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To investigate the clinical patterns and disease evolution of laryngopharyngeal reflux (LPR) patients.Patients with LPR diagnosed by hypopharyngeal-esophageal impedance-pH monitoring were prospectively followed in three medical centers. Symptoms and findings were assessed with reflux symptom score (RSS) and reflux sign assessment (RSA). Patients were treated with 3-to 9-month diet and combination of proton pump inhibitors, alginate or magaldrate. Patients were followed for 3 years to determine the clinical evolution of symptoms over time. LPR that did not recur was defined as acute. Recurrent LPR consisted of reflux with one or several recurrences yearly despite successful treatment. Chronic LPR was reflux with a chronic course of symptoms. Predictive indicators of clinical evolution were investigated.One hundred forty patients and 82 healthy individuals completed the evaluations. Among patients, 41 (29.3%), 57 (40.7%), and 42 (30.0%) had acute, recurrent, or chronic LPR respectively. Baseline quality of life-RSS (QoL-RSS) and RSS total scores were significantly higher in chronic LPR patients. The post-treatment decrease of QoL-RSS and RSS of acute LPR patients were significantly faster as compared to recurrent and chronic patients. QoL-RSS5 reported adequate sensitivity (94.2) and specificity (75.3). QoL-RSS thresholds defined acute (QoL-RSS = 6-25), recurrent (QoL-RSS = 26-38), and chronic (QoL-RSS 38) LPR.Baseline QoL-RSS may predict the clinical course of LPR patients: acute, recurrent, or chronic. A novel classification system that groups patients according to the longevity, severity, and therapeutic response of symptoms was proposed: the International Federation of Otorhinolaryngological Societies Classification of LPR.III Laryngoscope, 2022.

Figure S1 shows results od cell viability assays, PRKRA expressions and time course experiments. Figure S2 shows results of heatmap for gene expressions and IPA. Figure S3 shows results of cell viability assay, in vivo experiment. Figure S4 shows the results of experiments for PACT-Dicer or PACT- miR 515-3p interaction. Figure S5 shows the results of experiments for miR-515-3p-AXL interaction.

Table S1 shows antibody concentrations. Table S2 shows siRNA sequences. Table S3 shows qPCR primers sequences. Table S5 shows IC50 values of oxaliplatin.

Hepatocellular carcinoma (HCC) is a heterogeneous disease. Mouse models are commonly used as preclinical models to study hepatocarcinogenesis, but how well these models recapitulate molecular subtypes of human HCC is unclear. Here, integration of genomic signatures from molecularly and clinically defined human HCC (n = 11) and mouse models of HCC (n = 9) identified the mouse models that best resembled subtypes of human HCC and determined the clinical relevance of each model. Mst1/2 knockout (KO), Sav1 KO, and SV40 T antigen mouse models effectively recapitulated subtypes of human HCC with a poor prognosis, whereas the Myc transgenic model best resembled human HCCs with a more favorable prognosis. The Myc model was also associated with activation of β-catenin. E2f1, E2f1/Myc, E2f1/Tgfa, and diethylnitrosamine (DEN)-induced models were heterogeneous and were unequally split into poor and favorable prognoses. Mst1/2 KO and Sav1 KO models best resemble human HCC with hepatic stem cell characteristics. Applying a genomic predictor for immunotherapy, the six-gene IFNγ score, the Mst1/2 KO, Sav1 KO, SV40, and DEN models were predicted to be the least responsive to immunotherapy. Further analysis showed that elevated expression of immune-inhibitory genes (Cd276 and Nectin2/Pvrl2) in Mst1/2 KO, Sav1 KO, and SV40 models and decreased expression of immune stimulatory gene (Cd86) in the DEN model might be accountable for the lack of predictive response to immunotherapy.Implication: The current genomic approach identified the most relevant mouse models to human liver cancer and suggests immunotherapeutic potential for the treatment of specific subtypes. Mol Cancer Res; 16(11); 1713–23. ©2018 AACR.

Nanostring miRNA data

For mucinous ovarian cancer (MOC), standard platinum-based therapy is largely ineffective. We sought to identify possible mechanisms of oxaliplatin resistance of MOC and develop strategies to overcome this resistance. A kinome-based siRNA library screen was carried out using human MOC cells to identify novel targets to enhance the efficacy of chemotherapy. In vitro and in vivo validations of antitumor effects were performed using mouse MOC models. Specifically, the role of PRKRA/PACT in oxaliplatin resistance was interrogated. We focused on PRKRA, a known activator of PKR kinase, and its encoded protein PACT because it was one of the five most significantly downregulated genes in the siRNA screen. In orthotopic mouse models of MOC, we observed a significant antitumor effect of PRKRA siRNA plus oxaliplatin. In addition, expression of miR-515-3p was regulated by PACT–Dicer interaction, and miR-515-3p increased the sensitivity of MOC to oxaliplatin. Mechanistically, miR-515-3p regulated chemosensitivity, in part, by targeting AXL. The PRKRA/PACT axis represents an important therapeutic target in MOC to enhance sensitivity to oxaliplatin.

