Faculty Bibliography

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Preoperative localization for parathyroid disease has improved in recent years with the advent of dual-phase (99m) Tc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. However, dual-phase imaging is associated with increased cost, time, and radiation dose. The aim of this study was to investigate the need for late-phase imaging when using SPECT/CT for the preoperative localization of parathyroid disease. STUDY DESIGN/METHODS:Retrospective chart analysis. METHODS:A retrospective review of 75 patients who underwent preoperative imaging localization and subsequent surgical resection for parathyroid disease at a tertiary referral center was performed. Of these, 50 patients met study criteria including preoperative SPECT/CT imaging and specific reporting of early- and late-phase focal radiotracer uptake. Localization accuracy was verified with definitive surgical findings confirmed by histological analysis and evidence of biochemical cure. RESULTS:Accurate localization of adenoma(s) was seen in 78.0% of patients using dual-phase SPECT/CT. Early-phase imaging alone localized 76.0%, whereas late-phase imaging alone localized 74.0%. Sensitivity and specificity for dual-phase imaging was 84.8% and 89.6%, respectively. In comparison, early-phase localization alone was found to have a sensitivity/specificity of 84.4%/89.4%; sensitivity/specificity of late-phase scanning alone was found to be 80.4%/89.1%. Dual-phase SPECT/CT scanning did not provide a statistically significant improvement in adenoma localization when compared to early-phase scanning alone. CONCLUSIONS:Although further investigation is needed, the results of this study suggest that early-phase SPECT/CT scanning alone may obviate the need for dual-phase SPECT/CT scanning in the initial preoperative localization workup of parathyroid disease. LEVEL OF EVIDENCE/METHODS:4.

IMPORTANCE/OBJECTIVE:Few studies have examined quality-of-life (QOL) outcomes in patients who undergo transoral robotic surgery (TORS) alone (ie, without adjuvant radiotherapy or chemoradiotherapy). OBJECTIVE:To report QOL outcomes of patients with oropharyngeal squamous cell carcinoma who receive only TORS. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Medical records for all patients undergoing TORS for treatment of primary oropharyngeal squamous cell carcinoma from May 1, 2010, to March 31, 2014, at a tertiary care academic cancer center were examined from June through September 2014. Thirty-four patients who did not receive adjuvant therapy after TORS were included in the study. INTERVENTION/METHODS:Primary surgical resection via TORS. MAIN OUTCOMES AND MEASURES/METHODS:The University of Washington Quality of Life, version 4, questionnaire was completed by patients preoperatively and at 1-, 6-, 12-, and 24-month intervals after TORS. Demographic, clinicopathologic, and follow-up data were collected. RESULTS:Mean follow-up time was 14 months (May 1, 2010, to April 30, 2014). Most patients had T1 (20 [59%]) or T2 (13 [38%]) and N0 (13 [38%]) or N1 (16 [47%]) disease. Statistically significant improvement in QOL outcomes was noted in the following postoperative domains: chewing from 1 month (median, 50 [IQR, 50-100]) to 12 months (100 [IQR, 100-100]; P = .048), swallowing from 1 month (70 [IQR, 30-85]) to 6 months (100 [IQR, 70-100]; P = .047) and 1 to 24 months (100 [IQR, 70-100]; P = .048), pain from 1 month (38 [IQR, 25-75]) to 6 months (88 [IQR, 75-100]; P = .006) and 1 to 12 months after surgery (100 [IQR, 75-100]; P = .01), and activity from 1 month (63 [IQR, 50-88]) to 24 months (100 [IQR, 75-100]; P = .03). Two participants (6%) died during the follow-up period: 1 because of disease and 1 because of a myocardial infarction. Two patients (6%) required temporary gastrostomy tube placement, but none required tracheostomy. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Appropriately selected patients who undergo TORS alone for oropharyngeal squamous cell carcinoma experience acceptable short- and long-term QOL outcomes.

