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1.
Am J Otolaryngol ; 45(1): 104044, 2024.
Article in English | MEDLINE | ID: mdl-37734365

ABSTRACT

PURPOSE: To determine the prevalence and severity of depression and anxiety in patients with head and neck cancer (HNC) undergoing treatment with free-flap (FF) reconstruction. METHODS: Participants with HNC undergoing FF reconstruction were given the validated 9-item Patient Health Questionnaire (PHQ-9) and a 7-item Generalized Anxiety Disorder (GAD-7) questionnaire prior to surgery. Patient factors and responses were analyzed. RESULTS: Seventy-one patients were included. Mean (SD) pre-operative PHQ-9 was 7.6 (7.04) with 34 % (n = 24) having moderate to severe depression. Mean (SD) pre-operative GAD-7 was 6.5 (6.86) with 30 % (n = 21) having moderate to severe anxiety. CONCLUSION: Prevalence of depression and anxiety is high in this cohort and undiagnosed in 22 % and 18 % of patients, respectively. Due to the findings, it is prudent to screen HNC patients at initial diagnosis and offer mental health services.


Subject(s)
Free Tissue Flaps , Head and Neck Neoplasms , Humans , Depression/epidemiology , Depression/etiology , Anxiety Disorders/epidemiology , Anxiety Disorders/etiology , Anxiety Disorders/diagnosis , Anxiety/epidemiology , Anxiety/etiology , Anxiety/diagnosis , Head and Neck Neoplasms/surgery
2.
Int J Mol Sci ; 24(7)2023 Mar 23.
Article in English | MEDLINE | ID: mdl-37046992

ABSTRACT

Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence and is associated with a poor prognosis. Barrett's esophagus (BE) is a known precursor of esophageal adenocarcinoma. This review aims to explore Barrett's esophagus, esophageal adenocarcinoma, and the progression from the former to the latter. An overview of the definition, diagnosis, epidemiology, and risk factors for both entities are presented, with special attention being given to the areas of debate in the literature. The progression from Barrett's esophagus to esophageal adenocarcinoma is reviewed and the relevant molecular pathways are discussed. The definition of Barrett's esophagus remains debated and without international consensus. This, alongside other factors, has made establishing the true prevalence of Barrett's esophagus challenging. The degree of dysplasia can be a histological challenge, but is necessary to guide clinical management. The progression of BE to EAC is likely driven by inflammatory pathways, pepsin exposure, upregulation of growth factor pathways, and mitochondrial changes. Surveillance is maintained through serial endoscopic evaluation, with shorter intervals recommended for high-risk features.


Subject(s)
Adenocarcinoma , Barrett Esophagus , Esophageal Neoplasms , Humans , Barrett Esophagus/epidemiology , Barrett Esophagus/diagnosis , Disease Progression , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/etiology , Esophageal Neoplasms/diagnosis , Adenocarcinoma/epidemiology , Adenocarcinoma/etiology , Adenocarcinoma/diagnosis , Risk Factors
3.
Am J Otolaryngol ; 40(1): 89-92, 2019.
Article in English | MEDLINE | ID: mdl-30472132

ABSTRACT

PURPOSE: To build a murine model for tobacco smoke and electronic cigarette vapor exposure to characterize the inflammatory and immune responses in the larynx. MATERIALS AND METHODS: In this pilot study, twenty-four wild-type C57BL/6 mice were divided into four groups: smoke, vapor with nicotine, vapor without nicotine, and air only. Following daily exposure for 4 months, larynges were dissected and processed with cytokine detection arrays. Each laryngeal cytokine level between the four different groups was analyzed statistically by using statistical analysis software (SAS) to calculate the analysis of variance (ANOVA). RESULTS: IL-4 was the only cytokine found to achieve statistically significant different levels in this study, with elevated levels of IL-4 in the tobacco smoke and vapor with nicotine groups compared to the levels found in the vapor without nicotine and air only groups (p = 0.0418). While statistically non-significant, prominent findings revealed up-regulation of TGF-ß2 and TGF-ß3 in the smoke group, but near-normal levels of TGF-ß2 and TGF-ß3 and suppression of IL-10 in the vapor groups (p > 0.05). CONCLUSION: The potential utility of the murine model is established for studying the inflammatory and immune effects of tobacco smoke and vapor on the mammalian larynx. IL-4 levels in mice larynges were significantly elevated in the tobacco smoke and vapor with nicotine groups.


