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1.
Cancer Cell ; 2024 May 23.
Article En | MEDLINE | ID: mdl-38788720

The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse model of high-grade metastatic ONB exhibiting a NEUROD1+ immature neuronal phenotype. We demonstrate that globose basal cells (GBCs) are a permissive cell of origin for ONB and that ONBs exhibit cell fate heterogeneity that mimics normal GBC developmental trajectories. ASCL1 loss in RPM ONB leads to emergence of non-neuronal histopathologies, including a POU2F3+ microvillar-like state. Similar to small-cell lung cancer (SCLC), mouse and human ONBs exhibit mutually exclusive NEUROD1 and POU2F3-like states, an immune-cold tumor microenvironment, intratumoral cell fate heterogeneity comprising neuronal and non-neuronal lineages, and cell fate plasticity-evidenced by barcode-based lineage tracing and single-cell transcriptomics. Collectively, our findings highlight conserved similarities between ONB and neuroendocrine tumors with significant implications for ONB classification and treatment.

2.
Int Forum Allergy Rhinol ; 14(5): 881-886, 2024 May.
Article En | MEDLINE | ID: mdl-38526915

Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory bulbs and tracts. This results in postoperative anosmia that may significantly impact a patient's quality of life without definitive added benefit in survival. The prevalence of occult intracranial disease is low, especially for Hyams grade I and II tumors. A unilateral approach sparing the contralateral cribriform plate and olfactory system can be considered for select cases of early stage, low-grade tumors when the disease does not cross midline to involve the contralateral olfactory cleft or septal mucosa and when midline dural margins can be cleared with frozen pathology. Approximately half of patients who undergo unilateral resection may have residual olfaction even with adjuvant unilateral radiation. Early data suggest favorable disease-free survival and overall survival for patients who underwent the unilateral approach; however, larger sample studies are needed to confirm comparability to bilateral resections regarding oncologic outcomes.


Esthesioneuroblastoma, Olfactory , Nose Neoplasms , Humans , Esthesioneuroblastoma, Olfactory/surgery , Esthesioneuroblastoma, Olfactory/pathology , Nose Neoplasms/surgery , Nose Neoplasms/pathology , Nasal Cavity/surgery , Nasal Cavity/pathology , Smell , Treatment Outcome
3.
Otolaryngol Head Neck Surg ; 170(5): 1314-1318, 2024 May.
Article En | MEDLINE | ID: mdl-38219742

OBJECTIVES: Identify demographic and clinical characteristics that may help differentiate non-rhinogenic facial pain or pressure (NRFP) from sinusitis. STUDY DESIGN: Retrospective single-institution study. SETTING: Tertiary Care Center Rhinology Clinic. METHODS: All patients presenting with a complaint of facial pain or pressure over a 3-year period were included. Patients were categorized into either NRFP or sinusitis groups based on computed tomography imaging and nasal endoscopy. Data pertaining to demographics, history, and SNOT-22 questionnaire domains were compared via univariate analysis as well as logistic regression with backwards variable selection. RESULTS: A total of 296 patients met inclusion criteria, of which 128 had NRFP and 168 had sinusitis. A significantly greater percentage of patients in the NRFP group were women of childbearing age (40.6% vs 28.0%, P = .02). Backwards variable selection resulted in a model with four variables predicting a diagnosis of NRFP-female sex (odds ratio [OR] = 2.998, P < .0001), no history of prior sinonasal surgery (OR = 0.340 for history vs no history, P < .01), low nasal domain score (OR = 0.551, P < .0001), and high ear/facial domain score (OR = 1.453, P < .01). CONCLUSION: Accurately identifying patients with NRFP at initial presentation based on history would help direct patients to the appropriate care pathway and prevent ineffective treatments such as antibiotics and sinus procedures. Our findings suggest that the suspicion for NRFP should be higher in women of child-bearing age as well as patients with greater ear/facial symptoms or lesser nasal symptoms.


