Nucleolin mediates the binding of cancer cells to L-selectin under conditions of lymphodynamic shear stress.

Head and neck squamous cell carcinoma (HNSCC) cells bind to lymphocytes via L-selectin in a shear-dependent manner. This interaction takes place exclusively under low-shear stress conditions, such as those found within the lymph node parenchyma. This represents a novel functional role for L-selectin-selectin ligand interactions. Our previous work has characterized as-of-yet unidentified L-selectin ligands expressed by HNSCC cells that are specifically active under conditions of low shear stress consistent with lymph flow. Using an affinity purification approach, we now show that nucleolin expressed on the surface of HNSCC cells is an active ligand for L-selectin. Parallel plate chamber flow-based experiments and atomic force microscopy (AFM) experiments show that nucleolin is the main functional ligand under these low-force conditions. Furthermore, AFM shows a clear relationship between work of deadhesion and physiological loading rates. Our results reveal nucleolin as the first major ligand reported for L-selectin that operates under low-shear stress conditions.

PDGF-AA mediates mesenchymal stromal cell chemotaxis to the head and neck squamous cell carcinoma tumor microenvironment.

BACKGROUND: The robust desmoplasia associated with head and neck squamous cell carcinoma (HNSCC) suggests that the tumor microenvironment may be an important component in the pathophysiology of this cancer. Moreover, the high recurrence rate and poor clinical response to chemotherapy and radiation treatment further underscores that the non-cancerous cells of the microenvironment, such as mesenchymal stromal cells (MSCs), cancer associated fibroblasts (CAFs), and pericytes, may be important in the pathophysiology of HNSCC. METHODS: Confocal microscopy and immunohistomchemistry approaches were used to identify MSCs tumor microenvironment from patients with oral cavity and oral pharyngeal squamous cell carcinoma (SCC). In vitro Boyden chamber assays and multiplex magnetic bead assays were used to measure MSC chemotaxis and to identify the chemokines secreted by JHU-011, -012, -019, three cells lines derived from patients with oral pharyngeal SCC. RESULTS: We show here that MSCs reside in the tumor microenvironment of patients with oral cavity and oral pharyngeal SCC and are recruited via paracrine mediated tumor cell secretion of (platelet derived growth factor) PDGF-AA. The MSC markers CD90+, CD105+, and gremlin-1+ were found to co-localize on cells within the tumor microenvironment in oral cavity SCC specimens distinct from α-smooth muscle actin staining CAFs. The conditioned media from JHU-011, -012, and -019 caused a significant increase in MSC migration (>60%) and invasion (>50%; p < 0.0001) compared to oral keratinocyte (OKT) controls. Tumor cell induced MSC chemotaxis appears to be mediated through paracrine secretion of PDGF-AA as inhibition of the PDGF-AA receptor, PDGFR-α but not PDGFR-ß, resulted in near arrest of MSC chemotaxis (p < 0.0001). CONCLUSIONS: Tumor microenvironment expression of PDGFR-α has been shown to correlate with a worse prognosis in patients with prostate, breast, ovarian, non-small cell lung cancer and osteosarcoma. This is the first evidence that a similar signaling paradigm may be present in HNSCC. PDGFR-α inhibitors have not been studied as adjunctive treatment options in the management of HNSCC and may prove to be an important driver of the malignant phenotype in this setting.

Laminin interactions with head and neck cancer cells under low fluid shear conditions lead to integrin activation and binding.

Lymphatic metastasis of cancer cells involves movement from the primary tumor site to the lymph node, where the cells must be able to productively lodge and grow. It is there that tumor cells encounter cellular and non-cellular constituent elements that make up the lymph node parenchyma. Our work shows that head and neck squamous cell carcinoma (HNSCC) cell lines are able to bind to laminin, fibronectin, vitronectin, and hyaluronic acid, which are extracellular matrix elements within the lymph node parenchyma. HNSCC cell lines bound to laminin under lymphodynamic low shear stress (0.07 dynes/cm(2)), consistent with lymph flow via ß1 integrins, including α2ß1, α3ß1, and α6ß1. Binding occurred in the presence of shear stress and not in the absence of flow. Additionally, tumor cell binding to laminin under flow did result in calcium signaling. Our data indicate a novel role for ß1 integrin-mediated binding of HNSCC cells to laminin under conditions of lymphodynamic flow that results in intracellular calcium signaling within the cancer cell.