S1. Correlation of prognostic probability and risk scores for mouse HCCs. S2. Glycolytic gene expression signature in mouse liver. S3. Glycolytic expression signature in mouse HCC tumors from 9 models. S4. Correlation of hepatic stem cell probability with SOH probability. S5. Expression of hepatic stem cell markers in 9 mouse models. S6. Expression of Krt-7 in Sav1 KO liver issues. S7. Expression of downstream target genes in mouse tumors. S8. Expression of Pdcd1 and Cd274 and their correlation with IFNG6 score in mouse HCCs in nine models. S9. Regulation of Cd276 by Yap1.

To evaluate the prevalence of insomnia in patients with laryngopharyngeal reflux (LPR) and to analyze the relationship between the severity of insomnia and LPR-related symptoms.We analyzed 69 patients with LPR and 61 healthy controls. The LPR was confirmed via the 24-h hypopharyngeal-esophageal multichannel intraluminal impedance pH monitoring. Reflux symptoms and sleep disturbances were assessed using the Reflux Symptom Index and Insomnia Severity Index. We compared the prevalence of insomnia between the two groups. We analyzed the relationship between reflux symptoms and severity of insomnia.The prevalence of insomnia was significantly higher in patients with LPR than in healthy controls (46.3% vs. 29.5%; p = 0.049). The severity of reflux-related symptoms was correlated with insomnia severity (rho = 0.44; p 0.001). Patients with LPR with nighttime reflux were more likely to have sleep disturbances than patients with LPR without nighttime reflux.Patients with LPR are more likely to experience insomnia than healthy controls, and the severity of reflux symptoms was related to the severity of insomnia.

Purpose The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea.Materials and Methods Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals.Results Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001).Conclusion In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.

Objectives: We aimed to evaluate the trend of HPV infection status in oropharyngeal squamous cell carcinoma (OPSCC) according to various epidemiologic factors in the United States. Design: Retrospective cohort study. Setting: Surveillance, Epidemiology, and End Results (SEER) 2010-2016 database. Participants: A total of 13081 patients with OPSCC were enrolled. Patients were diagnosed with OPSCC primarily in the base of tongue, posterior pharyngeal wall, soft palate, and tonsil between 2010 and 2016 and were tested for HPV infection status. Main outcome measures: We analyzed how the number of OPSCC patients changed according to various demographic factors from 2010 to 2016. Additionally, we forecasted and confirmed the number of HPV (+) and (-) patients with OPSCC using the autoregressive integrated moving average (ARIMA) model. Results: The number of HPV (+) patients with OPSCC has increased over the past 7 years, but the degree of increase varied greatly according to the age, sex, and subsites. The number of HPV (-) patients increased until 2015 in all age groups for each site but did not change or decrease since then. Appropriate ARIMA models were applied to forecast HPV (+) and (-) patients, and the predicted data matched the actual data well. Conclusions: This large population-based study suggests that HPV (+) patients with OPSCC has increased and will continue to increase. However, the trends in HPV infection status in patients differed greatly according to various demographic factors. These results present a direction for establishing appropriate preventive measures to deal with HPV-related OPSCC in more detail.

To analyze the incidence of pharyngeal reflux in laryngopharyngeal reflux patients over a 24-hour period and find out the key timing of pharyngeal reflux.We reviewed 69 patients who visited our clinic with LPR-related symptoms and were proven to have pharyngeal reflux via 24-hour multichannel intraluminal impedance-pH (24hr MII-pH) monitoring. Quantitative analysis was conducted for the LPR profiles, such as the acidity of reflux, nighttime reflux, and positional reflux. The time series of pharyngeal reflux episodes and mealtimes were analyzed over a 24-hour period. Also, we recruited 26 normal controls. We compared the timing of pharyngeal reflux between LPR patients and asymptomatic controls.The quantitative analysis revealed that pharyngeal reflux occurred 4.88 ± 4.59 times over 24 hours. Weakly acidic pharyngeal reflux was more abundant than acidic or weakly alkaline reflux. Pharyngeal reflux occurred mainly during daytime in the upright position. The most frequent timing of pharyngeal reflux episodes was within 2 hours after meals. Additionally, there was no significant difference of the timing of post-prandial reflux between LPR patients and asymptomatic controls.The key timing of pharyngeal reflux in patients with LPR was post-prandial 2 hours.