Facial Pain , Sinusitis , Humans , Female , Male , Retrospective Studies , Facial Pain/etiology , Facial Pain/diagnosis , Adult , Sinusitis/complications , Sinusitis/diagnosis , Middle Aged , Pressure , Diagnosis, Differential , Tomography, X-Ray Computed , Otolaryngology , Surveys and Questionnaires , Endoscopy
4.
Ann Otol Rhinol Laryngol ; 133(1): 43-49, 2024 Jan.
Article En | MEDLINE | ID: mdl-37334915

BACKGROUND: With a rising incidence of cerebrospinal fluid (CSF) leaks, endoscopic endonasal CSF leak repair is increasingly performed. Current approaches utilize a variety of materials including free mucosal grafts and vascularized flaps, but post-op leaks continue to be reported. Steroid-eluting bioabsorbable stents (SES) are used during functional endoscopic sinus surgery for chronic rhinosinusitis to reduce inflammation and scarring while maintaining patency of sinus ostia. OBJECTIVE: The aim of this study is to assess the feasibility of SES as a graft/flap bolster for endoscopic endonasal CSF leak repair. METHODS: This is a retrospective review of patients undergoing endoscopic endonasal CSF leak repair with SES placed as part of the bolster technique at a tertiary care center between January 2019 and May 2022. Age, sex, BMI, comorbid idiopathic intracranial hypertension, pathology, location of CSF leak, intraoperative CSF leak flow, reconstruction type, and presence of post-op CSF leak were recorded. RESULTS: Twelve patients (mean age 52, median BMI 30.9, 58% female) had SES placement as part of the bolster technique. The most common pathology was meningoencephalocele (75%). Reconstruction was performed with either a free mucosal graft (6), or a flap (6). No post-op CSF leaks occurred at a reconstruction site with a stent, and no known complications were reported. All sinusotomies were patent at the last follow-up visit. CONCLUSIONS: SES placement as an adjunct to graft and/or flap bolster appears to be safe and feasible during anterior skull base reconstruction and CSF leak repair providing longer term structural support and preserving sinus drainage patency.


Drug-Eluting Stents , Plastic Surgery Procedures , Humans , Female , Middle Aged , Male , Plastic Surgery Procedures/adverse effects , Skull Base/surgery , Feasibility Studies , Surgical Flaps , Cerebrospinal Fluid Leak/epidemiology , Cerebrospinal Fluid Leak/etiology , Cerebrospinal Fluid Leak/surgery , Endoscopy/methods , Retrospective Studies
5.
Cancer Res Commun ; 3(6): 980-990, 2023 06.
Article En | MEDLINE | ID: mdl-37377616

Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis. We analyzed a total of 19 olfactory neuroblastoma samples with available bulk RNA-sequencing and survival data, along with 10 samples from normal olfactory epithelium. A bulk RNA-sequencing deconvolution model identified a significant increase in globose basal cell (GBC) and CD8 T-cell identities in high-grade tumors (GBC from ∼0% to 8%, CD8 T cell from 0.7% to 2.2%), and significant decreases in mature neuronal, Bowman's gland, and olfactory ensheathing programs, in high-grade tumors (mature neuronal from 3.7% to ∼0%, Bowman's gland from 18.6% to 10.5%, olfactory ensheathing from 3.4% to 1.1%). Trajectory analysis identified potential regulatory pathways in proliferative olfactory neuroblastoma cells, including PRC2, which was validated by immunofluorescence staining. Survival analysis guided by gene expression in bulk RNA-sequencing data identified favorable prognostic markers such as SOX9, S100B, and PLP1 expression. Significance: Our analyses provide a basis for additional research on olfactory neuroblastoma management, as well as identification of potential new prognostic markers.