Label-Free Imaging and Histo-Optical Evaluation of Head and Neck Cancers with Multiphoton Autofluorescence Microscopy.

Depth-resolved label-free optical imaging by the method of multiphoton autofluorescence microscopy (MPAM) may offer new ways to examine cellular and extracellular atypia associated with epithelial squamous cell carcinoma (SCC). MPAM was evaluated for its ability to identify cellular and microstructural atypia in head and neck tissues from resected discarded tumor tissue. Three-dimensional image volumes were obtained from tissues from the floor of the mouth, tongue, and larynx, and were then processed for histology. MPAM micrographs were evaluated for qualitative metrics of cell atypia and quantitative measures associated with nuclear pleomorphism. Statistical analyses correlated MPAM endpoints with histological grade from each imaged site. Cellular overcrowding, discohesion, anisonucleosis, and multinucleated cells, as observed through MPAM, were found to be statistically associated with dysplasia and SCC grading, but not in histologically benign regions. A quantitative measure of the coefficient of variance in nuclear size in SCC and dysplasia was statistically elevated above histologically benign regions. MPAM also allowed for the identification of cellular heterogeneity across transitional areas and other features, such as inflammatory infiltrates. In the future, MPAM could be evaluated for the non-invasive detection of neoplasia, possibly as an adjunct to traditional conventional examination and biopsy.

Laryngectomy: Social media analysis of patient perception.

BACKGROUND: Social media continues to grow as a relevant information source for the lay public and medical professionals. METHODS: A search of posts on Facebook and Instagram was conducted using the hashtag #laryngectomy. Posts were categorized based upon perspective, media type, timeframe, topic, tone, and popularity. RESULTS: Final analysis included 929 Instagram posts and 355 Facebook posts. Most Facebook posts were made by companies (38%) and physicians (17%) with information (30%) and advertisements (22%) being common topics. Patients (40%) were the largest group of Instagram authors with lifestyle (39%) being the most common topic. Greater than 90% of posts were either neutral or positive in tone across both platforms. CONCLUSIONS: Patient perspective was most commonly represented on Instagram, whereas Facebook more commonly included posts by physicians and companies. The majority of posts carried a neutral or positive tone, which is consistent with positive quality of life patients have shown postoperatively.

Combined large cell neuroendocrine carcinoma and squamous cell carcinoma of the oropharynx: A collision course of tumors.

Combined large cell neuroendocrine carcinoma (LCNEC) and squamous cell carcinoma (SCC) of the H&N are exceptionally rare. We present the case of combined p16 negative SCC and LCNEC of the oropharynx treated with combination chemotherapy. This is the third reported case of combined neuroendocrine carcinoma and SCC of the oropharynx.

Synchronous tonsillar tumors with differing histopathology: A case report and review of the literature.

BACKGROUND: Tonsillar squamous cell carcinoma (TSCC) due to human papillomavirus (HPV) infection has seen a dramatic increase in recent years. Bilateral tonsillar squamous cell carcinoma (biTSCC) has a much lower incidence than unilateral TSCC and three main hypotheses of biTSCC pathogenesis prevail: field carcinogenesis, single-clone, and multiple HPV infections. CASE: A 49-year-old Male with a remote history of chewing tobacco presented with symptoms of spitting up tissue and occasional hemoptysis. Physical exam showed a sole left tonsillar mass which was confirmed to be TSCC on biopsy. The patient's computed tomographic (CT) scan was consistent with this finding; however, positron emission tomography (PET) scan indicated a second tumor in the contralateral right tonsil. Surgical resection of both masses and selective neck dissection was performed, and the specimens were sent for further pathological analysis. No complications of surgery were noted and the final diagnosis of synchronous biTSCC was made. The tumors were a T2N0M0 left poorly differentiated TSCC (p16+, EGFR+, bcl2+) with basaloid features, and a T1N0M0 right well to moderately differentiated TSCC (p16+, EGFR+, bcl2-). CONCLUSION: Our present case was notable for differing tumor pathology and karyotype analysis between the right and left masses, directly supporting the multiple HPV infections hypothesis of biTSCC pathogenesis. Further genetic characterization of tonsillar tumors is needed to better characterize TSCC and best guide medical/surgical therapy.

Clinicopathological predictors of lymphatic metastasis in HNSCC: implications for molecular mechanisms of metastatic disease.

