Circulating tumor HPV DNA assessments after surgery for human papilloma virus-associated oropharynx carcinoma.

PURPOSE: To understand the utility of circulating tumor human papillomavirus DNA (ctHPVDNA) blood testing for HPV-associated oropharynx squamous cell carcinoma (HPV + OPSCC) after definitive surgery. MATERIALS AND METHODS: Prospective cohort study of HPV(+)OPSCC patients with ctHPVDNA test data to assess its accuracy in detecting biopsy-confirmed disease at various post-treatment time points. Eligible patients had p16(+)/HPV(+) OPSCC and ctHPVDNA testing performed at any time pre-operatively and/or postoperatively. In cases of recurrence, patients were excluded from analysis if ctHPVDNA testing was not performed within 6 months of biopsy. RESULTS: 196 all-treatment-type patients had at least one PT ctHPVDNA test. The initial post-treatment (PT) ctHPVDNA sensitivity, specificity, PPV, and NPV were 69.2 % (9/13), 96.7 % (177/183), 60.0 % (9/15), and 97.8 % (177/181). 61 surgery alone (SA) patients underwent 128 PT tests. The initial PT SA ctHPVDNA sensitivity, specificity, PPV, and NPV were 100 % (2/2), 96.0 % (48/50), 50 % (2/4), and 100 % (48/48). 35 of 61 (57.4 %) SA patients had NCCN-based histopathologic indications for adjuvant (chemo)radiation but declined. 3 of 35 (8.57 %) had a positive PT ctHPVDNA test of which 1 of 3 (33 %) had biopsy-proven recurrence. Prospectively, ten patients had a PreT positive ctHPVDNA, underwent SA, refused adjuvant treatment, had an undetectable ctHPVDNA within 2 weeks of SA, and remained free of disease (mean 10.3 months). CONCLUSION: The high specificity and NPV of ctHPVDNA after SA suggest ctHPVDNA may have a role in determining the omission of PT adjuvant (chemo)radiation in select patients.

Orbital floor reconstruction via autologous radial forearm free flap with palmaris longus tendon.

We describe reconstruction of the orbital floor following suprastructure maxillectomy for resection of maxillary squamous cell carcinoma utilizing an osteocutaneous radial forearm free flap and palmaris longus tendon.

Surgical salvage improves overall survival for patients with HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer.

BACKGROUND: Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for patients with distant metastatic disease are limited. METHODS: A retrospective analysis of patients with recurrent OPSCC from 2 institutions between 2000 and 2012 was performed. p16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival (OS) was examined using Kaplan-Meier and Cox proportional hazards methods. RESULTS: The current study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority of patients were HPV-positive (80 patients). HPV-positive tumor status was associated with longer time to disease recurrence (P<.01). Anatomic site distribution of disease recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR], 0.23; 95% confidence interval [95% CI], 0.09-0.58 [P = .002]), longer time to disease recurrence (≥ 1 year; aHR, 0.36; 95% CI, 0.18-0.74 [P = .006]), and surgical salvage (aHR, 0.26; 95% CI, 0.12-0.61 [P = .002]) were found to be independently associated with OS after disease recurrence. Surgical salvage was independently associated with improved OS compared with nonsurgical treatment among patients with both locoregional (aHR, 0.15; 95% CI, 0.04-0.56 [P = .005]) and distant (aHR, 0.19; 95% CI, 0.05-0.75 [P = .018]) metastatic disease recurrences. CONCLUSIONS: Surgical salvage was found to be associated with improved OS for patients with recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data are needed to confirm the role of surgical salvage for distant metastases.

Carbon Dioxide Laser Sequestrectomy for Osteoradionecrosis: A Case Series.

Objective: To demonstrate a new approach to sequestrectomy using a carbon dioxide (CO2) laser for a clinic-based technique. Background: Osteoradionecrosis (ORN) of the jaw is a debilitating complication of radiotherapy for head and neck malignancies. Often refractory to medical therapy, surgical intervention for early staged disease with curettage and mechanical bone removal has mixed success, making this disease extremely difficult to treat. Therefore, new approaches to treat ORN of the jaw is needed. Methods: We describe five cases of early-to-intermediate-staged ORN illustrating a novel clinic-based sequestrectomy technique using a CO2 laser. Results: The exposed bone lesions involved the mandibular fixed gingiva, maxillary fixed gingiva, and hard palate. None of the patients had diabetes. Four patients required a total of two laser treatments and one patient needed only one treatment. All five patients demonstrated an excellent response with complete resolution of their ORN-related pain and complete mucosal coverage of the exposed bone with durable results (follow-up range, 7-19 months). Conclusions: This small series demonstrates encouraging results for CO2 laser sequestrectomy for ORN. This novel office-based intervention merits further study in larger prospective series and exploration in other disease populations, such as medication-related osteonecrosis of the jaws.