To determine whether the concentration of pepsin in the saliva sample changes according to the storage period of the sample.Forty eight patients with suspected laryngopharyngeal reflux were included in this study. Saliva samples were collected from each patient and each sample divided into six and stored for different period of time. Pepsin concentration was measured using enzyme-linked immunosorbent assay. A comparison was made between the pepsin concentration measured immediately and the concentration measured after storage for 1 week, 2 weeks, 1 month, 3 months, and 6 months.No significant difference in pepsin concentrations were detected between the sample analyzed immediately and those analyzed at 1 week, 2 weeks, 1 month, and 3 months after saliva collection. A significant difference in pepsin concentration was observed in the sample analyzed immediately and the sample analyzed 6 months after saliva collection.Pepsin concentration in saliva samples did not demonstrate a significant difference between the concentration measured immediately and the concentration measured 3 months after saliva collection, although a significant difference was observed in the concentration measured 6 months after collection.

Although numerous studies have used systemic approaches to identify prognostic predictors in oral squamous cell carcinoma (OSCC), the effectiveness of these approaches has not been assessed clinically. Further, the mechanism underlying malignant behaviors in OSCC is poorly characterized. This study aimed to develop and verify accurate prognostic predictors for OSCC patients and assess the associated biology. We identified an OSCC-recurrence-related gene signature (ORGS) using a Cox regression analysis. Functional enrichment analysis was used to identify enriched pathways and biological processes to reveal the underlying mechanism of OSCC malignant behavior. The ORGS successfully divided OSCC patients into low- and high-risk groups with significantly different overall survivals. Pathway analysis revealed oxidative phosphorylation (OXPHOS) as a signaling pathway associated with the ORGS in OSCC. Interestingly, high OXPHOS status was strongly associated with poor overall survival in OSCC patients. Mediator complex subunit 30 (MED30) was a predicted upstream regulator of OXPHOS, and knockdown of MED30 reduced histone acetylation. We identified that the ORGS was strongly correlated with OXPHOS regulatory processes, suggesting OXPHOS as a key mechanism leading to poor prognosis in OSCC.

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition of the upper aerodigestive tract mucosa induced by reflux content from stomach. Some of vocal cord diseases are associated with laryngopharyngeal reflux. Because of the pathophysiological features, proton pump inhibitor shows therapeutic effect on some vocal cord diseases. As like that, the gastric reflux contents can make macroscopic or microscopic morphological changes in the upper aerodigestive tract mucosa. Although the pathophysiology of LPRD is relatively clear, clinical diagnosis is still difficult. The diagnosis of LPRD includes objective tests such as 24-hours multichannel intraluminal impedance-pH metry and subjective tests such as questionnaire method. However, the objective verification of reflux is difficult due to invasiveness of the method, and the questionnaire methods have limitations because many symptoms are not specific for LPRD. Moreover, most methods are not fully standardized until now. Despite these limitations, many researchers are struggling to standardize diagnosis and treatment of LPRD, and there are several new achievements recently. Therefore, the purpose of this article is to review the recent literature on the clinical presentation, diagnosis, and treatment of LPRD, and to systematize our knowledge.

Background This study aimed to investigate the survival benefit of postoperative radiotherapy in patients with resected human papilloma virus-positive oropharyngeal squamous cell carcinoma using data from the Surveillance, Epidemiology, and End Results database. Methods A total of 2,589 human papilloma virus-positive oropharyngeal squamous cell carcinoma patients who underwent surgery were identified from the Surveillance, Epidemiology, and End Results database. Propensity score matching was performed to balance the baseline characteristics between patients who received postoperative radiotherapy and those who did not. Overall survival and disease-specific survival were estimated. Results After propensity score matching, postoperative radiotherapy did not increase overall survival and disease-specific survival. The subgroup analysis revealed that overall survival and disease-specific survival benefits of postoperative radiotherapy were observed only among patients with N2 or N3 stage disease. Multivariate analysis revealed that old age and advanced T, N stages were prognostic factors for disease-specific survival in oropharyngeal squamous cell carcinoma patients who underwent surgery. Conclusion Postoperative radiotherapy might improve the survival of human papilloma virus-positive oropharyngeal squamous cell carcinoma patients with advanced N stage.

