Faculty Bibliography

An adolescent male presented to the office with a 3-month history of a small left ear mass located on the posterior helix. Although the patient was asymptomatic, the decision was made to remove the mass in the operating room and send for pathology. Following excision, the mass was stained and examined by the pathologist. Staining positive for Factor VIIIa and CD68, the lesion was also found to have a combination of histiocytes and fibroblastic spindle cells. The diagnosis of dermatofibroma, cellular type, was made and the patient required no further treatment. Seen in follow up several months after, there was complete resolution of the mass. <br /><br /> <em>J Drugs Dermatol.</em> 2016;15(10):1270-1272.

HSV-1 induced illness affects greater than 85% of adults worldwide with no permanent curative therapy. We used RNA-guided CRISPR/Cas9 gene editing to specifically target for deletion of DNA sequences of the HSV-1 genome that span the region directing expression of ICP0, a key viral protein that stimulates HSV-1 gene expression and replication. We found that CRISPR/Cas9 introduced InDel mutations into exon 2 of the ICP0 gene profoundly reduced HSV-1 infectivity in permissive human cell culture models and protected permissive cells against HSV-1 infection. CRISPR/Cas9 mediated targeting ICP0 prevented HSV-1-induced disintegration of promonocytic leukemia (PML) nuclear bodies, an intracellular event critical to productive HSV-1 infection that is initiated by interaction of the ICP0 N-terminus with PML. Combined treatment of cells with CRISPR targeting ICP0 plus the immediate early viral proteins, ICP4 or ICP27, completely abrogated HSV-1 infection. We conclude that RNA-guided CRISPR/Cas9 can be used to develop a novel, specific and efficacious therapeutic and prophylactic platform for targeted viral genomic ablation to treat HSV-1 diseases.

OBJECTIVES/HYPOTHESIS:To evaluate the increase in access to the maxillary sinus (MS) with transnasal endoscopic medial maxillary sinus wall transposition (TEMMT), while preserving major structures of the nasal cavity. STUDY DESIGN:The study was divided into three parts: anatomical, radiographic, and case series. METHODS:Three cadaveric dissections (total of six sides) confirmed the feasibility of the TEMMT approach. Radiographic measurements using maxillofacial computed tomography scans were taken to assess the maximal antrostomy. The TEMMT approach was performed on six consecutive patients with benign MS disease. RESULTS:The cadaveric measurements were consistent with the radiographic measurements, which confirmed the maximum access to the MS. The radiographic measurements ranged from 14.4 to 39.1 mm in the anteroposterior dimension, 8.2 to 23.7 mm in the superior-inferior dimension, and 36° to 98° in the angle between the medial and anterior wall of the MS. In the patient series, five patients presented with an odontogenic cyst, and one patient had an antrochoanal polyp in the MS. The TEMMT approach provided excellent access and adequate resection, as well as preservation of the nasolacrimal duct and inferior turbinate. Finally, the mucosal flap was sufficient to cover the inferior meatal antrostomy. CONCLUSIONS:TEMMT provides excellent access into the MS, especially the floor and anterior wall, without the morbidities of the Caldwell-Luc or medial maxillectomy approach. In addition, the transposition of the inferior turbinate and the mucosal flap provides coverage of the medial wall with preservation of the inferior meatus, inferior turbinate, and nasolacrimal duct for patients with benign MS disease. LEVEL OF EVIDENCE:NA Laryngoscope, 126:1504-1509, 2016.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Transoral robotic surgery (TORS) has increased for treatment of oropharyngeal squamous cell carcinoma (OPSCC). To define the adoption of TORS, we analyzed patterns of surgical treatment for OPSCC in the US. METHODS:Cases of T1-T3 OPSCC treated with surgery between 2010 and 2013 from the National Cancer Database were queried. RESULTS:Of 3,071 patients who underwent primary surgical management for T1-T3 OPSCC, 846 (28%) underwent TORS. On multivariable analysis, low tumor stage (T2 vs. T1: OR 0.75, CI 0.37-0.51, P < 0.0001; T3 vs. T1: O.R. 0.33, CI 0.28-0.38, P < 0.0001), treatment at an academic cancer center (O.R. 2.23, C.I. 1.29-3.88, P = 0.004) and treatment at a high volume hospital (34-155 cases vs. 1-4 cases: O.R. 9.07, C.I. 3.19-25.79, P < 0.0001) were associated with increased TORS approach. Significant geographic variation was observed, with high adoption in the Middle Atlantic. Positive margin rates were lower when TORS was performed at a high volume versus low volume hospital (8.2% vs. 16.7% respectively, P = 0.001). CONCLUSIONS:Tumor and non-tumor factors are associated with TORS adoption. This analysis suggests uneven diffusion of this technology in the treatment of OPSCC. J. Surg. Oncol. 2016;114:405-411. © 2016 Wiley Periodicals, Inc.

