Publications by authors named "Farhoud Faraji"

48 Publications

High rates of postoperative radiotherapy delay in head and neck cancer before and after Medicaid expansion.

Head Neck 2021 May 17. Epub 2021 May 17.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, UC San Diego School of Medicine, San Diego, California, USA.

Background: The objective is to study the effect of Medicaid expansion on postoperative radiation therapy (PORT) delay in patients with head and neck squamous cell carcinoma (HNSCC).

Methods: Patients from the National Cancer Database with HNSCC undergoing curative-intent surgery in the 2 years before and after Medicaid expansion were analyzed (n = 11 717) using the difference-in-differences technique to study the effect on PORT delay.

Results: The rate of PORT delay before and after expansion was 66.0% and 66.9%, respectively. Medicaid patients had more frequent PORT delay than privately insured patients (pre-expansion 77.2% vs. 59.4%, p < 0.001; post-expansion 76.5% vs. 60.9%, p < 0.001). Medicaid expansion had no effect on PORT delay [hazard ratio 0.95, 95% confidence interval 0.81-1.12]. Supplemental analyses revealed that pathologic stage, number of treating facilities, and comorbidities were among several factors associated with PORT delay in the cohort.

Conclusion: PORT delay is unacceptably frequent. Improvement in timely adjuvant therapy requires more than Medicaid expansion.
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http://dx.doi.org/10.1002/hed.26736DOI Listing
May 2021

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

Cancer 2021 May 6. Epub 2021 May 6.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.

Background: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear.

Methods: The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses.

Results: The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow-up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2-year overall salvage radiation need of 4.5% (9 of 200). The 2-year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0-2 N2a-N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59).

Conclusions: With careful selection, surgery alone for AJCC 7th pT0-2N0-N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short-term follow-up, these data support further investigation of treatment de-escalation in this population.
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http://dx.doi.org/10.1002/cncr.33611DOI Listing
May 2021

Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma.

J Clin Invest 2021 04;131(8)

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.

BACKGROUNDPatients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.
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http://dx.doi.org/10.1172/JCI145488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075166PMC
April 2021

Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms.

Chem Senses 2021 01;46

Clinical Surgery, Universidade Estadual de Londrina, Londrina, Brazil.

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
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http://dx.doi.org/10.1093/chemse/bjaa081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799216PMC
January 2021

Does Subglottic Squamous Cell Carcinoma Warrant a Different Strategy Than Other Laryngeal Subsites?

Laryngoscope 2021 04 26;131(4):E1117-E1124. Epub 2020 Aug 26.

Department of Otolaryngology-Head and Neck Surgery, Saint Louis University School of Medicine, St. Louis, Missouri, U.S.A.

Objectives/hypothesis: Subglottic squamous cell carcinoma (SSCC) is a rare cancer with limited evidence-based treatment guidelines. This study aimed to describe the treatment patterns for SSCC and to determine which treatments provide the best overall survival.

Study Design: Retrospective database review.

Methods: The National Cancer Database (NCDB) was queried for patients treated for SSCC from 2004 through 2014. Overall survival (OS) rates were determined by the Kaplan-Meier method. Clinicopathologic characteristics were assessed by univariable and multivariable Cox proportional hazards models, which corrected for age, sex, race, insurance status, income quartile, residence, Charlson-Deyo comorbidity score, facility type providing treatment, tumor grade, and clinical N and T category.

Results: In this cohort of 549 patients with SSCC, the 5-year OS was 48.2%. SSCC presented at an advanced stage (American Joint Committee on Cancer stage III or IV) in 60.1% of cases; 78.3% of cases had no nodal metastases. Among only stage IV cases, multivariable analysis showed that radiotherapy (RT) (hazard ratio [HR] = 5.944; 95% confidence interval [CI]: 2.76-12.8; P < .001) and chemoradiotherapy (CRT) (HR = 2.321; 95% CI: 1.36-3.97; P = .002) were both associated with decreased 5-year OS compared to a group consisting of all surgeries. When this analysis was repeated for only stage III cases, RT (HR = 1.134; 95% CI: 0.38-3.37; P = .821) and CRT (HR = 1.784; 95% CI: 0.78-4.08; P = .170) were equivalent to surgery.

Conclusions: Using the NCDB to study the largest cohort of SSCC with known staging and treatment, primary surgery may provide a better 5-year OS in advanced-stage SSCC.

Level Of Evidence: 4 Laryngoscope, 131:E1117-E1124, 2021.
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http://dx.doi.org/10.1002/lary.28946DOI Listing
April 2021

Recent smell loss is the best predictor of COVID-19: a preregistered, cross-sectional study.

medRxiv 2020 Jul 26. Epub 2020 Jul 26.

Background: COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19.

Methods: This preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery.

Results: Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing no significant model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ~50% of participants and was best predicted by time since illness onset.

Conclusions: As smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (10
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http://dx.doi.org/10.1101/2020.07.22.20157263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386529PMC
July 2020

Immunotherapy in sinonasal melanoma: treatment patterns and outcomes compared to cutaneous melanoma.

