Utilizing the AJCC 8th Staging to Discriminate Survival Outcomes in HPV-associated Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: The American Joint Committee on Cancer (AJCC) staging 8th edition introduced major changes in the TNM staging of oropharyngeal squamous cell carcinoma (OPSCC) based on the human papillomavirus (HPV) status. This study aimed to observe how well the AJCC staging 8th edition precisely discriminates survival outcomes in patients with HPV-associated OPSCC using a large population database. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database between 2010 and 2016, 7,448 patients with HPV-associated OPSCC were enrolled. Patients diagnosed with OPSCC and tested positive for HPV with information on the TNM staging according to the AJCC staging 7th edition were selected. Next, T-, N-, and clinical staging were reconstructed based on the AJCC staging 8th edition. Survival probabilities in both AJCC staging 7th and 8th editions were estimated and compared. RESULTS: Most patients (93.44%) were down-staged from the 7th to the 8th edition. The AJCC staging 8th edition showed more discriminatory power in predicting survival of patients with HPV-associated OPSCC than the AJCC staging 7th edition, regardless of the primary subsites. Additionally, clinical stage I patients with HPV-associated OPSCC according to the AJCC 8th edition showed better prognosis in case of high T staging than high N staging. Clinical staging according to the AJCC 8th edition compared to that of the 7th edition was an independent prognostic factor in patients with HPV-associated OPSCC. CONCLUSION: This study emphasizes the advantages of the new classification system for discriminating survival in HPV-associated OPSCC according to various factors.

Prognostic significance of senescence-related tumor microenvironment genes in head and neck squamous cell carcinoma.

The impact of the senescence related microenvironment on cancer prognosis and therapeutic response remains poorly understood. In this study, we investigated the prognostic significance of senescence related tumor microenvironment genes (PSTGs) and their potential implications for immunotherapy response. Using the Cancer Genome Atlas- head and neck squamous cell carcinoma (HNSC) data, we identified two subtypes based on the expression of PSTGs, acquired from tumor-associated senescence genes, tumor microenvironment (TME)-related genes, and immune-related genes, using consensus clustering. Using the LASSO, we constructed a risk model consisting of senescence related TME core genes (STCGs). The two subtypes exhibited significant differences in prognosis, genetic alterations, methylation patterns, and enriched pathways, and immune infiltration. Our risk model stratified patients into high-risk and low-risk groups and validated in independent cohorts. The high-risk group showed poorer prognosis and immune inactivation, suggesting reduced responsiveness to immunotherapy. Additionally, we observed a significant enrichment of STCGs in stromal cells using single-cell RNA transcriptome data. Our findings highlight the importance of the senescence related TME in HNSC prognosis and response to immunotherapy. This study contributes to a deeper understanding of the complex interplay between senescence and the TME, with potential implications for precision medicine and personalized treatment approaches in HNSC.

Preparation and characterization of water-reducible polyester resin based on waste PET for insulation varnish.

Water-reducible polyester resin (WRPE) for insulation varnish was prepared from waste polyethylene terephthalate (PET), glycerol (GL), and phthalic anhydride (PA) via depolymerization and condensation. PET was depolymerized via glycolysis at different molar ratios of PET/GL (PET repeating unit/GL molar ratios: 1.6, 1.3, and 1.0) with zinc acetate as a catalyst at 220-230 °C. The resulting glycolytic products (GPs) were reacted with PA at contents of 5, 7.5, 10, 12.5, and 15 wt%, based on the total weight. The prepared WRPEs were dissolved in phenol, neutralized with aqueous ammonia to pH = 7-7.5, and diluted in water. The WRPEs were cured with hexamethoxymethyl melamine resin (HMMM, WRPE : HMMM = 70 : 30, based on the dry mass) at 140 °C for 2 h. The formation of GPs, WRPE, and WRPE-HMMM was investigated using Fourier transformer infrared spectroscopy and proton nuclear magnetic resonance spectroscopy; the thermal properties were characterized using thermogravimetric analysis and differential scanning calorimetry. The electrical insulation strength and volume resistivity of the cured films with PA content were investigated. This strength and volume resistivity first increased with increasing PA content and then decreased above 10 wt%. The results show that WRPE with a PA content of 10 wt% exhibits optimal insulation properties.