Subject(s)
Interleukin-4/metabolism , Larynx/drug effects , Nicotine/pharmacology , Tobacco Smoking/adverse effects , Transforming Growth Factor beta/metabolism , Vaping/adverse effects , Animals , Interleukin-10/metabolism , Larynx/metabolism , Larynx/pathology , Mice , Mice, Inbred C57BL , Models, Animal , Smoke/adverse effects
4.
Am J Otolaryngol ; 37(2): 95-8, 2016.
Article in English | MEDLINE | ID: mdl-26954859

ABSTRACT

Intraoral midline mandibulotomy is a technique that can be used to increase exposure for transoral endoscopic laser microsurgery (TLS). We describe the case of a 51 year old male with persistent T1 glottic carcinoma. At initial diagnosis, he had been referred for curative radiotherapy as laryngeal access was not sufficient for TLS. For treatment of his recurrence, we describe the technique of performing a midline mandibular osteotomy to improve access to the larynx allowing for safe and effective transoral endoscopic laser microsurgery. Surgical access to the larynx was greatly improved, and we were able to perform TLS in a case that would have otherwise not been amenable to TLS. An intraoral midline mandibulotomy can improve access to the larynx and allow for successful transoral resection of laryngeal cancer in patients with otherwise inaccessible tumors.


Subject(s)
Carcinoma, Squamous Cell/surgery , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Mandibular Osteotomy/methods , Microsurgery/methods , Natural Orifice Endoscopic Surgery/methods , Carcinoma, Squamous Cell/diagnosis , Humans , Laryngeal Neoplasms/diagnosis , Male , Middle Aged , Mouth , Retrospective Studies
5.
Sci Prog ; 107(1): 368504241238080, 2024.
Article in English | MEDLINE | ID: mdl-38545797

ABSTRACT

Objective As population-based studies describing the characteristics of patients with refractory chronic cough (RCC) are sparse, the objective of this descriptive study was to identify and describe such patients using an algorithm developed for administrative claims databases and requiring validation in future. Methods We identified adults with chronic cough (N = 782,121) from Optum Clinformatics™ Data Mart as individuals with a 'cough event' (primary cough event; based on ICD codes/relevant prescriptions) and ≥2 cough events in the 56-180 preceding days. We applied several exclusion criteria to identify potential RCC cases and stratified them into probable, possible, and unlikely RCC cohorts by the number of cough events during 1-year follow up (≥3, 1-2 or 0 events, respectively). Patient characteristics were described during the year before the primary cough event and follow up. Results 16.8% (n = 131,772) of patients with chronic cough were potential RCC cases: 25.8% probable, 35.9% possible and 38.3% unlikely. The majority were female (66.4-70.5%); median age was 53-60 years. The most common comorbidities and cough-associated complications at baseline were: allergic rhinitis (30.7-39.1%), hypertension (37.3-47.7%), gastro-oesophageal reflux disease (23.7-34.3%), asthma (18.1-27.3%), insomnia (6.3-8.3%) and stress incontinence (2.5-3.9%). Among probable RCC cases, use of several medications was higher during follow up versus baseline: 52.7% versus 49.0% (cough treatments), 73.3% versus 69.0% (respiratory drugs), 40.5% versus 34.2% (gastrointestinal drugs) and 58.8% versus 56.1% (psychotherapeutics). Conclusion Our algorithm requires validation but provides a starting point to identify patients with RCC in claims databases in future studies.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Adult , Humans , Male , Female , Middle Aged , Carcinoma, Renal Cell/complications , Chronic Cough , Cough/epidemiology , Cough/complications , Kidney Neoplasms/complications , Algorithms
6.
Laryngoscope ; 134(4): 1614-1624, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37929860

ABSTRACT

OBJECTIVE: The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. METHODS: Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. RESULTS: After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. CONCLUSION: A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1614-1624, 2024.


Subject(s)
Laryngopharyngeal Reflux , Larynx , Humans , Laryngopharyngeal Reflux/diagnosis , Otolaryngologists , Electric Impedance , Surveys and Questionnaires , Esophageal pH Monitoring
7.
Am J Respir Crit Care Med ; 186(5): 402-3, 2012 Sep 01.
Article in English | MEDLINE | ID: mdl-22942344

ABSTRACT

Upper airway symptoms among responders to the terrorist attack on 9/11 are progressive and multifactorial. For those symptoms that are laryngeal in origin, we are using a multidisciplinary approach that includes respiratory retraining and laryngeal desensitization through a speech pathologist trained in airway disorders. Our treatment paradigm and laryngeal hypersensitivity are discussed in this essay.