Background and Objectives: Biomarkers of allergic rhinitis (AR) have been studied; however, little is known regarding their practical application in the diagnosis of AR. Previous studies collected samples using saline lavage, nasal brushing, or nasal biopsy. To utilize nasal fluid as a diagnostic tool, we need to standardize the method of sample collection. Therefore, this study aimed to evaluate the difference in concentration of biomarkers depending on the method of nasal fluid collection.Materials and Method: Forty-five AR patients who had greater than moderate AR symptoms and who had positive results on skin prick test and serum-specific IgE tests were enrolled in this study. Nasal fluid was collected using the direct method or saline lavage method. The concentration of each biomarker was analyzed using enzyme-linked immunosorbent assay and the values compared.Results: Nasal fluid samples were collected directly from 14 patients and were collected via saline lavage in 31 patients. No significant differences were found in the median value of each biomarker between the two methods of nasal sample collection.Conclusion: Nasal fluid collection method does not significantly affect biomarker concentration.

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.Prospective cohort study.A tertiary care otolaryngology clinic.Patients with typical LPR symptoms showing1 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'sEighty 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 (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.

The aim of the study was to investigate the association between metabolic diseases and the risk of head and neck cancer (HNC) using nationwide population-based big data. This retrospective cohort study was conducted using the Korean National Health Insurance Service health checkup database. A total of 4,575,818 participants aged >40 years who received a health checkup in 2008 were enrolled, and we studied the incidence of HNC until 2019. We analyzed the risk of HNC according to the presence of metabolic diseases, such as obesity, dyslipidemia, hypertension, and diabetes. Although metabolic syndrome itself was not associated with HNC, each component of metabolic syndrome was associated with HNC. Underweight and diabetes were risk factors for HNC (HR: 1.694). High total cholesterol and high low-density lipoprotein cholesterol levels were factors that decreased the risk (HR 0.910 and 0.839). When we analyzed men and women separately, low total cholesterol level, low low-density lipoprotein cholesterol level, and hypertension were risk factors only in men. In addition, pre-obesity, obesity, and central obesity decreased the risk only in men. Each metabolic disease affects HNC in different ways. Underweight and diabetes increased the risk of HNC, whereas high total cholesterol and high low-density lipoprotein cholesterol levels decreased the risk of HNC.

Background: Gastric adenocarcinoma (GAC) is heterogeneous lethal disease in genomic and clinical level. Although the clinical relevance of genomic and molecular subtypes of GAC has been demonstrated, their translation to the clinic has been hindered by discrepancies in classification methods. We aim to examine a consensus of genomic subtypes and correlate them with clinical outcomes. Method: We collected genomic data from 2527 GAC tumors and divided the data into discovery (n = 1427) and validation sets (n = 1100). By integrating 8 previously established genomic subtype algorithms, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs) in discovery set. For validation of clinical significance of new subtypes, we constructed GAC predictor of integrated consensus subtype with 120 genes (GPICS120) and applied it to validation data set. In systematic analysis of genomic and proteomic data, we estimated potential response rate of each subtype to standard and experimental treatments such as radiation therapy, target therapy, and immunotherapy and further validated their functional significance in cell line models. Results: Among identified 6 subtypes. CGS1 is characterized by poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 showed canonical epithelial gene expression patterns. CGS3 and CGS4 are characterized by high copy number alterations and low immune activity. However, CGS3 and CGS4 are different in high HER2 activation (CGS3) and SALL4 and KRAS activation (CSG4). CGS5 has highest mutation burden and moderately high immune activity that is characteristics of MSI-high tumors. Most of CGS6 tumors are EBV-positive and shows extremely high methylation and high immune activity. Most interestingly, CSG1 is most responsive to immunotherapy while CGS3 is significantly associated with benefit of chemoradiation therapy due to high basal level ferroptosis. In addition, we also identified potential therapeutic targets for each subtype. Conclusion: Consensus subtype is robust classification system and can be the basis for pre-clinical investigation of subtype-based targeted interventions and future clinical trials. Citation Format: Yun Seong Jeong, Young-Gyu Eun, Sung Hwan Lee, Sang-Hee Kang, Sun Young Yim, Eui Hyun Kim, Joo Kyung Noh, Bo Hwa Sohn, Ju-Seog Lee. Consensus genomic subtypes of gastric adenocarcinoma and their therapeutic implication. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4344.

This study aimed to analyze pharyngeal reflux episodes in patients with suspected LPR versus healthy subjects using 24-h MII-pH monitoring. 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. 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. 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.

To evaluate differences between manual and automated analyses of 24-hour multichannel intraluminal impedance-pH monitoring for diagnosis of laryngopharyngeal reflux.Case series with planned data collection.Academic center outpatient clinic.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.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.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.