Association between Metabolic Syndrome and Risk of Hypopharyngeal Cancer: A Nationwide Cohort Study from Korea.

This study evaluated the relationship between metabolic syndrome (MS) and the risk of hypopharyngeal cancer. This retrospective cohort study used data from the Korean National Health Insurance Research Database. A total of 4,567,890 participants who underwent a health checkup in 2008 were enrolled. The participants were followed until 2019, and the incidence of hypopharyngeal cancer was analyzed. We evaluated the risk of hypopharyngeal cancer according to the presence of MS, including obesity, dyslipidemia, hypertension, and diabetes, using a multivariate Cox proportional hazards model adjusted for age, sex, alcohol consumption, and smoking. During the follow-up period, 821 were newly diagnosed with hypopharyngeal cancer. MS was inversely associated with the risk of hypopharyngeal cancer (hazard ratio (HR), 0.83 [95% confidence interval (CI), 0.708-0.971]). Large waist circumference and high triglyceride levels among MS elements were both inversely related to the risk of hypopharyngeal cancer (HR: 0.82 [95% CI, 0.711-0.945] and 0.83 [95% CI, 0.703-0.978], respectively). The risk of hypopharyngeal cancer decreased with increasing comorbidity of MS in women (N = 0 vs. N = 1-2 vs. N ≥ 3; HR = 1 vs. HR = 0.511 [95% CI, 0.274-0.952] vs. HR = 0.295 [95% CI, 0.132-0.66]), but not in men. This study may improve our etiological understanding of hypopharyngeal cancer.

Association between cancer stem cell gene expression signatures and prognosis in head and neck squamous cell carcinoma.

BACKGROUND: Various cancer stem cell (CSC) biomarkers and the genes encoding them in head and neck squamous cell carcinoma (HNSCC) have been identified and evaluated. However, the validity of these factors in the prognosis of HNSCC has been questioned and remains unclear. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC, using five publicly available HNSCC cohorts. METHODS: To predict the prognosis of patients with HNSCC, we developed and validated the expression signatures of CSC biomarker genes whose mRNA expression levels correlated with at least one of the four CSC genes (CD44, MET, ALDH1A1, and BMI1). RESULTS: Patients in The Cancer Genome Atlas (TCGA) HNSCC cohort were classified into CSC gene expression-associated high-risk (CSC-HR; n = 285) and CSC gene expression-associated low-risk (CSC-LR; n = 281) subgroups. The 5-year overall survival and recurrence-free survival rates were significantly lower in the CSC-HR subgroup than in the CSC-LR subgroup (p = 0.04 and 0.02, respectively). The clinical significance of the CSC gene expression signature was validated using four independent cohorts. Analysis using Cox proportional hazards models showed that the CSC gene expression signature was an independent prognostic factor of non-oropharyngeal HNSCC which mostly indicates HPV (-) status. Furthermore, the CSC gene expression signature was associated with the prognosis of HNSCC patients who received radiotherapy. CONCLUSION: The CSC gene expression signature is associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC, especially in cases with HPV (-) status who were classified in more detail.

Prediction of survival in oropharyngeal squamous cell carcinoma using machine learning algorithms: A study based on the surveillance, epidemiology, and end results database.