Subject(s)
Emergency Responders , Laryngeal Diseases/therapy , Respiratory Hypersensitivity/therapy , Respiratory Therapy/methods , September 11 Terrorist Attacks , Speech Therapy/methods , Humans , Laryngeal Diseases/etiology , Laryngeal Diseases/psychology , Laryngismus/etiology , Laryngismus/psychology , Laryngismus/therapy , Respiratory Hypersensitivity/etiology , Respiratory Hypersensitivity/psychology , Syndrome
8.
Curr Med Res Opin ; 39(10): 1375-1381, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37736002

ABSTRACT

Chronic cough (CC) is associated with many conditions, so identifying contributing causes poses a diagnostic challenge. However, guidelines written for US physicians do not explicitly outline suggested roles for primary care providers (PCPs) in the approach to patients with CC, including refractory or unexplained CC. The objective of this review is to describe the role of PCPs in the diagnosis and treatment of CC in adults. This narrative review draws upon literature (identified via a PubMed search performed January 9, 2023, using primary care/disease state-related terms) and expertise from specialist physicians to provide recommendations for CC management in primary care. Cough is one of the top reasons patients seek care from PCPs; accordingly, PCPs are often the first physicians to conduct workup and initiate treatment. Patients with CC often experience a burdensome cough that lasts for years, have high healthcare resource utilization (HCRU), undergo multiple or failed treatment trials, and have limited success finding an etiology. Although specialist referral may be needed for many diagnostic tests, initial aspects of CC workup and management should be completed in primary care. Often more accessible than specialists, real-world evidence on HCRU suggests PCPs are important stakeholders in diagnosing and managing CC, including during initial workup and treatment for the most common causes of CC (i.e. upper-airway cough syndrome, asthma, noneosinophilic asthmatic bronchitis, and gastroesophageal reflux disease). Thorough workup at the primary care level may facilitate earlier identification of CC cause(s), improving patient journey to diagnosis and management.

9.
Laryngoscope ; 133(1): 59-69, 2023 01.
Article in English | MEDLINE | ID: mdl-35315085

ABSTRACT

EDUCATIONAL OBJECTIVE: At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus. OBJECTIVE: Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H+ /K+ ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H+ /K+ ATPase proton pumps. STUDY DESIGN: In vitro translational. METHODS: BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing. RESULTS: Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer. CONCLUSIONS: These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE. LEVEL OF EVIDENCE: NA Laryngoscope, 133:59-69, 2023.


Subject(s)
Barrett Esophagus , Esophageal Neoplasms , Humans , Proton Pumps , Pepsinogen A/metabolism , Proton Pump Inhibitors , Barrett Esophagus/complications , Esophageal Neoplasms/pathology , Pepsin A/metabolism , Carcinogenesis , Adenosine Triphosphatases/metabolism , Tumor Microenvironment
10.
Laryngoscope ; 133(5): 1191-1196, 2023 05.
Article in English | MEDLINE | ID: mdl-36054606

ABSTRACT

OBJECTIVE: Understanding the cough population is critical to addressing clinical needs and gaps in best practice. We sought to characterize and stratify cough patients with the hypothesis that there are opportunities to improve access to care in our health system and characterize the population. METHODS: Following institutional review board exempt status, a retrospective electronic record review was performed on all patients coded with ICD-9 786.2 or ICD-10 is R05 from January 1, 2001 through December 31, 2020 at our health system. Inclusion criteria were one or more visits for cough. The subgroup with more than one visit in each of 2 years was classified as multiple encounters. Patients were characterized by sex, age at first cough encounter, number of cough encounters, smoking status, and insurance status. Results were stratified by year, calculating frequencies, and percentages. RESULTS: There were 302,284 unique patients diagnosed with cough, among 1,764,387 patients seen in our health system, representing an average incidence of 3.0% (2.7%-3.7%) and prevalence of 4.9% (3.1%-5.6%). New single encounter cough patients totaled 179,963, and new multiple encounter cough patients totaled 122,321. Of the 39,828,073 total encounters, there were 469,802 for new or existing cough (1.17%-1.73% annually). The age at initial presentation demonstrated 36.5% seen <10 years old, with an even distribution over the remaining decades of life. The majority were seen for cough once, but 23.8% of group two patients had two or more visits for cough in a year. CONCLUSION: We demonstrate a lower-than-expected incidence and prevalence of cough in our health population, suggesting challenges with access to care when compared to 10% prevalence and 3% of encounters previously documented in the literature. The study also provides a platform to explore the importance of pediatric cough, as well as population health and the longitudinal journey of cough patients in underserved areas. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1191-1196, 2023.


