Pediatric cholesteatoma associated with congenital aural atresia and stenosis.

OBJECTIVE: Investigate presenting features, associated surgical treatment, and outcomes in patients with cholesteatoma associated with congenital aural atresia (CAA) or stenosis (CAS). METHODS: Colorado Multiple Institution Review Board approval was obtained. A retrospective chart review was performed at a single tertiary care children's hospital of all pediatric patients with congenital aural atresia or stenosis with associated cholesteatoma from January 1, 2003, to October 15, 2018. RESULTS: Of the 278 patients identified with CAA or CAS, twelve (4.3 %) were found to have a canal cholesteatoma. There was a male predominance (8:4). Nine patients (75 %) had conductive loss and three (25 %) had mixed loss. Four patients (33.3 %) exhibited canal cholesteatomas extending into the middle ear or mastoid cavity. All patients underwent surgery, and 25 % of patients required revision canalplasty while 58 % of patients required revision surgery for cholesteatoma recidivism. The average age at the time of surgery was 11.3 ± 3.7 years. CONCLUSION: Fewer than 5 % of pediatric patients with congenital aural atresia or stenosis were diagnosed with an acquired canal cholesteatoma. The need for revision surgery was common, occurring in >50 % of cases. Screening patients with CAA/CAS for cholesteatoma with imaging is recommended to avoid the morbidity of delayed identification.

Slide Tracheoplasty for Tracheal Cartilaginous Sleeve in a Patient With Apert Syndrome.

Apert syndrome is a form of acrocephalosyndactyly involving craniosynostosis, syndactyly, and less commonly, tracheal cartilaginous sleeve (TCS), a potential cause of tracheal stenosis. Slide tracheoplasty is performed in children with tracheal stenosis. No reports exist for its application in stenosis related to TCS. We present a case in which slide tracheoplasty was used for the expansion of long segment tracheal stenosis owing to TCS in a newborn with Apert syndrome. Using this technique, a safe and durable airway was achieved without tracheostomy.

Systematic Review of Outcomes After Cochlear Implantation in Children With X-Linked Deafness-2.

OBJECTIVE: Outcomes following cochlear implantation in children with X-linked deafness-2 are variable, resulting in challenges in appropriate preoperative counseling. To address this uncertainty, we performed a systematic review and synthesis of the literature on audiologic and speech outcomes after cochlear implantation in these patients to inform prognostic counseling. DATA SOURCES: PubMed, Embase, and Cochrane Library were queried for articles published between January 2000 and July 2019. REVIEW METHODS: We performed a systematic review of all studies published between 2000 and 2019 that reported on (1) children with confirmed X-linked deafness-2 undergoing cochlear implantation and (2) formal assessment of hearing and/or speech capabilities postimplantation. RESULTS: Our initial database search yielded 313 articles. Fourteen articles met inclusion criteria. These studies reported on 61 children with X-linked deafness-2 who underwent implantation at a wide age range (1-29 years) for severe-profound sensorineural hearing loss of prelingual onset. The mean follow-up duration after implant activation was 32 months (range, 12-61). Outcome domains assessed at follow-up were heterogeneous, though each study employed at least 1 assessment of hearing (eg, pure tone audiometry), speech perception (eg, Early Speech Perception Test), or auditory perception (eg, Categories of Auditory Perception scores). In 10 of 14 studies, cochlear implantation afforded significant improvement in hearing and speech capabilities relative to preoperative performance or as compared with age-matched, normal-hearing controls. CONCLUSION: The majority of studies demonstrate that cochlear implantation provides improvements in hearing and speech performance in patients with X-linked deafness-2. This information is valuable for decision making regarding cochlear implantation in these patients.

Head and neck paragangliomas: A two-decade institutional experience and algorithm for management.