A Network Landscape of HPVOPC Reveals Methylation Alterations as Significant Drivers of Gene Expression via an Immune-Mediated GPCR Signal.

HPV-associated oropharynx carcinoma (HPVOPC) tumors have a relatively low mutational burden. Elucidating the relative contributions of other tumor alterations, such as DNA methylation alterations, alternative splicing events (ASE), and copy number variation (CNV), could provide a deeper understanding of carcinogenesis drivers in this disease. We applied network propagation analysis to multiple classes of tumor alterations in a discovery cohort of 46 primary HPVOPC tumors and 25 cancer-unaffected controls and validated our findings with TCGA data. We identified significant overlap between differential gene expression networks and all alteration classes, and this association was highest for methylation and lowest for CNV. Significant overlap was seen for gene clusters of G protein-coupled receptor (GPCR) pathways. HPV16-human protein interaction analysis identified an enriched cluster defined by an immune-mediated GPCR signal, including CXCR3 cytokines CXCL9, CXCL10, and CXCL11. CXCR3 was found to be expressed in primary HPVOPC, and scRNA-seq analysis demonstrated CXCR3 ligands to be highly expressed in M2 macrophages. In vivo models demonstrated decreased tumor growth with antagonism of the CXCR3 receptor in immunodeficient but not immunocompetent mice, suggesting that the CXCR3 axis can drive tumor proliferation in an autocrine fashion, but the effect is tempered by an intact immune system. In conclusion, methylation, ASE, and SNV alterations are highly associated with network gene expression changes in HPVOPC, suggesting that ASE and methylation alterations have an important role in driving the oncogenic phenotype. Network analysis identifies GPCR networks, specifically the CXCR3 chemokine axis, as modulators of tumor-immune interactions that may have proliferative effects on primary tumors as well as a role for immunosurveillance; however, CXCR3 inhibition should be used with caution, as these agents may both inhibit and stimulate tumor growth considering the competing effects of this cytokine axis. Further investigation is needed to explore opportunities for targeted therapy in this setting.

Put your money where your mouth is.

Suspicion for battery ingestion should be maintained for any round radiopaque foreign body. Presence of the classic "double ring" sign on plain film should prompt emergent operative removal, although it is not pathognomonic.

Predictors of Quality-of-Life Improvements Following Global Head and Neck Surgery Trips to Underserved Regions.

OBJECTIVES/HYPOTHESIS: To conduct longitudinal postoperative follow-up and discern health-related quality-of-life (HR-QoL) changes using a validated questionnaire among patients undergoing head and neck surgeries during a short-term, global surgical trip in a resource-limited setting. To identify clinicodemographic predictors of post-operative HR-QoL improvements in this setting. STUDY DESIGN: Retrospective observational study with prospective follow-up. METHODS: Patients undergoing surgery at Moi Teaching and Referral Hospital in Eldoret, Kenya through the authors' short-term surgical trip (STST) between 2016 and 2019 were asked to complete preoperative Short Form-36 (SF-36) HR-QoL questionnaires, and postoperative SF-36 questionnaires during subsequent follow-up. Preoperative and postoperative SF-36 domain scores, and two composite scores (mental component summary [MCS] and physical component summary [PCS]) were compared. Linear regression models were fit to identify clinicodemographic factors predictors of general health (GH), MCS, and PCS scores. RESULTS: Among the 26 participating patients, significant improvements were seen in post-operative GH (mean change = 19.8) and MCS (mean change = 11.2) scores. Lower pre-operative GH, MCS, and PCS scores were predictive of greater improvement in the corresponding post-operative scores. Longer time to follow-up was associated with greater improvement in GH score. Mean follow-up interval was 23.1 months (SD = 1.8 months). CONCLUSIONS: Utilizing the SF-36 questionnaire, we found that patients' perception of their general and psychosocial health improved after undergoing head and neck surgeries through a global STST. This study provides important, preliminary evidence that that elective surgeries performed in low-resource settings convey substantial benefit to patient QoL. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2006-2010, 2021.