Background: We determined appropriate survival prediction machine learning models for patients with oropharyngeal squamous cell carcinoma (OPSCC) using the "Surveillance, Epidemiology, and End Results" (SEER) database. Methods: In total, 4039 patients diagnosed with OPSCC between 2004 and 2016 were enrolled in this study. In particular, 13 variables were selected and analyzed: age, sex, tumor grade, tumor size, neck dissection, radiation therapy, cancer directed surgery, chemotherapy, T stage, N stage, M stage, clinical stage, and human papillomavirus (HPV) status. The T-, N-, and clinical staging were reconstructed based on the American Joint Committee on Cancer (AJCC) Staging Manual, 8th Edition. The patients were randomly assigned to a development or test dataset at a 7:3 ratio. The extremely randomized survival tree (EST), conditional survival forest (CSF), and DeepSurv models were used to predict the overall and disease-specific survival in patients with OPSCC. A 10-fold cross-validation on a development dataset was used to build the training and internal validation data for all models. We evaluated the predictive performance of each model using test datasets. Results: A higher c-index value and lower integrated Brier score (IBS), root mean square error (RMSE), and mean absolute error (MAE) indicate a better performance from a machine learning model. The C-index was the highest for the DeepSurv model (0.77). The IBS was also the lowest in the DeepSurv model (0.08). However, the RMSE and RAE were the lowest for the CSF model. Conclusions: We demonstrated various machine-learning-based survival prediction models. The CSF model showed a better performance in predicting the survival of patients with OPSCC in terms of the RMSE and RAE. In this context, machine learning models based on personalized survival predictions can be used to stratify various complex risk factors. This could help in designing personalized treatments and predicting prognoses for patients.

Unusual Foreign Body, a Spoon, in the Esophagus of a Middle-Aged Female: A Case Report and Review of the Literature.

In adults, a large metal foreign body in the esophagus is rarely seen and is usually caused accidentally. Here, we have described an unusual case of foreign body (spoon) in the esophagus of an adult patient. A 48-year-old woman initially presented to the emergency department with marked dysphagia, drooling, and radiating pain to the chest. She had swallowed a spoon while trying to vomit because of feeling sick. Radiological images revealed a spoon stuck in the esophagus. The edge of the spoon was grabbed with forceps and safely extracted under hypnic anesthesia. No esophageal perforation was detected on evaluation with esophagography using Gastrografin on the next day. This case highlights an unusual situation in an adult patient showing long nonfood-type foreign body in the esophagus. It is important that an appropriate workup and removal of foreign body is performed according to the location and type.

Comparison Between Manual and Automated Analyses in Multichannel Intraluminal Impedance: pH Monitoring for Laryngopharyngeal Reflux.

OBJECTIVE: To evaluate differences between manual and automated analyses of 24-hour multichannel intraluminal impedance-pH monitoring for diagnosis of laryngopharyngeal reflux. STUDY DESIGN: Case series with planned data collection. SETTING: Academic center outpatient clinic. METHODS: The study group comprised 127 patients with symptoms suspicious of laryngopharyngeal reflux, who underwent 24-hour multichannel intraluminal impedance-pH monitoring. Automated and manual analyses were performed for each patient. The following parameters were compared between analyses: number of proximal reflux episodes, proximal exposure time, symptom index, and symptom association probability. RESULTS: The number of proximal reflux episodes detected by manual analysis was significantly lower than that detected by automated analysis, except in acid reflux cases. The false positive of automated analysis was 39.8%. In addition, the proximal exposure time for manual analysis was significantly lower than that for automated analysis, except in cases of acid reflux. Symptom index and symptom association probability values based on manual analysis were significantly lower than in automated analysis, except in heartburn cases. CONCLUSIONS: Automated analysis demonstrated a tendency of excessive reflux measurement when compared with manual analysis. It is necessary to increase the accuracy of laryngopharyngeal reflux diagnosis through manual analysis.

24-Hour Multichannel Intraluminal Impedance-pH in Proton Pump Inhibitor Nonresponders vs Responders in Patients With Laryngopharyngeal Reflux.

OBJECTIVE: This study aimed to evaluate the characteristics of reflux in proton pump inhibitor (PPI) nonresponders vs responders in patients with laryngopharyngeal reflux (LPR) by using 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring. STUDY DESIGN: Prospective cohort study. SETTING: A tertiary care otolaryngology clinic. METHODS: Patients with typical LPR symptoms showing >1 proximal reflux episode were considered to have LPR and investigated prospectively. Patients were prescribed high-dose PPI twice daily and followed up for at least 2 months. Patients with LPR showing a ≥50% decrease in the follow-up reflux symptom index score during treatment periods as compared with pretreatment were defined as responders; others were defined as nonresponders. Various parameters in 24-hour MII-pH monitoring between nonresponders and responders with LPR were compared with Student's t test and receiver operating characteristic curve. RESULTS: Eighty patients were diagnosed with LPR and categorized as nonresponders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in various MII parameters were higher in responders than in nonresponders (P = .0040 and .0216, respectively). Proximal all reflux time >0.000517% was a better cutoff value to predict responders with LPR as compared with the proximal longest reflux time >0.61 minutes (sensitivity + specificity: 1.317 vs 1.291). CONCLUSION: Proximal all reflux time in various 24-hour MII-pH monitoring parameters can be helpful to predict the response to PPI therapy in patients with LPR. These findings will help establish a personalized therapeutic scheme for patients with LPR.

