Faculty Bibliography

Juvenile ossifying fibroma is a rare, benign tumor that may present in the sinonasal area but has never been described arising from the middle turbinate. The lesion's locally aggressive behavior and close proximity to orbit and anterior skull base create a significant challenge for the patient and practitioner. This is a case presentation of a 7-year-old female with an invasive recurrent juvenile ossifying fibroma arising from the middle turbinate.

CONTEXT/BACKGROUND:Data suggest that anorexia nervosa (AN) and obesity are complicated by elevated fracture risk, but skeletal site-specific data are lacking. Traditional bone mineral density (BMD) measurements are unsatisfactory at both weight extremes. Hip structural analysis (HSA) uses dual-energy X-ray absorptiometry data to estimate hip geometry and femoral strength. Factor of risk (φ) is the ratio of force applied to the hip from a fall with respect to femoral strength; higher values indicate higher hip fracture risk. OBJECTIVE:The objective of the study was to investigate hip fracture risk in AN and overweight/obese women. DESIGN/METHODS:This was a cross-sectional study. SETTING/METHODS:The study was conducted at a Clinical Research Center. PATIENTS/METHODS:PATIENTS included 368 women (aged 19-45 y): 246 AN, 53 overweight/obese, and 69 lean controls. MAIN OUTCOME MEASURES/METHODS:HSA-derived femoral geometry, peak factor of risk for hip fracture, and factor of risk for hip fracture attenuated by trochanteric soft tissue (φ(attenuated)) were measured. RESULTS:Most HSA-derived parameters were impaired in AN and superior in obese/overweight women vs controls at the narrow neck, intertrochanteric, and femoral shaft (P ≤ .03). The φ(attenuated) was highest in AN and lowest in overweight/obese women (P < .0001). Lean mass was associated with superior, and duration of amenorrhea with inferior, HSA-derived parameters and φ(attenuated) (P < .05). Mean φ(attenuated) (P = .036), but not femoral neck BMD or HSA-estimated geometry, was impaired in women who had experienced fragility fractures. CONCLUSIONS:Femoral geometry by HSA, hip BMD, and factor of risk for hip fracture attenuated by soft tissue are impaired in AN and superior in obesity, suggesting higher and lower hip fracture risk, respectively. Only attenuated factor of risk was associated with fragility fracture prevalence, suggesting that variability in soft tissue padding may help explain site-specific fracture risk not captured by BMD.

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.

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.

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.

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.

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.