Socioeconomic Factors Affect Presentation Stage and Survival in Sinonasal Squamous Cell Carcinoma.

OBJECTIVES: Socioeconomic factors affect oncologic outcome in sinonasal squamous cell carcinoma (SNSCC). However, the relationship between these factors and stage at presentation (SAP)-a critical, early point in the care cycle-is not known. This study sought to determine the role of race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors in SAP and survival among patients with advanced SNSCC. STUDY DESIGN: Retrospective cohort study. METHODS: Using the National Cancer Database, 6,155 patients with SNSCC were identified and divided into those with "early" (Stage I or II; 2,212 (35.9%)) versus "advanced" (Stage III or IV; 3,943 (64.1%)) disease. Associations between sociodemographic and socioeconomic factors on SAP and survival were analyzed using multivariable logistic regression and Cox proportional hazard models. RESULTS: Black (odds ratio [OR]: 2.18, CI: 1.74-2.76), Asian and Pacific Islander (API) (OR: 2.37, CI: 1.43-4.14), and Medicaid or uninsured (OR: 2.04, CI: 1.66-2.53) patients were more likely to present with advanced disease. Among patients with advanced disease, API patients demonstrated the highest 10-year survival rate (30.2%), and Black patients had the lowest 2-, 5-, and 10-year survival rates (47.7%, 31.9% and 19.2%, respectively). Older age (HR:1.03, CI:1.03-1.04), Black race (HR:1.39, CI:1.21-1.59), Medicaid or uninsured status (HR:1.48, CI:1.27-1.71), and treatment at a community hospital (HR:1.25, CI:1.14-1.37) were associated with poorer overall survival among patients with advanced disease. CONCLUSIONS: Factors including race/ethnicity, treatment facility type, insurance status/carrier, and other socioeconomic factors influence SAP and survival in SNSCC. An improved understanding of how these factors relate to outcomes may elucidate opportunities to address gaps in education and access to care in vulnerable populations. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2421-2428, 2021.

Self-removing passive drain to facilitate postoperative care via telehealth during the COVID-19 pandemic.

BACKGROUND: Telehealth postoperative visits are an attractive strategy to minimize exposure, especially during the SARS-CoV-2 (COVID-19) pandemic. The use of a surgical drain often prevents this minimal-exposure approach in that patients return to the outpatient clinic for drain removal. METHODS AND RESULTS: Following unilateral neck dissection, the customary closed-suction drain was replaced with a self-removing, passive drain dressing to facilitate same-day discharge and telehealth postoperative follow-up. The patient removed the dressing and drain at home during a telehealth visit on postoperative day 4 and she healed favorably without any signs of infection or seroma. CONCLUSIONS: When thoughtfully applied in the appropriate clinical context, small practice adaptations like this can facilitate telehealth solutions that diminish unnecessary exposure for patients, their caregivers, and health care staff.

Mycosis Fungoides of the True Vocal Folds: A Case Report.

OBJECTIVES: To report a case of laryngeal involvement of mycosis fungoides and its symptomatic treatment with laser-assisted surgical ablation. METHODS: Case report and literature review. RESULTS: A 76-year-old woman with longstanding MF previously treated with Brentuximab Vedotin who developed persistent cough and dysphonia. The patient's laryngeal disease burden was treated with KTP-laser ablation and further reduced with doxorubicin and radiotherapy. CONCLUSIONS: Although laryngeal, and especially glottic, involvement is a rare finding, suspicion should be maintained in symptomatic patients with cutaneous mycosis fungoides. This the first reported surgical laser treatment of laryngeal symptoms in this context, which can greatly improve a patient's quality of life.

Follow-Up Adherence Is Associated with Outcomes After Endoscopic Sinus Surgery.

