapy. Patients with multiple cancer diagnoses, metastatic disease, or unknown PORT facility were excluded. Reporting facilities with >95th percentile annual case volume were classified as HVFs, the remainder were classified low-volume facilities (LVFs). RESULTS: A total of 7885 patients met inclusion criteria, of which 418 (5.3%) were treated at an HVF. Patients treated at an HVF had higher rates clinical nodal positivity (18.2% vs. 14.0%, p < 0.001) and clinical T3/T4 (27.3% vs. 20.7%, p = 0.001) disease. Patients at HVFs changed facility for PORT at lower rates (18.9% vs. 24.5%, p = 0.009). Patients treated at an HVF had higher 5-year overall survival (5-OS) than those treated at an LVF (79.0% vs. 72.0%, p = 0.042). Patients treated at an HVF that changed PORT facility had worse 5-OS (60.8% vs. 83.2%, p < 0.001). Radiation facility change was an independent predictor of worse survival in patients treated at an HVF (HR: 8.99 [3.15-25.67], p < 0.001) but not for patients treated at a LVF (HR: 1.11 [0.98-1.25], p = 0.109). CONCLUSIONS: Patients treated at an HVF changing facility for PORT for SGC experience worse survival. Our data suggest patients treated surgically at an HVF should be counseled to continue their PORT at the same institution. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Impact and determinants of door in-door out time for stroke thrombectomy transfers in a large hub-and-spoke network.

INTRODUCTION: The mantra "time is brain" cannot be overstated for patients suffering from acute ischemic stroke. This is especially true for those with large vessel occlusions (LVOs) requiring transfer to an endovascular thrombectomy (EVT) capable center. We sought to evaluate the spoke hospital door in-door out (DIDO) times for patients transferred to our hub center for EVT. METHODS: Individuals who first presented with LVO to a spoke hospital and were then transferred to the hub for EVT were retrospectively identified from a prospectively maintained database from January 2019 to November 2022. DIDO was defined as the time between spoke hospital door in arrival and door out exit. Baseline characteristics, treatments, and outcomes were compared, dichotomizing DIDO at 90 minutes based in the American Heart Association goal for DIDO ≤90 minutes for 50% of transfers. Multivariable regression analyses were performed for determinants of the 90-day ordinal modified Rankin Scale (mRS) and DIDO. RESULTS: We identified 194 patients transferred for EVT with available DIDO. The median age was 67 years (IQR 57-80), and 46% were female. The median National Institutes of Health Stroke Scale (NIHSS) was 16 (10-20), 50% were treated with intravenous thrombolysis at a spoke, and TICI 2B-3 reperfusion was achieved in 87% at the hub. The median DIDO was 120 minutes (97-149), with DIDO ≤90 minutes achieved in 18%. DIDO was a significant determinant of 90-day ordinal mRS (B = 0.007, 95% CI = 0.001-0.012, p = 0.013), even when accounting for the last known well-to-spoke door in, spoke door out-to-hub arrival, hub arrival-to-puncture, puncture-to-first pass, age, NIHSS, intravenous thrombolysis, TICI 2B-3, and symptomatic intracranial hemorrhage. Importantly, determinants of DIDO included Black race or Hispanic ethnicity (B = 0.918, 95% CI = 0.010-1.826, p = 0.048), atrial fibrillation or heart failure (B = 0.793, 95% CI = 0.257-1.329, p = 0.004), and basilar LVO location (B = 2.528, 95% CI = 1.154-3.901, p < 0.001). CONCLUSION: Spoke DIDO was the most important period of time for long-term outcomes of LVO stroke patients treated with EVT. Targets were identified to reduce DIDO and improve patient outcomes.

First multicenter study evaluating the utility of the BENCHMARKTM BMXTM 81 large-bore access catheter in neurovascular interventions.

