Faculty Bibliography

OBJECTIVE:Previously, we have reported the feasibility of retroauricular (RA) robotic thyroidectomy. Despite its promising surgical outcomes, there were certain intrinsic mechanical limitations inherent to the da Vinci Si System (Intuitive Surgical, Sunnyvale, California, U.S.A.). Since the advent of an upgraded model, the Xi System (Intuitive Surgical), we have actively incorporated the new model into performing RA thyroidectomy. Here, we intend to verify the feasibility of RA robotic thyroidectomy using the new da Vinci Xi System (Intuitive Surgical) with comparison of the former Si-applied surgery (Intuitive Surgical). STUDY DESIGN:Comparative analysis. METHODS:There were total 165 consecutive patients who received RA robotic thyroidectomy from January 2013 to February 2016. The patients were divided into two groups: Si group (n = 125) and Xi group (n = 40). Perioperative and treatment outcomes were compared and analyzed. RESULTS:Compared with the previous system, new da Vinci Xi system (Intuitive Surgical) enabled insertion of an extra third robotic instrumental arm. Unlike the previous robotic surgical technique, the robotic dissection could be initiated immediately after the establishment of working space and the resulting total operation time could be significantly decreased. There was no difference in the surgical completeness, as confirmed by postoperative thyroglobulin levels. Additionally, flexed EndoWrist (Intuitive Surgical) instruments equipped with the Erbe (Erbe USA Inc., Marietta, Georgia, U.S.A.) system could be mounted, which further facilitated the operation. There were no significant differences in postoperative complications between the two groups. CONCLUSION:The RA robotic thyroidectomy with the new Xi System (Intuitive Surgical) can greatly facilitate the robotic surgery with comparable or improved surgical outcomes. Its application is expected to open up a new era of robotic neck surgery. LEVEL OF EVIDENCE:4. Laryngoscope, 128:1730-1737, 2018.

Objectives To investigate the clinical predictors and survival implications of perineural invasion (PNI) in parotid gland malignancies. Study Design Case series with chart review. Setting Tertiary care medical center. Subjects and Methods Patients with parotid gland malignancies treated surgically from 2000 to 2015 were retrospectively identified in the Head and Neck Cancer Registry at a single institution. Data points were extracted from the medical record and original pathology reports. Results In total, 186 patients with parotid gland malignancies were identified with a mean follow-up of 5.2 years. Salivary duct carcinoma (45), mucoepidermoid carcinoma (44), and acinic cell carcinoma (26) were the most common histologic types. A total of 46.2% of tumors were found to have PNI. At the time of presentation, facial nerve paresis (odds ratio [OR], 64.7; P < .001) and facial pain (OR, 3.7; P = .002) but not facial paresthesia or anesthesia (OR, 2.8, P = .085) were predictive of PNI. Malignancies with PNI were significantly more likely to be of advanced T and N classification, be high-risk pathologic types, and have positive margins and angiolymphatic invasion. PNI positivity was associated with worse overall (hazard ratio, 2.62; P = .001) and disease-free survival (4.18; P < .001) on univariate Cox regression analysis. However, when controlling for other negative prognosticators, age, and adjuvant therapy, PNI did not have a statistically significant effect on disease-free or overall survival. Conclusions PNI is strongly correlated with more aggressive parotid gland malignancies but is not an independent predictor of worse survival. Facial paresis and pain were predictive of PNI positivity, and facial paresis correlated with worse overall and disease-free survival.

Human papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise in the oropharynx, where viral expression of the E6 and E7 oncoproteins promote cellular transformation, tumor growth, and maintenance. An important oncogenic signaling pathway activated by E6 and E7 is the PI3K pathway, a key driver of carcinogenesis. The PI3K pathway is also activated by mutation or amplification of PIK3CA in over half of HPV(+) HNSCC. In this study, we investigated the efficacy of PI3K-targeted therapies in HPV(+) HNSCC preclinical models and report that HPV(+) cell line- and patient-derived xenografts are resistant to PI3K inhibitors due to feedback signaling emanating from E6 and E7. Receptor tyrosine kinase profiling indicated that PI3K inhibition led to elevated expression of the HER3 receptor, which in turn increased the abundance of E6 and E7 to promote PI3K inhibitor resistance. Targeting HER3 with siRNA or the mAb CDX-3379 reduced E6 and E7 abundance and enhanced the efficacy of PI3K-targeted therapies. Together, these findings suggest that cross-talk between HER3 and HPV oncoproteins promotes resistance to PI3K inhibitors and that cotargeting HER3 and PI3K may be an effective therapeutic strategy in HPV(+) tumors.Significance: These findings suggest a new therapeutic combination that may improve outcomes in HPV(+) head and neck cancer patients. Cancer Res; 78(9); 2383-95. ©2018 AACR.

Objective To compare positive margin rates between the 2 most common subsites of oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the tonsil, as well as identify preoperative imaging characteristics that predispose toward positive margins. Study Design Case series with chart review. Setting Tertiary care referral center. Subjects and Methods We compared the final and intraoperative positive margin rate between TORS resections for tonsil and BOT oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT tumors to measure their dimensions and patterns of spread and provided a prediction of final margin results. Results Between January 2010 and May 2016, a total of 254 patients underwent TORS for OPSCC. A total of 140 patients who underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%, respectively, P = .004) and likewise for intraoperative margins of BOT and tonsil tumors (35.3% vs 12.4%, respectively; P = .002). A positive final margin is 10 times more likely to receive chemoradiation compared to a negative margin, controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95% confidence interval, 1.6-59.6; P = .02). Preoperative imaging characteristics and subjective radiologic examination of BOT tumors did not correlate with final margin status. Conclusion Positive margins are significantly more likely during TORS BOT resections compared to tonsil resections. More research is needed to help surgeons predict which T1/T2 tumors will be difficult to completely extirpate.

Carcinoma of unknown primary (CUP) comprises approximately 1%-5% of all head and neck malignancies. Primary site detection rates for metastatic cervical squamous cell carcinoma (SCC) remain variable, with current diagnostic imaging unable to identify all tumours. Prevailing evidence suggests that most head and neck CUP are located in the oropharynx. Diagnostic surgical efforts have been directed at sampling the entire oropharynx. Present techniques that make this possible include transoral robotic surgery (TORS). TORS Lingual tonsillectomy or tongue base mucosectomy performed in the setting of head and neck CUP increases the detection rate of occult tumour. The indication, surgical technique, evidence base, and controversies of performing TORS in the context of the unknown primary are presented.