Int Forum Allergy Rhinol 2020 09 5;10(9):1087-1095. Epub 2020 Jul 5.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California San Diego Health, La Jolla, CA.

Background: Although treatment with checkpoint blockade is now accepted as standard of care for cutaneous melanoma, few studies have investigated its role in sinonasal melanoma (SNM). We aimed to evaluate whether immunotherapy was associated with improved survival in SNM and to compare the effect of immunotherapy in metastatic sinonasal and cutaneous melanoma.

Methods: This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with sinonasal or cutaneous melanoma between 2012 and 2015 and had complete information regarding immunotherapy status. The primary outcome was overall survival. The influence of immunotherapy on overall survival was compared by Kaplan-Meier and Cox proportional hazards models. Propensity score matched analyses between SNM patients who received immunotherapy and those who did not were based on clinicopathological covariates associated with survival in univariate Cox models.

Results: The analytic cohort consisted of 704 patients with SNM, 94 of whom were treated with immunotherapy and 152,896 patients with cutaneous melanoma, 8055 of whom were treated with immunotherapy. Immunotherapy was not associated with survival in the propensity-score matched cohort (n = 195; hazard ratio [HR] = 1.0; 95% confidence interval [CI], 0.7 to 1.5; p = 0.88) or in adjusted Cox proportional hazards model (n = 549; HR = 1.0; 95% CI, 0.74 to 1.4; p = 0.88). Regimens including immunotherapy were associated with improved overall survival in metastatic cutaneous melanoma (HR = 0.57; 95% CI, 0.49 to 0.66; p < 0.0001), but not metastatic SNM (HR = 1.1; 95% CI, 0.67 to 1.7; p = 0.75).

Conclusion: Compared to current standard of care therapy, inclusion of immunotherapy as first-line therapy was not associated with improved survival in SNM.
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http://dx.doi.org/10.1002/alr.22628DOI Listing
September 2020

Electric scooter craniofacial trauma.

Laryngoscope Investig Otolaryngol 2020 Jun 7;5(3):390-395. Epub 2020 Apr 7.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery University of California San Diego California USA.

Objective: The use of standing electronic scooters associated with micromobility applications (e-scooters) has risen nationally. The aim of this study was to obtain a detailed view of soft tissue and bony craniofacial injury associated with e-scooter-related trauma.

Methods: Single-institution retrospective case series of patients presenting to a level 1 trauma center emergency department or trauma unit with documented e-scooter-related craniofacial injury.

Results: Of 203 included patients, 188 (92.6%) patients sustained craniofacial injury. One hundred thirty-one (64.5%) had exclusively soft tissue injury, 3 (1.5%) exclusively bony injury, 51 (25.1%) both soft and bony injuries, and twenty-five (12.3%) patients sustained dental injury. Aesthetic units most frequently sustaining acute soft tissue injury were the forehead (n = 106, 34.6%), scalp (n = 36, 11.8%), chin (n = 34, 11.1%), upper lip (n = 32, 10.5%), and cheek (n = 31, 10.1%). Aesthetic subunits most often sustaining acute soft tissue injury included the brow (42, 13.7%), central forehead (39, 12.7%), lateral forehead (n = 25, 8.2%), and upper lip vermillion (n = 23, 7.5%). Craniofacial osseous fracture most often occurred in the orbit (n = 42, 24.6%) and maxilla (n = 40, 23.4%). Individual osseous segments most frequently sustaining acute fracture included the anterior maxillary sinus wall (n = 22, 12.9%), nasal bone (n = 20, 11.7%), lateral orbital wall (n = 16, 9.4%), orbital floor (n = 15, 8.8%), and zygomatic bone (13, 7.6%).

Conclusions: Our analysis demonstrates that most patients presenting to our center with craniofacial trauma sustained acute bony fracture, most often to the midface. Our data of common injuries associated with e-scooter trauma could inform implementation in the form of facial safety equipment or safety skills training for e-scooter riders.

Level Of Evidence: 4.
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http://dx.doi.org/10.1002/lio2.380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314474PMC
June 2020

More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis.

Chem Senses 2020 10;45(7):609-622

Department of Anatomy, Faculty of Medicine, Mersin University, Çiftlikköy Campus, Yenişehir, Mersin, Turkey.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.
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http://dx.doi.org/10.1093/chemse/bjaa041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337664PMC
October 2020

Role of Olfaction in Human Health: A Focus on Coronaviruses.

Allergy Rhinol (Providence) 2020 Jan-Dec;11:2152656720928245. Epub 2020 Jun 5.

Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland.

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http://dx.doi.org/10.1177/2152656720928245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278301PMC
June 2020

An Analysis of 1-Year Charges for Head and Neck Cancer: Targets for Value-Based Interventions.

Otolaryngol Head Neck Surg 2020 Sep 26;163(3):546-553. Epub 2020 May 26.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, School of Medicine, University of California-San Diego, La Jolla, CA, USA.

Objective: To identify the dominant clinical factors associated with increased 1-year charges in treating head and neck cancer.

Study Design: Retrospective review.

Setting: Single academic institution.