Lymphatic metastasis is associated with up to a 50% decrease in survival, yet the molecular mechanisms driving their establishment remain poorly understood. This study assessed clinicopathological characteristics correlated to nodal metastasis among patients with head and neck squamous cell carcinoma for the identification of pathways on which to focus molecular studies. Pathology records were queried for cases diagnosed with invasive squamous cell cancer of the upper aerodigestive tract between 1993 and 2003. Charts and pathology reports were scored for 16 characteristics. The univariate association of each variable with lymph node status was assessed. Based on the univariate analysis, a multiple logistic regression model was developed to assess the simultaneous association of variables with lymph node status. Of the 644 cases identified, 234 had a surgical specimen analyzed. All variables were scored for 185 of the 234 cases. Multivariate stepwise regression analysis identified clinical stage (p = 0.0269), pathologic stage (p = 0.0162), grade (p = 0.0094), lymphovascular invasion (p = 0.0393), and family history of cancer (p = 0.0079) as independently predictive of lymphatic metastases. Our study confirms that grade, pathologic stage, clinical stage, and lymphovascular invasion are predictors of regional metastasis. These correlations suggest that studying the molecular mechanisms of differentiation, interstitial pressure at the primary tumor site, and peritumoral lymphangiogenesis may provide insight into lymphatic metastasis. Additionally, we identified family history of cancer as a new predictor of lymphatic metastasis. Thus, genetic analysis of families with cancer, irrespective of type, may identify genes important for regional metastasis.

Oral cavity squamous cell carcinoma and the clinically n0 neck: the past, present, and future of sentinel lymph node biopsy.

Oral cavity squamous cell carcinoma (OCSCC) has a yearly incidence of 274,000 patients. Twenty percent to 30% of patients will harbor occult regional metastases, an important feature that correlates with worse outcomes. Supraomohyoid neck dissection (SND) is the gold standard treatment, but because of recent successes of sentinel lymph node (SLN) biopsy in the management of breast cancer and melanoma, many have begun evaluating its use in head and neck mucosal cancers. SLN biopsy offers patients decreased morbidity compared with SND, and has shown reproducibly low false-negative rates, high-negative predictive values, and high sensitivities. Limitations with floor-of-mouth primaries and delayed secondary SNDs have been described, but a new agent designed to address these shortcomings, Lymphoseek (Neoprobe Corp.; Dublin, OH), is currently under investigation. This article reviews the current literature on SLN biopsy and introduces a phase 3 study evaluating the efficacy of Lymphoseek in SLN biopsy of OCSCCs.

3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics.

BACKGROUND AND PURPOSE: During angiogenesis, quiescent endothelial cells (ECs) are activated by various stimuli to form new blood vessels from pre-existing ones in physiological and pathological conditions. Many research groups have shown that hydrogen sulfide (H2 S), the newest member of the gasotransmitter family, acts as a proangiogenic factor. To date, very little is known about the regulatory role of 3-mercaptopyruvate sulfurtransferase (3-MST), an important H2 S-producing enzyme in ECs. The aim of our study was to explore the potential role of 3-MST in human EC bioenergetics, metabolism, and angiogenesis. EXPERIMENTAL APPROACH: To assess in vitro angiogenic responses, we used EA.hy926 human vascular ECs subjected to shRNA-mediated 3-MST attenuation and pharmacological inhibition of proliferation, migration, and tube-like network formation. To evaluate bioenergetic parameters, cell respiration, glycolysis, glucose uptake, and mitochondrial/glycolytic ATP production were measured. Finally, global metabolomic profiling was performed to determine the level of 669 metabolic compounds. KEY RESULTS: 3-MST-attenuated ECs subjected to shRNA or pharmacological inhibition of 3-MST significantly reduced EC proliferation, migration, and tube-like network formation. 3-MST silencing also suppressed VEGF-induced EC migration. From bioenergetic and metabolic standpoints, 3-MST attenuation decreased mitochondrial respiration and mitochondrial ATP production, increased glucose uptake, and perturbed the entire EC metabolome. CONCLUSION AND IMPLICATIONS: 3-MST regulates bioenergetics and morphological angiogenic functions in human ECs. The data presented in the current report support the view that 3-MST pathway may be a potential candidate for therapeutic modulation of angiogenesis. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.

