Faculty Bibliography

The surgical robot has been demonstrated to have useful applications in urologic, gynecologic, cardiac, general, and endocrine surgery. The development of robotic surgery has enhanced the precision and control of the surgeon in minimally invasive surgical situations specific to these specialties and, more recently, has been applied to the treatment of oropharyngeal tumors in the form of transoral robotic surgery (TORS). The elimination of the need for lip- and mandible-splitting approaches has allowed a reassessment of surgical options for the treatment of tumors that have until recently been primarily addressed nonoperatively with chemoradiation. The TORS approach has created the need to adapt current reconstructive options to robotic technology to manage the resultant tissue defects and to assess and compare the effectiveness of these procedures. This report details our early experience with the use of robot-assisted free tissue transfer for management of soft tissue defects of the oropharynx.

PURPOSE OF REVIEW: The palate is a critical structure, playing pivotal roles in speech, swallowing, and mastication. Reconstruction of the palate is among the most difficult challenges faced by head and neck reconstructive surgeons. The primary aims of this review are to catalog the evolution of the classification systems for palatal defects, discuss decision making surrounding the various options for hard palate reconstruction, and address the special challenges and techniques involved in soft palate reconstruction. RECENT FINDINGS: The Okay Classification System has become the standard by which most hard palatal defects are assessed. Free tissue transfer seems to be becoming an increasingly important therapeutic modality for many hard and soft palate defects. SUMMARY: Success in the management of palatal defects depends on accurate appreciation of the size and functional extent of each defect, careful patient selection, and specific attention to each patient's goals.

Objective: Glucocorticoids are commonly used treatments in otolaryngology, but guidelines about their use are vague and irregular. We sought to assess clinical practices with regard to glucocorticoid use for patients with laryngeal disease and to ascertain factors driving clinician drug choice. Method: A web-based survey was distributed to otolaryngologists via email using the Ear, Nose, and Throat (ENT) Journal database. This survey was composed of 20 questions and collected the following data from respondents: 1) indications for the use of glucocorticoids in their practice, 2) decision-making process influencing the choice of glucocorticoid, 3) background and demographics. Results: Two hundred eight otolaryngologists completed the survey, with 99% (n = 196) reporting that glucocorticoids were valuable to their practice. "Previous experience/results," "familiarity," and "use in practice" (n = 144, 114, and 79, respectively) were commonly cited reasons for choosing a particular glucocorticoid, whereas pharmacokinetic profile and "academic literature" were infrequently cited concerns. Only 54.4% (n = 106) of respondents said that they were more likely to prescribe glucocorticoids for vocal performers as compared to other patients. Additionally, most respondents said side effects only "occasionally" prevented them from prescribing glucocorticoids to patients. Conclusion: These results suggest that glucocorticoid prescription practices vary greatly between otolaryngologists, and drug choice is driven primarily by clinician preference rather than more objective factors. These findings indicate a need for further research about this powerful class of drugs, and the importance of establishing clear, appropriate guidelines regarding their use.

Objective: To report a case of sebaceoma of the auricle, and to discuss the differential diagnosis, histopathological features, surgical management and genetic associations of this entity. Methods: Case report and review of the medical literature. Results: A 79-year-old man presented with a slowly growing lesion of his auricle. Excision of the mass and histopathological review revealed a benign, basaloid, adnexal neoplasm consistent with sebaceoma. Due to its association with Muir-Torre syndrome and increased risk of visceral malignancy, the patient was followed closely for signs of malignancy. At 36 months post-excision, there were no signs of recurrence; thereafter, the patient continued to receive routine cancer surveillance follow up. Conclusion: Sebaceoma is a rarely encountered, benign, adnexal neoplasm which can occur in the head and neck. The treatment is surgical excision, and recurrence is rare. Sebaceoma can occur as part of Muir-Torre syndrome, and in these patients there is an increased risk of other sebaceous lesions and visceral malignancy; thus, genetic testing and surveillance should be strongly considered.

