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.

Elective Neck Dissection for cT1-4 N0M0 Head and Neck Verrucous Carcinoma.

OBJECTIVE: To investigate the survival benefit of elective neck dissection (END) over neck observation in cT1-4 N0M0 head and neck verrucous carcinoma (HNVC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2006 to 2017 National Cancer Database. METHODS: Patients with surgically resected cT1-4 N0M0 HNVC were selected. Linear, binary logistic, Kaplan-Meier, and Cox proportional hazards regression models were utilized. RESULTS: Of 1015 patients satisfying inclusion criteria, 223 (22.0%) underwent END. The majority of patients were male (55.4%) and white (91.0%) with disease of the oral cavity (67.6%) classified as low grade (90.0%) and cT1-2 (81.8%). The minority of ENDs (4.0%) detected occult nodal metastases. The rate of END increased from 2006 to 2017 for both cT1-2 (16.3% vs 22.0%, p = .126, R2 = 0.405) and cT3-4 (41.7% vs 70.0%, p = .424, R2 = 0.232) disease but these trends were not statistically significant. Independent predictors of undergoing END included treatment at an academic facility (adjusted odds ratio [aOR]: 1.75, 95% confidence interval [CI]: 1.19-2.55), cT3-4 disease (aOR: 3.31, 95% CI: 2.16-5.07), and tumor diameter (aOR: 1.09, 95% CI: 1.01-1.19) (p < 0.05). The 5-year overall survival (OS) of patients treated with and without END was 71.3% and 70.6%, respectively (p = .661). END did not significantly reduce the 5-year hazard of death (adjusted hazard ratio: 1.25, 95% CI: 0.91-1.71, p = .172). END did not significantly improve 5-year OS in univariate and multivariate analyses stratified by several patient, facility, tumor, and treatment characteristics. CONCLUSION: END does not confer an appreciable survival benefit in HNVC, even after stratifying univariate and multivariate analyses by several patient, facility, tumor, and treatment characteristics. LEVEL OF EVIDENCE: Level 4.

Adjuvant Radiation and Survival Following Surgical Resection of Sinonasal Adenocarcinoma.

OBJECTIVES: This study aims to investigate the utility of adjuvant radiation in patients who undergo surgical resection for the management of node-negative sinonasal adenocarcinoma (SNAC). STUDY DESIGN: Retrospective database review. METHODS: The 2004-2016 National Cancer Data Base (NCDB) was used to extract patients with surgically resected node-negative SNAC. Kaplan-Meier survival analysis and Cox-Proportional Hazards Modelling were used to analyze the impact of adjuvant radiation on overall survival (OS) following surgery. RESULTS: 349 patients with SNAC underwent surgical resection. Of these patients, 154 (44.1%) received adjuvant radiotherapy (RT). Although there was no significant difference in race, age, or sex of those receiving RT, those receiving RT have more advanced diseases and are more likely to have positive margins. Kaplan Meier analysis showed no significant difference in 5-year OS in patient who received adjuvant RT in comparison to those who underwent surgical resection alone (65.7% vs. 72.6%, respectively; p = 0.378). In addition, when looking at only patients with positive margins, 5-year OS still did not have a significant difference (73.8% vs. 61.6%, respectively; p = 0.101). Only patients with clinical AJCC T4 showed a statistically significant survival benefit with adjuvant RT (56.9% vs. 29.9%, respectively; p = 0.009). CONCLUSIONS: Adjuvant RT does not appear to provide a significant survival benefit in patients with resected SNAC, with the exception of those with clinically AJCC T4 disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2603-2612, 2023.

Utility of Elective Neck Dissection in Clinically Node-Negative Parotid Malignancy.

