Faculty Bibliography

Head and neck squamous cell carcinoma (HNSCC) causes more severe pain and psychological stress than other types of cancer. Despite clinical evidence linking pain, stress, and cancer progression, the underlying relationship between pain and sympathetic neurotransmission in oral cancer is unknown. We found that human HNSCC tumors and mouse tumor tissue are innervated by peripheral sympathetic and sensory nerves. Moreover, [beta]-adrenergic 1 and 2 receptors ([beta]-AR) are overexpressed in human oral cancer cell lines, and norepinephrine treatment increased [beta]-AR2 protein expression as well as cancer cell proliferation in vitro. We have recently demonstrated that inhibition of tumor necrosis factor alpha (TNF[alpha]) signaling reduces oral cancer-induced nociceptive behavior. Norepinephrine-treated cancer cell lines secrete more TNF[alpha] which, when applied to tongue-innervating trigeminal neurons, evoked a larger Ca2+ transient; TNF-TNFR inhibitor blocked the increase in the evoked Ca2+ transient. Using an orthotopic xenograft oral cancer model, we found that mice demonstrated significantly less orofacial cancer-induced nociceptive behavior during systemic [beta]-adrenergic inhibitory treatment with propranolol. Furthermore, chemical sympathectomy via guanethidine led to a significant reduction in tumor size and nociceptive behavior. We infer from these results that sympathetic signaling modulates oral cancer pain via TNF[alpha] secretion and tumorigenesis. Further investigation of the role of neuro-cancer communication in cancer progression and pain is warranted.

STUDY OBJECTIVES:To examine children with Down syndrome with residual obstructive sleep apnea (OSA) to determine if they are more likely to have positional OSA. METHODS:A retrospective chart review of children with Down syndrome who underwent adenotonsillectomy at a single tertiary children's hospital was conducted. Children with Down syndrome who had a postoperative polysomnogram with obstructive apnea-hypopnea index (OAHI) > 1 event/h, following adenotonsillectomy with at least 60 minutes of total sleep time were included. Patients were categorized as mixed sleep (presence of ≥ 30 minutes of both nonsupine and supine sleep), nonsupine sleep, and supine sleep. Positional OSA was defined as an overall OAHI > 1 event/h and a supine OAHI to nonsupine OAHI ratio of ≥ 2. Group differences are tested via Kruskal-Wallis test for continuous variables and Fisher's exact tests for categorical. RESULTS:= .002). Sixty (46%) of the mixed-sleep individuals had positional OSA, of which 29 (48%) had moderate/severe OSA. Sleeping off their backs converted 14 (48%) of these 29 children from moderate/severe OSA to mild OSA. CONCLUSIONS:Sleep physicians and otolaryngologists should be cognizant that the OAHI may be an underestimate if it does not include supine sleep. Positional therapy is a potential treatment option for children with residual OSA following adenotonsillectomy and warrants further investigation. CITATION:. 2023;19(1):171-177.

Although generally regarded as degradatory enzymes, certain proteases are also signaling molecules that specifically control cellular functions by cleaving protease-activated receptors (PARs). The four known PARs are members of the large family of G protein-coupled receptors. These transmembrane receptors control most physiological and pathological processes and are the target of a large proportion of therapeutic drugs. Signaling proteases include enzymes from the circulation, from immune, inflammatory epithelial and cancer cells, as well as from commensal and pathogenic bacteria. Advances in our understanding of the structure and function of PARs provide insights into how diverse proteases activate these receptors to regulate physiological and pathological processes in most tissues and organ systems. The realization that proteases and PARs are key mediators of disease, coupled with advances in understanding the atomic level structure of PARs and their mechanisms of signaling in subcellular microdomains, has spurred the development of antagonists, some of which have advanced to the clinic. Herein we review the discovery, structure and function of this receptor system, highlight the contribution of PARs to homeostatic control, and discuss the potential of PAR antagonists for the treatment of major diseases.

Purpose of Review: This review seeks to illuminate the challenges that arise in the use of steroids in the context of a performing voice, to review pharmacologic principles that can help to guide dosing regimens, to examine emerging science about the mechanistic action of glucocorticoids, and to provide a useful guide for clinicians who treat vocal performers. Recent Findings: Though perceptions and mythologies abound, most saliently (1) the incidence of vocal fold hemorrhage while taking oral steroids is extremely low; (2) appropriate dosing is likely to involve regimens that meet or exceed 30 mg oral Prednisone-equivalent daily to address edema acutely; (3) tapering after short courses may well be unnecessary. Summary: Steroids can be used safely and judiciously to treat vocal performers, guided by physical examination, sound clinical judgment, and a multidisciplinary approach to the individual needs of each unique voice and performer.

Agnathia-otocephaly complex (AOC), a first branchial arch defect, is characterized by mandibular hypoplasia or aplasia, ear abnormalities, microstomia, and macroglossia and is a rare and often fatal diagnosis. Herein, the technical considerations and details of mandibular reconstruction using virtual surgical planning (VSP) and a vascularized free fibula flap for further mandibular reconstruction in a 10-year-old boy are presented. The patient's preoperative examination was consistent with agnathia (absence of mandibular symphysis, bilateral mandibular bodies, condyles, coronoids, rami, and temporomandibular joint), severe microstomia, and a Tessier # 30 cleft (maintained to allow oral access until later in treatment). Virtual surgical planning was utilized to plan a 3-segment fibula for the reconstruction of the mandibular symphysis and bilateral body segments, and bilateral costochondral grafts were planned for the rami. To the authors' knowledge, this represents the first application of virtual surgical planning for mandibular reconstruction with a vascularized free fibula flap in a pediatric patient with severe agnathia-otocephaly complex.