Faculty Bibliography

Objective Although thyroglossal duct cysts (TGDCs) are relatively common, malignancies within these lesions are infrequent. As a result, there are no large-scale series describing clinical characteristics. Our objectives were to perform a systematic review of the literature evaluating patient demographics, pathology, management, and prognosis of these patients. Data Sources PubMed, Embase, Cochrane reviews, and Google Scholar were searched for relevant articles. Articles meeting inclusion criteria were reviewed for data detailing epidemiology, treatment, and outcomes. Review Methods Inclusion criteria included English-language articles with original reports on human subjects. Two investigators independently reviewed all articles for the data collected, including epidemiology, treatment, and outcomes. Results Ninety-eight articles comprising 164 patients were included in the final analysis. The mean age at presentation was 39.5 years (9-83 years); 68.3% of patients were female. In total, 73.3% of cases were found on final pathologic analysis. The most common pathology was papillary cancer (92.1%). Of the patients, 98.9% underwent a Sistrunk procedure and 61.0% underwent total thyroidectomy. There was a 4.3% recurrence rate with a mean time to recurrence of 42.1 months from initial treatment. One patient died of TGDC carcinoma, while all other patients were disease free at the time of last follow-up (mean follow-up was 46.1 months). Conclusion TGDC carcinoma is typically diagnosed on final pathology. While management encompasses a Sistrunk procedure, further consideration should be given to thyroidectomy among patients ≥45 years of age and individuals with aggressive disease. TGDC carcinoma harbors an exceedingly low rate of mortality.

OBJECTIVES:To describe the epidemiology and analyze factors determinant of survival in patients with oropharyngeal lymphoma, using the Surveillance Epidemiology and End Results (SEER) database. METHODS:2504 patients with oropharyngeal lymphoma were identified using the most recent SEER database entry from 1976 to 2016. Demographic information, Ann Arbor stage, tumor histopathology and location were collected. Multivariate analysis was used to analyze patient and tumor characteristics associated with survival. RESULTS:The mean age of the patients studied was 60.5years, 58.4% of the subjects were male and 81% were white. Diffuse large B cell lymphoma (DLBCL) was the most common histologic subtype involving 56.9% of cases. The most common subsite of origin was the tonsil, with 71% of lymphomas originating from there. The association of survival with stage, age, tumor location, presence of B symptoms, tumor pathology, gender and race was analyzed using multivariate regression. Decreased survival was significantly associated with patient age p<0.0001, Ann Arbor staging p=0.005, the presence of B symptoms p=0.003 and tumor histopathology (T cell tumors) p=0.01. Patients with tumors originating from the soft palate were significantly more likely to die asa result of their disease p=0.03. CONCLUSION:Oropharyngeal lymphoma most commonly originates from the tonsil. DLBCL is the most common subtype and has a good prognosis. The presence of B symptoms, tumors originating from the soft palate and patients with T cell tumors have the worst prognosis. This information can potentially be of great utility to the head and neck surgeon discussing prognosis with patients suffering from oropharyngeal lymphoma.

OBJECTIVES/OBJECTIVE:Pediatric rhinoplasty has traditionally raised numerous concerns, including its impact on growth as well as the psychological sequelae of undergoing a potentially appearance-altering procedure. Our objective was to critically evaluate available individual patient data relevant to pediatric rhinoplasty, and further discuss perioperative considerations. METHODS:A systematic review was conducted using PubMed/MEDLINE databases. Data extracted and analyzed from included studies included patient demographics, surgical indications, operative approaches, outcomes, complications, revision rates, and other clinical considerations. RESULTS:Seven studies encompassing 253 patients were included, with age ranging from 7 months to 19 years. Two-thirds of patients were male. 41.7% reported antecedent trauma, and common overall surgical indications included "functional aesthetic" (24.5%) followed by cleft lip nasal deformity (15.8%). The majority (79.1%) underwent open approaches, and 71.1% of patients underwent concomitant septal intervention. The most frequently used grafting materials were septal cartilage (52.8%) and conchal cartilage (16.5%). Surgical outcomes were heterogeneous among these studies. Complication rates were only specified in 5 of the 7 studies and totaled 57 patients (39.6%). Aesthetic dissatisfaction (11.8%) and postoperative nasal obstruction (5.6%) were the most commonly reported complications. Revisions were performed in 13.5%. CONCLUSION/CONCLUSIONS:Rhinoplasty is safe in the pediatric population, although revisions rates appear greater than those reported in adults. This study of 253 represents the largest pooled sample size to date; nonetheless, non-standardized outcome measures, minimal long-term followup data, and lack of discussion regarding psychological sequelae all contribute to the need for further high-quality studies evaluating this topic.