INTRODUCTION: This study is the first multicentric report on the safety, efficacy, and technical performance of utilizing a large bore (0.081″ inner diameter) access catheter in neurovascular interventions. METHODS: Data were retrospectively collected from seven sites in the United States for neurovascular procedures via large bore 0.081″ inner diameter access catheter (Benchmark BMX81, Penumbra, Inc.). The primary outcome was technical success, defined as the access catheter reaching its target vessel. Safety outcomes included periprocedural device-related and access site complications. RESULTS: There were 90 consecutive patients included. The median age of the patients was 63 years (IQR: 53, 68); 53% were female. The most common interventions were aneurysm embolization (33.3%), carotid stenting (12.2%), and arteriovenous malformation embolization (11.1%). The transradial approach was most used (56.7%), followed by transfemoral (41.1%). Challenging anatomic variations included severe vessel tortuosity (8/90, 8.9%), type 2 aortic arch (7/90, 7.8%), type 3 aortic arch (2/90, 2.2%), bovine arch (2/90, 2.2%), and severe angle (<30°) between the subclavian artery and target vessel (1/90, 1.1%). Technical success was achieved in 98.9% of the cases (89/90), with six cases requiring a switch from radial to femoral (6.7%) and one case from femoral to radial (1.1%). There were no access site complications or complications related to the 0.081″ catheter. Two postprocedural complications occurred (2.2%), unrelated to the access catheter. CONCLUSION: The BMX™ 81 large-bore access catheters was safe and effective in both radial and femoral access across a wide range of neurovascular procedures, achieving high technical success without any access site or device-related complications.

Retracted Publications in Otolaryngology-Head and Neck Surgery: What Mistakes Are Being Made?

Objectives: Retraction of publications is critical to maintaining scientific integrity, yet there is a lack of research on its occurrence in Otolaryngology. This study investigates characteristics, trends, and reasons for retraction of publications in otolaryngology journals. Study Design: Bibliometric analysis. Setting: PubMed, Scopus, Web of Science. Methods: A PubMed search for publications retracted during 1990 to 2022 from the top 60 journals with the subject "Otorhinolaryngology" using Scopus' CiteScore was performed. Publications were excluded if they were not in English, had missing information or did not have available abstracts or full-text. Publication and retraction dates, journal, country of origin, citation counts, journal impact factor (JIF), topic, and reason for retraction were recorded. Pearson correlation coefficients were calculated to identify potential associations in the data. Results: Fifty-three publications were included. The 2020s had the highest number of retractions per year (4.33), with publications being retracted on average, 35 months after initial publication. The most common retracted topic and country of origin were head and neck (26.4%) and China (17.0%), respectively. Most publications were retracted because of plagiarism or duplicate publication (52.8%). Mean citation count was 6.92 ± 8.32 and mean JIF was 2.80 ± 1.35. Citation count was positively associated with months until retraction (r = .432, P = .001). There was no significant correlation between months to retraction and JIF (r = .022, P = .878). Conclusion: The most cited reasons for retraction were plagiarism and duplicate publication. An understanding of the reasons for retraction can better position journals to enforce more meticulous review standards and reduce such publications from being published. Level of Evidence: Level 4.

Association between potentially inappropriate medications prescription and health-related quality of life among US older adults.

BACKGROUND: Potentially inappropriate medications (PIMs) are associated with worse health outcomes among older adults. Our objective was to examine the association between PIM prescription and health-related quality of life (HRQoL) among older adults in the United States using nationally representative data. METHODS: This was a retrospective study utilizing 2011-2015 Medical Expenditure Panel Survey (MEPS) data. Community dwelling US adults aged 65 years or older were included. A qualified definition operationalized from the 2019 American Geriatrics Society Beers Criteria® was used to define exposure to PIMs during the study period. The Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) were used to measure HRQoL. Survey-weighted linear regression models were constructed to investigate the association between PIM exposure and participants' PCS and MCS scores. Analyses were stratified across three age cohorts (65-74, 75-85, and ≥85 years). RESULTS: Unadjusted analysis showed poorer scores in the PIM exposed group for both PCS and MCS (all p < 0.001). PIM exposure was associated with poorer PCS scores across all age groups with those aged 65-74 years (adjusted regression coefficient = -1.60 [95% CI = -2.27, -0.93; p < 0.001]), those 75-84 years (adjusted regression coefficient: -1.49 [95% CI = -2.45, -0.53; p = 0.003]), and those 85 years and older (adjusted regression coefficient = -1.65 [95% CI = -3.03, -0.27; p = 0.02]). PIM exposure was also associated with poorer MCS scores in participants aged 65-74 years (adjusted regression coefficient = -0.69 [95% CI = -1.16, -0.22; p = 0.004]) and 85 years and older (adjusted regression coefficient = -2.01 [95% CI = -3.25, -0.78; p = 0.002]). CONCLUSIONS: Our results suggest that patients' exposure to PIMs is associated with poorer HRQoL. Further work is needed to assess whether interventions to deprescribe PIMs may help to improve patients' HRQoL.

