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.

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.

Laryngeal adenoid cystic carcinoma: A population-based perspective.

OBJECTIVES/HYPOTHESIS: Adenoid cystic carcinoma (ACC) occurs infrequently in the larynx. Consequently, no large samples describing its clinical behavior are available in the literature. Our objective was to use a nationally representative population-based resource to evaluate clinical behavior, patient demographics, and outcomes among patients diagnosed with laryngeal ACC (LACC). STUDY DESIGN: Retrospective database analysis. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was analyzed for patients diagnosed with LACC between 1973 and 2011. Patient demographics, incidence, treatment, and survival between LACC and other laryngeal malignancies were compared. RESULTS: Of 69 LACC patients, 63.8% were female, 78.2% Caucasian, and the median age was 54 years. LACC patients were much more likely to have subglottic lesions (44.9%) than individuals with other malignancies (1.6%). The incidence of LACC was 0.005/100,000 individuals. The majority of patients with LACC harbored T4 lesions at initial diagnosis, although 87.9% had N0 disease, and only 6.1% had distant metastasis at diagnosis. Disease-specific survival (DSS) was greater at 1 year for LACC compared to other laryngeal malignancies, but not at 5 or 10 years. Five-year DSS was greater for LACC patients who underwent surgery versus those who did not undergo surgery. CONCLUSIONS: This analysis notes that LACC has a low incidence with no significant change in incidence over the study period. Compared to other laryngeal malignancies, LACC has a female preponderance, is much more common in the subglottis, presents at a younger age, and more often presents with T4 disease. Surgery was noted to confer a survival advantage in LACC. LEVEL OF EVIDENCE: 4.

Calcineurin inhibitor effects on growth and phenotype of human airway epithelial cells in vitro.

Calcineurin inhibitors (CIs) cyclosporin and tacrolimus form the basis for immunosuppression in lung transplantation, yet also exert biological effects on nonlymphoid tissue. With the advent of inhaled cyclosporin, we hypothesize that the airway epithelium is also subject to CI effects at high doses. The aim of this study was to identify human tracheobronchial epithelial cell (hTBEC) calcineurin gene expression and quantify effects of CIs on hTBEC growth, interleukin-1-beta stimulated IL-8 production and hTBEC phenotype. Cyclophillin B and FK-associated binding protein, calcineurin A (alpha and beta), and NFATC3 and NFAT5 were detected in hTBEC cultures by RT-PCR. Acute and chronic cyclosporine treatment 1000 ng/mL significantly inhibited hTBEC proliferation, while tacrolimus did not (range of 10 ng/mL to 1000 ng/mL for acute treatment, 50 ng/mL for chronic treatment). Cyclosporin at 10,000 ng/mL significantly increased LDH release by well-differentiated hTBEC cultures (n = 6) and trended towards significance at 1000 ng/mL. IL1-beta stimulated IL-8 production was significantly increased in rapidly growing hTBEC cultures (n = 8) treated with cyclosporin (p = 0.049). Prolonged treatment of well-differentiated hTBECs at air-liquid-interface (ALI) with cyclosporin 1000 ng/mL significantly reduced intact multilayered mucociliary epithelium (p = 0.009). Inhibition of hTBEC growth, stimulation of IL-8 production and long-term effects on mucociliary phenotype and intact multi-layered epithelium suggest that cyclosporin may have a direct toxic effect on airway epithelium after transplantation.

PX3.102, a novel chinese herb extract, diminishes chronic airway allograft rejection.

More effective immunosuppressants are needed to improve lung-transplantation survival. PX3.102 is a novel immunosuppressant isolated from a mixture of traditional Chinese herbs. We tested its protective role on chronic lung rejection in the heterotopic tracheal transplant model. C57BL/6 mice received BALB/c tracheal grafts and were treated with PX3.102, cyclosporine A, or vehicle. PX3.102 improved tracheal allograft lumen patency (*P<0.01 vs. vehicle and P=0.14 vs. cyclosporine A) but not epithelialization (P>0.2 vs. vehicle). Subsequent in vitro studies demonstrated that PX3.10 was toxic to fully differentiated human tracheal epithelial cells in a dose-dependent manner. PX3.102 markedly suppressed antigen-specific lymphocyte proliferation in vitro at a concentration 10 times lower than cyclosporine A. In conclusion, PX3.102, a promising and potent immunosuppressant, although exhibiting toxicity to airway epithelial cells at high doses, is effective in inhibiting chronic airway allograft rejection.