OBJECTIVES/HYPOTHESIS:The aim of this study was to evaluate factors raised in malpractice litigation related to the diagnosis and management of melanoma and to further assess issues impacting outcome. STUDY DESIGN:Retrospective chart review. METHODS:The Westlaw legal database was searched for malpractice litigation resolved over the last 20 years relating to melanoma. Cases were evaluated for allegations, defendant specialty, outcome, and other issues raised. RESULTS:Of the 80 cases evaluated, 49% were resolved in the defendants' favor. In greater than 80% of cases, there was alleged misdiagnosis. In 35% of cases, the patient had expired secondary to melanoma at the time of litigation. There was no statistical difference in payments upon comparison of cases with and without mortality. A greater proportion of cases with dermatologists and pathologists as defendants involved alleged misdiagnosis. The most common locations for melanoma were the extremities and the head-and-neck region, at 32.5% and 22.5%, respectively. Location did not significantly impact the outcome of cases. CONCLUSION:Malpractice litigation relating to melanoma involves numerous physicians, including dermatologists, pathologists, and otolaryngologists. Alleged misdiagnosis of a pigmented lesion was the most common cause of litigation and involved physicians from numerous specialties. Patients who were misdiagnosed had a significantly higher likelihood of having active disease at the time of litigation. Ultimately improved methods of detecting concerning pigmented lesions need to be developed. Factors such as death and poor cosmetic outcome did not significantly impact litigation outcome. LEVEL OF EVIDENCE:NA Laryngoscope, 127:134-139, 2017.

Inactivation of NF2/Merlin causes the autosomal-dominant cancer predisposition syndrome familial neurofibromatosis type 2 (NF2) and contributes to the development of malignant pleural mesothelioma (MPM). To develop a targeted therapy for NF2-mutant tumors, we have exploited the recent realization that Merlin loss drives tumorigenesis by activating the E3 ubiquitin ligase CRL4^DCAF1, thereby inhibiting the Hippo pathway component Lats. Here, we show that MLN4924, a NEDD8-activating enzyme (NAE) inhibitor, suppresses CRL4^DCAF1 and attenuates activation of YAP in NF2-mutant tumor cells. In addition, MLN4924 sensitizes MPM to traditional chemotherapy, presumably as a result of collateral inhibition of cullin-RING ubiquitin ligases (CRL) involved in DNA repair. However, even in combination with chemotherapy, MLN4924 does not exhibit significant preclinical activity. Further analysis revealed that depletion of DCAF1 or treatment with MLN4924 does not affect mTOR hyperactivation in NF2-mutant tumor cells, suggesting that loss of Merlin activates mTOR independently of CRL4^DCAF1 Intriguingly, combining MLN4924 with the mTOR/PI3K inhibitor GDC-0980 suppresses the growth of NF2-mutant tumor cells in vitro as well as in mouse and patient-derived xenografts. These results provide preclinical rationale for the use of NAE inhibitors in combination with mTOR/PI3K inhibitors in NF2-mutant tumors. Mol Cancer Ther; 16(8); 1693-704. ©2017 AACR.

HYPOTHESIS:Custom prostheses could be used to recreate the ossicular chain and improve hearing. BACKGROUND:Ossicular discontinuity or fixation occurs in 55% of cases of conductive hearing loss, with most cases involving the incus. Reconstruction has been achieved by a variety of methods; however, there has been little improvement in hearing outcomes in decades. METHODS:Precise measurements of anatomic dimensions, weight, and center of gravity were taken from 19 cadaveric incudes. These measurements were combined with measurements from the medical literature and micro-computed tomography (micro-CT) of cadaveric temporal bones to generate a rasterizable incus model. As a proof of concept, incudal replacements including possible anatomic variations were then three-dimensionally (3-D) printed and inserted into a cadaveric temporal bone. RESULTS:Our measurements of cadaveric incudes corresponded well with those from the medical literature. These measurements were combined with anatomical information from micro-CT allowing identification of critical features of the incus, which remained constant. Other model features were modified to increase stability and facilitate synthesis, including broadening and thickening of the lenticular process and the incudomalleolar articulation. 3-D printed incudal replacements based on this model readily fit into a cadaveric temporal bone and successfully bridged the gap between malleus and incus. CONCLUSION:We have generated a model for custom 3-D synthesis of incudal prostheses. While current 3-D printing in biocompatible materials at the size required is limited, the technology is rapidly advancing, and 3-D printing of incudal replacements with polylactic acid (PLA) is of the correct size and shape.

The CRISPR or clustered regularly interspaced short palindromic repeats system is currently the most advanced approach to genome editing and is notable for providing an unprecedented degree of specificity, effectiveness, and versatility in genetic manipulation. CRISPR evolved as a prokaryotic immune system to provide an acquired immunity and resistance to foreign genetic elements such as bacteriophages. It has recently been developed into a tool for the specific targeting of nucleotide sequences within complex eukaryotic genomes for the purpose of genetic manipulation. The power of CRISPR lies in its simplicity and ease of use, its flexibility to be targeted to any given nucleotide sequence by the choice of an easily synthesized guide RNA, and its ready ability to continue to undergo technical improvements. Applications for CRISPR are numerous including creation of novel transgenic cell animals for research, high-throughput screening of gene function, potential clinical gene therapy, and nongene-editing approaches such as modulating gene activity and fluorescent tagging. In this prospect article, we will describe the salient features of the CRISPR system with an emphasis on important drawbacks and considerations with respect to eliminating off-target events and obtaining efficient CRISPR delivery. We will discuss recent technical developments to the system and we will illustrate some of the most recent applications with an emphasis on approaches to eliminate human viruses including HIV-1, JCV and HSV-1 and prospects for the future. J. Cell. Biochem. 118: 3586-3594, 2017. © 2017 Wiley Periodicals, Inc.