Subject(s)
Cough , Rural Health , Child , Humans , Retrospective Studies , Cough/epidemiology , Incidence , Prevalence
11.
OTO Open ; 7(3): e75, 2023.
Article in English | MEDLINE | ID: mdl-37736120

ABSTRACT

Objective: Assess the impact of positron emission tomography/computed tomography (PET/CT) on disease staging at presentation in patients with head and neck squamous cell carcinoma. Study Design: Retrospective cross-sectional review. Setting: Academic multicenter single institution (Geisinger Health System). Methods: All patients who had PET/CT imaging during workup for head and neck squamous cell carcinoma were included in the study. Pre- and post-PET/CT clinical staging were recorded. Statistical analyses were performed for patients with a change in clinical staging or detection of second primary malignancies on PET/CT. Results: A total of 292 patients were included in the study, 238 of whom underwent PET/CT imaging as part of their initial workup. Twenty-eight (11.9%) patients were clinically upstaged on PET/CT with 7 patients having treatment alterations based on imaging. Eighteen (7.6%) patients were found to have second primary malignancies on PET/CT. Conclusion: The current study further illustrates the importance of PET/CT in the workup of head and neck squamous cell carcinoma. Without the inclusion of PET/CT imaging, 19.3% of patients would have either been staged inappropriately or had second primary malignancies missed, again confirming the necessity of comprehensive functional imaging during the initial pretreatment workup.

12.
Int Arch Occup Environ Health ; 84(2): 131-7, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20589388

ABSTRACT

UNLABELLED: Following the World Trade Center (WTC) collapse on September 11, 2001, more than 40,000 people were exposed to a complex mixture of inhalable nanoparticles and toxic chemicals. While many developed chronic respiratory symptoms, to what degree olfaction was compromised is unclear. A previous WTC Medical Monitoring and Treatment Program study found that olfactory and nasal trigeminal thresholds were altered by the toxic exposure, but not scores on a 20-odor smell identification test. OBJECTIVES: To employ a well-validated 40-item smell identification test to definitively establish whether the ability to identify odors is compromised in a cohort of WTC-exposed individuals and, if so, whether the degree of compromise is associated with self-reported severity of rhinitic symptoms. METHODS: The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 99 WTC-exposed persons and 99 matched normal controls. The Sino-Nasal Outcomes Test (SNOT-20) was administered to the 99 WTC-exposed persons and compared to the UPSIT scores. RESULTS: The mean (SD) UPSIT scores were lower in the WTC-exposed group than in age-, sex-, and smoking history-matched controls [respective scores: 30.05 (5.08) vs 35.94 (3.76); p = 0.003], an effect present in a subgroup of 19 subjects additionally matched on occupation (p < 0.001). Fifteen percent of the exposed subjects had severe microsmia, but only 3% anosmia. SNOT-20 scores were unrelated to UPSIT scores (r = 0.20; p = 0.11). CONCLUSION: Exposure to WTC air pollution was associated with a decrement in the ability to identify odors, implying that such exposure had a greater influence on smell function than previously realized.