Subjects And Methods: We retrospectively reviewed 1-year charges for 196 consecutive patients with head and neck cancer (HNC) who were treated exclusively at our institution. We analyzed charges by department as well as factors associated with increased charges per multivariable regression.

Results: The mean age was 59.6 years (SD, 14.9). Most of the population was male (64%), white (70%), and commercially insured (46%). The most common primary sites were the oropharynx (25%; 76%, HPV positive), skin (19%), and thyroid (17%). Eighty-three percent of total charges were due to standard-of-care treatment for HNC: surgery ($16 million), radiation therapy ($22 million), or chemotherapy ($11 million). The median total charge per patient was $212,484 (interquartile range, $78,630-$475,823). Multivariable regression demonstrated that the following were associated with increased charges: nasopharynx subsite ($250,929 [95% CI, $93,290-$408,569]; effect size in US dollars, = .002), advanced stage (American Joint Committee on Cancer, seventh edition; $80,331 [$22,726-$137,936], = .007), therapeutic surgery ($281,893 [$117,371-$446,415], = .001), chemotherapy ($183,331 [$125,497-$241,165], < .001), radiation ($203,397 [$143,454-$263,341], < .001), surgical complication requiring return to the operating room ($147,247 [$37,240-$257,254], = .009), emergency department visits ($89,050 [$23,811-$154,289], = .008), and admissions ($140,894 [$82,895-$198,893], < .001; constant, -$233,927 [-$410,790 to -$57,064]). The top quartile accrued 55% of the total charges.

Conclusion: Radiation, followed by surgery and chemotherapy, were the most expensive components of HNC care. In this analysis, we identified the dominant clinical factors associated with increased charges.
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http://dx.doi.org/10.1177/0194599820921401DOI Listing
September 2020

Meta-analysis of risk of occult lymph node metastasis in the irradiated, clinically N0 neck.

Head Neck 2020 09 19;42(9):2355-2363. Epub 2020 May 19.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, San Diego, California, USA.

Background: Recurrent head and neck squamous cell carcinoma (HNSCC) after radiation is associated with poor survival, and management of the clinically negative (N0) neck during salvage surgery is controversial.

Methods: Studies were selected according to preferred reporting items for systematic reviews and meta-analyses guidelines. Inclusion criteria were patients with HNSCC, prior radiation to the lateral neck nodal basin, undergoing salvage surgery for local recurrence, persistence or second primary, and N0 at time of salvage. Eleven studies with a total of 382 patients met inclusion criteria.

Results: The rate of occult metastasis was 15.4%. The pooled rate of occult nodal metastasis was 16.2% for oral cavity, 12.9% for oropharynx, 23.7% for hypopharynx, and 27.3% for supraglottic or transglottic tumors. There was a significantly higher relative risk of occult metastasis for locally advanced tumors.

Conclusion: Elective neck dissection at time of salvage surgery should be considered based on subsite, T classification, and prior history of nodal metastasis.
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http://dx.doi.org/10.1002/hed.26248DOI Listing
September 2020

Reply to: Self-reported olfactory loss in COVID-19: is it really a favorable prognostic factor?

Int Forum Allergy Rhinol 2020 07 8;10(7):927-928. Epub 2020 Jun 8.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California San Diego Health, La Jolla, CA.

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http://dx.doi.org/10.1002/alr.22606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272966PMC
July 2020

Self-reported olfactory loss associates with outpatient clinical course in COVID-19.

Int Forum Allergy Rhinol 2020 07 7;10(7):821-831. Epub 2020 Jun 7.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California San Diego Health, La Jolla, CA.

Background: Rapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus has left many health systems around the world overwhelmed, forcing triaging of scarce medical resources. Identifying indicators of hospital admission for coronavirus disease 2019 (COVID-19) patients early in the disease course could aid the efficient allocation of medical interventions. Self-reported olfactory impairment has recently been recognized as a hallmark of COVID-19 and may be an important predictor of clinical outcome.

Methods: A retrospective review of all patients presenting to a San Diego Hospital system with laboratory-confirmed positive COVID-19 infection was conducted with evaluation of olfactory and gustatory function and clinical disease course. Univariable and multivariable logistic regression were performed to identify risk factors for hospital admission and anosmia.

Results: A total of 169 patients tested positive for COVID-19 disease between March 3 and April 8, 2020. Olfactory and gustatory data were obtained for 128 (75.7%) of 169 subjects, of which 26 (20.1%) of 128 required hospitalization. Admission for COVID-19 was associated with intact sense of smell and taste, increased age, diabetes, and subjective and objective parameters associated with respiratory failure. On adjusted analysis, anosmia was strongly and independently associated with outpatient care (adjusted odds ratio [aOR] 0.09; 95% CI, 0.01-0.74), whereas positive findings of pulmonary infiltrates and/or pleural effusion on chest radiograph (aOR 8.01; 95% CI, 1.12-57.49) was strongly and independently associated with admission.

Conclusion: Normosmia is an independent predictor of admission in COVID-19 cases. Smell loss in COVID-19 may be associated with a milder clinical course.
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http://dx.doi.org/10.1002/alr.22592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264572PMC
July 2020

Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms.