BACKGROUND: Clinical follow-up after endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) allows for assessment of the sinonasal cavity, debridement, and tailoring of medical therapies. Frequency and timing of postoperative clinical visits is debated, but the impact of adherence on disease-specific outcomes is not well understood. In this longitudinal study, we assessed the association between follow-up adherence and quality of life (QOL) outcomes in the 12 months after ESS. METHODS: A retrospective review of patients undergoing ambulatory ESS for CRS between 11/2016 and 1/2018 was performed. We assessed sociodemographic characteristics, radiographic severity, and QOL utilizing the 22-item sinonasal outcome test (SNOT-22). Patients were categorized as "non-adherent," "moderately-adherent," and "fully-adherent" to a 1-, 3- and 5-week postoperative visit schedule. RESULTS: A total of 166 patients met the inclusion criteria. Of these, 55 (33.1%) were fully-adherent, 105 (63.2%) were moderately-adherent, and 6 (3.6%) were non-adherent within the 6 weeks following ESS. In the immediate postoperative period, fully-adherent patients demonstrated worse QOL (SNOT-22: 31.2 ± 23.1 vs 27.5 ± 17.6, P = .047). This cohort also had greater psychological dysfunction at baseline and 12-months (P < .05) after ESS. Extra-nasal symptom scores increased at a lower rate in the fully-adherent cohort (0.12 vs 1.29 points per 6 months, P = .038), as did ear/facial symptoms (1.17 vs 3.05 points per 6 months, P = .044). CONCLUSION: Despite worse symptom severity in the immediate postoperative period, patients who are more adherent to the follow-up schedule demonstrated slower return of symptoms in the extra-rhinological and ear-facial domains. These findings suggest that clinical adherence and management may impact the long-term evolution of ESS outcomes.

Incidence and Predictive Factors for Additional Opioid Prescription after Endoscopic Skull Base Surgery.

Introduction Postoperative pain management and opioid use following endoscopic skull base surgery (ESBS) is not well understood. A subset of patients requires additional opioid prescription (AOP) in the postoperative period. The objective of this study is to describe the incidence of AOP, as well as evaluate patient and surgical characteristics that may predict additional pain management requirements following ESBS. Methods A retrospective review of cases undergoing ESBS between November 2016 and August 2018 was performed. We reviewed patients' sociodemographic and clinical data, and Controlled Substance Utilization Review and Evaluation System (CURES) records. Stepwise multivariable logistic regressions were performed to evaluate the factors associated with AOP within 60 days following surgery. Results A total of 42 patients were identified. Indications for ESBS included intracranial mass (64.2%), sinonasal malignancy (23.8%), and skull base reconstruction (9.5%). AOP were recorded in nine patients (21.4%). There were no significant differences in operative factors, including approach, lesion location, or perioperative analgesia between the two cohorts. On multivariable logistic regression, we found that younger age (odds ratio [OR]: 0.891, 95% confidence interval [CI]: 0.79-1.00, p = 0.050), comorbid depression (OR: 86.48, 95% CI: 1.40-5,379.07, p = 0.034), and preoperative opioid use (OR: 104.45, 95% CI: 1.41-7,751.10, p = 0.034) were associated with additional prescriptions postoperatively. Conclusion The requirement for extended postoperative opioid pain control is common after ESBS. Patient demographics including age and psychosocial factors, such as depression may predict the need for AOP after ESBS. These results suggest that patient-driven factors, rather than surgical characteristics, may determine the need for prolonged pain control requirements after ESBS.

Socioeconomic and demographic determinants of postoperative outcome after endoscopic sinus surgery.

OBJECTIVES/HYPOTHESIS: Socioeconomic and demographic factors have a significant impact on healthcare utilization and surgical outcomes. The effect of these variables on baseline symptom severity and quality of life (QOL) after endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) is not well established. Our goal was to investigate the association of sociodemographic factors on QOL before and after ESS, as reflected by the 22-item Sino-Nasal Outcome Test (SNOT-22) score. STUDY DESIGN: Retrospective case series. METHODS: From October 2016 to August 2018, 244 patients with chronic rhinosinusitis who underwent ESS were included. Socioeconomic and demographic data, surgical characteristics, and baseline and postoperative SNOT-22 scores were recorded. Univariate and multivariate regression were performed to identify determinants of baseline symptom severity and improvement following ESS. RESULTS: Nonwhite patients reported worse baseline symptoms severity (SNOT-22, 52.06 vs. 43.76, P = .021) compared to white patients, yet lower CRS symptoms at follow-up (SNOT-22, 23.38 vs. 28.63, P = .035). Relative improvement was higher in nonwhite patients as well (41.2% vs. 36.5%, Mann-Whitney U = 1,747, P = .015). In an adjusted multivariate logistic regression model, below-median income ($71,805 [California]) was associated with worse baseline symptom severity (ß = 7.72; 95% confidence interval [CI]: 1.10, 14.26). Nonmarried patients (ß = 6.78; 95% CI: 2.22, 13.48) and white patients (ß = 8.45; 95% CI: 0.40, 13.97) had worse QOL at follow-up. CONCLUSIONS: Nonwhite patients and those with below-median income present with more severe CRS symptoms at baseline. However, a greater degree of absolute and relative QOL improvement was found in nonwhite and married patients following ESS. Improved understanding of the significance of socioeconomic and demographic factors and attention to cultural differences/marital status could have a substantial impact on ESS outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:297-302, 2020.