Esthesioneuroblastoma, Olfactory , Nose Neoplasms , Mice , Humans , Animals , Esthesioneuroblastoma, Olfactory/genetics , Olfactory Mucosa/metabolism , Olfactory Pathways/pathology , Nose Neoplasms/genetics , RNA/metabolism
6.
Facial Plast Surg Aesthet Med ; 25(6): 457-465, 2023.
Article En | MEDLINE | ID: mdl-37130297

Background: Unilateral cleft lip nasal deformity (uCLND) is associated with olfactory dysfunction, but the underlying etiology remains poorly understood. Objective: To investigate the etiology of uCLND-associated olfactory dysfunction using clinical, computational, and histologic assessments. Methods: Inclusion criteria: uCLND patients >16 years undergoing septorhinoplasty. Exclusion criteria: prior septoplasty or rhinoplasty, pregnancy, sinusitis. Measured outcomes: patient-reported scores, rhinomanometry, smell identification and threshold tests, computational fluid dynamics (CFD) airflow simulations, and histologic analysis of olfactory epithelium. Results: Five uCLND subjects were included: 18-23 years, three male and two female, four left-sided cleft and one right-sided cleft. All subjects reported moderate to severe nasal obstruction. Smell identification and threshold tests showed varying degrees of hyposmia. Nasal resistance was higher on the cleft side versus noncleft side measured by rhinomanometry (median 3.85 Pa-s/mL, interquartile range [IQR] = 21.96, versus 0.90 Pa-s/mL, IQR = 5.17) and CFD (median 1.04 Pa-s/mL, IQR = 0.94 vs. 0.11 Pa-s/mL, IQR = 0.12). Unilateral olfaction varied widely and was dependent on unilateral percentage olfactory airflow. Biopsies revealed intact olfactory neuroepithelium. Conclusions: uCLND-associated olfactory dysfunction appears to be primarily conductive in etiology and highly susceptible to variations in nasal anatomy. Clinical Trial Registration number: NCT04150783.


Cleft Lip , Nasal Obstruction , Olfaction Disorders , Humans , Male , Female , Smell , Cleft Lip/complications , Cleft Lip/surgery , Nose/abnormalities , Nasal Obstruction/diagnosis , Nasal Obstruction/etiology , Nasal Obstruction/surgery , Olfaction Disorders/complications
7.
Am J Rhinol Allergy ; 37(1): 35-42, 2023 Jan.
Article En | MEDLINE | ID: mdl-36189818

BACKGROUND: Squamous cell carcinoma of the nasal cavity (NCSCC) is a rare, challenging malignancy. Surgical resection of this tumor can cause significant facial deformity, and indications for adjuvant or organ preservation therapies are not well-described. OBJECTIVE: To examine the impact of treatment regimen on survival outcomes in NCSCC and to compare surgical to non-surgical based therapies. METHODS: The National Cancer Database was queried for NCSCC from 2004 to 2014. Patient demographics, tumor characteristics, and treatment regimen were compared for the entire cohort. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen and surgical margins on overall survival (OS) for early and late-stage disease. RESULTS: A total of 1883 NCSCC patients were identified. The OS for the cohort was 83 months, and median age at diagnosis was 65 years. NCSCC patients who underwent surgery followed by adjuvant radiation therapy (RT) had a better OS compared to definitive RT (HR: 0.58, P < .001). In early stage NCSCC (T1/T2, N0), there was no significant difference in OS between patients treated with surgery only or surgery with adjuvant RT compared to definitive RT. In advanced stage NCSCC, surgery with adjuvant RT had a better OS compared to definitive chemoradiation. Having positive margins was shown to predict a worse OS when compared to negative margins in surgical patients despite adjuvant RT or chemoradiation. CONCLUSIONS: NCSCC appears to be best treated with surgery followed by adjuvant RT in advanced-stage disease whereas in early-stage disease, surgery does not improve OS compared to definitive RT.


Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Aged , Squamous Cell Carcinoma of Head and Neck/pathology , Nasal Cavity/pathology , Organ Preservation , Radiotherapy, Adjuvant , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Treatment Outcome , Margins of Excision , Retrospective Studies , Neoplasm Staging
8.
Sci Transl Med ; 14(676): eadd0484, 2022 12 21.
Article En | MEDLINE | ID: mdl-36542694

SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. Although animal and human autopsy studies have suggested mechanisms driving acute anosmia, it remains unclear how SARS-CoV-2 causes persistent smell loss in a subset of patients. To address this question, we analyzed olfactory epithelial samples collected from 24 biopsies, including from nine patients with objectively quantified long-term smell loss after COVID-19. This biopsy-based approach revealed a diffuse infiltrate of T cells expressing interferon-γ and a shift in myeloid cell population composition, including enrichment of CD207+ dendritic cells and depletion of anti-inflammatory M2 macrophages. Despite the absence of detectable SARS-CoV-2 RNA or protein, gene expression in the barrier supporting cells of the olfactory epithelium, termed sustentacular cells, appeared to reflect a response to ongoing inflammatory signaling, which was accompanied by a reduction in the number of olfactory sensory neurons relative to olfactory epithelial sustentacular cells. These findings indicate that T cell-mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post-COVID-19 smell loss.


COVID-19 , Olfaction Disorders , Animals , Humans , COVID-19/complications , Anosmia , SARS-CoV-2 , RNA, Viral/metabolism , Olfaction Disorders/epidemiology , Olfaction Disorders/etiology , Olfactory Mucosa , Gene Expression
9.
Stem Cell Reports ; 17(9): 1959-1975, 2022 09 13.
Article En | MEDLINE | ID: mdl-35985334

In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids. The small size and large surface-to-volume ratio of MOSs enable various applications including quantitative assessment of nutrient dependence, pathogen-host interaction for anti-viral drug screening, and a rapid potency assay for chimeric antigen receptor (CAR)-T therapy. An automated MOS imaging pipeline combined with machine learning overcomes plating variation, distinguishes tumorspheres from stroma, differentiates cytostatic versus cytotoxic drug effects, and captures resistant clones and heterogeneity in drug response. This pipeline is capable of robust assessments of drug response at individual-tumorsphere resolution and provides a rapid and high-throughput therapeutic profiling platform for precision medicine.


Antineoplastic Agents , Organoids , Antineoplastic Agents/pharmacology , Drug Evaluation, Preclinical/methods , Humans , Microfluidics , Precision Medicine
10.
bioRxiv ; 2022 Apr 18.
Article En | MEDLINE | ID: mdl-35478953

Most human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% of COVID patients report lasting olfactory dysfunction. While animal studies and human autopsy tissues have suggested mechanisms underlying acute loss of smell, the pathophysiology that underlies persistent smell loss remains unclear. Here we combine objective measurements of smell loss in patients suffering from post-acute sequelae of SARS-CoV-2 infection (PASC) with single cell sequencing and histology of the olfactory epithelium (OE). This approach reveals that the OE of patients with persistent smell loss harbors a diffuse infiltrate of T cells expressing interferon-gamma; gene expression in sustentacular cells appears to reflect a response to inflammatory signaling, which is accompanied by a reduction in the number of olfactory sensory neurons relative to support cells. These data identify a persistent epithelial inflammatory process associated with PASC, and suggests mechanisms through which this T cell-mediated inflammation alters the sense of smell.

11.
J Clin Invest ; 132(4)2022 02 15.
Article En | MEDLINE | ID: mdl-34990409

BACKGROUNDPresbyosmia, or aging-related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) is the peripheral organ for olfaction and is subject to acquired damage, suggesting a likely site of pathology in aging. Adult stem cells reconstitute the neuroepithelium in response to cell loss under normal conditions. In aged OE, patches of respiratory-like metaplasia have been observed histologically, consistent with a failure in normal neuroepithelial homeostasis.MethodsAccordingly, we have focused on identifying cellular and molecular changes in presbyosmic OE. The study combined psychophysical testing with olfactory mucosa biopsy analysis, single-cell RNA-Sequencing (scRNA-Seq), and culture studies.ResultsWe identified evidence for inflammation-associated changes in the OE stem cells of presbyosmic patients. The presbyosmic basal stem cells exhibited increased expression of genes involved in response to cytokines or stress or the regulation of proliferation and differentiation. Using a culture model, we found that cytokine exposure drove increased TP63, a transcription factor acting to prevent OE stem cell differentiation.ConclusionsOur data suggest aging-related inflammatory changes in OE stem cells may contribute to presbyosmia via the disruption of normal epithelial homeostasis. OE stem cells may represent a therapeutic target for restoration of olfaction.FundingNIH grants DC018371, NS121067, DC016224; Office of Physician-Scientist Development, Burroughs-Wellcome Fund Research Fellowship for Medical Students Award, Duke University School of Medicine.