Int Forum Allergy Rhinol 2020 07 1;10(7):806-813. Epub 2020 Jun 1.

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California San Diego Health, La Jolla, CA.

Background: Rapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases.

Methods: A single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity.

Results: A total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness.

Conclusion: In ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.
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http://dx.doi.org/10.1002/alr.22579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262089PMC
July 2020

An Atypical Cause of Difficulty Swallowing.

JAMA Otolaryngol Head Neck Surg 2020 05;146(5):501-503

Division of Otolaryngology-Head & Neck Surgery, Department of Surgery, University of California, San Diego.

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http://dx.doi.org/10.1001/jamaoto.2020.0133DOI Listing
May 2020

Prognostic significance of surgical margins after transoral laser microsurgery for early-stage glottic squamous cell carcinoma.

Oral Oncol 2019 10 29;97:105-111. Epub 2019 Aug 29.

Department of Otolaryngology - Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA. Electronic address:

Objectives: The impact of positive tumor margin status and other clinicopathological factors on prognosis in early stage glottic squamous cell carcinoma (SCC) treated with transoral laser microsurgery (TLM) remains unclear. This study examined overall survival (OS) rates of patients with positive tumor margin status compared to negative tumor margin status after TLM in clinical T1-2 glottic SCC.

Materials And Methods: The National Cancer Data Base (NCDB) was queried for patients who underwent resection of T1-2 glottic SCC by TLM. Patients were treated from 2004 to 2013. Overall survival was assessed with Kaplan-Meier curve analysis, and univariate and multivariate Cox proportional hazards analysis. Differences in clinicopathologic factors between positive and negative margin groups were compared using Pearson Chi-squared analysis.

Results: Of 747 patients meeting inclusion criteria, 598 (80.1%) had negative margins. Median follow-up time was 48.0 months. Unadjusted 5-year OS for positive margins (80.0%) was lower compared to that of negative tumor margins (82.9%), but this was not statistically significant (P = 0.265). This persisted after multivariate analysis (P = 0.960). When tumors were stratified by T stage (647 T1, 100 T2), unadjusted 5-year OS based on margin status remained statistically insignificant for both T1 (P = 0.933) and T2 tumors (P = 0.350).

Conclusion: Positive margins did not negatively impact overall survival among patients with TLM-treated early-stage glottic cancer. This finding might be useful clinically in deciding treatment modality for early stage glottic SCC.
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http://dx.doi.org/10.1016/j.oraloncology.2019.08.005DOI Listing
October 2019

Computed tomography performance in predicting extranodal extension in HPV-positive oropharynx cancer.

Laryngoscope 2020 06 14;130(6):1479-1486. Epub 2019 Aug 14.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.

Objectives: To evaluate the performance characteristics of seven predetermined imaging features on pretreatment computed tomography (CT) in identifying extranodal extension (ENE) in cervical lymph node metastases from human papillomavirus-positive oropharyngeal carcinoma (HPV-OPC).

Study Design: Retrospective study.

Methods: Seventy-three patients with HPV-OPC who underwent primary surgery and cervical lymph node dissection were included. Preoperative contrast-enhanced CT (cCT) imaging was evaluated by two radiologists blinded to pathological results. Each cCT was scored for seven imaging features of interest: 1) indistinct capsular contours, 2) irregular nodal margins, 3) perinodal fat stranding, 4) perinodal fat planes, 5) nodal necrosis, 6) intranodal cysts, and 7) nodal matting. Logistic regression was employed to determine radiologist-specific odds ratios (OR) of predicting ENE for each imaging feature and radiologist-specific receiver operating characteristics (sensitivity [Sn], specificity [Sp], area under the curve [AUC], positive predictive value [PPV], negative predictive value [NPV]) for each imaging feature.

Results: Thirty-two (44%) patients had ENE-positive lymph nodes. The presence of irregular margins (OR = 12.3, 95% confidence interval [CI] = 2.3-65.9; OR = 7.0, 95% CI = 1.4-36.3) and absence of perinodal fat plane (OR = 6.8, 95% CI = 2.0-23.3; OR = 14.2, 95% CI = 1.7-120.5) were significantly associated with ENE for each radiologist. Irregular nodal margin status was most specific for ENE (Sn = 45%, Sp = 94%, AUC = 69%, PPV = 82%, NPV = 73%; Sn = 28%, Sp = 95%, AUC = 61%, PPV = 80%, NPV = 64%). Absence of perinodal fat plane was most sensitive for ENE (Sn = 87%, Sp = 50%, AUC = 69%, PPV = 59%, NPV = 62%; Sn = 96%, Sp = 34%, AUC = 65%, PPV = 53%, NPV = 63%).

Conclusions: Of the seven imaging features hypothesized to be associated with ENE-status, the presence of irregular nodal margins and absence of perinodal fat plane were the most specific and sensitive features, respectively.

Level Of Evidence: 4 Laryngoscope, 130:1479-1486, 2020.
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http://dx.doi.org/10.1002/lary.28237DOI Listing
June 2020

A systematic review of the nasal septal turbinate: An overlooked surgical target.