Clinical significance of FAT1 gene mutation and mRNA expression in patients with head and neck squamous cell carcinoma.

The FAT1 gene functions as a tumor suppressor or promoter and remains incompletely understood. We examined the clinical significance of FAT1 in head and neck squamous cell carcinoma (HNSCC) using four publicly available HNSCC cohorts and one HNSCC cohort enrolled at a tertiary medical center. We developed FAT1 signatures reflecting FAT1 mutations and mRNA expression using one cohort. Patients with HNSCC were classified into FAT1-associated low risk (FAT1-LR; n = 195) and FAT1-associated high risk (FAT1-HR; n = 371) subgroups. The five-year overall survival and recurrence-free survival rates were significantly lower in the FAT1-HR subgroup than in the FAT1-LR subgroup (P = 0.01 and 0.003, respectively). The clinical significance of FAT1 was validated using four independent cohorts. Cox proportional hazards models showed that the FAT1 signature was an independent prognostic factor for HNSCC patients. In addition, FAT1 signature was associated with the response to radiotherapy, advanced stage, and human papilloma virus (HPV) status in HNSCC patients. In conclusion, the FAT1 gene signature was associated with prognosis of HNSCC and may help to provide personalized treatments for HNSCC patients.

Voice Outcome After Cold Knife Surgery According to the Characteristics of Vocal Fold Polyp.

PURPOSE: Voice change is one of the major symptoms in patients with vocal fold polyp. As a result, phonomicrosurgery is commonly required in these patients. Since voice outcomes after polyp treatment can be variable according to polyp characteristics, we aimed to investigate the predicting factors of postoperative voice improvements in terms of polyp characteristics in patients with vocal fold polyp who underwent cold knife surgery. MATERIALS AND METHODS: A total of 77 patients who were diagnosed with vocal fold polyp and underwent phonomicrosurgery with cold knife instruments. The polyp characteristics of color, size, shape, and location were evaluated at baseline. Acoustic and aerodynamic analyses, voice handicap index questionnaire and grade, roughness, breathiness, asthenia, strain scale were evaluated at baseline and 6 weeks after surgery. RESULTS: All values of postoperative voice parameters improved after cold knife surgery. (P < 0.05) In patient with an organized vocal fold polyp, less improvement in postoperative values of maximum phonation time were observed. (P < 0.05) Likewise, less improvement of voice handicap index questionnaire score and grade, roughness, breathiness, asthenia, strain scale after surgery was shown in organized vocal fold polyp. (P < 0.05) CONCLUSIONS: Among the various polyp characteristics, the organized polyp was significantly related to relatively less improvement of objective and subjective voice parameters after surgery. These polyp characteristics would help to predict postoperative voice improvement and plan for personalized treatment in patients with vocal fold polyp.

SOD2- and NRF2-associated Gene Signature to Predict Radioresistance in Head and Neck Cancer.

BACKGROUND: We propose a novel prognostic biomarker-based strategy for increasing the efficacy of radiotherapy (RT) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: We identified genes associated with superoxide dismutase 2 (SOD2) and nuclear factor erythroid-2-related factor 2 (NRF2) from gene-expression data of The Cancer Genome Atlas (TCGA) by calculating Pearson correlation. Patients were divided into two groups using hierarchical clustering. Colony-formation assay was performed to determine radioresistance in HNSCC cell line CAL27. Pathway analysis was conducted using The Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: We developed a 49-gene signature with SOD2- and NRF2-associated genes. Using mRNA expression data for the 49-gene signature, we performed hierarchical clustering to stratify patients into two subtypes, subtype A and B. In the TCGA cohort, subgroup A demonstrated a better prognosis than subgroup B in patients who received RT. The signature robustness was evaluated in other independent cohorts. We showed through colony-formation assay that depletion of SOD2 or NRF2 leads to increased radiosensitivity. CONCLUSION: We identified and validated a robust gene signature of SOD2- and NRF2-associated genes in HNSCC and confirmed their link to radioresistance using in vitro assay, providing a novel biomarker for the evaluation of HNSCC prognosis.