Hemostasis is a critical component of otologic and neurotologic surgery. In these surgeries the surgical field is small; thus, even a small amount of bleeding can obstruct the view of critical and extremely small structures. Additionally, relatively large vascular structures traverse the area; if they are encroached on by trauma or disease, bleeding must be controlled within a very small space in a meticulous fashion that does not encroach on structures of the middle ear and mastoid. The authors discuss several hemostatic agents in the middle ear, mastoid, and lateral skull base, highlighting their origins, mechanisms, advantages, and complications.

OBJECTIVES/OBJECTIVE:To investigate the effect of high flow nasal cannula oxygen therapy (HFOT) on middle ear pressure. MATERIALS/METHODS/METHODS:Ten patients (eight males and two females) with oxygen desaturations requiring HFOT were recruited with 19 ears available for our study. The study group was aged 29-90years (mean 65.3±16.5). All patients underwent a review of medical history, questioned about subjective hearing loss and underwent a standard otologic exam, with middle ear pressures measured with a GSI TympStar tympanometer. RESULTS:The middle ear peak pressures in our study group ranged from 25 to -200daPa (mean -13.7±56.3daPa). Volume of HFOT was delivered at 20-40L (mean 30.5±9L) and fraction of inspired oxygen required was 30-70% (mean 58±13%). There was a positive correlation between liters of oxygen delivery and middle ear pressure with a Pearson coefficient (R) of 0.436, although lacking statistical significance (p=0.06). CONCLUSION/CONCLUSIONS:Previous studies have shown that HFOT delivered in the range of 35-40L/min produces pharyngeal pressures at or above 5cm H2O. Since pharyngeal pressures of 5cm H2O produced via CPAP have shown to produce middle ear pressures above 40daPa, we expected HFOT to result in similar middle ear pressures of 35-40L/min. However, although our results show an increase in middle ear pressures with flow volume, HFOT did not produce significant increases in middle ear pressures. This may make HFOT an appropriate option of oxygen delivery to patients who require otologic procedures.

Spermatogenesis is an extraordinary complex process. The differentiation of spermatogonia into spermatozoa requires the participation of several cell types, hormones, paracrine factors, genes and epigenetic regulators. Recent researches in animals and humans have furthered our understanding of the male gamete differentiation, and led to clinical tools for the better management of male infertility. There is still much to be learned about this intricate process. In this review, the critical steps of human spermatogenesis are discussed together with its main affecting factors.

BACKGROUND:The sublingual mucosa has been used for many years to apply allergenic extracts for the purpose of specific immunotherapy (IT). Although sublingual IT (SLIT) is both safe and efficacious, the density of antigen-presenting cells is higher in other regions of the oral cavity and vestibule, which make them a potentially desirable target for IT. OBJECTIVE:To present the concept of oral mucosal IT (OMIT) and to provide pilot data for this extended application of SLIT. METHODS:An open-label, 12-month, prospective study was undertaken as a preliminary step before a full-scale clinical investigation. Twenty-four individuals with allergic rhinitis received IT by applying allergenic extracts daily to either the oral vestibule plus oral cavity mucosa by using a glycerin-based toothpaste or to the sublingual mucosa by using 50% glycerin liquid drops. Adverse events, adherence rates, total combined scores, rhinoconjunctivitis quality-of-life questionnaire scores, changes in skin reactivity, and changes in serum antibody levels were measured for each participant. RESULTS:No severe adverse events occurred in either group. The adherence rate was 80% for the OMIT group and 62% for the SLIT group (p = 0.61). Decreased total combined scores were demonstrated for both the OMIT group (15.6%) and the SLIT group (22.3%), although this decrease did not reach statistical significance in either group. Both groups achieved a meaningful clinical improvement of at least 0.5 points on rhinoconjunctivitis quality-of-life questionnaire. A statistically significant rise in specific immunoglobulin G4 (IgG4) was seen in both groups over the first 6 months of treatment. CONCLUSION/CONCLUSIONS:OMIT and SLIT demonstrated similar safety profiles and adherence rates. Measurements of clinical efficacy improved for both groups, but only changes in IgG4 achieved statistical significance. These pilot data provide enough evidence to proceed with a full-scale investigation to explore the role of OMIT in the long-term management of allergic rhinitis.