Am J Otolaryngol 2019 Nov - Dec;40(6):102188. Epub 2019 Mar 4.

University of California, San Diego, Department of Surgery, Division of Otolaryngology-Head & Neck Surgery, San Diego, CA, United States of America.

Objective: The nasal septal turbinate (NST) is a conspicuous structure located in the anterior nasal cavity that impacts the internal nasal valve. Its structure and function is often thought to be poorly characterized, and it is rarely addressed surgically. The authors perform a systematic review in an attempt to synthesize what has been learned of this structure and to evaluate its potential as a treatment target.

Methods: A query of the Medline, Embase, Web of Science and Cochrane databases was undertaken in search of studies evaluating the NST. This qualitative systematic review was performed in accordance with PRISMA guidelines. Study quality and risk of bias were assessed with established criteria.

Results: Of the initial 1069 hits from the four databases, 16 articles were ultimately included in the review, which varied in quality and risk of bias. The included articles consisted predominantly of radiographic and histopathologic studies. Four studies evaluated NST treatment outcomes. The NST represents a fusiform-shaped region of erectile tissue, similar in structure and function to that of the inferior turbinates. Preliminary treatment outcomes suggest the NST represents an important surgical target in nasal airway surgery.

Conclusion: When evaluating nasal obstruction patients, surgeons should assess the NST and consider addressing it surgically.
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http://dx.doi.org/10.1016/j.amjoto.2019.03.003DOI Listing
April 2020

Priorities of human papillomavirus-associated oropharyngeal cancer patients at diagnosis and after treatment.

Oral Oncol 2019 08 4;95:11-15. Epub 2019 Jun 4.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 601 N. Caroline Street, Baltimore, MD 21287, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, United States. Electronic address:

Introduction: Little is known regarding how human papillomavirus-positive oropharyngeal cancer (HPV-OPC) patient goals change with treatment. This study evaluates whether patient ranking of non-oncologic priorities relative to cure and survival shift after treatment as compared to priorities at diagnosis.

Materials And Methods: This is a prospective study of HPV-OPC patient survey responses at diagnosis and after treatment. The relative importance of 12 treatment-related priorities was ranked on an ordinal scale (1 as highest). Median rank (MR) was compared using Wilcoxon matched-pairs signed-rank tests. Prevalence of high concern for 11 treatment-related issues was compared using paired t-test. The effect of patient characteristics on change in priority rank and concern was evaluated using linear regression.

Results: Among 37 patients, patient priorities were generally unchanged after treatment compared with at diagnosis, with cure and survival persistently ranked top priority. Having a moist mouth uniquely rose in importance after treatment. Patient characteristics largely did not affect change in priority rank. Concerns decreased after treatment, except concern regarding recurrence.

Discussion: Treatment-related priorities are largely similar at diagnosis and after treatment regardless of patient characteristics. The treatment experience does not result in a shift of priorities from cure and survival to non-oncologic domains over cure and survival. The rise in importance of moist mouth implies that xerostomia may have been underappreciated as a sequelae of treatment. A decrease in most treatment-related concerns is encouraging, whereas the persistence of specific areas of concern may inform patient counseling.
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http://dx.doi.org/10.1016/j.oraloncology.2019.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662631PMC
August 2019

Tumor-infiltrating lymphocyte quantification stratifies early-stage human papillomavirus oropharynx cancer prognosis.

Laryngoscope 2020 04 9;130(4):930-938. Epub 2019 May 9.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.

Objectives/hypothesis: To evaluate if a simple method for assessing tumor-infiltrating lymphocytes (TIL) in primary tumor specimens improves the prognostic value of the American Joint Committee on Cancer, 8th Edition (AJCC8) cancer staging system in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-OPC).

Study Design: Retrospective study.

Methods: In this study, TIL density was quantified on hematoxylin and eosin (H&E)-stained specimens from patients presenting to Johns Hopkins Hospital between 2009 and 2017 who underwent primary surgical therapy and had primary tumor specimens available for analysis. The prognostic effect of TIL density was evaluated by Kaplan-Meier method and Cox proportional hazards models considering recurrence-free survival (RFS) as the primary outcome.

Results: This study included 132 patients. Ninety-five percent were classified by clinical criteria with AJCC8 early-stage disease (stage I: 82%, stage II: 13%). After 84 months of follow-up, 15 recurrences were observed. Among clinically early-stage disease, TIL status was associated with improved RFS compared to TIL (P = .002). Adjusted analysis showed TIL status was associated with 79% lower risk of recurrence than TIL (adjusted hazard ratio [aHR]: 0.210, 95% confidence interval [CI]: 0.061-0.723). In clinical stage I disease, TIL status was associated with improved RFS compared to TIL in both univariate and multivariate analyses (hazard ratio: 0.235, P = .021; aHR: 0.218; 95% CI: 0.058-0.822). TIL density similarly stratified risk in pathologically staged disease.

Conclusions: In patients with AJCC8 stage I disease, low TIL density was associated with diminished RFS. Our data suggest that assessing TIL density on H&E-stained primary tumor specimens may enhance the prognostic resolution of the AJCC8 staging criteria for HPV-OPC.