Subject(s)
Air Pollutants/toxicity , Inhalation Exposure , Occupational Exposure , Olfaction Disorders/chemically induced , Respiratory Tract Diseases/chemically induced , September 11 Terrorist Attacks , Adult , Age Factors , Analysis of Variance , Case-Control Studies , Female , Humans , Linear Models , Male , Middle Aged , New York City/epidemiology , Odorants , Respiratory Tract Diseases/epidemiology , Retrospective Studies , Smell
13.
Laryngoscope ; 131(2): 282-287, 2021 02.
Article in English | MEDLINE | ID: mdl-32277707

ABSTRACT

OBJECTIVES/HYPOTHESIS: To characterize the effects of tracheotomy timing at our institution on intensive care unit (ICU) length of stay (LOS) and overall hospital LOS. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective study was performed at a tertiary care medical center for patients undergoing tracheotomy over 2.5 years from January 1, 2016 through June 30, 2018. Demographics, survival, duration of endotracheal intubation, timing of tracheotomy, and ICU and overall hospital LOS were assessed. Tracheotomy was considered early (ET) if it was performed by day 7 of mechanical ventilation and late (LT) thereafter. Readmission, mortality, and costs were also tabulated for each aggregate group. Nonparametric statistics were used to compare results. RESULTS: Of the 536 patients included in the analysis, 160 received tracheotomy early and 376 late. Differences between age and sex were not statistically significant. Duration of total ICU stay was shortened by 65% (12.84 ± 17.69 days vs. 38.49 ± 26.61 days; P < .0001), and length of overall hospital course was reduced by 54% (22.71 ± 26.65 days vs. 50.37 ± 34.20 days; P < .0001) in the early tracheotomy group. Observed/expected (O/E) values standardized results to case mix index and revealed LOS of 1.5 for ET and 2.5 for LT, and mortality of 0.76 for ET and 1.25 for LT, and comparable readmissions of both groups. CONCLUSIONS: Early tracheotomy in ICU patients is associated with earlier ICU discharge, decreased length of overall hospital stay, and lower mortality when controlling for case mix index. Opportunities exist to optimize patient outcomes and O/E performance. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:282-287, 2021.


Subject(s)
Critical Care/statistics & numerical data , Diagnosis-Related Groups/statistics & numerical data , Intensive Care Units/statistics & numerical data , Time Factors , Tracheotomy/statistics & numerical data , Aged , Critical Care Outcomes , Critical Illness/economics , Critical Illness/mortality , Critical Illness/therapy , Diagnosis-Related Groups/economics , Female , Health Care Costs/statistics & numerical data , Humans , Intensive Care Units/economics , Intubation, Intratracheal/economics , Intubation, Intratracheal/mortality , Intubation, Intratracheal/statistics & numerical data , Length of Stay/economics , Length of Stay/statistics & numerical data , Male , Middle Aged , Respiration, Artificial/economics , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Tertiary Care Centers , Tracheotomy/economics , Tracheotomy/mortality
14.
Otolaryngol Head Neck Surg ; 164(6): 1153-1159, 2021 06.
Article in English | MEDLINE | ID: mdl-33170765

ABSTRACT

OBJECTIVE: This state-of-the-art article reviews the epidemiology, diagnosis, and management of vocal fold leukoplakia, with focus on recent advances. It focuses on the clinical challenges that otolaryngologists face balancing both oncological efficacy and functional outcomes in leukoplakia and presents the current philosophies and techniques to consider when managing such patients. DATA SOURCES: PubMed/MEDLINE. REVIEW METHODS: We conducted a detailed review of publications related to vocal cord and laryngeal leukoplakia, dysplasia, hyperkeratosis, leukoplakia endoscopy, and leukoplakia management focusing specifically on oncologic outcomes, voice preservation, current and emerging diagnosis, and management techniques. CONCLUSIONS: There has been a paradigm shift away from performing "vocal cord stripping" procedures that can cause irreversible hoarseness toward voice preservation surgery while achieving comparable oncologic control. Surgical technical and instrumental developments have been designed to maximally treat superficial disease while preserving underling vibratory mucosa. Recent improvements in histopathological grading systems and advances in biomarker classification may allow for improved oncologic risk stratification. Furthermore, improvements in endoscopic imaging capabilities and contact endoscopy are currently being studied for their potential diagnostic significance. IMPLICATIONS FOR PRACTICE: To optimally manage vocal fold leukoplakia, the otolaryngologist should become familiar with the oncologic implications of the disease and the importance of obtaining pathologic diagnosis to rule out malignancy. In addition, the surgeon should maintain surgical techniques and knowledge of available instruments and lasers that can assist in surgical management while prioritizing the preservation of vibratory tissue and voice quality. Finally, the surgeon and the patient should understand the clinical importance of routine endoscopic surveillance.