Elective neck dissection for T3/T4 cN0 sinonasal squamous cell carcinoma.

BACKGROUND: In locally advanced sinonasal squamous cell carcinoma (SNSCC), management of the clinically node-negative (cN0) neck is variable and elective neck dissection (END) remains controversial. METHODS: Patients with surgically treated T3/T4 cN0 M0 SNSCC were identified using the NCDB. Overall survival (OS) was assessed by Cox proportional hazard analysis in propensity score-matched cohorts. Factors associated with END were evaluated with logistic regression. RESULTS: Two hundred twenty patients underwent END (19.6%). END did not correlated with OS in propensity score-matched cohorts (HR 0.971, 95% CI 0.677-1.392), a maxillary sinus tumor subgroup (HR 1.089, 95% CI 0.742-1.599), or by radiation status [radiation: (HR 0.802, 95% CI 0.584-1.102); no radiation: (HR 0.852, 95% CI 0.502-1.445)]. The occult metastasis rate in the END cohort was 12.7%. CONCLUSION: END did not significantly improve OS in this study. Further information on disease-free survival is necessary to determine its role in advanced-stage SNSCC.

Facial Paralysis Following Core Needle Biopsy of a Deep Lobe Parotid Tumor: A Case Report.

OBJECTIVES:: To report a case of total facial paralysis as the result of a core needle biopsy. METHODS:: Case report and literature review. RESULTS:: A 70-year-old man was diagnosed with a deep lobe parotid tumor on computed tomography. During a core needle biopsy, he developed complete facial paralysis. The cause was discovered to be a direct stab injury to the main trunk of the facial nerve. CONCLUSIONS:: When biopsying parotid lesions adjacent to the main trunk of the facial nerve, the use of smaller-gauge needles and additional patient counseling should be considered.

Acoustic Nanomotors for Detection of Human Papillomavirus-Associated Head and Neck Cancer.

OBJECTIVE: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is a lethal disease with increasing incidence; however, technologies for early detection are limited. Nanomotors are synthetic nanostructures that can be powered by different mechanisms and functionalized for specific applications, such as biosensing. The objective of this investigation was to demonstrate an in vitro proof of concept for a novel nanomotor-based cancer detection approach toward in vivo detection of HPV-OPC. STUDY DESIGN: In vitro cell line incubated with ultrasound-propelled nanomotors. SETTING: Basic science and engineering laboratories. SUBJECTS AND METHODS: Ultrasound-powered gold nanowire nanomotors were functionalized with graphene oxide and dye-labeled single-stranded DNA for the specific intracellular detection of HPV16 E6 mRNA transcripts. Nanomotors were incubated with HPV-positive or HPV-negative human OPC cells under static conditions or with an applied ultrasound field for 15 minutes. The resulting intracellular fluorescence was assessed with fluorescence microscopy and analysis software. RESULTS: Nanomotors incubated with RNA extracted from HPV-positive OPC cells resulted in 60.7% of maximal fluorescence recovery, while incubation with RNA extracted from HPV-negative cells produced negligible fluorescence. Nanomotor incubation with intact HPV-negative cells produced minimal fluorescence (0.01 au), while incubation with HPV-positive cells produced a detectable signal (0.43 au) under static conditions and had 2.3-times greater intensity when powered with ultrasound. CONCLUSION: Acoustically powered nanomotors can successfully identify HPV16 E6 mRNA transcripts extracellularly and within intact cells. This work represents the first step toward a novel, practical approach to address the challenge of visually detecting HPV-OPC in real time.