Level Of Evidence: 4 Laryngoscope, 130:930-938, 2020.
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http://dx.doi.org/10.1002/lary.28044DOI Listing
April 2020

Basaloid Squamous Cell Carcinoma of the Larynx: A National Cancer Database Analysis.

Otolaryngol Head Neck Surg 2019 05 5;160(5):847-854. Epub 2019 Feb 5.

1 Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Saint Louis University, Saint Louis, Missouri, USA.

Objective: Basaloid squamous cell histology is a rare variant that accounts for about 2% of all head and neck squamous cell laryngeal carcinomas. The purpose of this study was to examine overall survival rates of patients according to treatment, stage, and laryngeal subsite.

Study Design: Retrospective analysis.

Setting: National Cancer Database (NCDB).

Subjects And Methods: The NCDB was queried for patients with basaloid squamous cell carcinoma (BSCC) who were treated from 2004 to 2014. Five-year overall survival rates were determined by the Kaplan-Meier method. Univariate and multivariate analysis was used to identify factors correlated with 5-year overall survival.

Results: The NCDB identified 440 patients meeting inclusion criteria. Median follow-up time was 31.2 months. On univariate analysis, the treatment modalities assessed (surgery alone, surgery with radiotherapy, surgery with chemoradiotherapy, radiotherapy, chemoradiotherapy) did not differ in their survival benefit. On multivariate analysis, only chemoradiotherapy (hazard ratio, 0.587; 95% CI, 0.37-0.93; P = .022) was associated with improved survival. All treatment modalities performed similarly between stage I and II tumors ( P = .340) and stage III and IV tumors ( P = .154).

Conclusion: This study represents the largest laryngeal BSCC series to date. We found that chemoradiotherapy was associated with improved 5-year overall survival of laryngeal BSCC on multivariate analysis.
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http://dx.doi.org/10.1177/0194599818816299DOI Listing
May 2019

Bullous Pemphigoid Presenting as Oropharyngeal Hemorrhage.

JAMA Otolaryngol Head Neck Surg 2019 Mar;145(3):288-290

Division of Otolaryngology-Head & Neck Surgery, Department of Surgery, University of California, San Diego.

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http://dx.doi.org/10.1001/jamaoto.2018.4051DOI Listing
March 2019

Priorities, concerns, and regret among patients with head and neck cancer.

Cancer 2019 04 15;125(8):1281-1289. Epub 2019 Jan 15.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.

Background: In the era of deintensification, little data are available regarding patients' treatment preferences. The current study evaluated treatment-related priorities, concerns, and regret among patients with head and neck squamous cell cancer (HNSCC).

Methods: A total of 150 patients with HNSCC ranked the importance of 10 nononcologic treatment goals relative to the oncologic goals of cure and survival. The level of concern regarding 11 issues and decision regret was recorded. Median rank was reported overall, and factors associated with odds of rank as a top 3 priority were modeled using logistic regression.

Results: Among the treatment effects analyzed, the odds of being a top 3 priority was especially high for cure (odds, 9.17; 95% confidence interval [95% CI], 5.05-16.63), followed by survival and swallow (odds, 1.26 [95% CI, 0.88-1.80] and odds, 0.85 [95% CI, 0.59-1.21], respectively). Prioritization of cure, survival, and swallow was similar based on human papillomavirus (HPV) tumor status. By increasing decade of age, older participants were found to be significantly less likely than younger individuals to prioritize survival (odds ratio, 0.72; 95% CI, 0.52-1.00). Concerns regarding mortality (P = .04) and transmission of HPV to the patient's spouse (P = .03) were more frequent among participants with HPV-associated HNSCC. Regret increased with additional treatment modalities (P = .02).

Conclusions: Patients with HNSCC overwhelming prioritize cure, followed by survival and swallow. The decreased prioritization of survival by older age supports further examination of treatment preference by age. The precedence of oncologic over nononcologic priorities among patients regardless of HPV tumor status supports the conservative adoption of deintensification regimens until the interplay between competing oncologic and nononcologic treatment goals is better understood.
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http://dx.doi.org/10.1002/cncr.31920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443481PMC
April 2019

The prevalence of human papillomavirus in oropharyngeal cancer is increasing regardless of sex or race, and the influence of sex and race on survival is modified by human papillomavirus tumor status.

Cancer 2019 03 6;125(5):761-769. Epub 2018 Dec 6.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: The purpose of this study was to evaluate the influence of sex and race/ethnicity upon prevalence trends of human papillomavirus (HPV) in oropharyngeal cancer (OPC) and survival after OPC.

Method: This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with OPC between 2010 and 2015. Outcomes were HPV status of tumor specimens and overall survival. Sex- and race-stratified trends in HPV prevalence were estimated using generalized linear modeling. The influence of sex, race, and HPV tumor status on overall survival was compared by Kaplan-Meier method and Cox Proportional Hazards models.