A comprehensive review on the pharmacological role of gut microbiome in neurodegenerative disorders: potential therapeutic targets.

Neurological disorders, including Alzheimer and Parkinson's, pose significant challenges to public health due to their complex etiologies and limited treatment options. Recent advances in research have highlighted the intricate bidirectional communication between the gut microbiome and the central nervous system (CNS), revealing a potential therapeutic avenue for neurological disorders. Thus, this review aims to summarize the current understanding of the pharmacological role of gut microbiome in neurological disorders. Mounting evidence suggests that the gut microbiome plays a crucial role in modulating CNS function through various mechanisms, including the production of neurotransmitters, neuroactive metabolites, and immune system modulation. Dysbiosis, characterized by alterations in gut microbial composition and function, has been observed in many neurological disorders, indicating a potential causative or contributory role. Pharmacological interventions targeting the gut microbiome have emerged as promising therapeutic strategies for neurological disorders. Probiotics, prebiotics, antibiotics, and microbial metabolite-based interventions have shown beneficial effects in animal models and some human studies. These interventions aim to restore microbial homeostasis, enhance microbial diversity, and promote the production of beneficial metabolites. However, several challenges remain, including the need for standardized protocols, identification of specific microbial signatures associated with different neurological disorders, and understanding the precise mechanisms underlying gut-brain communication. Further research is necessary to unravel the intricate interactions between the gut microbiome and the CNS and to develop targeted pharmacological interventions for neurological disorders.

Outcomes with General Anesthesia Compared to Conscious Sedation for Endovascular Treatment of Medium Vessel Occlusions: Results of an International Multicentric Study.

BACKGROUND: Optimal anesthetic strategy for the endovascular treatment of stroke is still under debate. Despite scarce data concerning anesthetic management for medium and distal vessel occlusions (MeVOs) some centers empirically support a general anesthesia (GA) strategy in these patients. METHODS: We conducted an international retrospective study of MeVO cases. A propensity score matching algorithm was used to mitigate potential differences across patients undergoing GA and conscious sedation (CS). Comparisons in clinical and safety outcomes were performed between the two study groups GA and CS. The favourable outcome was defined as a modified Rankin Scale (mRS) 0-2 at 90 days. Safety outcomes were 90-days mortality and symptomatic intracranial hemorrhage (sICH). Predictors of a favourable outcome and sICH were evaluated with backward logistic regression. RESULTS: After propensity score matching 668 patients were included in the CS and 264 patients in the GA group. In the matched cohort, either strategy CS or GA resulted in similar rates of good functional outcomes (50.1% vs. 48.4%), and successful recanalization (89.4% vs. 90.2%). The GA group had higher rates of 90-day mortality (22.6% vs. 16.5%, p < 0.041) and sICH (4.2% vs. 0.9%, p = 0.001) compared to the CS group. Backward logistic regression did not identify GA vs CS as a predictor of good functional outcome (OR for GA vs CS = 0.95 (0.67-1.35)), but GA remained a significant predictor of sICH (OR = 5.32, 95% CI 1.92-14.72). CONCLUSION: Anaesthetic strategy in MeVOs does not influence favorable outcomes or final successful recanalization rates, however, GA may be associated with an increased risk of sICH and mortality.

Elective Neck Dissection in cT1-4 N0M0 Head and Neck Basaloid Carcinoma.

OBJECTIVE: To investigate the survival benefit of elective neck dissection (END) over neck observation in surgically resected cT1-4 N0M0 head and neck basaloid carcinoma (HNBC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2006 to 2017 hospital-based National Cancer Database. METHODS: Patients with surgically resected cT1-4 N0M0 HNBC were selected. Linear, binary logistic, Kaplan-Meier, and Cox proportional hazards regression models were implemented. RESULTS: Of 857 patients satisfying inclusion criteria, the majority were male (77.0%) and white (88.1%) with disease of the oral cavity (21.5%) or oropharynx (42.9%) classified as high grade (76.9%) and cT1-2 (72.9%). 389 (45.4%) patients underwent END. END utilization between 2006 and 2017 increased for cT1-2 disease (33.3% vs 56.9%, R2 = .699) but remained relatively constant for cT3-4 disease (66.7% vs 57.9%, R2 = .062). One-hundred and fifteen (29.6%) ENDs detected occult nodal metastases (ONMs). The 5-year overall survival (OS) of patients undergoing neck observation and END was 65.6% and 66.8%, respectively (P = .652). END was not associated with improved OS in survival analyses stratified by patient demographics, clinicopathologic features, and adjuvant therapy. Compared with surgery alone, adjuvant radiotherapy (adjusted hazard ratio: 0.74, 95% confidence interval [CI]: 0.57-0.97, P = .031) was associated with improved OS. END (hazard ratio [HR]: 0.96, 95% CI: 0.71-1.28, P = .770) and ONM (HR: 1.12, 95% CI: 0.78-1.61, P = .551) were not associated with OS. CONCLUSION: END is performed in nearly half of patients with HNBC but is not associated with improved OS, even after stratifying survival analyses by patient demographics, clinicopathologic features, and adjuvant therapy. The rate of ONM approaching 30%, however, justifies inclusion of END in the surgical management of HNBC.