OBJECTIVES/OBJECTIVE:Fine-needle aspiration (FNA) is useful in the evaluation of salivary gland tumors, but currently no standard terminology or risk stratification model exists. METHODS:FNA smears were reviewed and categorized based on cytonuclear features, stromal characteristics, and background characteristics. Risk of malignancy was calculated for each category. Classifications as benign, neoplasm of uncertain malignant potential (NUMP), suspicious for malignancy, and positive for malignancy were used to aggregate categories into similar risk groups. RESULTS:Categorization of salivary gland aspirates into morphologic categories resulted in the expected risk stratification. Grouping of categories maintained risk stratification, providing classes with malignancy risk as follows: benign, 2%; NUMP, 18%; suspicious for malignancy, 76%; and positive for malignancy, 100%. CONCLUSIONS:Salivary gland FNA categorization into commonly encountered morphologic categories provides risk stratification, which translates to a simplified classification scheme of benign, NUMP, suspicious, and positive for malignancy similar to the paradigm in other organ systems.

The objective of this study is to establish normative waveform data for the external branch of the superior laryngeal nerve (SLN) utilizing laryngeal surface electrodes and intraoperative neurophysiological monitoring (IONM) in conjunction with a clinical neurophysiologist. A retrospective chart review of 91 consecutive at-risk SLN were identified in 51 patients in whom IONM using laryngeal surface electrodes was performed by a clinical neurophysiologist using Dragonfly (Neurovision Medical Products, Ventura, CA) recording electrodes and a Protektor (Natus Medical Inc., San Carlos, CA)16 channel- intraoperative nerve monitoring system. Inclusion criteria were met for 30 SLN. Data collected included preoperative diagnosis, surgical procedure, rates of nerve identification and stimulation, and waveform characteristics. Waveform analysis for 30 SLN yielded a peak latency of 4.0 ± 0.2 ms, onset latency 2.3 ± 0.1 ms, peak-to-peak amplitude of 220.4 ± 31.1 µV, onset-to-peak amplitude of 186.0 ± 25.0 µV, and stimulation current threshold of 0.55 ± 0.03 mA (data = mean ± SEM). Two patients had abnormal SLN function documented clinically on postoperative laryngoscopic examination. Laryngeal surface electrodes were successfully utilized to identify and monitor SLN function intraoperatively. IONM using laryngeal surface electrodes enables analysis of waveform morphology and latency in addition to threshold and amplitude data obtained with the traditional NIM system, potentially improving the performance of nerve monitoring during thyroid surgery.

IMPORTANCE/OBJECTIVE:Randomized clinical trials demonstrate no benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in unselected patients with head and neck squamous cell carcinoma (HNSCC). However, a patient with stage IVA HNSCC received 13 days of neoadjuvant erlotinib and experienced a near-complete histologic response. OBJECTIVE:To determine a mechanism of exceptional response to erlotinib therapy in HNSCC. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Single patient with locally advanced HNSCC who received erlotinib monotherapy in a window-of-opportunity clinical trial (patients scheduled to undergo primary cancer surgery are treated briefly with an investigational agent). Whole-exome sequencing of pretreatment tumor and germline patient samples was performed at a quaternary care academic medical center, and a candidate somatic variant was experimentally investigated for mediating erlotinib response. INTERVENTION/METHODS:A brief course of erlotinib monotherapy followed by surgical resection. MAIN OUTCOMES AND MEASURES/METHODS:Identification of pretreatment tumor somatic alterations that may contribute to the exceptional response to erlotinib. Hypotheses were formulated regarding enhanced erlotinib response in preclinical models harboring the patient tumor somatic variant MAPK1 E322K following the identification of tumor somatic variants. RESULTS:No EGFR alterations were observed in the pretreatment tumor DNA. Paradoxically, the tumor harbored an activating MAPK1 E322K mutation (allelic fraction 0.13), which predicts ERK activation and erlotinib resistance in EGFR-mutant lung cancer. The HNSCC cells with MAPK1 E322K exhibited enhanced EGFR phosphorylation and erlotinib sensitivity compared with wild-type MAPK1 cells. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Selective erlotinib use in HNSCC may be informed by precision oncology approaches.