OBJECTIVE: We sought to investigate the utility of elective neck dissection (END) in clinically node-negative parotid malignancy through the evaluation of factors that are associated with receiving END and survival analysis of patients who received END. STUDY DESIGN: Retrospective cohort database study. SETTING: The National Cancer Database (NCDB). METHODS: The NCDB was used to extract patients with clinically node-negative parotid malignancy. END was defined as having 5 or more lymph nodes examined pathologically, as previously defined in the literature. Univariate and multivariate analyses were used to compare predictors of receiving END, rates of occult metastasis, and survival. RESULTS: Of the 9405 included patients, 3396 (36.1%) underwent an END. END was most frequently performed for squamous cell carcinoma (SCC) and salivary duct histology. All other histologies were significantly less likely to undergo END compared to SCC (p < .05). Salivary ductal carcinoma and adenocarcinoma had the greatest rates of occult node disease (39.8% and 30.0%, respectively), followed by SCC (29.8%). Kaplan-Meier survival analysis showed a statistically significant increase in 5-year overall survival in patients who received END with poorly differentiated mucoepidermoid (56.2% vs 48.5%, p = .004) along with moderately and poorly differentiated SCC (43.2% vs 34.9%, p = .002; 48.9% vs 36.2%, p < .001, respectively). CONCLUSION: Histological classification is a benchmark for determining which patients should receive an END. We demonstrated an increase in overall survival in patients who undergo END with poorly differentiated tumors of mucoepidermoid and SCC histology. As such, histology should be considered along with clinical T-stage and rate of occult nodal metastasis to determine eligibility for END.

Impact of Prolonged Operative Time on Complications Following Endoscopic Sinonasal Surgery.

OBJECTIVE: To determine how prolonged operative time (POT) impacts 30-day outcomes in patients undergoing endoscopic sinonasal surgery (ESNS). STUDY DESIGN: Retrospective study. METHODS: Data from patients who underwent ESNS (nonsinus, sinus, and extended sinus) between 2005 to 2018 were collected from the American College of Surgeons National Surgical Quality Improvement database. Univariate and multivariate analyses were performed to evaluate the effect of POT on postoperative outcomes. RESULTS: Among 1,994 ESNS cases, 495 nonsinus procedures, 1,191 sinus procedures, and 308 extended sinus procedures were identified. Median OT was 90 minutes (interquartile range [IQR], 51-165 minutes) for nonsinus procedures, 113 minutes (IQR, 66-189 minutes) for sinus procedures, and 187 minutes (IQR, 137-251 minutes) for extended sinus procedures. Other than older age (P = .008), POT was not significantly associated with baseline demographics and comorbidities for patients undergoing non-sinus procedures. Older age (P < .001), White and Black race (P < .001), ASA physical classifications III or IV (P < .001), and several preoperative comorbidities, including obesity (P = .045), and hypertension (P < .001) were associated with POT for sinus procedures. Older age (P = .030), male sex (P = .010), and lower body mass index (P = .004) were associated with POT for extended sinus procedures. After risk-adjustment, POT was independently associated with prolonged hospital stay (LOS) for all procedure categories, and associated with overall surgical complications and postoperative bleeding for sinus and extended sinus procedures specifically. CONCLUSION: POT is independently associated with several adverse outcomes following ESNS, including prolonged LOS, overall surgical complications, and bleeding. Preoperative planning should include optimizing modifiable patient risk factors for POT and identifying surgeon-specific factors to enhance surgical efficiency. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:51-58, 2023.

Extent of Surgery for Follicular Thyroid Carcinoma.

OBJECTIVES: To examine the association between the extent of surgery and overall survival in follicular thyroid cancer (FTC) patients. STUDY DESIGN: Retrospective analysis of the National Cancer Database (NCDB). METHODS: Patients who underwent surgical intervention for FTC from 2004 to 2015 were selected. Patients were >18 years old, with tumor size 1-4 cm, no other malignancies, and >0 follow up time. Patients were divided into two cohorts based on extent of surgery: lobectomy (≥1 lobe resected) and thyroidectomy (total or near total resection). Pearson's chi-squared analysis was used to compare cohorts. Kaplan-Meier survival and Cox hazards models were utilized to determine overall survival between two cohorts with p < 0.05 used for significance. RESULTS: A total of 6871 patients were identified with FTC, of which 1507 patients underwent lobectomy and 5364 patients underwent total thyroidectomy. There were no significant differences in patient demographics, comorbidity index, local spread, or tumor grade. Patients undergoing lobectomy had mean survival of 12.94 versus 12.71 years for those undergoing thyroidectomy. Extent of surgery was not associated with a significant difference in survival (5 years OS = 96% in lobectomy and 95.5% in total thyroidectomy, p = 0.08). Stratification by tumor grade resulted in no significant difference in survival between lobectomy and thyroidectomy. CONCLUSION: Survival time was not significantly different in patients with more extensive resection of FTC. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:993-999, 2023.

Utility of Preoperative Laboratory Testing for Ambulatory Endoscopic Sinonasal Surgery in Low-Risk Patients.

