Search Results (26)

Background/Objectives: The association between gastroesophageal reflux disease (GERD) and extraesophageal malignancies remains unclear. This study aimed to systematically evaluate the relationship between GERD and these cancers. Methods: PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched for studies reporting risk estimates—risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), or standardized incidence ratios (SIRs)—of GERD and extraesophageal malignancies. Mendelian randomization (MR) studies with available risk estimates and 95% confidence intervals (CIs) were also included. Pooled estimates with 95% CIs were calculated using a random-effects model. Results: As of 21 May 2025, a total of 37 studies were included in the analysis. GERD was significantly associated with an increased risk of several extraesophageal malignancies, including pharyngeal cancer (pooled RR = 2.04; 95% CI: 1.38–3.02), with a particularly high risk observed for hypopharyngeal cancer (RR = 2.95; 95% CI: 1.99–4.37; I² = 60.24%). Elevated risks were also identified for laryngeal cancer (RR = 2.23; 95% CI: 1.41–3.52) and lung cancer (RR = 1.20; 95% CI: 1.01–1.42). No significant association was found between GERD and colorectal cancer (RR = 1.19; 95% CI: 0.68–2.09), and findings regarding oral cancer were inconsistent across studies. Six MR studies confirmed a positive causal relationship between GERD and lung cancer, while one MR study suggested a potential causal association with oral cancer and another with pancreatic cancer. Conclusions: Our findings suggest that GERD may be a significant risk factor for pharyngeal, laryngeal and lung cancers. Appropriate evaluation and surveillance in patients with GERD may be warranted. Full article

Background: The relationship between Helicobacter pylori (H. pylori) infection and gastroesophageal reflux disease (GERD) remains a topic of ongoing debate. In particular, the intragastric distribution of H. pylori—whether localized in the antrum or corpus—may influence gastric acid secretion and esophageal physiology in different ways. However, its potential effects on esophageal motility and reflux parameters have not been comprehensively evaluated using combined diagnostic tools. This study aimed to assess whether H. pylori positivity, based on its histologically confirmed intragastric localization, is associated with alterations in endoscopic, manometric, and reflux monitoring findings in patients with typical GERD symptoms. Methods: This retrospective study included 213 patients with typical reflux symptoms who underwent upper gastrointestinal endoscopy with gastric biopsies, high-resolution esophageal manometry (HREM), and 24 h multichannel intraluminal impedance–pH (MII-pH) monitoring. Based on histopathology, patients were classified into three groups: H. pylori-negative, antrum-predominant infection, and corpus-predominant infection. Clinical symptoms, endoscopic findings, reflux characteristics, and esophageal motility parameters were compared. Results: Of 213 patients, 90 were H. pylori-positive (60 antrum-predominant, 30 corpus-predominant). There were no significant differences between groups in terms of typical GERD symptoms, endoscopic esophagitis, DeMeester scores, acid exposure time, or mean nocturnal baseline impedance (MNBI). Nausea and chronic laryngitis were significantly more frequent in antral H. pylori-positive patients. Notably, contraction front velocity (CFV) was significantly lower in patients with antral H. pylori compared with H. pylori-negative individuals (p = 0.002), indicating subtle slowing of esophageal peristalsis. Although this reduction in CFV did not correlate with symptom severity or bolus clearance, it may represent early functional impairment of esophageal motility. Conclusions: Although H. pylori infection—particularly when antrum-predominant—is not associated with increased reflux burden or esophagitis, it may contribute to extra-esophageal symptoms and minor motility alterations such as reduced CFV. These findings suggest that routine H. pylori eradication in GERD patients may not be necessary solely based on reflux parameters. However, treatment decisions should be individualized based on symptom profiles and endoscopic findings, including the presence of peptic ulcers, premalignant gastric lesions, or a family history of gastric malignancy, in accordance with general H. pylori eradication criteria. Full article