Aging/metabolism , Cell Differentiation , Gene Expression Regulation , Olfaction Disorders/metabolism , Olfactory Mucosa/metabolism , Stem Cells/metabolism , Aged , Aged, 80 and over , Epithelial Cells/metabolism , Female , Humans , Male , Middle Aged , Prospective Studies
12.
Am J Rhinol Allergy ; 36(3): 307-312, 2022 May.
Article En | MEDLINE | ID: mdl-34806427

BACKGROUND: Endoscopic sinus surgery is a well-established treatment for chronic rhinosinusitis in patients with cystic fibrosis, though its benefits seem to be limited to improving sinonasal symptoms rather than affecting lung function. OBJECTIVE: This study aims to identify clinical and demographic factors that may influence sinonasal and pulmonary outcomes after surgery. METHODS: This is a six-year retrospective analysis of adult cystic fibrosis patients who underwent endoscopic sinus surgery at a tertiary care center. 22-Item Sino-Nasal Outcomes Test scores and mean forced expiratory volume data at baseline and three to six months after surgery were analyzed using t-test and stepwise regression with the following covariates: age, gender, lung transplant, revision surgery, and pseudomonas on sinus culture. RESULTS: 119 surgeries were performed on 88 patients, with 69% on patients with transplant. The overall mean (Standard Deviation) improvement in 22-Item Sino-Nasal Outcomes Test score was 9.42 (18.15) for the entire cohort (P < .001). Pseudomonas on culture was associated with less improvement in sinonasal scores (P = .002). There was no significant change in forced expiratory volume after surgery (P = .94). Revision surgery (P = .004) and older age (P = .007) were associated with less favorable change of pulmonary function on stepwise regression (P = .002). There was no correlation between change in sinonasal scores and pulmonary function. CONCLUSION: Although surgery was associated with a clinically and statistically significant improvement in sinonasal scores in cystic fibrosis patients, patients with pseudomonas may experience less benefit. Revision surgery and older age may be associated with less favorable pulmonary outcomes. Awareness of such variables may help when deciding which cystic fibrosis patients should undergo surgery.


Cystic Fibrosis , Rhinitis , Sinusitis , Adult , Chronic Disease , Cystic Fibrosis/complications , Endoscopy , Humans , Lung , Retrospective Studies , Rhinitis/diagnosis , Sinusitis/diagnosis
13.
Healthcare (Basel) ; 9(7)2021 Jun 25.
Article En | MEDLINE | ID: mdl-34201975

OBJECTIVES: Chronic rhinosinusitis (CRS) is a common and costly health problem in the United States. While often associated with younger adults, CRS can affect the elderly. As the aging population increases in the United States, the cost burden of CRS in older adults is important to assess. The objective of this study is to characterize healthcare resource utilization (HCRU) and healthcare expenditure (HCE) for CRS in this population. METHODS: Patients meeting criteria for CRS with three years of continuous data were identified on IBM® Marketscan Research Databases over a five-year period (2013-2017). Medication utilization, outpatient visits, surgery, and expenditures related to CRS were assessed for older adults (>65) and compared with other age groups. As a secondary analysis, multivariable generalized linear models were utilized to compare HCE while adjusting for baseline medication utilization. RESULTS: A total of 238,825 patients met the inclusion criteria, of which 20,927 were older adults. Older adults had the highest overall prevalence of nasal polyps (10%) and asthma (16%) among adult groups. Surgery rate was lower than other adult groups, but medication utilization was the highest. Mean overall HCE at two years was highest in older adults (USD 2545 vs. 2298 in young adults). However, HCE was highest for the young adult group after adjusting for baseline medication usage. CONCLUSION: Older adults had a higher rate of CRS-related co-morbidities as well as the highest CRS-related medication utilization and unadjusted two-year HCE. Although the reasons for this are unclear, possibilities include greater disease severity and preference for medical versus surgical management. HCE for CRS is expected to increase as the aging population grows.