Purpose Few studies have been conducted on the association between oral cavity cancer and metabolic diseases. This study aimed to investigate the relationship between oral cavity cancer and metabolic diseases. Methods This cohort study used the database of the Korean National Health Insurance Service, which contains medical data of 97% of the Korean population. Oral cavity cancer occurred in a total of 2,718 patients. Metabolic syndrome was defined according to IDF criteria. The Cox proportional hazard regression model was used. Results The HR for oral cavity cancer in patients with metabolic syndrome was 1.113(95% CI, 1.006–1.232), which was significantly higher than that in normal patients, especially in males (p = 0.0386). When the number of metabolic syndrome factors was ≥ 3, the HR of oral cavity cancer was 1.191(95% CI, 1.026–1.383), which was significantly higher than that of 0 metabolic syndrome factors, especially in males (p = 0.0218). When the number of metabolic syndrome factors was ≥ 3, the HR for oral cavity cancer was 1.439(95% CI, 1.066–1.942), which was significantly higher than that of 0 metabolic syndrome factors, especially in males aged

To evaluate the differences in diagnostic rates according to the age and sex of patients with suspected laryngopharyngeal reflux (LPR) symptoms and completed the 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH (24h-HEMII-pH) monitoring.Patients with LPR symptoms underwent the 24h-HEMII-pH monitoring. We compared the diagnostic rates of LPR in patients with LPR symptoms according to age and sex. The number of reflux episodes and type of reflux were compared among patients who were confirmed to have LPR according to age and sex.A total of 249 patients with suspected LPR symptoms who completed 24h-HEMII-pH monitoring were analyzed. A total of 170 patients (68.3%) were diagnosed with LPR after 24h-HEMII-pH monitoring. There were 57 (67.1%) men and 113 (68.9%) women. The old age group (older than 55 years) showed a statistically significant higher diagnostic rate than the young age group (73.5%, 60.8%, p=0.034). Women's diagnostic rate was statistically higher in the old age group than that in the young age group (75% vs. 58.3%, p=0.026). There were no specific differences in the number of refluxes in the diagnosed patients between the age groups, and there were no differences in the initial reflux symptom index.Among those who visited the clinic with suspected LPR symptoms and performed 24h-HEMII-pH monitoring, the diagnostic rate of LPR was higher in the older age group than that in the younger age group.

Background: Various cancer stem cell (CSC) biomarkers and 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 to be ascertained. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC by using five publicly available HNSCC cohorts.Methods: To predict the prognosis of patients with HNSCC, we developed and validated CSC gene signatures whose mRNA expression was correlated with at least one of four CSC genes, CD44, MET, ALDH1A1, and BMI1.Results: Patients in TCGA HNSCC cohort were classified into CSC gene-associated high-risk (CSC-HR; n=285) and CSC gene-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 signature was validated using four independent cohorts. Cox proportional hazards models showed that the CSC gene signature was an independent prognostic factor for patients with HNSCC. Furthermore, CSC gene signature was associated with the prognosis of patients with HNSCC who received radiotherapy or those with HPV (-) status.Conclusion: The CSC gene signature was associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC.

To study the management of laryngopharyngeal reflux (LPR) among the subspecialties of practicing otolaryngology-head and neck surgeons and their trainees. A survey was sent to over 8000 otolaryngologists (OTOHNS) over 65 countries, utilizing membership lists of participating otolaryngological societies. The outcomes were answers to questions regarding LPR knowledge and practice patterns, and included queries about its definition, prevalence, clinical presentation, diagnosis, and treatment. Of the 824 respondents, 658 practiced in one specific otolaryngologic subspecialty. The symptoms and findings thought to be the most related to LPR varied significantly between subspecialists. Extra-laryngeal findings were considered less by laryngologists while more experienced OTOHNS did not often consider digestive complaints. Compared with colleagues, otologists, rhinologists and laryngologists were less aware of the involvement of LPR in otological, rhinological and laryngological disorders, respectively. Irrespective of subspecialty, OTOHNS consider symptoms and signs and a positive response to empirical therapeutic trial to establish a LPR diagnosis. Awareness regarding the usefulness of impedance pH-studies is low in all groups. The therapeutic approach significantly varies between groups, although all were in agreement for the treatment duration. The management of non-responder patients demonstrated significant differences among laryngologists who performed additional examinations. The majority of participants (37.1%) admitted to being less than knowledgeable about LPR management. LPR knowledge and management vary significantly across otolaryngology subspecialties. International guidelines on LPR management appear necessary to improve knowledge and management of LPR across all subspecialties of otolaryngology.