Dynamic biochemical tissue analysis detects functional selectin ligands on human cancer tissues.

Cell adhesion mediated by selectins (expressed by activated endothelium, activated platelets, and leukocytes) binding to their resepective selectin ligands (expressed by cancer cells) may be involved in metastasis. Therefore, methods of characterizing selectin ligands expressed on human tissue may serve as valuable assays. Presented herein is an innovative method for detecting functional selectin ligands expressed on human tissue that uses a dynamic approach, which allows for control over the force applied to the bonds between the probe and target molecules. This new method of tissue interrogation, known as dynamic biochemical tissue analysis (DBTA), involves the perfusion of molecular probe-coated microspheres over tissues. DBTA using selectin-coated probes is able to detect functional selectin ligands expressed on tissue from multiple cancer types at both primary and metastatic sites.

Epidemiology and trends of anaphylaxis in the United States, 2004-2016.

BACKGROUND: No national study has examined the epidemiology of anaphylaxis after introduction of the codes of the International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, Clinical Modification (ICD-10 CM). Our objective was to examine the trends in incidence and hospitalization rates in the United States utilizing ICD-9 and ICD-10 CM codes. METHODS: We used the Clinformatics database from 2004 to 2016. Our outcome measures included incidence of anaphylaxis and hospitalization trends. Multivariable logistic regression was used to assess the predictors of anaphylaxis and hospitalization. RESULTS: There were a total of 462,906 anaphylaxis cases. The incidence increased from 153 in 2004 to 218 in 2016 (per 100,000). Women were 1.19 (95% confidence interval, 1.18-1.20) times more likely to present with anaphylaxis. Medication-induced anaphylaxis increased 15-fold. CONCLUSION: This is the first population-based study that included ICD-10 CM codes to describe the epidemiology of anaphylaxis in the United States. ICD-10 codes improved the accuracy of medication-induced anaphylaxis, the most likely etiology to result in hospitalization.

Factors influencing recurrent emergency department visits for epistaxis in the elderly.

OBJECTIVE: Our objective is to determine the risk factors associated with recurrent epistaxis requiring emergency department (ED) visits in the elderly. METHODS: We used a 5% national sample of Medicare data from January 2012 through December 2013. Our cohort included patients with a new diagnosis of epistaxis in the ED, defined as no epistaxis in the prior 12 months. We assessed the rates of ED visits for recurrent epistaxis in the 12 months following the incident visit. Our variables included demographics, geographic location, procedures performed during the incident visit and comorbidities. RESULTS: Out of the 4120 patients with incident epistaxis, 775 were readmitted with recurrent epistaxis within 12 months. 60% presented in the first 30days and 75% within 90 days. There was a significant increase in ED visits for patients over 75 years of age and in men compared to women. Recurrent ED visits for epistaxis was higher in patients with congestive heart failure, diabetes mellitus, and obstructive sleep apnea compared to those without these comorbidities. CONCLUSION: Additional ED visits for epistaxis are more common in the elderly and in males. Congestive heart failure, diabetes mellitus and obstructive sleep apnea were found to be independent risk factors.

Outcomes and Complications of Balloon and Conventional Functional Endoscopic Sinus Surgery.

Background Since the Food and Drug Administration approval of balloon sinuplasty (BSP) in 2005, no nationally representative population-based studies have examined the outcomes and adverse events of BSP. Objective To assess the rates of complications and revision surgery in patients who received BSP, functional endoscopic sinus surgery (FESS), or a hybrid procedure. Methods Using one of the nation's largest commercial insurance databases, we conducted a retrospective cohort study of pediatric and adult patients diagnosed with chronic rhinosinusitis between 2011 and 2014 who underwent BSP, conventional FESS, or a hybrid procedure. The primary outcomes were surgical complication and revision rates within 6 months of initial surgery. Results A total of 16,040 patients who underwent sinus surgery were included. Overall, 2,851 patients underwent BSP, 11,955 underwent conventional FESS, and 1 234 underwent a hybrid procedure. BSP surgery was more likely to have been performed in an office setting (86.53%) compared to FESS (0.74%). The complication rate was 5.26% for BSP and 7.35% for conventional FESS. Revision rates were 7.89% for BSP, 16.85% for FESS, and 15.15% for a hybrid procedure. Conclusion Despite the low overall risk, major complications occur with BSP including cerebrospinal fluid leak, pneumocephalus, orbital complications, and severe bleeding. Otolaryngologists should discuss these risks with their patients. Prospective studies are still needed to compare outcomes of BSP with those of FESS.