Objectives: To investigate the reliability and validity of the Singer Reflux Symptom Score (sRSS), a new patient-reported outcome questionnaire documenting the severity of reflux symptoms in singing voice is proposed. Methods: Amateur and professional singers consulting the European Reflux Clinic for laryngopharyngeal reflux disease (LPRD) symptoms and findings were prospectively recruited from January 2022 to February 2023. The diagnosis was based on a Reflux Symptom Score (RSS) > 13 and Reflux Sign Assessment (RSA) > 14. A control group of asymptomatic singer subjects was recruited from the University of Mons. The sRSS was rated within a 7-day period to assess test–retest reliability. Internal consistency was measured using Cronbach’s α in patients and controls. A correlation analysis was performed between sRSS and Singing Voice Handicap Index (sVHI) to evaluate convergent validity. Responsiveness to change was evaluated through pre- to post-treatment sRSS changes. The sRSS threshold for suggesting a significant impact of LPRD on singing voice was determined by receiver operating characteristic (ROC) analysis. Results: Thirty-three singers with suspected LPRD (51.5% female; mean age: 51.8 ± 17.2 years) were consecutively recruited. Difficulty reaching high notes and vocal fatigue were the most prevalent LPRD-related singing complaints. The sRSS demonstrated high internal consistency (Cronbach-α = 0.832), test–retest reliability, and external validity (correlation with sVHI: r = 0.654; p = 0.015). Singers with suspected LPRD reported a significant higher sRSS compared to 68 controls. sRSS item and total scores significantly reduced from pre-treatment to 3 months post-treatment except for the abnormal voice breathiness item. ROC analysis revealed superior diagnostic accuracy for sRSS (AUC = 0.971) compared to sRSS-quality of life (AUC = 0.926), with an optimal cutoff at sRSS > 38.5 (sensitivity: 90.3%; specificity: 85.0%). Conclusions: The sRSS is a reliable and valid singer-reported outcome questionnaire for documenting singing symptoms associated with LPRD leading to personalized management of Singers. Future large-cohort studies are needed to evaluate its specificity for LPRD compared to other vocal fold disorders in singers. Full article

Background: Chronic rhinosinusitis with or without nasal polyps (CRSwNPs/CRSsNPs) is an inflammatory disease that is becoming increasingly associated with laryngopharyngeal reflux disease (LPRD). Although symptom-based questionnaires, such as the Reflux Symptom Index (RSI) and Reflux Symptom Score (RSS), are widely used, there is a lack of objective endoscopic tools for assessing the nasopharyngeal and nasal manifestations of reflux. The Nasopharyngeal Reflux Endoscopic Score (NRES) is a novel endoscopic scoring system that was developed to address this issue. Objective: The objective of this study was to evaluate the diagnostic accuracy of the NRES in identifying LPRD in patients with CRS, compared with a clinical reference standard. Methods: A prospective diagnostic accuracy cohort study was conducted at two tertiary care centers in Astana, Kazakhstan, from September 2023 to February 2025. A total of 216 adults were enrolled and divided into three groups: CRS with suspected LPRD (n = 116), CRS without LPRD (n = 69), and healthy controls (n = 31). CRS was diagnosed according to the EPOS 2020 criteria. LPRD was defined using a composite reference standard comprising clinical assessment, RSS > 13, RSI, and selective 24 h pH monitoring and gastrointestinal endoscopy. All participants underwent nasopharyngeal and laryngeal endoscopy, with NRES, L-K, RFS, RSI, and RSS assessments at baseline and at 6 and 12 months. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance, and Wilcoxon tests were used to analyze the changes in scores. Correlation and regression analyses were used to explore associations between scales and predictive factors. Results: At baseline, NRES scores were significantly higher in the CRS with LPRD group (mean: 11.59) than in the CRS without LPRD group (mean: 3.10) and the healthy control group (mean: 2.16) (p < 0.001). ROC analysis demonstrated excellent diagnostic accuracy, with an area under the curve (AUC) of 0.998 (95% confidence interval (CI): 0.994–1.000), a sensitivity of 98% (95% CI: 94–100%) and a specificity of 96% (95% CI: 91–99%) at an optimal cut-off point of 8.5. NRES scores showed strong correlations with RSI, RSS, and RFS scores (r > 0.76, p < 0.001). A longitudinal assessment revealed significant reductions in all scores after treatment with proton pump inhibitors and lifestyle modifications, with sustained improvement at 12 months. Regression analysis found no significant effect of age, gender, or GERD severity (LA classification) on NRES scores. Conclusions: The NRES is a highly sensitive and specific endoscopic tool for identifying nasopharyngeal changes associated with LPRD in CRS patients. It demonstrates strong correlations with established symptom-based and laryngoscopic reflux assessments and responds to anti-reflux therapy over time. The NRES may, therefore, be a valuable objective adjunct in the comprehensive evaluation and longitudinal monitoring of LPRD-associated CRS. Full article