15.
J Healthc Leadersh ; 13: 129-136, 2021.
Article En | MEDLINE | ID: mdl-34007234

PURPOSE: To analyze self and 360-evaluation scores of the professionalism intelligence model domains within an academic Otolaryngology-Head and Neck Surgery Department. METHODS: A leadership course was introduced within the Department of Head and Neck Surgery & Communication Sciences at Duke University Medical Center. A 360 evaluation assessing domains of the professional intelligence model was recorded for all participants. Participant demographics included gender (male vs female), generation group (generation Y vs older generations) and physician status of participants (physician vs non-physician). Differences in mean self-scores were modeled using linear regression. When analyzing the evaluator scores, gaps were defined as self-score minus evaluator-score for each member of a participant's evaluator groupings (supervisor, peer, and direct report). Two types of linear mixed models were fit with a random intercept to account for the correlated gaps in the same participant. RESULTS: Scores of 50 participants and 394 evaluators were analyzed. The average age was 40.6 (standard deviation 9.3) years, and 50% (N=25) of participants were females. Physicians accounted for 36% (N=18) of the cohort, and 61% (N=11) of physicians were residents. Physicians scored themselves lower than non-physicians when assessing leadership intelligence, interpersonal relations, empathy, and focused thinking. On average, participants under-rated themselves compared to their evaluators with direct reports giving higher scores than managers and peers. When compared with generation Y, older generations tended to rate themselves lower than their peers and managers in cognitive intelligence. No significant association was observed between gender and any scores. CONCLUSION: Participants rate themselves lower on average than their evaluators. This work is important in understanding how perceived leadership qualities are assessed and developed within an academic surgical department. Finally, the results presented could serve as a model to address the gap between self- and other-perceptions of defined leadership virtues in future leadership development activities.

16.
Am J Otolaryngol ; 42(2): 102851, 2021.
Article En | MEDLINE | ID: mdl-33385873

BACKGROUND: Sinonasal carcinoma with neuroendocrine differentiation (SCND) is a rare group of tumors with poor prognosis. Treatment and sequence of therapies are still unclear. The goal of this study is to analyze treatment outcomes in SCND using a national database. METHODS: The National Cancer Database was queried for SCND from 2004 to 2014. Patient demographics, tumor characteristics and treatment paradigms were tabulated. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on overall survival (OS). RESULTS: A total of 415 patients were identified. Most patients were male (61.2%), with a median age of 58 years and the most common primary site was the nasal cavity (52.5%). T4 tumors were observed in 67.7% of cases. Unimodality (41.9%) and bimodality (43.9%) therapies were the most common treatment modalities. Radiation therapy was the only treatment administered in 30% of the patients, while 27.2% received definitive chemoradiation (CRT) and 11.6% had surgery with adjuvant CRT. In our Cox-PH model, age (HR = 1.04, p < 0.001), T4 (HR = 2.6, p = 0.004) and N2/N3 (HR = 2.18, p = 0.001) were associated with worse survival. Trimodality (HR = 0.49, p = 0.005) and bimodality (HR = 0.65, p = 0.009) therapies had a better OS compared to unimodality. Patients treated with definitive CRT or surgery with adjuvant CRT had a significant increase in OS (p = 0.01 and 0.002 respectively). CONCLUSION: SCND appears to be best treated using a multimodality approach with definitive CRT or surgery followed by CRT. Neoadjuvant chemotherapy could be helpful in selecting the best treatment strategy.


