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Introduction: Oral cavity squamous cell carcinoma (OSCC) occurs most frequently in patients >60 years old with a history of tobacco and alcohol use. Epidemiological studies describe increased incidence of OSCC in younger adults (<45 years). Despite its poor prognosis, knowledge of OSCC tumor microenvironment (TME) characteristics in younger adults is scarce and could help inform possible resistance to emerging treatment options. Methods: Patients with OSCC were evaluated using TCGA-HNSC (n=121) and a stage and subsite-matched institutional cohort (n=8) to identify differential gene expression focusing on the extracellular matrix (ECM) and epithelialmesenchymal transition (EMT) processes in younger (=45 years) vs. older adults (=60 years). NanoString nCounter analysis was performed using isolated total RNA from formalin-fixed paraffin-embedded (FFPE) tumor samples. Stained tumor slides from young and old OSCC patients were evaluated for CD8+ Tcell counts using immunohistochemistry. Results: Younger OSCC patients demonstrated significantly increased expression of ECM remodeling and EMT process genes, as well as TME immunosuppression. Gene set enrichment analyses demonstrated increased ECM pathways and concurrent decreased immune pathways in young relative to old patients. Transcripts per million of genetic markers involved in ECM remodeling including LAMB3, VCAN, S100A9, COL5A1, and ITGB2 were significantly increased in tumors of younger vs. older patients (adjusted p-value < 0.10). Young patient TMEs demonstrated a 2.5-fold reduction in CD8+ T-cells as compared to older patients (p < 0.05). Conclusion: Differential gene expression impacting ECM remodeling and TME immunosuppression may contribute to disease progression in younger adult OSCC and has implications on response to evolving treatment modalities, such as immune checkpoint inhibitor therapy. [ABSTRACT FROM AUTHOR]

Background: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications. Methods: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017–2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. Regression analysis to estimate odds ratios was performed. Results: A total of 463 patients met inclusion criteria. Free flap reconstruction constituted 28.9% of patients and TORS constituted 71.1% of patients. nICI was administered in 83 of 463 (17.9%) patients. There was no statistically significant difference in surgical, medical, or overall complications between patients receiving surgery with or without nICI. In the unmatched cohort, multivariable model identified non‐White race, former/current smoking history, free flap surgery, and perineural invasion as factors significantly associated with increased complications. In the matched cohort, multivariable model identified advanced age and free flap surgery as factors significantly associated with increased complications. Plain Language Summary: It is safe to give immunotherapy before major surgery in patients who have head and neck cancer.Advanced age, non‐White race, current/former smoking, free flap surgery, and perineural invasion may be associated with increased the odds of surgical complications. In this study, neoadjuvant immune checkpoint inhibitors (nICI) did not increase the risk of overall complications after adjusting for important confounders. Definitive surgery can be conducted safely after nICI. [ABSTRACT FROM AUTHOR]

Objective: To assess whether preoperative tracheostomy (PreOT) increases risk of complications after total laryngectomy (TL) and to determine if timing of tracheostomy creation is associated with an increased risk. Study Design: Retrospective cohort study. Setting: Tertiary care hospital between 2007 and 2020. Methods: Inclusion criteria were patients who underwent primary or salvage TL for oncologic treatment. Dependent variables of interest included surgical complications, such as wound dehiscence, infection, hematoma, complete flap failure, fistula formation, and stoma stenosis, as well as medical complications. Categorical variables were compared with chi‐square test or Fisher exact test, and continuous variables were compared with an independent t test. Multivariable regression was conducted to assess predictors of complications after laryngectomy. Results: A total of 306 patients were included. Primary TL was performed in 161 (53%) patients and salvage in 145 (47%) patients. Of the patients undergoing primary laryngectomy, 105 (65%) received a PreOT. Of the patients undergoing salvage laryngectomy, 86 (59%) received a PreOT. In both primary and salvage cases, there was no association between PreOT and surgical or medical complications. Additionally, there was no significant association between timing of tracheostomy and surgical complications. On multivariable analysis, the presence of a PreOT was not associated with surgical complications. In salvage cases, those with a PreOT had a significantly longer average length of stay than those without a PreOT (12 vs 9 days, P =.008). Conclusion: PreOT in patients undergoing primary and salvage laryngectomies was not associated with surgical or medical complications postlaryngectomy. Timing of tracheostomy in relation to laryngectomy was not found to adversely affect clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Few standardized methods exist for evaluating the postoperative outcomes of osteocutaneous free flaps. We propose an anatomic‐based scoring system for midface free flap reconstruction. Methods: One hundred and twelve patients across four institutions underwent osteocutaneous reconstruction of the midface. Postoperative scans were scored based on the number of independent osseous subunits reconstructed (Subunit Score), the number of different bony appositions with bony contact (Contact Score), and the number of osseous segments in anatomic position (Position Score). These were added together to create a Total Score. Results: Osteocutaneous radial forearm flaps had the lowest Subunit Score (p = 0.001). Fibula flaps had the highest Contact Score (p = 0.0008) and Position Score (p = 0.001). Virtual surgical planning was associated with an increased Subunit Score (p = 0.02) and Total Score (p = 0.04). Conclusions: We propose a novel scoring system for osseous midface reconstruction based on postoperative imaging scans. This can help guide management decisions and create a common language to compare outcomes. [ABSTRACT FROM AUTHOR]