Cough is a common presenting symptom for patients in a primary care setting and significantly impacts a patient’s quality of life. Cough involves a complex reflex arc beginning with the stimulation of sensory nerves that function as cough receptors that stimulate the cough center in the brain. This “cough center” functions to receive these impulses and produce a cough by activating efferent nervous pathways to the diaphragm and laryngeal, thoracic, and abdominal musculature. Drugs that suppress the neural activity of cough are non-specific as those treatments are not directed toward pathogenic causes such as inflammation and oxidative stress. Moreover, they block a reflex called the watchdog of the lung and have a defense mechanism. Acute respiratory infections of the upper and lower airways most commonly cause acute cough. In contrast, the most common causes of chronic cough are upper airway cough syndrome, asthma, and gastroesophageal reflux disease, all associated with an inflammatory reaction at the level of the cough receptors. The use of natural compounds or herbal drugs such as carob syrup, dry blackcurrant extract, dry extract of caraway fruit, dry extract of ginger rhizome, dry extract of marshmallow root, and dry extract of ivy leaves, to name a few, not only have anti-inflammatory and antioxidant activity, but also act as antimicrobials, bronchial muscle relaxants, and increase gastric motility and empty. For these reasons, these natural substances are widely used to control cough at its deep roots (i.e., contrasting its causes and not inhibiting the arch reflex). With this approach, the lung watchdog is not put to sleep, as with peripheral or central inhibition of the cough reflex, and by contrasting the causes, we may control cough that viruses use at self-advantage to increase transmission. Full article

Dysfunctional breathing (DB) describes a respiratory condition that is mainly characterized by abnormal breathing patterns, affecting both children and adults, often leading to intermittent or chronic complaints and influencing physiological, psychological, and social aspects. Some symptoms include breathlessness; dizziness; palpitations; and anxiety, while its classification lies in breathing pattern disorders and upper airway involvement. Its prevalence among the pediatric population varies with a female overrepresentation, while the existence of comorbidities in DB, such as asthma, gastro-esophageal reflux, nasal diseases, and anxiety/depression, frequently leads to misdiagnosis or underdiagnosis and complicates therapeutic approaches. The basic diagnostic tools involve a detailed history, physical examination, and procedures such as structured light plethysmography, cardiopulmonary exercise testing, and laryngoscopy when a laryngeal obstruction is present. The management of DB presumes a multidimensional approach encompassing breathing retraining, disease-specific advice through speech and language therapy in the presence of laryngeal obstruction, psychotherapy for fostering self-efficacy, and surgical therapy in a structural abnormality. The current review was developed to provide a summary of classifications of DB and epidemiological data concerning the pediatric population, comorbidities, diagnostic tools, and therapeutic approaches to enhance the comprehension and management of DB in children. Full article

In recent years, the prevalence of laryngopharyngeal reflux has risen, especially among pediatric patients. The diagnosis of laryngopharyngeal reflux relies on patient history and clinical assessment using the Reflux Finding Score and Reflux Symptom Index as crucial diagnostic tools. Some studies have proposed a link between pepsin and laryngopharyngeal reflux, potentially triggering palatine tonsil hypertrophy. Our study aimed to investigate the correlation between laryngeal and pharyngeal manifestations of laryngopharyngeal reflux through two questionnaires and the presence of pepsin in saliva and palatine tonsils in a pediatric population. Pepsin in saliva was detected using a Western blot method, while immunohistochemistry assessed its presence in palatine tonsils. Although no statistically significant differences in Reflux Finding Score and Reflux Symptom Index were found between the immunohistochemistry-positive (IHC-positive) and immunohistochemistry-negative (IHC-negative) groups, median reflux symptom index and Reflux Finding Score values consistently trended higher in the IHC-positive group. This suggests a potential connection between elevated index values and pepsin presence in tonsillar tissue. Further investigations are essential to fully comprehend the clinical implications of these findings. Full article

Objective: To review the current findings of the literature on the existence of several profiles of laryngopharyngeal reflux (LPR) patients and to propose personalized diagnostic and therapeutic approaches. Methods: A state-of-the art review of the literature was conducted using the PubMED, Scopus, and Cochrane Library databases. The information related to epidemiology, demographics, clinical presentations, diagnostic approaches, and therapeutic responses were extracted to identify outcomes that may influence the clinical and therapeutic courses of LPR. Results: The clinical presentation and therapeutic courses of LPR may be influenced by gender, age, weight, comorbidities, dietary habits and culture, anxiety, stress, and saliva enzyme profile. The clinical expression of reflux, including laryngopharyngeal, respiratory, nasal, and eye symptoms, and the hypopharyngeal–esophageal multichannel intraluminal impedance-pH monitoring profile of patients are important issues to improve in patient management. The use of more personalized therapeutic strategies appears to be associated with better symptom relief and cures over the long-term. The role of pepsin in LPR physiology is well-established but the lack of information about the role of other gastrointestinal enzymes in the development of LPR-related mucosa inflammation limits the development of future enzyme-based personalized diagnostic and therapeutic approaches. Conclusion: Laryngopharyngeal reflux is a challenging ear, nose, and throat condition associated with poor therapeutic responses and a long-term burden in Western countries. Artificial intelligence should be used for developing personalized therapeutic strategies based on patient features. Full article

