Faculty Bibliography

BACKGROUND:Pharyngeal stenosis is a complication of head and neck cancer and sleep apnea treatment that results in functional impairment. Due to the location of the stenosis and tendency to recur, surgical management is challenging. Robotic surgery may allow these areas to be treated with surgical technique that would be difficult using traditional approaches. METHODS:A retrospective chart review was performed to identify patients who underwent transoral robotic surgery (TORS) for pharyngeal stenosis at a tertiary hospital system. RESULTS:Five patients were identified, ages 8-75 years. Length of follow-up ranged from 1-12 months. There was one failure, a 74 year old male with a history of chemoradiation to the area who has required additional procedures. CONCLUSION/CONCLUSIONS:TORS may offer improved surgical access to the pharynx in patients who require complex reconstruction that would otherwise be very difficult. Appropriate patient selection is necessary and long-term follow-up is warranted for the selected cases.

BACKGROUND:Cosmesis is of increasing importance to the otolaryngology patient population. This is the first report of clinical outcomes of robot-assisted neck dissection by North American groups. METHODS:This is a retrospective case-control study. Cases included three patients who underwent isolated, ipsilateral robot-assisted neck dissection. Operative time, estimated blood loss, lymph node retrieval, total drainage, hospital stay and complications from this group were compared against the outcomes of six consecutive patients who underwent conventional neck dissection. RESULTS:Operative times were longer in robot-assisted neck dissection (mean 234 min) compared with the conventional neck dissection (mean 110 min). There were no significant differences between the two groups in other outcomes. CONCLUSIONS:Robot-assisted selective neck dissection of levels II-IV is feasible through a modified facelift incision. Our initial data suggest that this procedure is surgically sound. It should be applied by experienced surgeons who wish to avoid a cervical incision.

This study demonstrates variations in the vascular anatomy of the parapharyngeal space (PPS) as seen from the transoral approach compared with the transcervical approach. The PPS was dissected in injected cadaveric specimens. Anatomical measurements, including those of branches of the external and internal carotid arteries (ECA and ICA) and the styloglossus and stylopharyngeus muscles, were recorded and analyzed. In 67% (8/12) of cases, the ascending palatine artery (APA) originated from the facial artery and crossed the styloglossus muscle. The diameter of the APA at its origin was 1.4 ± 0.3 mm. In 75% (9/12) of cases, the ascending pharyngeal artery (aPA) arose from the medial surface of the ECA near its origin. In 58% (7/12) of cases, the aPA ascended vertically between the ICA and the lateral pharynx to the skull base, along the longus capitus muscle. The aPA crossed the styloglossus muscle 12.6 ± 3.9 mm from the insertion into the tongue. In 92% (11/12) of cases, the ECA and ICA were separated by the styloid diaphragm and pharyngeal venous plexus. In 8% (1/12), the ECA bulged into the parapharyngeal fat between the styloglossus and stylopharyngeus muscles adjacent to the pharyngeal constrictors. Knowledge of the precise anatomy of the PPS is important for transoral robotic surgery (TORS). Control of the vessels that supply and traverse the PPS can help the TORS surgeon avoid those critical structures and reduce surgical morbidity and potential hemorrhage.

PURPOSE/OBJECTIVE:Tumor metastasis is the leading cause of death in patients with cancer. However, the mechanisms that underlie metastatic progression remain unclear. We examined TMEM16A (ANO1) expression as a key factor shifting tumors between growth and metastasis. EXPERIMENTAL DESIGN/METHODS:We evaluated 26 pairs of primary and metastatic lymph node (LN) tissue from patients with squamous cell carcinoma of the head and neck (SCCHN) for differential expression of TMEM16A. In addition, we identified mechanisms by which TMEM16A expression influences tumor cell motility via proteomic screens of cell lines and in vivo mouse studies of metastasis. RESULTS:Compared with primary tumors, TMEM16A expression decreases in metastatic LNs of patients with SCCHN. Stable reduction of TMEM16A expression enhances cell motility and increases metastases while decreasing tumor proliferation in an orthotopic mouse model. Evaluation of human tumor tissues suggests an epigenetic mechanism for decreasing TMEM16A expression through promoter methylation that correlated with a transition between an epithelial and a mesenchymal phenotype. These effects of TMEM16A expression on tumor cell size and epithelial-to-mesenchymal transition (EMT) required the amino acid residue serine 970 (S970); however, mutation of S970 to alanine does not disrupt the proliferative advantages of TMEM16A overexpression. Furthermore, S970 mediates the association of TMEM16A with Radixin, an actin-scaffolding protein implicated in EMT. CONCLUSIONS:Together, our results identify TMEM16A, an eight transmembrane domain Ca2+-activated Cl- channel, as a primary driver of the "Grow" or "Go" model for cancer progression, in which TMEM16A expression acts to balance tumor proliferation and metastasis via its promoter methylation.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To assess the feasibility of performing robotic-assisted laryngeal cleft repair in the pediatric population. STUDY DESIGN/METHODS:Retrospective chart review at a tertiary academic children's hospital. METHODS:All patients underwent transoral robotic-assisted laryngeal cleft repair from March 2011 to June 2013. Demographics, robotic docking time, operative time, and postoperative course and swallowing function were collected and analyzed. RESULTS:Five children, three male and two female, underwent successful transoral robotic-assisted laryngeal cleft repair for closure of a type I laryngeal cleft. Mean age at time of surgery was 21.6 months (standard deviation 6.1 months; range, 15-29 months). From case 1 to case 5, robotic docking time (18-10 minutes), robotic operative time (102-36 minutes), and total operating room time (173-105 minutes) decreased. There were no complications with time until extubation (range, 2-3 days), length of intensive care unit stay (range, 3-4 days), and total hospital stay (range, 3-5 days) within acceptable range following laryngeal cleft repair. Modified barium swallow (two patients) or fiberoptic endoscopic evaluation of swallowing (three patients) was performed postoperatively, with all patients showing complete resolution of penetration and aspiration. In addition, all patients experienced subjective resolution of dysphagia and/or choking with feeds postoperatively. CONCLUSIONS:Transoral robotic-assisted laryngeal cleft repair may offer specific advantages over a traditional endoscopic approach. In our experience, the procedure was well tolerated and associated with definitive surgical cure in all patients. The scope of robotic technology continually expands and should be considered a feasible tool at an institution-based level.