Impact of margin status on survival after surgery for sinonasal squamous cell carcinoma.

BACKGROUND: Sinonasal squamous cell carcinoma (SNSCC) is the most common malignancy of the paranasal sinuses. Surgery is the mainstay of treatment, yet positive surgical margins (PSM) are common and the prognostic impact on overall survival (OS) is mixed. Given the heterogeneity of impact of PSM on OS within the literature, we hypothesized that extent of tumor extirpation (microscopic PSM vs macroscopic PSM) may play a role in OS. METHODS: Patients with SNSCC were identified in the National Cancer Database (NCDB, n = 7808). Of these, 4543 patients underwent surgery, 3265 patients underwent nonsurgical therapy. Kaplan-Meier curves were used to compare OS between negative surgical margin (NSM), micro-PSM, and macro-PSM cohorts vs patients undergoing primary nonsurgical therapy in a propensity-score-matched analysis. Multivariable analysis of factors associated with macro-PSM was also performed. RESULTS: One thousand thirty-three (22.0%) of the surgery patients had PSM, and approximately half (n = 521, 50.6%) of these had macro-PSM. When compared with nonsurgical treatment, propensity-score-matched results demonstrated improved OS in patients with NSM and micro-PSM (p < 0.001), but macro-PSM patients did not demonstrate improvement (p = 0.20). Tumor within the paranasal sinuses and advanced nodal classification (N2/N3) (odds ratio [OR], 1.18; p = 0.02; and OR, 15.09; p = 005, respectively) was associated with increased odds of macro-PSM on multivariable analysis. CONCLUSION: We demonstrate that the degree of tumor extirpation correlates with OS. Macro-PSM did not confer a benefit to OS when compared with nonsurgical therapy, and factors including tumor location and advanced nodal status affect whether surgery will result in macro-PSM. Given these findings, informed, shared decisionmaking between patient and surgeon regarding nonsurgical alternatives should occur before electing to proceed with surgery in SNSCC.

Opioid prescribing practices in patients undergoing surgery for oral cavity cancer.

OBJECTIVES: Opioids have been overprescribed after general and orthopedic surgeries, but prescribing patterns have not been reported for head and neck surgery. The objectives of this retrospective review are to describe postoperative opioid prescriptions after oral cancer surgery and determine which patients receive higher amounts. METHODS: A single institution retrospective review was performed for 81 adults with oral cavity tumors undergoing surgery. Opioid prescriptions upon discharge were reported in daily oral morphine equivalents (OME). High opioids were defined as > 90 mg daily and > 200 mg total, commensurate with U.S. Center for Disease Control and Prevention and state guidelines. Multivariable logistic regression was performed to investigate factors associated with high opioids. RESULTS: The median number of doses dispensed was 30 (interquartile range [IQR] 30-45; range 3-120). The median daily dose was 30 mg (IQR 20-45 mg; range 15-240 mg). Five patients (6%) received higher than the recommended daily dose. The median total dispensed amount was 225 mg (IQR 150-250 mg; range 15-1200 mg). Fifty-one (63%) received greater than the recommended total dose. On multivariable logistic regression, advanced tumor stage (odds ratio [OR] 11.5; 95% confidence interval [CI] 1.2-109.4; P = 0.034) and inpatient pain scores (OR 1.3 per 1-unit increase; 95% CI 1.0-1.7; P = 0.039) were associated with receiving high total opioids after surgery. CONCLUSION: The majority of patients received greater than the recommended 200 mg total OME. Advanced stage and higher inpatient pain scores were associated with receiving more opioids for discharge. Consensus-driven analgesic plans are needed to reduce excess opioids after discharge following head and neck surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2361-2366, 2018.

Association of Ultrasound Characteristics With Extranodal Extension in Metastatic Papillary Thyroid Carcinoma.