This comprehensive review explores two antiretroviral drugs, Etravirine (ETV) and Darunavir (DRV), a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor, that are commonly used in human immunodeficiency virus (HIV) infection treatment, often in combination with each other. The pharmacokinetic properties of these drugs are covered as well as the clinical trials of these two drugs combined. This paper also delves into the possible repurposing of these two drugs for other diseases, with drug repurposing being a significant factor in addressing global health challenges. DRV was extensively studied for treating COVID-19, as well as other infections, such as candidiasis and cryptococcosis, while ETV proved to be efficient in hampering Zika virus brain infection. The focus on cancer repurposing is also explored, with the results revealing that ETV has a particular inhibitory effect on ovarian cancer in vitro and on cancer molecules, such as anterior gradient protein 2 homolog (AGR2) and casein kinase 1 (CK1ε), and that DRV has an in silico inhibitory effect on human lactate dehydrogenase A (LDHA) and induces the in vitro and in vivo inhibition of pepsin, consequent laryngopharyngeal reflux, and possible laryngeal and hypopharyngeal carcinomas. The significance of fresh methods of drug development is emphasized in this work, as is the enormous potential for new therapeutic uses of the antiretroviral drugs ETV and DRV in viral and non-viral disorders. Full article

Purpose: Pediatric laryngopharyngeal reflux (P-LPR) is associated with the development of common otolaryngological symptoms and findings. In the present study, the findings about epidemiology, clinical presentation, diagnostic and therapeutic outcomes of pediatric population were reviewed. Methods: A PubMed, Cochrane Library, and Scopus literature search was conducted about evidence-based findings in epidemiology, clinical presentation, diagnostic and therapeutic outcomes of P-LPR. Findings: The prevalence of LPR remains unknown in infant and child populations. The clinical presentation depends on age. Infants with LPR symptoms commonly have both gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux and related digestive, respiratory and ear, nose and throat symptoms. The GERD prevalence appears to decrease over the growth, and the clinical picture is increasingly associated with LPR symptoms and findings without GERD. The prevalence of LPR and proximal acid and nonacid esophageal reflux events may be high in some prevalent otolaryngological conditions (chronic otitis media, laryngolomalacia and apnea). However, the lack of use of hypopharyngeal–esophageal multichannel intraluminal impedance pH monitoring (HEMII-pH) limits the establishment of etiological associations. Proton pump inhibitors are less effective in P-LPR patients compared to GERD populations, which may be related to the high prevalence of weakly or nonacid reflux events. Conclusions: Many gray areas persist in P-LPR and should be not resolved without the establishment of diagnostic criteria (guidelines) based on HEMII-pH. The unavailability of HEMII-pH and the poor acid-suppressive therapeutic response are all issues requiring future investigations. Future controlled studies using HEMII-pH and enzyme measurements in ear, nose or throat fluids may clarify the epidemiology of P-LPR according to age and its association with many otolaryngological conditions. Full article

Background: Voice and swallowing problems are frequently associated with thyroidectomy. Intermittent nerve monitoring (i-IONM) seems to provide a positive effect in reducing its prevalence. The aim of this study was to test the hypothesis that continuous intraoperative nerve monitoring (c-IONM) may reduce the prevalence of these disorders even further than i-IONM. Methods: This 3-arm prospective bi-institutional study compared 179 consecutive patients that underwent thyroidectomy: 56 without IONM, 55 with i-IONM and 67 with c-IONM. Neck dissections and laryngeal nerve palsies were excluded. Two questionnaires (VHI-10 for voice disorders and EAT-10 for swallowing disorders; both validated for Italian language use) were administered before and 1 month after surgery. Statistical significance was analyzed by the chi-squared test. Results: After thyroidectomy, no statistically significant differences were found in the three groups concerning EAT-10. although these symptoms seemed to be influenced by gastro-esophageal reflux. VHI-10 worsened in the “no-IONM” group compared with both i-IONM (p < 0.09, not quite statistically significant) and c-IONM (p < 0.04). Conclusion: Both i- and c-IONM improve voice quality independently of laryngeal nerve integrity. Reduced dissection and particularly restrained manipulation could explain these results, being particularly favorable for c-IONM. Full article

