Sameer Alvi

Secretory Autophagy in Cancer-Associated Fibroblasts Promotes Head and Neck Cancer Progression and Offers a Novel Therapeutic Target

Despite therapeutic advancements, there has been little change in the survival of patients with head and neck squamous cell carcinoma (HNSCC). Recent results suggest that cancer-associated fibroblasts (CAF) drive progression of this disease. Here, we report that autophagy is upregulated in HNSCC-associated CAFs, where it is responsible for key pathogenic contributions in this disease. Autophagy is fundamentally involved in cell degradation, but there is emerging evidence that suggests it is also important for cellular secretion. Thus, we hypothesized that autophagy-dependent secretion of tumor-promoting factors by HNSCC-associated CAFs may explain their role in malignant development. In support of this hypothesis, we observed a reduction in CAF-facilitated HNSCC progression after blocking CAF autophagy. Studies of cell growth media conditioned after autophagy blockade revealed levels of secreted IL6, IL8, and other cytokines were modulated by autophagy. Notably, when HNSCC cells were cocultured with normal fibroblasts, they upregulated autophagy through IL6, IL8, and basic fibroblast growth factor. In a mouse xenograft model of HNSCC, pharmacologic inhibition of Vps34, a key mediator of autophagy, enhanced the antitumor efficacy of cisplatin. Our results establish an oncogenic function for secretory autophagy in HNSCC stromal cells that promotes malignant progression. Cancer Res; 77(23); 6679-91. ©2017 AACR.

Outcomes of HPV-related nasal squamous cell carcinoma

Human papilloma virus (HPV) infection has been shown to play an integral role in the development and prognosis of various head and neck cancers. Generational changes in sexual behavior may have led to an increased incidence of positivity in recent years. HPV positivity in both benign and malignant lesions of the sinonasal cavities has been shown in previous studies (estimates range from 20%–30% for malignancy). We intend to investigate if HPV positivity affected survival outcomes in our patient cohort.

Endoscopically Assisted Drilling, Exposure of the Fundus through a Presigmoid Retrolabyrinthine Approach: A Cadaveric Feasibility Study:

The presigmoid retrolabyrinthine approach to the cerebellopontine angle is traditionally described to not provide access to the internal auditory canal (IAC). We aimed to evaluate the extent of the IAC that could be exposed with endoscopically assisted drilling and to measure the percentage of the IAC that could be visualized with the microscope and various endoscopes after drilling had been completed. Presigmoid retrolabyrinthine approaches were performed bilaterally on 4 fresh cadaveric heads. We performed endoscopically assisted drilling to expose the fundus of the IAC, which resulted in exposure of the entire IAC in 8 of 8 temporal bone specimens. The microscope afforded a mean view of 83% (n = 8) of the IAC. The 0°, 30°, 45°, and 70° endoscope each afforded a view of 100% of the IAC in 8 of 8 temporal bone specimens. In conclusion, endoscopic drilling of the IAC of can provide an extradural means of exposing the entire length of the IAC while preserving the labyrinth.

Clinical manifestations of neuroblastoma with head and neck involvement in children

OBJECTIVE The purpose of our study is to review our 15-year experience with pediatric patients who have been diagnosed with neuroblastoma, and to determine their most frequent head and neck manifestations and symptoms. STUDY DESIGN Retrospective chart review of electronic medical record. SETTING An academic, tertiary care pediatric hospital. SUBJECTS AND METHODS IRB approval from the Office of Research Integrity at Childrens Mercy Hospital was obtained. The hospital tumor database was analyzed to identify patients with neuroblastoma, ganglioneuroblastoma, and esthesioneuroblastoma diagnosed between 1997 and 2012. We recorded the various clinical signs and symptoms these patients displayed at their initial presentation, focusing on patients with head and neck involvement. We then determined the relative incidence of these various findings. RESULTS Our review yielded 118 patients diagnosed with neuroblastoma, ganglioneuroblastoma, or esthesioneuroblastoma over our 15 year study period. 7 of the 118 patients were diagnosed with primary tumors of the head and neck. Another 19 patients had metastatic head and neck involvement. For those with primary disease, presence of a neck mass and signs of Horners syndrome were the most common findings. For metastatic disease, craniofacial bony metastasis was the most frequent finding in our study. CONCLUSIONS Based on our data, there are a handful of findings that occur frequently in pediatric head and neck neuroblastoma. Any persistent neck mass, unexplained Horners syndrome, or periorbital ecchymosis should be carefully evaluated. This study should serve as an aid for the otolaryngologist to be aware of the possible manifestations of this malignancy in children.

Alginate Ototoxicity in the Mouse Model

Objective To determine whether alginate exposure to the round window of the mouse causes any measurable ototoxicity. Study Design Prospective animal study. Setting Basic science laboratory affiliated with a tertiary care university medical center. Subjects and Methods After Institutional Animal Care and Use Committee approval, 5 adult mice were obtained and underwent bullostomy and round window niche application of alginate. Auditory brainstem response (ABR) tests were completed at baseline prior to the procedure and also 5, 14, and 30 days postprocedure. Results were compared. At termination of procedure, the mice were sacrificed with harvest of the cochleae, which were viewed under histologic section. Results There were no significant increases in ABR thresholds in any of the test animals at all test periods after alginate exposure compared to baseline. There were also no observable behavioral changes after the procedure to indicate vestibular dysfunction. Cochlear sectioning revealed no evidence of histologic damage. Conclusion Exposure of alginate to the round window does not cause any obvious ototoxicity in the mouse model. Further clinical trials will be needed to elucidate the effect of alginate in the human middle ear.