Smoking impacts outcomes in transcervical Zenker's diverticulectomy.

PURPOSE: There is sparse literature discussing the impact of smoking on postoperative outcomes following surgical treatment of Zenker's diverticulum. In this study, we seek to characterize differences in the management and outcomes of open Zenker's diverticulectomy based on patient smoking status. METHODS AND MATERIALS: This paper is a retrospective cohort review. The 2005-2018 American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) database was queried for patients undergoing open Zenker's diverticulectomy. Chi-square and multivariable logistic regression were performed to determine statistical associations between postoperative outcomes and smoking status. RESULTS: Of the 715 identified patients, 70 (9.8 %) were smokers and 645 (91.2 %) were non-smokers. Smokers were younger than non-smokers (mean 63.9 vs. 71.7 years, p < 0.001) and more likely to have a prolonged operative time (20.0 % vs. 11.6 %, p = 0.044). On multivariable regression analysis controlling for demographics and comorbidities, smokers had greater odds than non-smokers for developing overall postoperative complications (OR: 2.776, p = 0.013), surgical infections (OR: 3.194, p = 0.039), medical complications (OR: 3.563, p = 0.011), and medical infections (OR: 1.247, p = 0.016). Smokers also had greater odds for requiring ventilation/intubation (OR: 8.508, p = 0.025) and having a prolonged postoperative stay (OR: 2.425, p = 0.030). CONCLUSION: In a cohort of patients undergoing transcervical Zenker's diverticulectomy, smokers are at increased risk for overall complications, medical complications, medical infections, surgical infections, prolonged postoperative stay, and ventilation/intubation.

A core-lab adjudicated analysis of single-stent assisted coiling of wide-neck bifurcation aneurysms.

BACKGROUND AND PURPOSE: Core-lab adjudicated data regarding the efficacy of the single-stent assisted aneurysm coiling technique 'L-stenting' are lacking. We present a multicenter, core-lab adjudicated study evaluating the safety and effectiveness of single-stent assisted coiling in the treatment of wide-neck bifurcation aneurysms (WNBAs). METHODS: Consecutive patients who underwent L-stenting for WNBAs at three academic institutions between 2015 and 2019 were included in this retrospective study. Clinical safety and efficacy outcomes were gathered from the patient chart, and angiographic imaging was evaluated by core lab analysis. Safety and efficacy outcomes were summarized and predictors of safety and efficacy were calculated. RESULTS: Of 128 patients treated, 124 had angiographic outcome data at last follow-up. Of those, 110 had adequate (core-lab adjudicated modified Raymond Roy (mRR) score of 1 or 2) occlusion (88.7%). During follow-up, 19 patients (14.8%) required retreatment. There were 17 complications experienced in 12 patients: intraoperative (n=8, 6.25%), perioperative (n=5, 3.9%), or delayed (n=6; n=4 attributed to device/procedure, 3.1%). Significant predictors of complete occlusion were smaller aneurysm size and use of the jailing technique (P=0.0276). Significant predictors of retreatment were larger size, neck size, and larger dome to neck ratio (P=0.0008). CONCLUSION: This study provides multicenter, core-lab adjudicated angiographic data regarding the efficacy of single-stent assisted coiling for WNBAs. This study acts as a validated comparator for future studies investigating novel devices or techniques for treating this challenging subgroup of aneurysms.

The Impact of Preprocedural Platelet Function Testing on Periprocedural Complication Rates Associated With Pipeline Flow Diversion: An International Multicenter Study.