Subject(s)
Laryngeal Diseases , Leukoplakia , Vocal Cords , Humans , Laryngeal Diseases/diagnosis , Laryngeal Diseases/epidemiology , Laryngeal Diseases/therapy , Leukoplakia/diagnosis , Leukoplakia/epidemiology , Leukoplakia/therapy
15.
Otolaryngol Head Neck Surg ; 164(4): 751-758, 2021 04.
Article in English | MEDLINE | ID: mdl-32988279

ABSTRACT

OBJECTIVE: To explore biomarkers that are candidates for understanding potential degeneration to malignancy of vocal fold leukoplakia (VFL), with the goal of guiding future diagnostic and treatment recommendations. DATA SOURCES: PubMed and Medline search engines. REVIEW METHODS: A systematic review was conducted by searching the following key words: vocal fold or laryngeal, coupled with leukoplakia or dysplasia, and combined with the term prognostic markers. We collated the biomarkers and their significance, followed by observing the power of their evidence by assessing the quality of the studies according to guidelines of tumor marker prognostic studies (REMARK). CONCLUSIONS: Prognostic biomarkers in the 16 studies are generally divided into 3 categories according to their biological roles: proliferation (Ki-67, CK-1 RS14024 SNP), cell cycle control (P53, p16, cyclin D1, p57kip2, interleukin-10 [IL-10], miR-10a, and miR-34c), cell adhesion, and invasion (neutrophil-to-lymphocyte ratio, OPN/CD44v6 axis, MMP-1, vascular endothelial growth factor A, MMP-9, serpin peptidase inhibitor 1, plasminogen activator, CTNN/B1, ß-catenin, NANOG, HERG1). The prognostic use of these biomarkers is limited due to the variable methodologies, study design, assay methods, and statistical analysis performed. IMPLICATIONS FOR PRACTICE: Prognostic factors in vocal fold leukoplakia have important clinical implications regarding the potential for malignant degeneration. Although further study is needed, the currently available evidence suggests that p53, p16, cyclin D1, IL-10, NLR, OPN and CD44v6, CTNNB1, and CTTN and FAK might be of particular interest in determining prognosis of VFL as related to malignancy. Future, large, well-designed, prospective studies are expected to determine the prognostic power of these biomarkers before their implementation in routine clinical practice.


Subject(s)
Biomarkers, Tumor/blood , Cell Transformation, Neoplastic , Laryngeal Diseases/blood , Laryngeal Diseases/pathology , Leukoplakia/blood , Leukoplakia/pathology , Vocal Cords , Humans , Prognosis
16.
Laryngoscope ; 131(1): 130-135, 2021 01.
Article in English | MEDLINE | ID: mdl-32250454

ABSTRACT

OBJECTIVES: The gastric H+/K+ ATPase proton pump has previously been shown to be expressed in the human larynx, however its contribution to laryngopharyngeal reflux (LPR) signs, symptoms and associated diseases such as laryngeal cancer is unknown. Proton pump expression in the larynx of patients with LPR and laryngeal cancer was investigated herein. A human hypopharyngeal cell line expressing the proton pump was generated to investigate its effects. STUDY DESIGN: In-vitro translational. METHODS: Laryngeal biopsies were obtained from three LPR and eight LSCC patients. ATP4A, ATP4B and HRPT1 were assayed via qPCR. Human hypopharyngeal FaDu cell lines stably expressing proton pump were created using lentiviral transduction and examined via transmission electron microscopy and qPCR for genes associated with inflammation or laryngeal cancer. RESULTS: Expression of ATP4A and ATP4B was detected in 3/3 LPR, 4/8 LSCC-tumor and 3/8 LSCC-adjacent specimens. Expression of ATP4A and ATP4B in FaDu elicited mitochondrial damage and expression of IL1B, PTGS2, and TNFA (P < .0001); expression of ATP4B alone did not. CONCLUSIONS: Gastric proton pump subunits are expressed in the larynx of LPR and LSCC patients. Mitochondrial damage and changes in gene expression observed in cells expressing the full proton pump, absent in those expressing a single subunit, suggest that acid secretion by functional proton pumps expressed in upper airway mucosa may elicit local cell and molecular changes associated with inflammation and cancer. LEVEL OF EVIDENCE: NA Laryngoscope, 131:130-135, 2021.