Outcomes after free tissue transfer for composite oral cavity resections involving skin

Resections involving oral cavity mucosa, bone, and skin present a unique challenge. Optimizing outcomes often requires technically demanding reconstruction. The purpose of this study is to evaluate outcomes of several reconstructive approaches for patients with composite through‐and‐through defects, with a focus on the osteocutaneous radial forearm free flap (RFFF).

Steroid Versus Antibiotic Drops in the Prevention of Postoperative Myringotomy Tube Complications

Objectives: To determine the incidence of early postoperative tympanostomy tube insertion otorrhea and obstruction in pediatric patients receiving antibiotic ear drops with or without steroid perioperatively. Methods: A retrospective chart review was performed on patients who underwent outpatient myringotomy and tube placement. Patients from June 2013 to February 2014 received ciprofloxacin/dexamethasone perioperatively while patients from May 2014 to April 2015 received ofloxacin. Statistical analysis was performed to compare outcomes between the cohorts. Results: One hundred thirty-four patients received topical ciprofloxacin/dexamethasone, and 116 patients received topical ofloxacin. The rate of postoperative otorrhea was 5.2% for the ciprofloxacin/dexamethasone group and 8.2% for the ofloxacin group. Tube obstruction was seen in 6.0% of the ciprofloxacin/dexamethasone group and 5.2% in the ofloxacin group. Neither outcome had a statistically significant difference (P = .21 and .85, respectively). There was no difference in the rate of effusion at the time of tube placement between the 2 cohorts (P = .16), and this included subgroup analysis based on effusion type (mucoid, purulent, serous). Patients with a mucoid effusion at the time of surgery were more likely to experience otorrhea/obstruction than patients with dry ears (odds ratio = 2.23, P = .02). Conclusion: No significant difference in the incidence of immediate postoperative tympanostomy tube otorrhea or obstruction was seen between the antibiotic-steroid and antibiotic alone cohorts, regardless of effusion type. Overall, patients with mucoid effusions are more likely to develop tube otorrhea or obstruction at follow-up. Cost-effective drops should be used when prescribing topical therapy to prevent complications after ear tubes.

Bilateral Ossicular Head Dehiscence Into the Middle Cranial Fossa

Objectives: To describe a unique case of bilateral dehiscence of the malleus and incus heads into the middle fossa making contact with the temporal lobes, along with its clinical implications. Methods: An analysis of a patient case and review of pertinent literature were performed. Results: A patient with a history of right-sided mastoidectomy for cholesteatoma was evaluated for persistent conductive hearing loss. On computed tomography (CT) and magnetic resonance imaging (MRI), the patient had a complete dehiscence of the tegmen tympani on the right, with ossicular heads being located above the floor of the middle cranial fossa. A similar finding to a milder degree was noted on the left. The patient underwent revision tympanoplasty with mastoidectomy with removal of the incus and ossicular chain reconstruction and middle fossa craniotomy for repair of the right epitympanic dehiscence. Conclusions: We present some of the unique imaging and operative findings involved in an unusual presentation of encephalocele in which the bilateral malleus and incus heads rise above the level of the middle fossa floor.

Priorities in the Neurotology Fellowship Match: A Survey Study of Program Directors and Fellows.

Objectives: To ascertain motivations and priorities for neurotology fellowship applicants and program directors during the match process. Methods: Anonymous online survey distributed to 20 fellowship program directors and 40 current and incoming neurotology fellows. A 5-point Likert scale was used to assess the priorities of fellowship applicants and program directors in the match process. Results: Twenty-four of 40 (60%) current or incoming fellows and 14 of 20 (65%) program directors responded to the survey. Fellows rated surgical exposure and volume as their highest priorities. In addition to neurotology case load, fellows highly valued exposure to otologic surgery. Salary, call, and work/life balance were among the lowest rated factors among fellows. Program directors attached the highest priority to the applicant interview performance, followed by strength of letters of recommendation and quality of prior research. Ethnicity, sex, and likelihood of an applicant ranking a program highly were the lowest rated factors among program directors. Conclusion: Among neurotology fellows, operative case load and breadth of surgical exposure are highly valued components of accredited fellowship training. Among neurotology fellowship program directors, candidates’ performance during the fellowship interview appears to be highly valued, more so than the strength of applicants’ letters of recommendation or prior research credentials.

Tinnitus perception in patients after vagal nerve stimulator implantation for epilepsy

PURPOSE Vagal nerve stimulation in conjunction with sound therapy has been proposed as a treatment for subjective tinnitus. The purpose of this study is to retrospectively review the effect of VNS on perception of tinnitus in epilepsy patients. We explore the incidence of tinnitus and its perceived reduction in patients requiring implantation of VNS for medically refractory seizures. MATERIALS AND METHODS A phone survey was conducted in adult patients with prior VNS implantation. A questionnaire including the visual analog scale (VAS) of tinnitus loudness was used to determine the presence and severity of tinnitus. RESULTS Out of the 56 patients who had completed the phone survey, 20 (35%) reported the presence of pre-operative tinnitus. The tinnitus positive group was significantly older (p = 0.019). Of the 20 pre-operative tinnitus positive patients, all patients continued to have tinnitus post-operatively. Four (20%) noted no changes in VAS of tinnitus loudness while 16 (80%) had at least a one-point decrease. The mean difference between pre- and post-operative VAS of loudness was 2.05, with a standard deviation of 1.84 and this was statistically significant (p < 0.001). CONCLUSIONS In this study, we evaluate the potential of vagal nerve stimulation to alter the perception of tinnitus in patients with refractory epilepsy. Eighty percent of patients noted some level of subjective tinnitus improvement after VNS implantation. Given this finding, there may be a potential additional benefit to the use of VNS in patients with epilepsy.