Injury of the ICA is a particular risk with these procedures and can occur in up to 9% of cases, though this may be under-reported.[4] ICA injury has a high mortality rate of up to 10% and may lead to acute and late neurologic morbidity secondary to ischemic injuries. The transcervical approach allows for an early determination of whether the ICA is invaded by tumor, which may warrant ICA sacrifice, grafting, or aborting the case. Keywords: endonasal endoscopic nasopharyngectomy; maxillary swing; internal carotid artery; transcervical approach; nasopharyngeal carcinoma EN endonasal endoscopic nasopharyngectomy maxillary swing internal carotid artery transcervical approach nasopharyngeal carcinoma 105 108 4 12/15/22 20230101 NES 230101 Nasopharyngeal tumors in the proximity of the internal carotid artery are often difficult to dissect. Improved visualization and dissection of the ICA through a combined approach may improve tumor clearance and oncologic outcomes when the tumor is found to be close or adherent to the ICA (Fig. [Extracted from the article]

Objective: Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction. Study Design: Retrospective review of prospectively collected databases. Methods: Consecutive patients undergoing head and neck microvascular free flap reconstruction between January 2010 and December 2019 (n = 1972) were included. Preoperative, operative and postoperative variables were correlated with discharge destination (home, skilled nursing facility [SNF], rehabilitation facility, death). Results: The mean age of patients discharged home was lower (60 SD ± 13, n = 1450) compared to those discharged to an SNF (68 SD ± 14, n = 168) or a rehabilitation facility (71 SD ± 14, n = 200; p < 0.0001). Operative duration greater than 10 h correlated with a higher percentage of patients being discharged to a rehabilitation or SNF (25% vs. 15%; p < 0.001). Patients were less likely to be discharged home if they had a known history of cardiac disease (71% vs. 82%; p < 0.0001). Patients were less likely to be discharged home if they experienced alcohol withdrawal (67% vs. 80%; p = 0.006), thromboembolism (59% vs. 80%; p = 0.001), a pulmonary complication (46% vs. 81%; p < 0.0001), a cardiac complication (46% vs. 80%; p < 0.0001), or a cerebral vascular event (25% vs. 80%; p < 0.0001). There was no correlation between discharge destination and occurrence of postoperative wound infection, salivary fistula, partial tissue necrosis or free flap failure. Thirty‐day readmission rates were similar when stratified by discharge destination. Conclusion: There was no correlation with the anatomic site, free flap donor selection, or free flap survival and discharge destination. Patient age, operative duration and occurrence of a medical complication postoperatively did correlate with discharge destination. Level of Evidence: 4 Laryngoscope, 133:95–104, 2023 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To assess the efficacy and mechanism of action of a novel approach to mitigate acute and chronic radiation toxicity in a validated animal model. Study Design: Randomized, prospective study using an in vivo rat model. Methods: Experimental animal study utilizing Sprague–Dawley rats divided into three cohorts: 1) radiation + dimethyl sulfoxide (DMSO) (inert vehicle); 2) radiation + RTA‐408 (therapeutic drug); and 3) no radiation + DMSO. All animals in the radiation cohorts underwent 40 Gy of radiation with subsequent inferior epigastric axial rotational flap 30 days later in all cohorts with percentage of flap necrosis and vascular density calculated by blinded observers. In a second experiment, an additional three cohorts, underwent serial punch biopsies of the abdominal skin before, during, and after radiation and drug/vehicle control treatment. Transcriptome analysis utilizing gene set enrichment analysis and digital polymerase chain reaction were performed at various time points. Results: The first experiment revealed average flap necrosis of 20% (95% confidence interval [CI] 16–45) in the radiation control group, 3% (95% CI 0–11) in the nonirradiated control, and 3% (95% CI 0.2–10) in the radiation group treated with RTA‐408. Vascular density was preserved in the treatment group as compared to the radiated control. Nine rats were included in the second experiment, and transcriptome analyses in the treatment group revealed robust activation of antioxidant pathways with induced expression of genes associated with hypoxia and adipogenesis/angiogenesis. Conclusions: Administration of RTA‐408 during radiation treatment in a rat model resulted in transcriptome changes which appear to mitigate the toxic effects of radiation, preserving capillary networks and improving flap survival and tissue healing after subsequent surgery. Level of Evidence: Foundational Evidence, Animal Research Laryngoscope, 132:1196–1204, 2022 [ABSTRACT FROM AUTHOR]