Subject(s)
H(+)-K(+)-Exchanging ATPase/biosynthesis , Laryngeal Neoplasms/enzymology , Laryngopharyngeal Reflux/enzymology , Larynx/enzymology , Cells, Cultured , Gene Expression Regulation , H(+)-K(+)-Exchanging ATPase/genetics , Humans , Hypopharynx/cytology , Laryngeal Neoplasms/genetics , Laryngopharyngeal Reflux/genetics , Tumor Cells, Cultured
17.
Int J Mol Sci ; 11(7): 2715-45, 2010 Jul 16.
Article in English | MEDLINE | ID: mdl-20717533

ABSTRACT

The free radical nitric oxide (NO(*)) is known to play a dual role in human physiology and pathophysiology. At low levels, NO(*) can protect cells; however, at higher levels, NO(*) is a known cytotoxin, having been implicated in tumor angiogenesis and progression. While the majority of research devoted to understanding the role of NO(*) in cancer has to date been tissue-specific, we herein review underlying commonalities of NO(*) which may well exist among tumors arising from a variety of different sites. We also discuss the role of NO(*) in human physiology and pathophysiology, including the very important relationship between NO(*) and the glutathione-transferases, a class of protective enzymes involved in cellular protection. The emerging role of NO(*) in three main areas of epigenetics-DNA methylation, microRNAs, and histone modifications-is then discussed. Finally, we describe the recent development of a model cell line system in which human tumor cell lines were adapted to high NO(*) (HNO) levels. We anticipate that these HNO cell lines will serve as a useful tool in the ongoing efforts to better understand the role of NO(*) in cancer.


Subject(s)
Nitric Oxide/metabolism , Animals , Cytotoxins/metabolism , Cytotoxins/pharmacology , Epigenesis, Genetic , Glutathione S-Transferase pi/metabolism , Humans , Models, Biological , Neoplasms/genetics , Neoplasms/metabolism , Nitric Oxide/pharmacology , Reactive Nitrogen Species/metabolism
18.
Ear Nose Throat J ; : 145561320951647, 2020 Oct 12.
Article in English | MEDLINE | ID: mdl-33044841

ABSTRACT

There is a high prevalence of dysphagia in patients with neuromuscular diseases and stroke, and consequences can be profound. However, the correlation of dysarthria and oral-oropharyngeal dysphagia remains unclear. This review aimed to define the clinical co-presentation of dysarthria and dysphagia in this population. A PubMed search to identify literature on the prevalence of dysarthria and dysphagia was systematically conducted in the English language literature since 1995. Subjective and objective outcomes instruments were identified for both dysarthria and dysphagia. Studies that included prevalence and co-presentation were included. Inclusion and exclusion criteria were applied according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA). Of the 1,056 articles identified in the search, 20 articles met the search criteria. An additional 4 articles were examined for a total of 24 articles for analysis. Dysarthria and dysphagia were found to be highly prevalent among patients with neuromuscular disease (NMD). Overall, there was a higher prevalence of dysarthria than dysphagia. Of those patients with dysphagia, some reports estimate 76-90% of patients with NMD also had dysarthria. Dysarthria is a strong clinical clue to the presence of dysphagia. Existing subjective questionnaires may not reveal the presence of oropharyngeal dysphagia, but objective measures are more revealing. Further study to correlate the degree of dysarthria and severity of oral-oropharyngeal dysphagia are warranted.

20.
J Allergy Clin Immunol Pract ; 7(6): 1750-1755, 2019.
Article in English | MEDLINE | ID: mdl-31078514

ABSTRACT

Cough is an increasingly important public health concern, and diagnosis and treatment can be challenging in these complex patients. The purpose of this review is to address the roles of otolaryngology in understanding pathophysiology, and unique aspects in their diagnosis and management. Evidence-based best practice through clinical practice guidelines for cough is emphasized. A step-wise description of the interrelated pathophysiology is used to gain a deeper understanding of contributing disease states and the importance of synergistic effects on cough. Unique perspectives exist from an otolaryngology perspective regarding chronic cough. Included here are the premier role of the larynx, immunity, and the microbiome in the Unified Airway, the interconnected nature of reflux disease with respiratory physiology, a spectrum of neurologic diseases tying aspiration to cough, and maladaptive neuro-based behaviors. Otolaryngology aspects of chronic cough encompass the composite nature of the disease with all of its contributions.


Subject(s)
Cough/diagnosis , Gastroesophageal Reflux/diagnosis , Humans , Nervous System Diseases/diagnosis
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