Differences in the viral genome between HPV-positive cervical and oropharyngeal cancer.

Human papillomavirus (HPV)-driven oropharyngeal cancer incidence in the United States has steadily increased in the past decades and has now become the most frequently diagnosed HPV-associated cancer type, surpassing cervical cancer. Variations in the HPV genome correlate with tumorigenic risk, and the distribution of genetic variants is extensively studied in cervical cancer, but very little is known about new mutations or the distribution of HPV types and variants in oropharyngeal cancer. Here we present an archival tissue cohort study that compares genomic characteristics of HPV associated with cervical versus oropharyngeal tumors using DNA sequence analysis. We found HPV16 to be more prevalent in oropharyngeal samples than in cervical samples (91.2% versus 52.9%), while HPV18 (1.5% versus 18.2%) and HPV45 (0.7% versus 9.9%) were much less prevalent. Differences between cervix and oropharynx in HPV16 variants distribution were more subtle, but the combined European + Asian (EUR+AS) variant group was more prevalent (90.2% versus 71.4%), while the American Asian 1 + American Asian 2 (AA1+AA2) variant group was much less prevalent (4.4% versus 22.5%) in oropharyngeal cancers. HPV prevalence in oropharyngeal cancers showed an increasing trend from 60% in 2003 to 80% in 2016. We also identified over nine times more nonsynonymous mutations in the HPV E6 gene amplified from oropharyngeal samples, but for E7 the difference in mutation rates between the two anatomical locations was not significant. Overall, we showed that HPV genome in oropharyngeal cancer presents important differences when compared to cervical cancer and this may explain the distinct pathomechanisms and susceptibility to treatment of HPV-associated oropharyngeal cancer.

Pectoralis major flap in composite lateral skull base defect reconstruction.

OBJECTIVE: To report our experience with the pectoralis major myocutaneous flap (PMF) for the reconstruction of composite lateral temporal bone defects extending beyond the temporal line. DESIGN: Retrospective review and illustration of specific technical modifications. SETTING: Academic tertiary care center. PATIENTS: Eight patients with composite lateral skull base defects that were reconstructed with the PMF between February 2001 and February 2006. INTERVENTION: Reconstruction with the modified pedicled PMF. MAIN OUTCOME MEASURES: Reconstruction outcomes and complications. RESULTS: Eight patients (median age, 80 years) underwent total or near-total auriculectomy, wide skin excision, and lateral temporal bone resection as part of the surgical ablation, thus requiring obliteration of the middle ear cavity as well as extensive replacement of skin cover. All patients received radiation therapy. The median postsurgical follow-up was 9 months. Complete healing of the reconstructed surgical defect with no flap loss was achieved in all cases. CONCLUSION: With specific technical modifications, the PMF can be reliably used for the reconstruction of composite lateral skull base defects extending up to and beyond the temporal line, making this flap an important alternative to free flap reconstruction in selected cases.

Prevalence of oral human papillomavirus by vaccination status among young adults (18-30years old).

BACKGROUND: Although there is evidence that human papillomavirus (HPV) vaccination may protect against oral HPV infection, no current research has demonstrated this in the general population. METHODS: We used repeated cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2014. Participants 18-30years who indicated whether they had received the HPV vaccine and provided an adequate oral sample were included (N=3040). Oral HPV types were grouped by vaccine-type (types 6, 11, 16, 18) and by risk (high or low risk). Chi-square analyses compared oral HPV prevalence by vaccination status. RESULTS: Vaccinated adults had a lower prevalence of vaccine-type oral HPV (types 6, 11, 16, 18) compared to unvaccinated adults. Prevalence of non-vaccine high-risk oral HPV was similar between HPV vaccinated and unvaccinated participants. CONCLUSIONS: HPV vaccination appears to provide protection against vaccine-type oral HPV infection among males and females in the general population.

Racial and Ethnic Disparities in Nasopharyngeal Cancer Survival in the United States.