Objectives: Paragangliomas of the head and neck and cranial base are typically benign, slow-growing tumors arising within the jugular foramen, middle ear, carotid bifurcation, or vagus nerve proper. The objective of this study was to provide a comprehensive characterization of our institutional experience with clinical management of these tumors and posit an algorithm for diagnostic evaluation and treatment. Methods: This was a retrospective cohort study of patients undergoing treatment for paragangliomas of the head and neck and cranial base at our institution from 2000-2017. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic work-up, pre-treatment cranial nerve palsy, treatment modality, utilization of preoperative angiographic embolization, complications of treatment, tumor control and recurrence, and hereditary status (ie, succinate dehydrogenase mutations) were collected and summarized. Results: The mean (SD) age of our cohort was 51.8 (±16.1) years with 123 (63.4%) female patients and 71 (36.6%) male patients. Catecholamine-secreting lesions were found in nine (4.6%) patients. Fifty-one patients underwent genetic testing, with mutations identified in 43 (20 SDHD, 13 SDHB, 7 SDHD, 1 SDHA, SDHAF2, and NF1). Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were variably employed as treatment approaches across anatomic subsites. Conclusion: An algorithmic approach to clinical management of these tumors, derived from our longitudinal institutional experience and current empiric evidence, may assist otolaryngologists, radiation oncologists, and geneticists in the care of these complex neoplasms. Level of Evidence: 4.

Novel method of cell line establishment utilizing fluorescence-activated cell sorting resulting in 6 new head and neck squamous cell carcinoma lines.

BACKGROUND: The purpose of this study was to present the establishment of new cell lines, which is important to cancer research. METHODS: Six new head and neck squamous cell carcinoma cell lines were established using a novel fluorescence-activated cell sorting (FACS) method in order to overcome the barrier of fibroblast overgrowth and the susceptibility of primary tumors to fail in vitro. RESULTS: Antibodies chosen for specific targeting of epithelial cells and fibroblasts successfully separated cells for line establishment in 6 of 12 attempts, providing an alternative method of establishing head and neck squamous cell carcinoma cell lines. Each attempt at cell line establishment resulted in an epithelial carcinoma population, which was genotyped and catalogued as a unique cell line, and a corresponding fibroblast population. CONCLUSION: The selection of antibody markers could be optimized to aid in the establishment of any cancer cell line derived from any tumor tissue; this method is not limited to head and neck cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E459-E467, 2016.

Epigenetic alterations in metastatic cutaneous carcinoma.

BACKGROUND: Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the 2 most common cutaneous carcinomas. Molecular profiles predicting metastasis of these cancers have not been identified. METHODS: Epigenetic profiles of 37 primary cases of cutaneous SCC and BCC were quantified via the Illumina Goldengate Cancer Panel. Differential protein expression by metastatic potential was analyzed in 110 total cases by immunohistochemical (IHC) staining. RESULTS: Unsupervised hierarchical clustering analysis revealed that metastatic BCCs had a methylation profile resembling cutaneous SCCs. Metastatic cutaneous SCCs were found to be hypermethylated at FRZB (median methylation: 46.7% vs 4.7%; p = 4 × 10(-5) ). Metastatic BCCs were found to be hypomethylated at MYCL2 (median methylation: 3.8% vs 83.4%; p = 1.9 × 10(-6) ). Immunohistochemical staining revealed few differences between metastatic and nonmetastatic cancers. CONCLUSION: Metastatic primary BCCs and cutaneous SCCs had distinct epigenetic profiles when compared to their nonmetastatic counterparts. Epigenetic profiling may prove useful in future diagnosis and prevention of advanced nonmelanoma skin cancers.

Cancer stem cells: mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma.

BACKGROUND: Cancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain. METHODS: Wound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44(high) and aldehyde dehydrogenase [ALDH](+)) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patient-derived primary HNSCC specimens were analyzed for CSC-proportion compared to clinical variables. RESULTS: CSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than non-CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival. CONCLUSION: HNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSC-proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis.

The role of head and neck squamous cell carcinoma cancer stem cells in tumorigenesis, metastasis, and treatment failure.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Despite advances in diagnostic and therapeutic methods, survival of HNSCC remains unchanged over the last 30 years with treatment failure and metastases being the strongest indicators of poor outcome. Cancer stem cells (CSC) have been identified in multiple other solid tumors, including breast, prostate, and pancreatic carcinoma. Recently, a subpopulation of tumor cells has been identified in HNSCC based on the overexpression of the cellular marker CD44 and increased activity of aldehyde dehydrogenase. These cells have been designated CSC based on their stem cell-like properties: self-renewal, tumorigenesis, and the ability to recapitulate a heterogeneous tumor. Recent work looking at the role of HNSCC CSC in tumorigenesis has shown that CSC have a greater capacity for tumor growth, increased motility, and invasive characteristics; in vivo experiments confirm greater metastatic potential in CSC compared to non-CSC. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure, and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC.