Faculty Bibliography

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.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To determine posttreatment quality of life (QOL) in head and neck cancer patients, stratifying by human papillomavirus (HPV)/p16 status and primary treatment modality. STUDY DESIGN/METHODS:Retrospective study. METHODS:One hundred and seventy-seven patients (N=177) with head and neck squamous cell carcinoma and known HPV/p16 status were included. All patients completed at least one baseline or posttreatment University of Washington QOL survey. QOL scores were averaged and compared across patients, stratifying by HPV/p16 status and primary treatment modality (surgical vs. nonsurgical). In the analysis, p16 was used as a surrogate marker for HPV. RESULTS:Of the 177 patients, 80 (45.2%) were p16-positive and 49.7% of subsites were oropharyngeal. Nearly 60% (105/177) of patients underwent primary surgery, 26.7% (28/105) of patients with transoral robotic or laser techniques. The remainder 40.7% of patients underwent primary radiation and/or chemotherapy. Overall, QOL scores were better for p16-positive patients compared to p16-negative patients at baseline (P=0.008), at 6 months posttreatment (P=0.034), and at greater than 1 year posttreatment (P=0.013). P16-positive patients had better QOL scores in speech (P=0.0009), chewing (P=0.0004), and swallowing (P=0.021) after 1 year posttreatment compared to p16-negative patients. Primary treatment modality did not affect overall QOL or any of the 12 QOL categories in p16-positive patients at any time point. At over 1 year posttreatment, QOL was at or above baseline in both p16-positive treatment groups. CONCLUSION/CONCLUSIONS:The p16-positive patients had better baseline and posttreatment overall QOL compared to p16-negative patients. The overall and category specific QOL scores for p16-positive patients were not affected by primary treatment modality. LEVEL OF EVIDENCE/METHODS:4.

OBJECTIVE:To evaluate the cost-effectiveness of transoral robotic surgery (TORS) for the diagnosis and treatment of cervical unknown primary squamous cell carcinoma (CUP). STUDY DESIGN:Case series with chart review. SETTING:Tertiary academic hospital. SUBJECTS AND METHODS:A retrospective chart review was performed on patients with new occult primary squamous cell carcinoma of the head and neck with nondiagnostic imaging and/or endoscopy who were treated with TORS at a tertiary hospital between 2009 and 2012. Direct costs were obtained from the hospital's billing system, and national data were used for inpatient hospital costs and physician fees. The proportion of tumors found in 3 strategies was used as effectiveness to calculate the incremental cost-effectiveness ratio. RESULTS:In total, 206 head and neck robotic cases were performed at our institution between December 2009 and December 2012. Three surgeons performed TORS on 22 patients for occult primary squamous cell carcinoma. The primary tumor was located in 19 of 22 patients (86.4%). The incremental cost-effectiveness ratio for sequential and simultaneous examination under anesthesia with tonsillectomy (EUA) and TORS base of tongue resection was $8619 and $5774 per additional primary identified, respectively. CONCLUSION:Sequential EUA followed by TORS is associated with an incremental cost-effectiveness ratio of $8619 compared with traditional EUA alone. Bilateral base of tongue resection should be considered in the workup of these patients, particularly if the palatine tonsils have already been removed.

Anoctamin 1 (TMEM16A, Ano1) is a recently identified Ca(2+)-activated chloride channel and a member of a large protein family comprising 10 paralogues. Before Ano1 was identified as a chloride channel protein, it was known as the cancer marker DOG1. DOG1/Ano1 is expressed in gastrointestinal stromal tumours (GIST) and particularly in head and neck squamous cell carcinoma, at very high levels never detected in other tissues. It is now emerging that Ano1 is part of the 11q13 locus, amplified in several types of tumour, where it is thought to augment cell proliferation, cell migration and metastasis. Notably, Ano1 is upregulated through histone deacetylase (HDAC), corresponding to the known role of HDAC in HNSCC. As Ano1 does not enhance proliferation in every cell type, its function is perhaps modulated by cell-specific factors, or by the abundance of other anoctamins. Thus Ano6, by regulating Ca(2+)-induced membrane phospholipid scrambling and annexin V binding, supports cellular apoptosis rather than proliferation. Current findings implicate other cellular functions of anoctamins, apart from their role as Ca(2+)-activated Cl(-) channels.

INTRODUCTION/BACKGROUND:The number of robot-assisted surgeries performed with the da Vinci surgical system has increased significantly over the past decade. The articulating movements of the robotic surgical grasper are controlled by grip controls at the master console. The user interface has been implicated as one contributing factor in surgical grasping errors. The goal of our study was to characterize and evaluate the user interface of the da Vinci surgical system in controlling surgical graspers. MATERIALS AND METHODS/METHODS:An angular manipulator with force sensors was used to increment the grip control angle as grasper output angles were measured. Input force at the grip control was simultaneously measured throughout the range of motion. Pressure film was used to assess the maximum grasping force achievable with the endoscopic grasping tool. RESULTS:The da Vinci robot's grip control angular input has a nonproportional relationship with the grasper instrument output. The grip control mechanism presents an intrinsic resistant force to the surgeon's fingertips and provides no haptic feedback. The da Vinci Maryland graspers are capable of applying up to 5.1 MPa of local pressure. CONCLUSIONS:The angular and force input at the grip control of the da Vinci robot's surgical graspers is nonproportional to the grasper instrument's output. Understanding the true relationship of the grip control input to grasper instrument output may help surgeons understand how to better control the surgical graspers and promote fewer grasping errors.