PURPOSE: Although microdissection testicular sperm extraction has become first line therapy for sperm retrieval in men with nonobstructive azoospermia, there are challenges to the procedure, including difficulty differentiating between seminiferous tubules with normal and abnormal spermatogenesis. Multiphoton microscopy illuminates tissue with a near infrared laser to elicit autofluorescence, which enables real-time imaging of unprocessed tissue without labels. We hypothesized that we could accurately characterize seminiferous tubular histology in humans using multiphoton microscopy. MATERIALS AND METHODS: Seven men with normal or abnormal spermatogenesis underwent testicular biopsies, which were imaged by multiphoton microscopy. We assessed these images in blinded fashion. The diagnosis rendered with multiphoton microscopy was then correlated with that of hematoxylin and eosin stained tissue. We evaluated the ability of multiphoton microscopy to differentiate normal from abnormal seminiferous tubules by examining autofluorescence characteristics and diameters, as imaged by multiphoton microscopy. Assessment was repeated with stained slides and results were compared. RESULTS: The overall concordance rate between multiphoton microscopy and stained slides was 86%. The seminiferous tubules of patients with nonobstructive azoospermia were smaller than those of controls when measured by multiphoton microscopy and staining (p <0.05). The proportion of normal tubules and the diameters obtained with multiphoton microscopy were not different from those obtained with hematoxylin and eosin (p >0.05). CONCLUSION: Multiphoton microscopy can be used to differentiate normal from abnormal spermatogenesis. Its characterization of seminiferous tubular architecture is similar to that provided by hematoxylin and eosin staining. Further investigation of the clinical applications of multiphoton microscopy may improve surgical sperm retrieval outcomes for patients with nonobstructive azoospermia.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:First bite syndrome (FBS) refers to facial pain characterized by a severe cramping or spasm in the parotid region with the first bite of each meal that diminishes over the next several bites.1, 2 It is a potential sequela of surgery involving the infratemporal fossa (ITF), parapharyngeal space (PPS), and/or deep lobe of the parotid gland. The incidence, risk factors, treatment options, and outcomes of FBS are poorly understood. We hypothesized that certain clinical and tumor variables independently predict the development of FBS. STUDY DESIGN/METHODS:Retrospective cohort study. METHODS:We reviewed the records of 499 patients (mean age, 50 years; range, 12-81 years) undergoing surgery of the deep lobe of the parotid gland, PPS, and/or ITF between 1992 and 2010. Minimum follow-up time was 3 months (median, 39 months). Patient, tumor, and FBS characteristics were analyzed. Incidence was calculated using the Kaplan-Meier method. Univariate analyses and multivariate logistic regression were used to identify independent risk factors for FBS. Patients developing FBS were interviewed to assess the efficacy of various treatment modalities. RESULTS:FBS developed in 45 patients (incidence, 9.6%), at a mean time of 97 (range, 6-877) days from surgery. On multivariate analysis, three variables were significant independent risk factors for FBS: sympathetic chain sacrifice (odds ratio [OR], 4.7; P = .008), PPS dissection (OR, 8.7; P = .001), and resection of only the deep lobe of the parotid gland (OR, 4.2; P = .002). FBS developed in 48.6% of patients undergoing sympathetic chain sacrifice, 22.4% of patients undergoing PPS dissection, 38.4% of patients undergoing isolated deep lobe parotid resection, and 0.8% of patients undergoing total parotidectomy. Partial resolution of FBS symptoms occurred in 69% and complete resolution in 12%. Of 45 FBS patients, 15 (33%) underwent at least one type of treatment for symptomatic relief. No treatment consistently provided effective symptomatic relief. CONCLUSIONS:The strongest independent risk factors for FBS are PPS dissection, deep lobe of parotid resection, and sympathetic chain sacrifice. Patients undergoing surgery with dissection and/or manipulation in these anatomical sites and structures should be thoroughly counseled about the risk of developing FBS.

OBJECTIVE: To investigate the hypothesis that prophylactic triamcinolone modulates acute vocal fold inflammatory and profibrotic signaling during acute phonotrauma. STUDY DESIGN: In vivo rabbit phonation model. SETTING: Academic medical center. SUBJECTS AND METHODS: Forty New Zealand white breeder rabbits were randomly assigned to 1 of 4 groups: control (no intervention), no treatment (30 minutes of raised intensity phonation), sham treatment (bilateral intralaryngeal triamcinolone acetonide injection at 0 microg/25 microL followed by 30 minutes of raised intensity phonation), or steroid treatment (bilateral intralaryngeal triamcinolone acetonide injection at 400 microg/25 microL followed by 30 minutes of raised intensity phonation). Quantitative polymerase chain reaction (qPCR) was used to investigate gene expression levels of cyclooxygenase-2 (COX-2), interleukin (IL)-1beta, and transforming growth factor (TGF)-beta1. RESULTS: Results revealed a significant main effect for COX-2 (P = .002). Post hoc testing revealed that rabbits receiving no treatment (15.10) had higher COX-2 gene expression than control (5.90; P < .001). There were no significant differences in COX-2 expression between treatment groups. Results revealed a significant main effect for IL-1beta (P < .001). Post hoc testing revealed that rabbits receiving no treatment (14.70) had higher IL-1beta gene expression than control (6.30) (P = .001). There were no significant differences in IL-1beta gene expression between treatment groups. There were no significant differences in TGF-beta1 gene expression (P = .525) between treatment and control groups. CONCLUSION: Given conflicting evidence, further studies are necessary to investigate vocal fold steroid injections prior to and following the induction of phonotrauma. Prophylactic administration of triamcinolone immediately prior to acute phonotrauma resulted in no significant changes in COX-2, IL-1beta, and TGF-beta1 gene transcript levels.

UNLABELLED:Despite evidence implicating transcription factors, including STAT3, in oncogenesis, these proteins have been regarded as "undruggable." We developed a decoy targeting STAT3 and conducted a phase 0 trial. Expression levels of STAT3 target genes were decreased in head and neck cancers following injection with the STAT3 decoy compared with tumors receiving saline control. Decoys have not been amenable to systemic administration due to instability. To overcome this barrier, we linked the oligonucleotide strands using hexaethylene glycol spacers. This cyclic STAT3 decoy bound with high affinity to STAT3 protein, reduced cellular viability, and suppressed STAT3 target gene expression in cancer cells. Intravenous injection of the cyclic STAT3 decoy inhibited xenograft growth and downregulated STAT3 target genes in the tumors. These results provide the first demonstration of a successful strategy to inhibit tumor STAT3 signaling via systemic administration of a selective STAT3 inhibitor, thereby paving the way for broad clinical development. SIGNIFICANCE/CONCLUSIONS:This is the fi rst study of a STAT3-selective inhibitor in humans and the fi rst evidence that a transcription factor decoy can be modifi ed to enable systemic delivery. These findings have therapeutic implications beyond STAT3 to other “undruggable” targets in human cancers.