BACKGROUND AND OBJECTIVES: Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using pipeline embolization device (PED). We aimed to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel. METHODS: Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT before treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72 h of embolization were identified. Complication rates were compared between PFT and non-PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or χ 2 tests. A P -value <.05 was statistically significant. RESULTS: 580 patients underwent PED embolization with 262 patients dichotomized to the PFT group and 318 patients to the non-PFT group. 13.7% of PFT group patients were clopidogrel nonresponders requiring changes in their pre-embolization DAPT regimen. Five percentage of PFT group [2.8%, 8.5%] patients experienced thromboembolic complications vs 1.6% of patients in the non-PFT group [0.6%, 3.8%] ( P = .019). Two (15.4%) PFT group patients with thromboembolic complications experienced permanent neurological disability vs 4 (80%) non-PFT group patients. 3.7% of PFT group patients [1.5%, 8.2%] and 3.5% [1.8%, 6.3%] of non-PFT group patients experienced hemorrhagic intracranial complications ( P > .9). CONCLUSION: Preprocedural PFT before PED treatment of intracranial aneurysms in patients premedicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure-related intracranial complications.

Sex-Stratified Predictors of Prolonged Operative Time and Hospital Admission in Outpatient Parathyroidectomy.

Our retrospective database study investigates sex-stratified predictors of prolonged operative time (POT) and hospital admission following parathyroidectomy for primary hyperparathyroidism (PHPT). The 2016 to 2018 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was queried for patients with PHPT undergoing parathyroidectomy. Cases analyzed were all outpatient status, arrived from home, coded as non-emergent, and elective. POT was defined by the 75th percentile. Hospital admission was defined as LOS ≥ 1 day. Univariate and multivariable binary logistic regressions were utilized. Of 7442 cases satisfying inclusion criteria, the majority were female (78.0%) and White (78.5%). Median OT (IQR) for females and males was 77 (58-108) and 81 (61-109) minutes, respectively (P = 0.003). 1965 (33.9%) females and 529 (32.3%) males required hospital admission. Independent predictors of POT included ASA class III/IV (aOR 1.342, 95% CI 1.007-1.788) and obesity (aOR 1.427, 95% CI 1.095-1.860) for males (P < 0.05). Independent predictors of hospital admission included age (aOR 1.008, 95% CI 1.002-1.014), ASA class III/IV (aOR 1.490, 95% CI 1.301-1.706), obesity (aOR 1.309, 95% CI 1.151-1.489), dyspnea (aOR 1.394, 95% CI 1.041-1.865), chronic steroid use (aOR 1.674, 95% CI 1.193-2.351), and COPD (aOR 1.534, 95% CI 1.048-2.245) for females (P < 0.05); and ASA class III/IV (aOR 1.931, 95% CI 1.483-2.516) and bleeding disorder (aOR 2.752, 95% CI 1.443-5.247) for males (P < 0.005). In conclusion, predictors of POT and hospital admission following parathyroidectomy for PHPT differed by patient sex. Identifying patients at risk for POT and hospital admission may optimize healthcare resource utilization. Level of Evidence: IV. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04444-3.

Extranodal extension in laryngeal squamous cell carcinoma.

Objective: Although large retrospective database studies have associated extranodal extension (ENE) with worse survival in several head and neck cancers, the prognostic significance of ENE in laryngeal squamous cell carcinoma (LSCC) remains unclear. Our study examines ENE and overall survival (OS) in LSCC. Methods: The 2006-2017 National Cancer Database was queried for patients with LSCC undergoing surgical resection and neck dissection, with or without adjuvant therapy. Kaplan-Meier and multivariable Cox regression survival analyses were implemented to identify the independent impacts of pathologic nodal (pN) classification and ENE on OS. Results: Of 4208 patients satisfying inclusion criteria, 2343 (55.7%) were pN0/ENE-negative, 1059 (25.2%) were pN1-2/ENE-negative, and 806 (19.2%) were pN1-2/ENE-positive. The 5-year OS of pN0/ENE-negative, pN1-2/ENE-negative, and pN1-2/ENE-positive patients was 62.8%, 56.7%, and 32.9%, respectively (p < .001). Among pN1-2/ENE-positive patients undergoing no adjuvant therapy, adjuvant radiotherapy alone, and adjuvant chemoradiotherapy, 5-year OS was 24.1%, 30.7%, and 36.7%, respectively (p < .001). After adjusting for patient demographics, clinicopathologic features, and adjuvant therapy, ENE-positivity was associated with worse OS than ENE-negativity (adjusted hazard ratio [aHR] 1.76, 95% confidence interval [CI] 1.53-2.02, p < .001). pN1/ENE-positivity (aHR 1.82, 95% CI 1.31-2.54) and pN2/ENE-positivity (aHR 1.89, 95% CI 1.49-2.40) were associated with worse OS than pN1/ENE-negativity (p < .001). Microscopic (aHR 1.83, 95% CI 1.54-2.18) and macroscopic ENE-positivity (aHR 1.75, 95% 1.35-2.26) were associated with worse OS than ENE-negativity (p < .001). Conclusion: ENE-positivity has prognostic significance in LSCC and is associated with worse OS than ENE-negativity. pN classification did not have prognostic significance independent of ENE. ENE should be carefully considered when determining the prognosis of LSCC and selecting adjuvant therapy. Level of Evidence: 4.