IMPORTANCE: The presence of extranodal extension (ENE) in metastatic papillary thyroid carcinoma (PTC) has emerged as an important prognostic factor, independently associated with tumor persistence after initial resection, decreased likelihood of complete biochemical response, and worse cause-specific survival. Therefore, the ability to determine ENE before surgery is desirable and advantageous but to date has not yet been evaluated. OBJECTIVE: To evaluate the use of preoperative ultrasound characteristics in predicting pathologic ENE in patients with metastatic PTC. DESIGN, SETTING, AND PARTICIPANTS: Single-institutional, retrospective analysis of patients with metastatic PTC between December 1, 2007, and May 31, 2012. The dates of the analysis were September 1, 2014, to July 31, 2015. Clinicodemographic and histopathologic data were extracted. Preoperative ultrasound images were scored for characteristics of interest by 2 independent radiologists masked to radiology and pathology reports. The setting was an academic tertiary care center. Patients were excluded if they were younger than 18 years, did not have clinical or imaging follow-up after surgery, were found to have histologic diagnoses other than PTC, or were being treated for recurrent disease. EXPOSURES: Preoperative ultrasound and neck dissection. MAIN OUTCOMES AND MEASURES: Association of ultrasound characteristics with ENE. RESULTS: Data from 29 patients with metastatic PTC and available preoperative ultrasound images and pathologic data from neck dissection were included. The patients had a median age at diagnosis of 47 years (age range, 19-85 years); and 76% (22 of 29) were female. Among 29 patients, 11 (38%) had ENE. There were no significant differences in distributions of clinicodemographic or histopathologic characteristics between patients with vs without ENE. The following ultrasound characteristics were significantly associated with ENE positivity: node matting (odds ratio [OR], 6.67; 95% CI, 1.01-44.10; P = .049), presence of node matting or cystic areas (OR, 11.70; 95% CI, 1.85-74.19; P = .009), composite score of 3 or more ultrasound characteristics (OR, 14.00; 95% CI, 2.06-95.09; P = .007), and presence of node matting, perinodal edema, unclear margins, or cystic areas (OR, 10.00; 95% CI, 1.05-95.24; P = .045), as well as presence of node matting, perinodal edema, or unclear margins (OR, 7.07; 95% CI, 1.17-42.85; P = .03). A composite score of 3 or more ultrasound characteristics had the highest accuracy (79.3%) for predicting ENE positivity. CONCLUSIONS AND RELEVANCE: This study identifies preoperative ultrasound characteristics of metastatic PTC that are significantly associated with pathologically determined ENE and supports prospective analyses to further evaluate this use of preoperative ultrasound.

Changes in Unknown Primary Squamous Cell Carcinoma of the Head and Neck at Initial Presentation in the Era of Human Papillomavirus.

IMPORTANCE: The presence of human papillomavirus (HPV) in unknown primary squamous cell carcinoma (UPSCC) of the head and neck at initial presentation focuses the investigation for the primary tumor on the oropharynx. The trends, frequency, and detection rate of UPSCCs have not been evaluated in the context of HPV tumor status. OBJECTIVES: To determine the frequency of UPSCC over time and to evaluate the proportion of HPV-positive UPSCCs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, single-institutional case series of patients diagnosed with UPSCC and evaluated at the Johns Hopkins Hospital from January 1, 2005, to June 1, 2014. Human papillomavirus tumor status was determined by p16 immunohistochemical analysis and/or high-risk HPV DNA by in situ hybridization as clinically available. MAIN OUTCOMES AND MEASURES: Number and clinical characteristics of UPSCC cases over time. RESULTS: Eighty-four UPSCC cases were eligible for analysis. The mean age of the patients was 57.3 years (range 29-80 years), and 88.1% (n = 74) were male. The frequency of UPSCC increased significantly over time (P for trend = .01) and was significantly higher during later calendar periods (14 cases during 2005-2008 vs 39 cases during 2012-2014, P = .03). A total of 69 cases (90.7%) with available HPV tumor status were HPV-positive. The patients with HPV-positive UPSCC were significantly more likely to be male (91% vs 42.9%, P = .005) and younger (56.1 vs 67.7 years, P = .002) than the HPV-negative patients with UPSCC. The overall primary tumor site detection rate was 59.3% (n = 48). There was a nonsignificant increase in the detection rate from calendar periods 2005-2008 to 2012-2014 (50.0% vs 64.9%, P = .38). Since transoral robotic surgery was adopted in the diagnostic evaluation of UPSCC in 2011, a nonsignificant increase in the detection of primary tumors was observed (53.8% vs 64.3%, P = .34). CONCLUSIONS AND RELEVANCE: The frequency of UPSCC has increased significantly in recent calendar periods, and most cases are HPV-positive. As expected, patients with HPV-positive UPSCC tend to be male and younger.