Pharyngeal reflux episodes in patients with suspected laryngopharyngeal reflux versus healthy subjects: a prospective cohort study.

PURPOSE: This study aimed to analyze pharyngeal reflux episodes in patients with suspected LPR versus healthy subjects using 24-h MII-pH monitoring. METHODS: One hundred twenty-one patients who visited our clinic with a chief complaint of LPR-related symptoms and underwent 24-h MII-pH monitoring were enrolled prospectively. Also, 27 healthy subjects were enrolled and underwent 24-h MII-pH monitoring during the same period. We analyzed sensitivity, specificity, and accuracy comprehensively to determine appropriate cut-off values of pharyngeal reflux episodes in 24-h MII-pH monitoring to diagnose patients with LPR. RESULTS: Twenty-nine of 121 patients with suspected LPR showed no pharyngeal reflux episodes, while 92 showed more than one pharyngeal reflux event. In contrast, the 22 healthy subjects showed no pharyngeal reflux episodes, three showed one reflux event, and two showed two reflux events. A cut-off value of ≥ 1 showed best accuracy reflected by combined sensitivity and specificity values, while ≥ 2 demonstrated better specificity with slight loss of sensitivity and slightly lower overall accuracy, suggesting cut-off value of ≥ 1 pharyngeal reflux episodes is a good clinical indicator. CONCLUSION: A cut-off value of ≥ 1 in pharyngeal reflux episodes on 24-h MII-pH monitoring in patients with suspected LPR might be an acceptable diagnostic tool for LPR.

Gene signature for prediction of radiosensitivity in human papillomavirus-negative head and neck squamous cell carcinoma.

PURPOSE: The probability of recurrence of cancer after adjuvant or definitive radiotherapy in patients with human papillomavirus-negative (HPV(-)) head and neck squamous cell carcinoma (HNSCC) varies for each patient. This study aimed to identify and validate radiation sensitivity signature (RSS) of patients with HPV(-) HNSCC to predict the recurrence of cancer after radiotherapy. MATERIALS AND METHODS: Clonogenic survival assays were performed to assess radiosensitivity in 14 HNSCC cell lines. We identified genes closely correlated with radiosensitivity and validated them in The Cancer Genome Atlas (TCGA) cohort. The validated RSS were analyzed by ingenuity pathway analysis (IPA) to identify canonical pathways, upstream regulators, diseases and functions, and gene networks related to radiosensitive genes in HPV(-) HNSCC. RESULTS: The survival fraction of 14 HNSCC cell lines after exposure to 2 Gy of radiation ranged from 48% to 72%. Six genes were positively correlated and 35 genes were negatively correlated with radioresistance, respectively. RSS was validated in the HPV(-) TCGA HNSCC cohort (n = 203), and recurrence-free survival (RFS) rate was found to be significantly lower in the radioresistant group than in the radiosensitive group (p = 0.035). Cell death and survival, cell-to-cell signaling, and cellular movement were significantly enriched in RSS, and RSSs were highly correlated with each other. CONCLUSION: We derived a HPV(-) HNSCC-specific RSS and validated it in an independent cohort. The outcome of adjuvant or definitive radiotherapy in HPV(-) patients with HNSCC can be predicted by analyzing their RSS, which might help in establishing a personalized therapeutic plan.

Management of Laryngopharyngeal Reflux in Asia.