Objective Determine if age correlated with surgical or medical complications following head and neck free flap reconstruction. Study Design: Retrospective review of prospectively collected databases. Methods: Patients undergoing head and neck free flap reconstruction at three tertiary care institutions were included (n = 1972). Cohorts were based on age (<65, 65–75, 75–85, and >85). Outcomes reviewed operative duration, length of stay, surgical complications (free flap failure, fistula, hematoma, dehiscence, and infection), and medical complications (thromboembolism, stroke, cardiac, and pulmonary). Results: Anatomic site (P <.0001) and donor site varied by age (P <.0001). There was no difference in operative duration (P =.3) or length of hospitalization (P =.8) by age. The incidence of medical complications increased with increasing age. Pulmonary complication rates: <65 (3.9%), 65 to 75 (4.8%), 75 to 85 (7.1%), and >85 (11%) (P =.02). Cardiac complication rates: <65 (2.0%), 65 to 75 (7.3%), 75 to 85 (6.1%), and >85 (16.4%) (P <.0001). Mortality increased with age: <65 (0.4%), 65 to 75 (0.8%), 75 to 85 (1.1%), and >85 (4.1%) (P <.003). Medical complications correlated with mortality rates: pulmonary (3.5% vs. 0.6%; OR: 5.5; 95% CI: 1.5–20.0; P =.004); cardiac (3.3% vs. 0.6%; OR: 6.0; 95% CI: 1.6–21.8; P =.002); thromboembolism (4.6% vs. 0.7%; OR: 7.3; 95% CI: 1.6–33.6; P =.003); stroke (42% vs. 0.5%; OR: 149; 95% CI: 40–558; P <.0001); and sepsis (5% vs. 0.7%; OR 7.5; 95% CI: 1.0–60.5; P =.03). Age did not correlate with free flap success (P =.5), surgical complications (hematoma, P =.33; fistula, P =.23; infection, P =.07; and dehiscence, P =.37), or thirty‐day readmission (P =.3). Conclusion: Following free flap reconstruction, patient age did not correlate with development of a surgical complication. Patient age did correlate with development of a medical complication. Postoperative medical complications were found to correlate with perioperative mortality. Level of Evidence: 4 Laryngoscope, 132:772–780, 2022 [ABSTRACT FROM AUTHOR]

Precancerous lesions provide insight into tumor development as well as prognostication, since distinguishing high‐risk from benign disease will stratify clinical management. In a recent issue of The Journal of Pathology, Ghosh et al performed comprehensive genomic characterization of the precancerous lesion leukoplakia, comparing RNA and DNA with peripheral blood, normal mucosa, and squamous cell carcinoma (SCC) of the gingivobuccal region of the oral cavity from the same 28 individuals. The data paint a picture of increasing mutation and early caspase‐8 inactivation on the background of inflammation with decreasing immune surveillance in the progression from benign leukoplakia to SCC. This research points to an opportunity for disease intercept at the premalignant niche prior to the development of malignancy. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]