Surgical Resection Improves Overall Survival in cT4b Major Salivary Gland Cancer.

OBJECTIVE: To compare surgical and nonsurgical definitive treatment in cT4b major salivary gland cancer (MSGC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2004 to 2019 National Cancer Database. METHODS: The NCDB was queried for patients with cT4b MSGC (N = 976). Patients undergoing definitive treatment with (1) surgical resection + adjuvant therapy, (2) radiotherapy (RT) alone, or (3) chemoradiotherapy (CRT) were included in Kaplan-Meier and Cox survival analyses. RESULTS: Of 219 patients undergoing definitive treatment, 148 (67.6%) underwent surgical resection + adjuvant therapy and 71 (32.4%) underwent RT or CRT. There were no documented mortalities within 90 days of surgical resection. Tumor diameter and nodal metastasis were associated with decreased odds of undergoing definitive treatment (P < 0.025). Patients with positive surgical margins (PSM) had higher 5-year overall survival (OS) than those undergoing definitive RT or CRT (48.5% vs 30.1%, P = 0.018) and similar 5-year OS as those with negative margins (48.5% vs 54.0%, P = 0.205). Surgical resection + adjuvant therapy (adjusted hazard ratio: 0.55, 95% confidence interval [CI]: 0.37-0.84) was associated with higher OS than definitive RT or CRT (P < 0.025). A separate cohort of 961 patients with cT4a tumors undergoing surgical resection + adjuvant therapy was created; cT4a and cT4b (hazard ratio: 1.02, 95% CI: 0.80-1.29, P = 0.896) tumors had similar OS. CONCLUSION: A minority of patients with cT4b MSGC undergo definitive treatment. Surgical resection + adjuvant therapy was safe and associated with higher OS than definitive RT or CRT, despite high rate of PSM. In the absence of clinical trial data, appropriately selected patients with cT4b MSGC may benefit from surgical resection.

Pathogenic Roles for RNASET2 in Clear Cell Renal Cell Carcinoma.

A specific splicing isoform of RNASET2 is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). However, the interplay between wild-type RNASET2 and its splice variant and how this might contribute to the pathogenesis of ccRCC remains poorly understood. We sought to better understand the relationship of RNASET2 in the pathogenesis of ccRCC and the interplay with a pathogenic splicing isoform (RNASET2-SV) and the tumor immune microenvironment. Using data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium, we correlated clinical variables to RNASET2 expression and the presence of a specific RNASET2-SV. Immunohistochemical staining with matched RNA sequencing of ccRCC patients was then utilized to understand the spatial relationships of RNASET2 with immune cells. Finally, in vitro studies were performed to demonstrate the oncogenic role of RNASET2 and highlight its potential mechanisms. RNASET2 gene expression is associated with higher grade tumors and worse overall survival in The Cancer Genome Atlas cohort. The presence of the RNASET2-SV was associated with increased expression of the wild-type RNASET2 protein and epigenetic modifications of the gene. Immunohistochemical staining revealed increased intracellular accumulation of RNASET2 in patients with increased RNA expression of RNASET2-SV. In vitro experiments reveal that this accumulation results in increased cell proliferation, potentially from altered metabolic pathways. RNASET2 exhibits a tumor-promoting role in the pathogenesis of ccRCC that is increased in the presence of a specific RNASET2-SV and associated with changes in the cellular localization of the protein.