BACKGROUND: Preoperative laboratory tests (PLTs) are often obtained prior to outpatient surgical procedures. The objective of this study is to examine the current practice of routine PLT in low-risk patients undergoing ambulatory endoscopic sinonasal surgery (ESS) and to assess whether such testing impacts surgical outcomes. METHODS: Patients undergoing ambulatory ESS were identified from the 2011 to 2018 NSQIP database. Low-risk patients were defined as American Society of Anesthesiologist class 1 or 2. PLTs were grouped into hematologic, chemistry, coagulation, and liver function tests. Chi-square analyses and independent samples t-tests were conducted to compare categoric and continuous variables, respectively. RESULTS: A total of 664 cases met the inclusion criteria, of which 419 (62.1%) underwent at least one PLT. Of these, the most frequent PLT obtained was a complete blood cell count (92.4%). Major complications occurred in 1.5% of patients. There were no statistically significant differences in overall postoperative complications between those with and without PLT (P = .264). Specifically, no significant difference was seen in the incidence of postoperative bleeding (P = .184), urinary tract infection (P = .444), pulmonary embolism (P = .444), or wound infection (P = .701). On multivariable analyses, PLT status was not significantly associated with any complication (P = .097) or unplanned readmission (P = .898). CONCLUSIONS: Our analysis did not reveal an association between the use of PLT and postoperative morbidity or unplanned readmission in low-risk patients undergoing outpatient ESS.

Reduction of opioid use using regional anesthetic blocks after inguinal hernia repair in a high risk, safety net population.

OBJECTIVE: The transversus abdominis plane (TAP) block is currently being used perioperatively to reduce postoperative opioid requirements. It is unclear whether TAP blocks reduce postoperative opioid requirements for inguinal hernia repairs. The purpose of this retrospective chart study was to determine whether a TAP block reduces postoperative opioid requirements after an inguinal hernia repair in a safety net hospital. DESIGN: This was a retrospective chart review that evaluated patients at University Hospital in Newark, NJ, who had inguinal hernia repairs from January 2011 to July 2019. Patients were divided into two groups depending on whether they had a TAP block or not. The primary outcome was the amount of opioid required in the first 24 hours postoperatively by a patient reported as morphine equivalent dosing (MED). RESULTS: The group that received the TAP block had a mean (95 percent CI) MED of 7.01 mg (6.70, 7.33), and the control group (no TAP block) had a mean MED of 11.6 mg within 24 hours of the inguinal hernia (p = 0.03). There was no significant difference for postoperative visual analog scale (VAS) pain score, presence of nausea, or length of stay. CONCLUSIONS: Patients with TAP block required less morphine equivalence of opioid within a 24 hours period after an inguinal hernia repair.

Uric acid released from poly(ε-caprolactone) fibers as a treatment platform for spinal cord injury.

Spinal cord injury (SCI) is characterized by a primary mechanical phase of injury, resulting in physical tissue damage, and a secondary pathological phase, characterized by biochemical processes contributing to inflammation, neuronal death, and axonal demyelination. Glutamate-induced excitotoxicity (GIE), in which excess glutamate is released into synapses and overstimulates glutamate receptors, is a major event in secondary SCI. GIE leads to mitochondrial damage and dysfunction, release of reactive oxygen species (ROS), DNA damage, and cell death. There is no clinical treatment that targets GIE after SCI, and there is a need for therapeutic targets for secondary damage in patients. Uric acid (UA) acts as an antioxidant and scavenges free radicals, upregulates glutamate transporters on astrocytes, and preserves neuronal viability in in vitro and in vivo SCI models, making it a promising therapeutic candidate. However, development of a drug release platform that delivers UA locally to the injured region in a controlled manner is crucial, as high systemic UA concentrations can be detrimental. Here, we used the electrospinning technique to synthesize UA-containing poly(ɛ-caprolactone) fiber mats that are biodegradable, biocompatible, and have a tunable degradation rate. We optimized delivery of UA as a burst within 20 min from uncoated fibers and sustained release over 2 h with poly(ethylene glycol) diacrylate coating. We found that both of these fibers protected neurons and decreased ROS generation from GIE in organotypic spinal cord slice culture. Thus, fiber mats represent a promising therapeutic for UA release to treat patients who have suffered a SCI.

Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

PURPOSE: The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. METHODS: A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. RESULTS: Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. CONCLUSIONS: An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.