Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma.

The incidence of human papilloma virus-mediated oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past 40 years, particularly among young individuals with a favorable prognosis; however, current therapy often leads to unfortunate side effects, such as dysphagia. Despite the emphasis on dysphagia in previous studies, there is an important research gap in understanding the correlation between neuronal changes and patient-reported and functional outcomes in patients with OPSCC. To address this issue, we examined pathologic tissue samples from patients with OPSCC using multiplex immunofluorescence staining and machine learning to correlate tumor-associated neuronal changes with prospectively collected patient-reported and functional outcomes. We found that tumor enrichment of adrenergic (TH+) and CGRP+ sensory-afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43+) and immature cholinergic (ChAT+DCX+) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP+ nerves were correlated with impaired swallowing. Preclinical interventional studies also supported the independent contributions of CGRP+ and cholinergic (ChAT+) nerves to dysphagia in treated mouse models of OPSCC. Our results suggest that CGRP+ and ChAT+ neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC. These insights may guide early interventions for swallow preservation and the repurposing of neurology-related drugs, such as CGRP blockers, in clinical oncology and survivorship.

Neoadjuvant Approaches to Non-Melanoma Skin Cancer.

Surgery and external-beam radiation therapy are the primary treatment modalities for locally advanced NMSC, but they can lead to impairment of function and disfigurement in sensitive areas such as the head and neck. With the advent of targeted systemic therapies and immunotherapy, physicians have explored the ability to offer neoadjuvant therapy for NMSC in order to reduce surgically induced morbidity. Provided herein is a guide to current applications of neoadjuvant systemic therapies for NMSC and future directions.

Current Treatment Strategies and Risk Stratification for Oral Carcinoma.

Management of oral cavity squamous cell carcinoma (OSCC) involves a multidisciplinary team approach. Surgery is ideally the primary treatment option for nonmetastatic OSCC, and less invasive curative surgical approaches are preferred in early-stage disease to minimize surgical-related morbidity. For patients at high risk of recurrence, adjuvant treatment using radiation therapy or chemoradiation is often used. Systemic therapy may also be used in the neoadjuvant setting (for advanced-stage disease with the intent of mandibular preservation) or in the palliative setting (for nonsalvageable locoregional recurrence and/or distant metastases). Patient involvement in treatment decision is the key for patient-driven management, particularly in clinical situation with poor prognosis, for example, early postoperative recurrence before planned adjuvant therapy.

Congenital cholesteatoma in identical twins.

Congenital cholesteatoma in identical twins has only been described once in Otolaryngology literature thus far. This report describes a case of monozygotic twins with a history of recurrent acute otitis media and bilateral middle ear effusions without tympanic membrane perforation. Upon myringotomy with pressure equalization tube insertion, both were found to have right-sided cholesteatoma with nearly identical location and pattern of progression. In the context of previous case series demonstrating familial clustering and reports of possible genetic associations of this condition, the authors present an important addition to the current understanding of congenital cholesteatoma disorder.

Acetylcholine in Carcinogenesis and Targeting Cholinergic Receptors in Oncology.

Tumor cells modulate and are modulated by their microenvironments, which include the nervous system. Accumulating evidence links the overexpression and activity of nicotinic and muscarinic cholinergic receptor subtypes to tumorigenesis in breast, ovarian, prostate, gastric, pancreatic, and head and neck cancers. Nicotinic and muscarinic receptors have downstream factors are associated with angiogenesis, cell proliferation and migration, antiapoptotic signaling, and survival. Clinical trials analyzing the efficacy of various therapies targeting cholinergic signaling or downstream pathways of acetylcholine have shed promising light on novel cancer therapeutics. Although the evidence for cholinergic signaling involvement in tumor development is substantial, a more detailed understanding of the acetylcholine-induced mechanisms of tumorigenesis remains to be unlocked. Such an understanding would enable the development of clinical applications ranging from the identification of novel biomarkers to the utilization of existing drugs to modulate cholinergic signaling to the development of novel cancer therapies, as discussed in this review.

