Faculty Bibliography

Pediatric robotic surgery is a relatively new technology that has been shown to be safe and feasible for a number of pediatric procedures. Our literature analysis was performed using Pubmed database between January 2005 and December 2015, using key words: "robotic," "robotic surgery," "TORS," "pediatric," "children," "head and neck," and "da Vinci". We selected only publications in English. Eight published reports met the selection criteria. We totally found 41 patients, and the age range was between 2 months and 19 years. The cases are 16 only lingual tonsillectomy, nine base of tongue and lingual tonsillectomy, two malignant disease in the oropharynx (high-grade undifferentiated sarcoma and biphasic synovial sarcoma), one tongue base thyroglossal duct cyst, 11 laryngeal cleft cyst, one posterior glottic stenosis, and one congenital true vocal cord paralysis surgeries. One intraoperative complication was reported. No patient needed postoperative tracheotomy. Hospital duration time had a range of 1-16 days. TORS is new for pediatric patients in head and neck areas, and there were few reports. It is becoming increasingly used in head and neck surgeries and those reports above are encouraging for pediatric robotic airway surgeries in otolaryngology in the future.

ANO1 is a calcium-activated chloride channel that is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and other cancers. While ANO1 expression negatively correlates with survival in several cancers, its epigenetic regulation is poorly understood. We analyzed HNSCC samples from TCGA and a separate dataset of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples to identify differentially methylated regions. E6 and E7 transfected normal oral keratinocytes (NOK) were used to induce hypermethylation of the ANO1 promoter. We found three CpG islands that correlated with ANO1 expression, including two positively correlated with expression. Using two HNSCC datasets with differential expression of ANO1, we showed hypermethylation of positively correlated CpG islands potentiates ANO1 expression. E7 but not E6 transfection of NOK cells led to hypermethylation of a positively correlated CpG island without a change in ANO1 expression. ANO1 promoter methylation was also correlated with patient survival. Our results are the first to show the contribution of positively correlated CpG's for regulating gene expression in HNSCC. Hypermethylation of the ANO1 promoter was strongly correlated with but not sufficient to increase ANO1 expression, suggesting methylation of positively correlated CpG's likely serves as an adjunct to other mechanisms of ANO1 activation.

Despite a well-established role for the epidermal growth factor receptor (EGFR) in tumorigenesis, EGFR activities and endocytosis in tumors in vivo have not been studied. We labeled endogenous EGFR with GFP by genome-editing of human oral squamous cell carcinoma cells, which were used to examine EGFR-GFP behavior in mouse tumor xenografts in vivo. Intravital multiphoton imaging, confocal imaging of cryosections and biochemical analysis revealed that localization and trafficking patterns, as well as levels of phosphorylation and ubiquitylation of EGFR in tumors in vivo closely resemble patterns and levels observed in the same cells treated with 20-200 pM EGF in vitro. Consistent with the prediction of low ligand concentrations in tumors, EGFR endocytosis was kinase-dependent and blocked by inhibitors of clathrin-mediated internalization; and EGFR activity was insensitive to Cbl overexpression. Collectively, our data suggest that a small pool of active EGFRs is sufficient to drive tumorigenesis by signaling primarily through the Ras-MAPK pathway.

OBJECTIVE:Endoscopic endonasal transsphenoidal surgery (EETS) is a widely accepted technique for sellar tumors. Common findings during preoperative assessment include septal deviations and turbinate hypertrophy. This study evaluated quality of life changes after concurrent septoplasty and/or inferior turbinoplasty during EETS. METHODS:A retrospective review was performed of a prospectively collected database including all patients undergoing EETS at our institution during a 10-month period between 2015 and 2016. Patients were divided into a septoplasty/inferior turbinoplasty group and a no septoplasty/inferior turbinoplasty group. The Sino-Nasal Outcome Test (SNOT-22) was used to evaluate quality of life. Mean preoperative scores were compared with 1- and 3-month postoperative scores within each cohort. The SNOT-22 was also reorganized into 5 distinct subdomains. Average subdomain scores were calculated, and preoperative and 1- and 3-month postoperative subdomain scores were compared within each cohort. A paired Student t test was used. P values < 0.05 were considered statistically significant. RESULTS:All 24 patients met inclusion criteria by completing preoperative and postoperative SNOT-22 surveys. In the septoplasty/inferior turbinoplasty group, preoperative and 3-month postoperative scores showed a clinically significant difference (P = 0.047). The septoplasty/inferior turbinoplasty group specifically showed a significant difference in the psychiatric and sleep SNOT-22 subdomains when comparing preoperative with 3-month postoperative scores (P = 0.03, P = 0.01). CONCLUSIONS:Patients who underwent concurrent septoplasty and/or turbinoplasty with EETS had a significantly improved quality of life compared with preoperative assessment, specifically regarding psychological and sleep symptoms.