OBJECTIVES: This study was conducted to investigate the current practices of Asian otolaryngologists for laryngopharyngeal reflux (LPR). METHODS: An online survey about LPR was sent to 2,000 members of Asian otolaryngological societies, and a subgroup analysis was performed between Western and Eastern Asian otolaryngologists. The survey was conducted by the Laryngopharyngeal Reflux Study Group of Young Otolaryngologists of the International Federation of Oto-rhino-laryngological Societies. RESULTS: Among approximately 1,600 Asian otolaryngologists, 146 completed the survey (62 from Western Asian countries, 84 from Eastern Asian countries). A substantial majority (73.3%) of the otolaryngologists considered LPR and gastroesophageal reflux disease to be different diseases. The symptoms thought to be closely related to LPR were coughing after lying down, throat clearing, and globus sensation. The findings thought to be closely related to LPR were posterior commissure granulations and hypertrophy, arytenoids, and laryngeal erythema. The respondents indicated that they mostly diagnosed LPR (70%) after an empirical therapeutic trial of proton pump inhibitors (PPIs). Although multichannel intraluminal impedance-pH (MII-pH) monitoring is a useful tool for diagnosing nonacid or mixed LPR, 78% of Asian otolaryngologists never or very rarely used MII-pH. Eastern Asian otolaryngologists more frequently used once-daily PPIs (64.3% vs. 45.2%, P=0.021), whereas Western Asian otolaryngologists preferred to use twice-daily PPIs (58.1% vs. 39.3%, P=0.025). The poor dietary habits of patients were considered to be the main reason for therapeutic failure by Asian otolaryngologists (53.8%). Only 48.6% of Asian otolaryngologists considered themselves to be adequately knowledgeable and skilled regarding LPR. CONCLUSION: Significant differences exist between Western and Eastern Asian otolaryngologists in the diagnosis and treatment of LPR. Future consensus statements are needed to establish diagnostic criteria and therapeutic regimens.

Changes in Pharyngeal Baseline Impedance in Patients With Laryngopharyngeal Reflux.

OBJECTIVE: Few studies have investigated pharyngeal intraluminal baseline impedance (BI) levels in patients with laryngopharyngeal reflux (LPR). The aim of this study was to compare intraluminal BI levels between patients with LPR and healthy controls. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: We conducted a retrospective analysis of 24-hour multichannel intraluminal impedance (MII)-pH monitoring results from patients with suspected LPR complaining of reflux symptoms. Patients with suspected LPR were divided into 2 groups according to the 24-hour MII-pH monitoring (LPR group: patients with symptoms with reflux events ≥1, symptom but no reflux [SNR] group: patients with symptoms but no reflux event). Healthy controls were recruited and also underwent 24-hour MII-pH monitoring. We compared the esophageal and pharyngeal BI levels and ratios between 3 groups. RESULTS: Pharyngeal BI levels in the LPR group were significantly higher than in the healthy controls. In addition, the pharyngeal BI levels in the SNR group were significantly higher than in the healthy controls. All ratios of pharyngeal to distal esophageal BI levels in the LPR and SNR group were significantly higher than in the healthy controls. However, there were no significant differences in esophageal BI levels and ratios between the 3 groups. CONCLUSION: We found that the pharyngeal BI levels were higher in patients with LPR than in healthy controls. In addition, the pharyngeal BI levels measured by 24-hour MII-pH monitoring in patients with LPR symptoms, but without a reflux episode, were higher than in the healthy controls.

Correlation of Nasal Fluid Biomarkers and Symptoms in Patients with Persistent Allergic Rhinitis.

OBJECTIVES: This study investigated whether the biomarkers present in nasal fluid reflect the severity of symptoms in patients with persistent allergic rhinitis (PAR). METHODS: We enrolled 29 PAR patients complaining of nasal symptoms and testing positive to skin prick test. Patients' total nasal symptom score (TNSS) was measured and their nasal lavage fluid (NALF) was collected. The levels of biomarkers including Clara cell protein 16 (CC16), tryptase, and interleukin 5 (IL-5) in NALF were determined via enzyme-linked immunosorbent assay (ELISA). RESULTS: PAR patients were classified into persistent mild and persistent moderate-to-severe groups according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The CC16 alone was significantly negatively correlated with TNSS (P < .05). Further, the CC16 level was significantly lower in persistent moderate-to-severe group than persistent mild group of patients (P < .05). CONCLUSIONS: The levels of CC16 alone among several NALF biomarkers showed an inverse correlation with symptoms of PAR patients.