In head and neck squamous cell cancer (HNSCC), four intrinsic subtypes (or groups) have been identified, and each one possesses a unique biology that will require specific treatment strategies. We previously reported that mesenchymal (group 2) tumors exhibit reduced levels of Trop2 expression. In this study, we investigated the functional role of Trop2 in HNSCC and find that loss results in autocrine activation of the EGFR family member ErbB3 via neuregulin-1. Trop2 localizes to both the cell surface and cytosol of HNSCC cells and forms a complex with neuregulin-1, which is predominantly cytosolic. Inactivation of Trop2 increases the concentration of neuregulin-1 at the cell surface where it is cleaved to activate ErbB3. In primary HNSCC, detection of ErbB3 activation was limited to Trop2 negative tumors. An analysis of the Cancer Genome Atlas (TCGA) HNSCC dataset confirms enrichment for ErbB3 activity in mesenchymal tumors. Notably, Trop2 loss triggers sensitivity to anti-ErbB3 antibodies, which results in reduced proliferation and tumorigenic growth of Trop2 negative HNSCC cancer cells. These results uncover a molecular mechanism by which tumor cells control the amount of cell-surface neuregulin-1 available for cleavage and ErbB3 activation. Moreover, we demonstrate that Trop2 is a potential surrogate biomarker to identify tumors with ErbB3 activation and may therefore respond to anti-ErbB3 therapeutics.

Keloids are benign fibroproliferative tumors of the skin which commonly occur after injury mainly in darker skinned patients. Medical treatment is fraught with high recurrence rates mainly because of an incomplete understanding of the biological mechanisms that lead to keloids. The purpose of this project was to examine keloid pathogenesis from the epigenome perspective of DNA methylation. Genome-wide profiling used the Infinium HumanMethylation450 BeadChip to interrogate DNA from 6 fresh keloid and 6 normal skin samples from 12 anonymous donors. A 3-tiered approach was used to call out genes most differentially methylated between keloid and normal. When compared to normal, of the 685 differentially methylated CpGs at Tier 3, 510 were hypomethylated and 175 were hypermethylated with 190 CpGs in promoter and 495 in nonpromoter regions. The 190 promoter region CpGs corresponded to 152 genes: 96 (63%) were hypomethylated and 56 (37%) hypermethylated. This exploratory genome-wide scan of the keloid methylome highlights a predominance of hypomethylated genomic landscapes, favoring nonpromoter regions. DNA methylation, as an additional mechanism for gene regulation in keloid pathogenesis, holds potential for novel treatments that reverse deleterious epigenetic changes. As an alternative mechanism for regulating genes, epigenetics may explain why gene mutations alone do not provide definitive mechanisms for keloid formation.

NA Laryngoscope, 127:70-78, 2017.

No abstract

This study supports the concept of a proportionate response in the management of scaphocephaly. Less-aggressive procedures do not yield less-desirable results when properly selected to match the clinical situation of the individual patient.

NA Laryngoscope, 126:E319-E324, 2016.

Background:Modern microsurgical techniques enable en bloc resection of complex skull base tumors. Anterior cranial base surgery, particularly, has been associated with a high rate of postoperative cerebrospinal fluid (CSF) leak, meningitis, intracranial abscess, and pneumocephalus. We introduce simple modifications to already existing surgical strategies designed to minimize the incidence of postoperative CSF leak and associated morbidity and mortality.Methods:Medical records from 1995 to 2013 were reviewed in accordance with the Institutional Review Board. We identified 21 patients who underwent operations for repair of large anterior skull base defects following removal of sinonasal or intracranial pathology using standard craniofacial procedures. Patient charts were screened for CSF leak, meningitis, or intracranial abscess formation.Results:A total of 15 male and 6 female patients with an age range of 26–89 years were included. All patients were managed with the same operative technique for reconstruction of the frontal dura and skull base defect. Spinal drainage was used intraoperatively in all cases but the lumbar drain was removed at the end of each case in all patients. Only one patient required re-operation for repair of persistent CSF leak. None of the patients developed meningitis or intracranial abscess. There were no perioperative mortalities. Median follow-up was 10 months.Conclusion:The layered reconstruction of large anterior cranial fossa defects resulted in postoperative CSF leak in only 5% of the patients and represents a simple and effective closure option for skull base surgeons.

BACKGROUND Research evaluating the efficacy of multimodal therapy for the treatment of keloids has reported combination regimens are most effective. OBJECTIVE To compare recurrence rates for keloids treated with surgery plus one adjuvant intervention (dual therapy) versus surgery plus 2 or more adjuvant interventions (triple therapy). MATERIALS AND METHODS Systematic literature review and meta-analysis of combination treatment for keloids. RESULTS After full-text review, we included 60 articles representing 5,547 keloids: 5,243 received dual therapy, 259 received triple therapy, and 45 received quadruple therapy (the latter 2 groups were combined for analysis). The difference in recurrence rates between dual (19%) and triple therapy (11.2%) was not significant (p = .343). However, the difference in recurrence rates between dual therapy using surgery and radiation (18.7%) and triple therapy using surgery, radiation, and a third intervention (7.7%) was significant (p = .002). The differences for surgery and intralesional triamcinolone (TAC) showed trends toward significance, because keloids treated with dual therapy (21.7%) had a higher recurrence rate than those treated with triple therapy comprised of surgery, TAC, and another intervention (13.7%; p = .099). CONCLUSION Triple therapy using surgery plus radiation and/or TAC as one of the adjuvant treatment modalities may achieve the lowest recurrence rates for keloids.