Objective To determine whether patient race and ethnicity affect nasopharyngeal cancer survival. Study Design Retrospective database analysis. Setting National Cancer Institute's SEER database (Surveillance, Epidemiology, and End Results), 1988-2010. Subjects and Methods Nasopharyngeal carcinoma cases were extracted according to site codes and histology recode-broad groupings. The cohort of 5427 patients was used to calculate disease-specific survival in regard to race and ethnicity. Extracted data were further analyzed through direct comparisons and multivariable Cox regression models controlling for patient, tumor, and treatment characteristics. Results Unadjusted survival curves for all nasopharyngeal carcinomas considered together showed a statistically significant better disease-specific survival for the African American race ( P = .02) and Asian ethnicity ( P = .01) relative to Caucasian patients. The survival advantage for both these groups was eliminated after controlling for the age and sex of the patients. Conclusion African American and Asian patients with nasopharyngeal cancer have better disease-specific survival as compared with Caucasian patients, while Hispanic ethnicity has no effect relative to Caucasians. This disparity is accounted for by diagnosis at an older age in Caucasian patients but remains poorly explained in regard to Hispanic patients.

Demographic, Seasonal, and Geographic Differences in Emergency Department Visits for Epistaxis.

Objective To determine the demographics and seasonal and geographic variation of epistaxis in the United States. Study Design Retrospective cohort analysis based on data from Medicare claims. Setting Emergency department visits. Subjects and Methods We used a 5% sample of Medicare data from January 2012 to December 2012. Our cohort included patients with an incident diagnosis of epistaxis during a visit to the emergency department, excluding those with a diagnosis in the prior 12 months. Demographics included age, sex, race, and ethnicity. We compared the rate of emergency department visits for epistaxis by geographic division and individual states. Results In the 5% sample of Medicare data, 4120 emergency department visits for incident epistaxis were identified in 2012. Our results showed an increase in the emergency department visits for epistaxis with age. Compared with patients <65 years old, patients who were 66 to 76, 76 to 85, and >85 years old were 1.36 (95% confidence interval [95% CI], 1.23-1.50), 2.37 (95% CI, 2.14-2.62), and 3.24 (95% CI, 2.91-3.62) more likely to present with epistaxis, respectively. Men were 1.24 (95% CI, 1.17-1.32) times more likely to present with epistaxis than women. Blacks were 1.23 (95% CI, 1.10-1.36) times more likely to present with epistaxis when compared with non-Hispanic whites. Epistaxis emergency department visits were 40% lower in the summer months versus winter. The seasonal variation was more pronounced in the northern versus southern United States. Conclusion Emergency department visits for epistaxis increase with age and appear to be seasonal, with a more pronounced variation in the northern versus southern United States.

Use of balloon sinuplasty in patients with chronic rhinosinusitis in the United States.

BACKGROUND: Over the past decade, the use of balloon sinuplasty has increased widely in the United States. Since its introduction, no nationally representative, population-based study has examined its use among chronic rhinosinusitis (CRS) patients. METHODS: We conducted a retrospective cohort study of patients diagnosed with CRS between 2011 and 2014, and compared the prevalence of conventional functional endoscopic sinus surgery (FESS), balloon sinuplasty, and hybrid sinus surgery according to surgical site and calendar year. RESULTS: Out of 11 million to 11.4 million enrollees per year, a total of 661,738 patients with the diagnosis of CRS were included in the analyses. There was an increase in the use of balloon sinuplasty as a stand-alone procedure from 5% in 2011 to 22.5% in 2014. Conventional FESS continued to be the most commonly performed sinus procedure over the study period. Multinomial logistic regression analyses showed a linear increase in balloon sinuplasty and hybrid procedures from 2011 to 2014. Compared to patients over 60 years, patients younger than 30 years had lower odds of having a balloon sinuplasty as a stand-alone procedure compared to FESS. Compared to patients in the West, patients in the South, Northeast, and Midwest were significantly more likely to have balloon sinuplasty as a stand-alone procedure. Assessment of the sinus surgery site showed that patients with additional frontal sinus surgery were more likely to have a balloon-only procedure (odds ratio [OR], 4.67; 95% confidence interval [CI], 4.21 to 5.17) or a hybrid procedure (OR, 8.69; 95% CI, 7.48 to 10.11) than conventional FESS when compared to patients with conventional maxillary surgery only. CONCLUSION: From 2011 to 2014 there was an increase in the use of balloon sinuplasty and a modest decrease in the use of conventional FESS in the United States. Patients with frontal or sphenoid sinus surgical sites were more likely to have a balloon or hybrid procedure.