Carcinoma, Neuroendocrine/therapy , Nasal Cavity , Nose Neoplasms/therapy , Paranasal Sinuses , Age Factors , Carcinoma, Neuroendocrine/mortality , Carcinoma, Neuroendocrine/pathology , Chemoradiotherapy, Adjuvant , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Nose Neoplasms/mortality , Nose Neoplasms/pathology , Otorhinolaryngologic Surgical Procedures/methods , Radiotherapy , Survival Rate , Treatment Outcome
17.
Ann Otol Rhinol Laryngol ; 130(4): 350-355, 2021 Apr.
Article En | MEDLINE | ID: mdl-32819161

BACKGROUND: Exposure to cigarette smoke has been associated with a higher incidence of postoperative complications across a variety of surgical specialties. However, it is unclear if smoking increases this risk after endoscopic sinus surgery (ESS). Because complication rates after ESS are relatively low, a large national database allows for a statistically meaningful study of this topic. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) dataset from 2005 to 2016 was analyzed. Patients who underwent ESS were identified. Thirty-day postoperative complication rates between smokers and nonsmokers were compared. Complications included infection, thromboembolic events, reintubation, readmission, acute renal failure, and cardiovascular events. RESULTS: 921 patients who underwent ESS were identified. 182 (20%) were smokers and 739 (80%) were nonsmokers. 609 patients underwent outpatient ESS, while 312 patients underwent inpatient ESS. A total of 12 patients experienced postoperative surgical site infections involving the deeper tissues beyond the wound (organ/space SSI). On univariate analysis, smoking was associated with a higher incidence of organ/space SSI (P = .0067) and pulmonary embolism (P = .0321) after ESS. On multivariate logistic regression, smoking was associated with increased odds (4.495, 1.11- 8.17, P = .0347) of organ/space SSI after ESS. CONCLUSIONS: This study demonstrates an association between exposure to cigarette smoke and potentially serious surgical site infections in the 30-day postoperative period after ESS. Our findings may help when counseling smokers who are considering ESS. Further study is required to understand the nature of these infections and ways to prevent them.Level of Evidence: 2c ("health outcomes").


Cigarette Smoking/epidemiology , Natural Orifice Endoscopic Surgery , Otorhinolaryngologic Surgical Procedures , Postoperative Complications , Sinusitis/surgery , Databases, Factual/statistics & numerical data , Female , Humans , Incidence , Male , Middle Aged , Natural Orifice Endoscopic Surgery/adverse effects , Natural Orifice Endoscopic Surgery/methods , Otorhinolaryngologic Surgical Procedures/adverse effects , Otorhinolaryngologic Surgical Procedures/methods , Paranasal Sinuses/surgery , Patient Readmission/statistics & numerical data , Postoperative Complications/classification , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Quality Improvement/organization & administration , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , Smokers/statistics & numerical data , United States/epidemiology
18.
Laryngoscope ; 131(4): E1040-E1048, 2021 04.
Article En | MEDLINE | ID: mdl-32959912

OBJECTIVE: Sinonasal squamous cell carcinoma (SCC) is rare with no consensus on treatment regimen. Our goal is to analyze treatment outcomes in poorly differentiated SCC (PDSCC) using a large national database. STUDY DESIGN: Retrospective database study. METHODS: The National Cancer Database was queried for sinonasal invasive SCC, grade 3 (poorly differentiated) from 2004 to 2014. Patient demographics and tumor and treatment characteristics were tabulated. Kaplan-Meier (KM) analysis was performed to compare overall survival (OS) between histology subtype and primary site. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on OS. RESULTS: A total of 1,074 patients were identified. The maxillary sinus was the most common site (45%). T4 tumors were observed in 50% of patients, with most patients treated at high-volume facilities (77%). In KM analysis, spindle cell SCC histological subtype, primary tumors of the maxillary sinus, and poorly differentiated grade had worse OS. In our Cox-PH model, higher T stage and age were associated with worse OS. Those treated at a high-volume facility and those who underwent surgical resection followed by adjuvant radiation had improved OS. Chemotherapy within the treatment regimen did not confer survival benefit except in surgical patients when positive margins were present, and surgery with adjuvant chemoradiation trended toward improved survival. CONCLUSIONS: Sinonasal PDSCC appears to be best treated at high-volume centers with surgical resection followed by adjuvant radiation. Poorly differentiated grade has worse OS compared to more differentiated tumors. Chemotherapy along with adjuvant radiation may have a role in patients with positive surgical margins. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1040-E1048, 2021.


Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Paranasal Sinus Neoplasms/mortality , Paranasal Sinus Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/therapy , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Paranasal Sinus Neoplasms/therapy , Retrospective Studies , Survival Rate , United States
19.
Otolaryngol Head Neck Surg ; 163(5): 986-991, 2020 11.
Article En | MEDLINE | ID: mdl-32600116

OBJECTIVE: To determine whether treatment of sinonasal squamous cell carcinoma (SCC) at a high-volume facility affects survival. STUDY DESIGN: Retrospective database analysis. SETTING: National Cancer Database (2004-2014). SUBJECTS AND METHODS: The National Cancer Database was queried for sinonasal SCC from 2004 to 2014. Patient demographics, tumor characteristics and classification, resection margins, treatment regimen, and facility case-specific volume-averaged per year and grouped in tertiles as low (0%-33%), medium (34%-66%), and high (67%-100%)-were compared. Overall survival was compared with Cox proportional hazards regression analysis. RESULTS: A total of 3835 patients treated for sinonasal SCC between 2004 and 2014 were identified. Therapeutic options included surgery alone (18.6%), radiotherapy (RT) alone (29.1%), definitive chemoradiation (15.4%), surgery with adjuvant RT (22.8%), and combinations (14.1%) of the aforementioned treatments. Patients who underwent surgery with adjuvant RT had better overall survival (hazard ratio [HR], 0.74; P < .001; 95% CI, 0.63-0.86). As for treatment volume per facility, 7.4% of patients were treated at a low-volume center, 17.5% at a medium-volume center, and 75.1% at a high-volume center. Univariate analysis showed that treatment at a high-volume facility conferred a significantly better overall survival (HR, 0.77; P = .002). Multivariable Cox proportional hazards regression analysis, adjusting for age, sex, tumor classification, and treatment regimen, demonstrated that patients who underwent treatment at a high-volume facility (HR, 0.81; P < .001) had significantly improved survival. CONCLUSION: This study shows a better overall survival for sinonasal SCC treated at high-volume centers. Further study may be needed to understand the effect of case volume on the paradigms of sinonasal SCC management.


Carcinoma, Squamous Cell/therapy , Hospitals, High-Volume , Paranasal Sinus Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Chemoradiotherapy , Combined Modality Therapy , Databases, Factual , Female , Humans , Male , Margins of Excision , Middle Aged , Multivariate Analysis , Paranasal Sinus Neoplasms/mortality , Paranasal Sinus Neoplasms/surgery , Proportional Hazards Models , Radiotherapy, Adjuvant , Retrospective Studies , Survival Rate , United States , Young Adult
20.
Int Forum Allergy Rhinol ; 10(10): 1158-1164, 2020 10.
Article En | MEDLINE | ID: mdl-32470227

BACKGROUND: Recent studies have demonstrated a dramatic increase in the use of balloon sinus dilation (BSD) in the United States. However, the use of BSD specifically in revision sinus surgery has not been investigated. This study addresses the question of how BSD is utilized as a tool in revision sinus surgery. METHODS: Data from MarketScan (Truven Health) over a 5-year period (2012-2016) were analyzed. Patients who underwent a sinus procedure with a minimum of 2 years of follow-up were included. RESULTS: A total of 62,304 patients met inclusion criteria; 6847 (10.99%) underwent revision. Age >55 years, the South geographical region, and medical comorbidities increased the odds of revision on multivariate analysis. For patients undergoing revision, BSD was used 11%, 21%, and 13% of the time for revisions of the maxillary, frontal, and sphenoid sinuses, respectively. For a sinus that underwent revision after an initial BSD, a repeat BSD was done close to 40% of the time. CONCLUSION: BSD is used frequently in the revision setting, especially for the frontal sinus and for patients who had already undergone an initial BSD. Our findings highlight the prevalent role of BSD in revision surgery and the need to evaluate such practices.


Endoscopy , Frontal Sinus , Catheterization , Chronic Disease , Dilatation , Frontal Sinus/surgery , Humans , Middle Aged , Reoperation , Treatment Outcome
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