Faculty Bibliography

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.

BACKGROUND: Typically, thyroid follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cases show moderate to marked cellularity and scant or absent colloid. Recently, cases have been noted with microfollicular cellularity in the background of moderate to abundant amount of colloid. The purpose of this study was to compare these "colloid-rich" FN/SFN cases to the typical FN/SFN cases. METHODS: Thyroid cytology specimens with the features of FN/SFN were searched in cytopathology files from September 2008 to June 2012. Cases with absent or minimal colloid were designated "typical colloid-poor" FN/SFN and cases with moderate to abundant colloid were designated "colloid-rich" FN/SFN. From these cases, those with surgical pathology resection follow-up were identified. Cytologic, surgical pathology resection, and molecular features (BRAF, RAS, RET/PTC, and PAX8-PPARgamma) were investigated for the typical colloid-poor FN/SFN cases and were compared with those of the colloid-rich FN/SFN cases. RESULTS: Of 431 FN/SFN cases with surgical pathology resection follow-up, 360 (83.5%) cases showed features of typical colloid-poor FN/SFN and 71 (16.5%) cases showed features of colloid-rich FN/SFN. Papillary carcinoma was the most common malignant outcome for the 2 groups. Although the proportion of malignant outcome was similar for the 2 groups, the "colloid-rich" FN/SFN cases showed a greater proportion of nodular hyperplasia among the cases with benign outcome. In addition, the "colloid-rich" FN/SFN cases demonstrated a greater proportion of cases with a mutation. CONCLUSIONS: Approximately one-sixth of cases of FN/SFN show "colloid-rich" features. Comparison to the typical colloid-poor FN/SFN demonstrated similar risk for malignancy but contrasting resection outcome and molecular characteristics.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To evaluate the transoral anatomy of the tonsillar fossa and lateral pharyngeal wall and to correlate these findings with radiographic measurements and transoral robotic surgery (TORS) of patients with early tonsillar tumor. STUDY DESIGN/METHODS:Preclinical cadaveric study and patient cohort. METHODS:Six complete cadaveric dissections were performed to identify key anatomic landmarks, and these landmarks were validated in two consecutive patients with T1 human papillomavirus-positive squamous cell carcinoma of the tonsil treated by TORS. For radiographic landmark analysis, 25 patients who underwent contrast-enhanced computed tomography (CT) of the neck for a variety of endoscopic skull base procedures were selected. Measurements were taken from the lateral pharyngeal wall at C2-C3 interspace and greater horn of hyoid (C6) to the external carotid artery (ECA). RESULTS:The glossopharyngeal (IX) nerve was consistently identified deep to the superior constrictor musculature and at the intersection of the posterior tonsillar pillar with the base of tongue. The styloglossus muscle forms the deep plane medial to the ECA. The mean measurements for left C2-C3 interspace to the ECA and right C2-C3 interspace to ECA were 17.6 ± 0.8 mm and 18.4 ± 0.8 mm, respectively. Similarly, the mean measurements for left hyoid to ECA and right hyoid to ECA were 3.4 ± 0.8 mm and 4.3 ± 0.6 mm, respectively. CONCLUSIONS:A systematic approach to dissect the tonsillar fossa and lateral pharyngeal wall can be performed using key anatomic landmarks. CT measurements taken at the C2-C3 interspace and greater horn of hyoid bone (C6 level) to the ECA are consistently and reliably achieved.

OBJECTIVES/OBJECTIVE:To evaluate the impact of margin sampling on local recurrence in patients with pT1-2 pN0 conventional squamous cell carcinoma of the oral tongue. MATERIALS AND METHODS/METHODS:Based on margin sampling, 126 cases were divided into group 1 (margins sampled from the glossectomy specimen only), group 2 (with revision of glossectomy margins), and group 3 (margins primarily sampled from the tumor bed). RESULTS:The probability of local progression-free survival at 3years was .90, .76 and .73 (p=.0389) in groups 1, 2, and 3, respectively. Groups differed by frequency of positive glossectomy specimen margins (p=<.0001) and by the average distance from carcinoma to the closest margin (4.5, 2.4, and 3.0mm for Groups 1, 2, and 3, respectively; p=.0009). Tumor bed margin status (positive vs. negative) and other parameters (e.g., pattern and depth of invasion) did not correlate with local recurrence. Status of the glossectomy specimen margins did correlate with outcome. A positive glossectomy margin conferred a relative risk of 2.5 (95% confidence interval, CI, 1 - 6.3) for local recurrence. A proportional hazards regression model for margin width found a hazard ratio of 0.67 (95% CI=.57-.98) comparable to a 33% decrease in risk of local recurrence for an increase of 1mm of margin width (p=.0271). CONCLUSIONS:Status of the glossectomy specimen margins rather than that of tumor bed margins was prognostically relevant. Reliance on tumor bed margins appears to be associated with worse local control, perhaps due to the narrower initial resection.