Management of Regional Lymph Nodes in Head and Neck Melanoma.

The utilization of sentinel lymph node (SLN) biopsy has transformed the workup and staging of intermediate-thickness cutaneous melanomas. SLN biopsy, performed at the time of primary tumor excision, accurately maps lymph nodes at risk of harboring occult metastatic deposits from head and neck cutaneous melanomas and represents the current standard of care. Completion lymphadenectomy identifies additional tumor in 12% to 24% of SLN biopsy positive cases but does not affect melanoma-specific survival.

Electrostatic Discharge (ESD) as a Cause of Facial Nerve Stimulation After Cochlear Implantation: A Case Report.

OBJECTIVE: To discuss persistent facial nerve stimulation (FNS) related to repeated electrostatic discharge (ESD) shock following cochlear implantation. METHODS: Single case report with literature review. RESULTS: FNS is a feared complication after cochlear implantation, occurring in approximately 7% of cases, with most patients having anatomic abnormalities. The presented case has no anatomical abnormalities but reported frequent environmental static shock. FNS during the first 1 to 3 seconds of processor attachment caused a significant decrease in the patient's quality of life, requiring subsequent re-implantation with full resolution. CONCLUSIONS: FNS is a complication of cochlear implantation that can cause a great deal of distress and discomfort. Frequent electrostatic discharge (ESD) contributed to device malfunctioning and FNS in a patient with otherwise normal anatomy and should be avoided if possible.

Ethosuximide induced macroglossia and oropharyngeal edema.

Acute macroglossia and laryngeal edema are rare adverse side effects that can cause life-threatening airway obstruction. We report a case of acute macroglossia that began after initiation of ethosuximide in a 15-year-old female with severe medically refractory epilepsy. Macroglossia worsened over the next two weeks of ethosuximide administration, preventing extubation. Macroglossia and laryngeal edema improved upon ethosuximide wean, and completely resolved after discontinuation. The patient was extubated successfully, with precautionary nasal trumpet placement and dexamethasone administration prior to extubation. In medically complex patients on multiple pharmacologic agents, anti-epileptic drugs should be suspected as a possible cause of acute macroglossia.

Polysomnography in children with obstructive sleep apnoea and neurocognitive disorders.

OBJECTIVE: The neurocognitive associations in paediatric obstructive sleep apnoea (OSA) are well known; however, whether polysomnographic features can predict these associations is unknown. Therefore, the primary objective of this study was to compare common polysomnographic parameters in children with OSA in the presence and absence of neurocognitive dysfunction. METHODS: Polysomnography data for children ages 3-6 years with mild-moderate OSA who as defined by AHI between 5 and 10 were analysed from a single sleep centre at a tertiary paediatric hospital from January 2016 to December 2018. The following parameters were identified: arousals per hour, percentage of time asleep, apnoea-hypopnoea index (AHI), oxygen desaturation nadir during sleeps, baseline oxygen saturation during sleep, time spent with SpO2 less than 90%, maximum transcutaneous CO2, per cent of the total sleep time spent with TcCO2 greater than 50 mmHg, age, body mass index (BMI), gender and type of disability in the neurocognitive dysfunction group. Neurocognitive diagnoses were recorded. Those with syndromic comorbidities were excluded. The study cohort was then compared to a cohort of 200 subjects with OSA and no neurocognitive disorders matched for age, gender and BMI. A paired column analysis by chi-squared analysis was then undertaken between the two groups. RESULTS: A total of 200 children were identified (126 males and 74 females) in the neurocognitive dysfunction group (OSA with neurocognitive dysfunction) and compared with 200 children in the control group (OSA without neurocognitive dysfunction) (113 males and 87 females). There were no statistical differences between groups. CONCLUSION: Commonly used polysomnographic indices are not predictive of neurocognitive dysfunction in paediatric OSA.