The tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) is comprised of cancer-associated fibroblasts (CAFs), immune cells, and other supporting cells. Genetic changes in the carcinoma cells, such as alterations to TP53, NOTCH1, and specific gene expression profiles, contribute to derangements in cancer and microenvironment cells such as increased ROS, overproduction of cytokines, and epithelial to mesenchymal transition (EMT). CAFs are among the most critical elements of the TME contributing to proliferation, invasion, and metastasis. The adaptive immune response is suppressed in HNSCC through overexpression of cytokines, triggered apoptosis of T cells, and alterations in antigen processing machinery. Overexpression of critical cytokines, such as transforming growth factor-β (TGF-β), contributes to EMT, immune suppression, and evolution of CAFs. Inflammation and hypoxia are driving forces in angiogenesis and altered metabolism. HNSCC utilizes glycolytic and oxidative metabolism to fuel tumorigenesis via coupled mechanisms between cancer cell regions and cells of the TME. Increased understanding of the TME in HNSCC illustrates that the long-held notion of "condemned mucosa" reflects a process that extends beyond the epithelial cells to the entire tissue comprised of each of these elements.

Objective Nasal obstruction is the principal symptom that drives patients with rhinosinus disease to seek medical treatment. However, patient perception of obstruction often bears little relationship to actual measured physical obstruction of airflow. This lack of an objective clinical tool hinders effective diagnosis and treatment. Previous work has suggested that the perception of nasal patency may involve nasal trigeminal activation by cool inspiratory airflow; we attempt to derive clinically relevant variables following this phenomenon. Study design Prospective healthy cohort. Methods Twenty-two healthy subjects rated unilateral nasal patency in controlled room air using a visual analog scale, followed by rhinomanometry, acoustic rhinometry and butanol lateralization thresholds (BLT). Each subject then immediately underwent a CT scan, enabling the construction of a “real-time” computational fluid dynamics (CFD) nasal airway model, which was used to simulate nasal mucosa heat loss during steady resting breathing. Results Among all measured and computed variables, only CFD-simulated peak heat loss posterior to the nasal vestibule significantly correlated with patency ratings (r=−0.46, p<0.01). Linear discriminant analysis predicted patency categories with 89% success rate, with BLT and rhinomanometric nasal resistance being two additional significant variables. As validation, CFD simulated nasal resistance significantly correlated with rhinomanometrically measured resistance (r=0.41, p<0.01). Conclusion These results reveal that our noses are sensing patency via a mechanism involving localized peak nasal mucosal cooling. The analysis provides a strong rationale for combining the individualized CFD with other objective and neurological measures to create a novel clinical tool to diagnose nasal obstruction and to predict and evaluate treatment outcomes.

This is the first CFD examination of nasal aerodynamics in a large cohort of ENS patients. The results indicated that a combination of loss of neural sensitivity and poorer inferior air-mucosal stimulation may potentially lead to ENS symptomology.

Objective/Hypothesis: Elevation of the superficial musculoaponeurotic system (SMAS) with or without fat graft interposition during superficial parotidectomy prevents a concave facial deformity and Frey's syndrome.Study Design: Retrospective, case-control study. Methods: Charts for 248 patients who underwent superficial parotidectomy were reviewed for pathologic, radiographic, clinical, and operative data. Sixteen patients who underwent SMAS elevation and 34 patients who underwent SMAS elevation with fat graft interposition were included in two study groups. Nonreconstructed controls were randomly selected from a pool of patients who had unilateral, superficial parotidectomy and were matched based on pathologic specimen volume. Patients were surveyed for their postoperative symptoms.Results: Patients undergoing SMAS elevation alone (n ϭ 16) compared with controls (n ϭ 19) had greater facial symmetry (12% vs. 32%, P ϭ .147) and a lower incidence of symptomatic Frey's syndrome (6.3% vs. 18.6%, P ϭ .382). Patients undergoing SMAS elevation and fat graft interposition (n ϭ 34) compared with controls (n ϭ 38) had less facial asymmetry (9% vs. 39%, P ϭ .002) and a lower incidence of symptomatic Frey's syndrome (6% vs. 28%, P ϭ .04). Complications among the study and control groups were comparable.Conclusions: Simultaneous reconstruction of a superficial parotidectomy defect using SMAS elevation with or without fat grafting may improve postoperative facial symmetry and decrease the incidence of symptomatic Frey's syndrome without increasing complications.

Although complete or near-complete olfactory loss has been extensively documented and described, few published reports have documented severe generalized gustatory loss (across qualities and neural fields) with rigorous psychophysical testing, and none have explored the prevalence or causes of such losses in a large clinical population. This study retrospectively reviews our chemosensory clinic's experience of 1,176 patients evaluated for complaints of chemosensory dysfunction in order to address these issues. Our series confirms that despite the complex, bilateral innervation and regenerative capacity of the gustatory system, severe generalized taste loss does occur as a clinical entity, albeit rarely: only 0.85% (n = 10) of our patients evidenced such a deficit, as compared to 32% (n = 371) who were found to have a profound olfactory deficit. Combinations of systemic and/or acute events may underlie many cases of severe taste loss, and in half of our cases, these patients evidenced moderate to complete smell loss as well.

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Amyloidosis of the upper aerodigestive tract generally behaves as a benign, localized condition treatable by surgical resection. Regular follow-up with laryngoscopy is indicated for early diagnosis of recurrence, and multiple surgical procedures may be required to control symptoms.

Transduction mechanisms were investigated in human olfactory neurons by determining characteristics of odorant-induced changes in intracellular calcium concentration ([Ca2+]i). Olfactory neurons were freshly isolated from nasal biopsies, allowed to attach to coverslips, and loaded with the calcium-sensitive indicator fura-2. Changes in [Ca2+]i were studied in response to exposure to individual odors, or odorant mixtures composed to distinguish between transduction pathways mediated by adenosine 3'5'-monophosphate (cAMP; mix A) or inositol 1,4,5-trisphosphate (InsP3; mix B). Overall, 52% of biopsies produced one or more odorant-responsive olfactory neurons, whereas 24% of all olfactory neurons tested responded to odorant exposure with a change in [Ca2+]i. As in olfactory neurons from other species, the data suggest that odorant exposure elicited calcium influx via second-messenger pathways involving cAMP or InsP3. Unlike olfactory neurons from other species that have been tested, some human olfactory neurons responded to odorants with decreases in [Ca2+]i. Also in contrast with olfactory neurons from other species, human olfactory neurons were better able to discriminate between odorant mixtures in that no neuron responded to more than one type of odor or mixture. These results suggest the presence of a previously unreported type of olfactory transduction mechanism, and raise the possibility that coding of odor qualities in humans may be accomplished to some degree differently than in other vertebrates, with the olfactory neuron itself making a greater contribution to the discrimination process.