Results: This analysis included 20,886 HPV-positive and 10,364 HPV-negative OPC patients. The prevalence of HPV-positive tumors was higher among men (70.6%) than women (56.3%) and increased significantly over time at a rate of 3.5% and 3.2% per year among men and women, respectively. The prevalence of HPV-positive tumors was highest among whites (70.2%), followed by Hispanics (61.3%), Asians (55.8%), and blacks (46.3%). Blacks and Hispanics experienced significantly more rapid increases in prevalence of HPV-positive tumors over time compared with whites (6.5% vs 5.6% vs 3.2% per year, respectively). In HPV-positive OPC, neither sex nor race/ethnicity was associated with survival among patients with HPV-positive OPC. In contrast, for HPV-negative OPC, risk of death was significantly higher for women versus men (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.08-1.26) and blacks versus whites (aHR, 1.21; 95% CI, 1.10-1.33).

Conclusion: The prevalence of HPV-positive tumors is increasing for all sex and race/ethnicity groups in the United States. Sex and race are independently associated with survival for HPV-negative but not HPV-positive OPC.
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http://dx.doi.org/10.1002/cncr.31841DOI Listing
March 2019

Oropharyngeal cancer is no longer a disease of younger patients and the prognostic advantage of Human Papillomavirus is attenuated among older patients: Analysis of the National Cancer Database.

Oral Oncol 2018 08 27;83:147-153. Epub 2018 Jun 27.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 601 N Caroline St. 6(th) Floor, Baltimore, MD 21287, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, United States. Electronic address:

Objectives: HPV-positive oropharyngeal cancer (OPC) patients have been observed to be younger than patients with HPV-negative OPC at diagnosis. We evaluated recent trends in age at OPC diagnosis, and whether older age attenuates the survival benefit of HPV-positive tumor status.

Materials And Methods: Patients diagnosed with OPC from 2004 to 2014 represented in the National Cancer Database were included. HPV tumor status was available after 2010. Trends in age by calendar year were compared using linear regression. Overall survival was compared using Cox Proportional Hazards models.

Results: The mean age of OPC patients (N = 119,611) increased significantly from 2004 to 2014 (ß = 0.21 years of age per calendar year, 95% confidence interval [CI] = 0.19-0.23). The increase in age from 2010 to 2014 was similar for HPV-positive (N = 21,880; ß = 0.63, 95%CI = 0.53-0.72) and HPV-negative (N = 11,504; ß = 0.59, 95%CI = 0.45-0.74) patients. Between 2010 and 2014, the proportion of OPCs that were HPV-positive increased significantly for all age groups, including for patients ≥70 years old (from 45% to 60%, p < 0.001). Although patients ≥70 years with HPV-OPC had improved survival compared to those with HPV-negative OPC (adjusted hazard ratio [aHR] = 0.65, 95%CI = 0.55-0.76), the survival benefit of HPV-positive tumor status was significantly attenuated compared to younger HPV-OPC patients (50-59 years: aHR = 0.45, 95%CI = 0.39-0.51; p < 0.001).

Conclusion: The age at OPC diagnosis is increasing for both HPV-positive and HPV-negative patients, and a rising proportion of older patients have HPV-positive tumors. These findings dispel the notion that HPV-positive OPC is a disease of younger patients, identify a growing elderly population of HPV-positive OPC patients with reduced survival, and have implications for evolving treatment paradigms.
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http://dx.doi.org/10.1016/j.oraloncology.2018.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500732PMC
August 2018

Diagnostic dilemmas of mechanical restriction of the medial rectus: A case report.

Allergy Rhinol (Providence) 2018 Jan-Dec;9:2152656718764231. Epub 2018 Apr 12.

Department of Otolaryngology-Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri.

Background: Due to the proximity of the maxillary sinus and ethmoid sinuses to the orbit, inflammatory processes that originate in the sinonasal region have the potential to extend into the orbit.

Objective: We presented a case of ptosis and restrictive strabismus of the medial rectus muscle.

Methods: A case report with a literature review of possible diagnoses.

Results: Biopsy, imaging, and laboratory evaluation by otolaryngology, ophthalmology, and rheumatology services were unable to identify the cause of the fibrosis after 22 months of follow-up. A response to oral steroids indicated an inflammatory process.

Conclusion: Unilateral mechanical restriction of the medial rectus muscle is a rare complication of nasal disease. Inflammatory processes and iatrogenic injury are known to cause fibrosis of surrounding tissue. We presented a unique case of medial rectus fibrosis that did not meet the diagnostic criteria of recognized etiologies.
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http://dx.doi.org/10.1177/2152656718764231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028159PMC
April 2018

Stereotactic radiotherapy in three weekly fractions for the management of vestibular schwannomas.

Am J Otolaryngol 2018 Sep - Oct;39(5):561-566. Epub 2018 Jun 22.

Saint Louis University School of Medicine, Department of Otolaryngology - Head and Neck Surgery, 3635 Vista Ave, 6FDT, St. Louis, MO 63110, USA. Electronic address:

Purpose: This study evaluates the rates of tumor control, hearing preservation and cranial nerve toxicity with the use of CyberKnife stereotactic radiotherapy consisting of 2100 cGy to the 80% isodose line delivered in three weekly fractions to treat vestibular schwannomas.