The epidermal growth factor receptor (EGFR) contributes to the pathogenesis of head&neck squamous cell carcinoma (HNSCC). However, only a subset of HNSCC patients benefit from anti-EGFR targeted therapy. By performing an unbiased proteomics screen, we found that the calcium-activated chloride channel ANO1 interacts with EGFR and facilitates EGFR-signaling in HNSCC. Using structural mutants of EGFR and ANO1 we identified the trans/juxtamembrane domain of EGFR to be critical for the interaction with ANO1. Our results show that ANO1 and EGFR form a functional complex that jointly regulates HNSCC cell proliferation. Expression of ANO1 affected EGFR stability, while EGFR-signaling elevated ANO1 protein levels, establishing a functional and regulatory link between ANO1 and EGFR. Co-inhibition of EGFR and ANO1 had an additive effect on HNSCC cell proliferation, suggesting that co-targeting of ANO1 and EGFR could enhance the clinical potential of EGFR-targeted therapy in HNSCC and might circumvent the development of resistance to single agent therapy. HNSCC cell lines with amplification and high expression of ANO1 showed enhanced sensitivity to Gefitinib, suggesting ANO1 overexpression as a predictive marker for the response to EGFR-targeting agents in HNSCC therapy. Taken together, our results introduce ANO1 as a promising target and/or biomarker for EGFR-directed therapy in HNSCC.

PURPOSE OF REVIEW/OBJECTIVE:This article reviews recent information on outcomes, indications, techniques, and cost of transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC). New information on comparisons between TORS, conventional surgery techniques, and chemoradiation is also highlighted. RECENT FINDINGS/RESULTS:Consistent with prior reports, recent studies show excellent oncologic and functional outcomes with TORS for OPSCC. As surgeon experience with this relatively new technique has increased, outcomes continue to improve and complications are rare. TORS may also have a role in management of carcinoma of unknown primary site. Compared with other treatment modalities, TORS for OPSCC may result in similar oncologic outcomes, improved functional outcomes, and decreased cost. SUMMARY/CONCLUSIONS:TORS for OPSCC results in excellent functional and oncologic outcomes. Randomized clinical trials are needed to compare TORS with adjuvant therapy to definitive chemoradiation and will determine whether adjuvant therapy and associated morbidity can be decreased without compromising survival.

PURPOSE/OBJECTIVE:Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. METHODS AND MATERIALS/METHODS:From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m(2) on day -7 and then 250 mg/m(2) on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity. RESULTS:Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively. CONCLUSIONS:SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time.

OBJECTIVE:In a human cadaver study, a single-port operator-controlled flexible endoscope (Flex® System), facilitated with a high-definition camera and two accessory channels was tested for skull base surgery. DESIGN/METHODS:Skull base surgery was performed on human cadavers (n=4) using the Flex® System. A modified surgical midfacial approach, performed by rigid standard tools, was used for access to the sinus system, the skull base, and the middle cranial fossa. RESULTS:Endoscopic skull base visualization with the Flex® System is feasible. Surgical procedures performed included extended sinus surgery, anterior skull base approach, and visualization of the brain stem in the posterior cranial fossa. Important landmarks of the anterior skull base were visualized and manipulated by flexible compatible tools. CONCLUSION/CONCLUSIONS:The Flex® System allows for manipulation of the anterior skull base and visualization of the posterior cranial fossa in a preclinical setting. Further studies as well as development of supplemental tools are in progress.

INTRODUCTION/BACKGROUND:Transoral resection of pharyngeal tumors with acceptable oncological and functional results can be challenging due to their location in a narrow anatomic space. CASE PRESENTATION/METHODS:In this case report, we demonstrate successful visualization and resection of a squamous cell carcinoma of the oropharynx using the novel Medrobotics(®) Flex(®) System. The Medrobotics(®) Flex(®) System (Medrobotics Corp., Raynham, MA, USA) is an operator controlled flexible endoscope system that includes a rigid endoscope and computer-assisted controllers, with two external channels for the use of compatible, 3.5mm flexible instruments. DISCUSSION/CONCLUSIONS:In a 74-year old female patient a T1 squamous cell carcinoma of the oropharynx was visualized and completely resected using this system. The Medrobotics(®) Flex(®) System is a promising device for transoral approaches in resection of tumors within the pharynx. CONCLUSION/CONCLUSIONS:Good visualization, access, and flexibility of the endoscope and instruments are hereby clear advantages of the system compared to commonly used systems.