OBJECTIVE:Cancer of an unknown primary (CUP) squamous cell carcinoma metastatic to cervical lymph nodes is a challenging problem for the treating physician. Our aim is to determine if identification of the primary tumor is associated with improved oncologic outcomes and/or tumor characteristics including human papilloma virus (HPV) status. STUDY DESIGN:Retrospective, matched-pairs analysis contrasting 2 cohorts based upon discovery of primary lesion. SETTING:Tertiary teaching hospital. SUBJECTS AND METHODS:Records of 136 patients initially diagnosed as carcinoma of unknown primary were retrospectively reviewed (1980-2010) and divided into 2 cohorts based on discovery of the primary lesion. Primary outcome measures were overall survival and time to recurrence according to Kaplan-Meier analysis. A nested subset of 22 patients in which the primary was discovered were matched to 22 patients remaining undiscovered according to nodal stage and age. RESULTS:Discovered lesions were more likely to exhibit HPV positivity (P < .001). Matched-pairs analyses demonstrated that discovery of the primary was associated with better overall survival (HR = 0.125; 95% confidence interval [CI], 0.019-0.822; P = .030). Discovery of the primary was associated with improved cause-specific survival (HR = 0.142; 95% CI, 0.021-0.93; P = .0418) and disease-free survival (HR = 0.25; 95% CI, 0.069-0.91; P = .03). CONCLUSION:HPV positivity is associated with discovery of the primary tumor. Discovery of the primary lesion is associated with improved overall survival, cause-specific survival, and disease-free survival in patients initially presenting as CUP in matched-pair and cohort comparison analyses.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Locoregional recurrence remains the primary failure pattern following salvage surgery for previously irradiated head and neck cancer; randomized trials have suggested a complimentary role for adjuvant chemotherapy and conventional reirradiation at the expense of significant increases in toxicity. We aimed to identify if stereotactic body radiotherapy (SBRT) ± cetuximab improves tumor control while reducing treatment-related toxicity following salvage surgery. STUDY DESIGN/METHODS:Retrospective review (2005-2011) of 28 patients with high-risk features (positive surgical margins or extranodal extension) following macroscopic complete (R0/R1) salvage surgery treated with adjuvant SBRT±cetuximab. METHODS:SBRT consisted of 40 to 44 Gy in five fractions over 1 to 2 weeks with concurrent cetuximab (n=7) administered at 400 mg/m2 day -7+250 mg/m2 days 0 and +8. Toxicity was physician recorded, and University of Washington Quality of Life Revised surveys were prospectively collected. RESULTS:All patients received prior radiotherapy (median, 70 Gy; range, 54-99 Gy) with a median reirradiation interval of 25 months (range, 6-156 months). At a median follow-up of 14 months (range, 2-69 months), the 1-year locoregional control, distant control, disease-free survival, and overall survival were 51%, 90%, 49%, and 64%, respectively. Rates of acute and late severe (≥grade 3) toxicity were low at 0% and 8%, respectively. At a median follow-up survey time of 6 months, 56% of patients reported improved/stable overall quality-of-life scores. CONCLUSIONS:Adjuvant SBRT±cetuximab following salvage surgery is well tolerated with acceptable oncologic outcomes and little toxicity. Future prospective trials should evaluate adjuvant SBRT±cetuximab versus a wait-and-see approach for recurrent head and neck cancers with high-risk features following salvage surgery. LEVEL OF EVIDENCE/METHODS:4.