OBJECTIVE:A significant proportion of children with congenital hearing loss who are candidates for cochlear implants (CIs) may have inner ear malformations (IEMs). Surgical and speech outcomes following CI in these children have not been widely reported. METHODS:The charts of children who were evaluated for a CI between 1/1/1986 and 12/31/2014 at a university-based tertiary level pediatric cochlear implant center were reviewed. Principal inclusion criteria included (i) age 1-18 years, (ii) history of bilateral severe to profound sensorineural hearing loss, and (iii) limited benefit from binaural amplification. Exclusion criteria included (i) underlying diagnosis of neurodevelopmental disorder and (ii) lack of follow up for speech assessment if a CI was performed. The following outcome measures were reviewed: (i) imaging findings with magnetic resonance imaging or high resolution computed tomography, (ii) intraoperative complications, and (iii) speech perception categorized as the ability to perceive closed set, open set, or none. RESULTS:The prevalence of IEMs was 27% (102 of 381), of which 79% were bilateral. Cochlear dysplasia accounted for 30% (40 of 136) of the anomalies. Seventy-eight of the 102 patients received a CI (78%). Surgery was noted to be challenging in 24% (19 of 78), with a perilymphatic gusher being the most common intraoperative finding. Cochlear dysplasia, vestibular dysplasia and cochlear nerve hypoplasia were associated with poor speech perception (open OR closed set speech recognition scores, 0-23%), although the outcomes in children with enlarged vestibular aqueduct were similar to those of children with normal inner ear anatomy (65%). CONCLUSIONS:Cochlear implantation is safe in children with IEMs. However, the speech perception outcomes are notably below those of patients with normal anatomy, with the exception of when an enlarged vestibular aqueduct is present.

BACKGROUND:Postoperative cerebrospinal fluid leak after endoscopic pituitary surgery ranges from 1.9% to 10% in different series. Vascularized flaps have reduced the incidence of leak; however, this carries nasal morbidity. This study presents a technique for sellar reconstruction with free mucosal graft from the nasal cavity floor including inferior meatus mucosa. This technique aims to standardize sellar reconstruction without the use of the nasoseptal flap and to keep the advantage of mucosal coverage of the defect in all cases. METHODS:Fifty consecutive patients who had endoscopic surgery for pituitary tumors and reconstruction with nasal cavity floor free mucosal graft were retrospectively reviewed. There were a total of 50 patients with postoperative follow-up from 3 to 16 months. Collagen dural graft was used inlay and free mucosal graft overlay to cover the sellar defect. No fat grafts or lumbar drains were used. A Sinonasal Outcome Test-22 (SNOT-22) was performed before, 1 and 3 months after surgery. RESULTS:There were 40% detected intraoperative leaks and no postoperative leaks. Nasal endoscopy performed at 1 month follow-up showed complete healing of the graft to the skull base and near total or complete mucosalization of the donor site. No significant difference was found in the SNOT-22 comparing the total preoperative and 1-month scores. CONCLUSIONS:The nasal cavity floor free mucosal graft is an easy and safe technique, with minimal nasal morbidity. There were no postoperative cerebrospinal fluid leaks, despite aggressive tumor resection. No lumbar drains or fat graft were used. The harvest of mucosal graft does not worsen the quality of life measured with the SNOT-22 test.

Objective To determine the impact of unilateral vagal sacrifice for vagal schwannoma on postoperative swallowing function. Study Design Case series, chart review. Setting Academic medical institution. Subjects and Methods Ten patients underwent vagus nerve sacrifice for vagal schwannoma resection. Archived pathology records dating from 1985 through 2012 at our institution were retrospectively queried for cases of vagal schwannoma with vagus nerve sacrifice. Medical records were abstracted for demographic and disease information as well as cranial nerve and swallowing function. Preoperative and postoperative cranial nerve function, subjective and objective measures of swallowing function, Functional Oral Intake Scale (FOIS) level, and need for vocal fold medialization were variables collected. Data were analyzed with summary statistics. Results The patients who underwent vagal sacrifice for vagal schwannoma at our institution had a mean age of 42.3 years (median, 44 years; range, 15-63 years) and follow-up of 35.6 months (median, 9 months; range, 1-115 months). Most presented with no preoperative cranial nerve deficit or difficulty swallowing. Immediately postoperatively, 90% had a vagus nerve deficit, but 50% had no subjective difficulty swallowing, and 70% had a FOIS level of 7 at postoperative hospital discharge. Within 1 month after surgery, 70% had normal swallowing function according to a modified barium swallow study. A full diet was tolerated by mouth within an average of 2.7 days (median, 2 days; range, 1-6 days) after surgery in this cohort. Seventy percent required vocal fold medialization postoperatively for incomplete glottic closure. Conclusion Vagal nerve sacrifice during resection of vagal schwannoma can be performed with normal postoperative swallowing function.