Materials And Methods: Retrospective chart review of vestibular schwannoma patients treated with CyberKnife stereotactic radiotherapy or undergoing watchful waiting between 2006 and 2017 was performed. For inclusion, patients receiving CyberKnife stereotactic radiotherapy must have had pretreatment magnetic resonance imaging and audiography, and 2 follow-up magnetic resonance imaging and audiograms. Watchful waiting patients must have had a minimum of 2 magnetic resonance imaging and 2 audiograms.

Results: Forty patients met inclusion criteria. Twenty-two underwent CyberKnife stereotactic radiotherapy. Eighteen remain in watchful waiting. Crude tumor control was 86.4% at mean radiographic follow-up of 52.3 months. Kaplan-Meier progression-free survival was 76.9% at 5 years. Kaplan-Meier survival from radiographic growth was 61.5% at 5 years. Kaplan-Meier hearing preservation was 17.5% at 5 years. All patients undergoing watchful waiting presenting with serviceable hearing maintained serviceable hearing. Serviceable hearing among CyberKnife stereotactic radiotherapy patients was 42.9% prior to treatment and 14.2% through mean follow-up of 53.7 months. One patient experienced trigeminal nerve toxicity 45 months after SRT. 95.5% of CyberKnife stereotactic radiotherapy patients were complication-free.

Conclusions: Our fractionation regimen provides tumor control consistent with current literature. Hearing outcomes, however, should be discussed with patients prior to CyberKnife stereotactic radiotherapy.
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http://dx.doi.org/10.1016/j.amjoto.2018.06.017DOI Listing
January 2019

Platelets Promote Metastasis via Binding Tumor CD97 Leading to Bidirectional Signaling that Coordinates Transendothelial Migration.

Cell Rep 2018 Apr;23(3):808-822

Laboratory of Genitourinary Cancer Pathogenesis, NCI, Bethesda, MD 20892, USA. Electronic address:

Tumor cells initiate platelet activation leading to the secretion of bioactive molecules, which promote metastasis. Platelet receptors on tumors have not been well-characterized, resulting in a critical gap in knowledge concerning platelet-promoted metastasis. We identify a direct interaction between platelets and tumor CD97 that stimulates rapid bidirectional signaling. CD97, an adhesion G protein-coupled receptor (GPCR), is an overexpressed tumor antigen in several cancer types. Purified CD97 extracellular domain or tumor cell-associated CD97 stimulated platelet activation. CD97-initiated platelet activation led to granule secretion, including the release of ATP, a mediator of endothelial junction disruption. Lysophosphatidic acid (LPA) derived from platelets induced tumor invasiveness via proximal CD97-LPAR heterodimer signaling, coupling coincident tumor cell migration and vascular permeability to promote transendothelial migration. Consistent with this, CD97 was necessary for tumor cell-induced vascular permeability in vivo and metastasis formation in preclinical models. These findings support targeted blockade of tumor CD97 as an approach to ameliorate metastatic spread.
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http://dx.doi.org/10.1016/j.celrep.2018.03.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6574118PMC
April 2018

Evaluating oropharyngeal carcinoma with transcervical ultrasound, CT, and MRI.

Oral Oncol 2018 03 20;78:177-185. Epub 2018 Feb 20.

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address:

Objective: To compare transcervical ultrasonography (US) to standard cross-sectional imaging for the visualization of human papillomavirus-related oropharyngeal cancer (HPV-OPC).

Materials And Methods: Patients with HPV-OPC and available standard imaging (CT and/or MRI) were identified in clinic and prospectively enrolled. US was performed to visualize the oropharynx and lymph nodes. Tumor characteristics across imaging modalities were evaluated (CT versus MRI, and US versus standard imaging (SI)).

Results: Forty-three patients were included. The overall blinded detection rates for CT and MRI were 83% and 71%, respectively. The unblinded detection rate for US was 98%. Agreement of tumor anatomic subsite was moderate for both CT vs MRI (κ = 0.59) and US vs SI (κ = 0.47). Comparison of tumor size by CT and MRI showed statistically significant correlations in craniocaudal (CC), anteroposterior (AP), and mediolateral (ML) dimensions (Rho = 0.51, p = 0.038; Rho = 0.81, p < 0.0001; Rho = 0.57, p = 0.012). Tumor size estimates by US and SI showed statistically significant correlations in CC and AP, but not ML (Rho = 0.60, p = 0.003; Rho = 0.71, p < 0.0001; Rho = 0.30, p = 0.08). Tumor volume estimates improved correlations between US and SI (Rho = 0.66, p < 0.0001). Stratification of US patients into early and late imaging studies demonstrated an increase in correlation strength from early (Rho = 0.32, p = 0.32) to late groups (Rho = 0.77, p < 0.0001) demonstrating that ultrasound accuracy improved with experience.

Conclusions: Our findings suggest that transcervical ultrasonography is a sensitive and relatively accurate adjunct to standard imaging for the evaluation of oropharyngeal tumors. Its cost, portability, and potential for in-clinic and serial imaging render US an attractive modality to further develop for imaging oropharyngeal tumors.
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http://dx.doi.org/10.1016/j.oraloncology.2018.01.016DOI Listing
March 2018