Purpose: To investigate the prevalence of symptoms and signs of laryngopharyngeal reflux (LPR) and to compare them with the otolaryngologist-estimated prevalence of the most common LPR-related symptoms and signs. Methods: The prevalence of LPR symptoms and signs was determined through the clinical data of 403 patients with a positive LPR diagnosis on hypopharyngeal–esophageal multichannel intraluminal impedance pH monitoring. The otolaryngologist-estimated prevalence was assessed through an international survey investigating the thoughts of 824 otolaryngologists toward LPR symptom and sign prevalence. The determination of potential over- or underestimation of LPR symptoms and findings was investigated through a data comparison between the ‘true’ prevalence and the ‘estimated prevalence’ of symptoms and findings by otolaryngologists. Results: The prevalence of breathing difficulties, coated tongue, and ventricular band inflammation was adequately evaluated by otolaryngologists. The prevalence of hoarseness, throat pain, odynophagia, dysphagia, throat clearing, globus sensation, excess throat mucus, tongue burning, heartburn, regurgitations, halitosis, cough after eating or lying down, and troublesome cough was overestimated by otolaryngologists (p < 0.01), while the prevalence of chest pain was underestimated as an LPR symptom. Most laryngeal signs, e.g., arytenoid/laryngeal erythema, inter-arytenoid granulation, posterior commissure hypertrophy, retrocricoid edema/erythema, and endolaryngeal sticky mucus, were overestimated (p < 0.01). The occurrence of anterior pillar erythema and tongue tonsil hypertrophy was underestimated by participants. Conclusion: Most laryngopharyngeal reflux symptoms and laryngeal signs were overestimated by otolaryngologists, while some non-laryngeal findings were underestimated. Future studies are needed to better understand the reasons for this phenomenon and to improve the awareness of otolaryngologists toward the most and least prevalent reflux symptoms and signs. Full article

This is the first study assessing the clinical management of severe, isolated dysphonia during post-COVID-19 syndrome. One hundred and fifty-eight subjects met the inclusion criteria for the post-COVID-19 condition as specified by the WHO. Six patients were diagnosed with isolated severe dysphonia, constituting 3.8% of the initial group. The pre- and post-examination protocol consisted of subjective voice self-assessment and routine laryngological examination, followed by an instrumental examination by means of Laryngovideostroboscopy (LVS) and High-Speed Videolaryngoscopy (HSV). The treatment included short-term systemic steroids in decreasing doses, moisturizing inhalations with hyaluronic acid, and protective agents against Laryngopharyngeal Reflux. The kinematic imaging of the glottis performed by means of HSV before treatment showed deviations in the regularity and symmetry of vocal fold vibrations, absence of mucosal wave, and incomplete glottal closure. Improvement of the structural and functional state of the larynx was observed post-treatment. Kymographic sections and Glottal Width Waveform (GWW) graphs obtained from post-treatment HSV recordings showed improvement in vocal fold vibrations. The decrease in mean Jitter and Shimmer was observed, with the following mean values of 3.16 pre-treatment and 2.97 post-treatment for Jitter and 7.16 pre-treatment and 2.77 post-treatment for Shimmer. The post-treatment self-evaluation of voice showed considerable improvement in vocal function and voice quality in all the examined patients. Severe dysphonia in patients with post-COVID-19 syndrome requires urgent ENT diagnosis using instrumental assessment with the evaluation of laryngeal phonatory function and intensive comprehensive treatment. Full article

Objective: To investigate post-acute laryngeal injuries and dysfunctions (PLID) in coronavirus disease 2019 (COVID-19) patients. Methods: Three independent investigators performed a systematic review of the literature studying PLID in patients with a history of COVID-19. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Epidemiological, clinical, hospitalization features, laryngeal diseases, and voice outcomes were extracted from the included papers. Results: Eight papers met our inclusion criteria (393 patients) corresponding to five uncontrolled prospective and three retrospective studies. The most prevalent PLID were vocal fold dysmotility (65%), vocal fold edema (35%), muscle tension dysphonia (21%), and laryngopharyngeal reflux (24%). Posterior glottic stenosis (12%), granuloma (14%), and posterior glottic diastasis (12%) were the most common injuries. Most patients with PLID were obese and had a history of intensive care unit hospitalization, and orotracheal intubation. The delay between the discharge and the laryngology office consultation ranged from 51 to 122 days. The mean duration of intubation ranged from 10 to 34 days. Seventy-eight (49%) intubated patients were in the prone position. The proportion of patients requiring surgical treatment ranged from 39% to 70% (mean = 48%). There was an important heterogeneity between studies about inclusion, exclusion criteria, and outcomes. Conclusions: COVID-19 appeared to be associated with PLID, especially in patients with a history of intubation. However, future controlled studies are needed to evaluate if intubated COVID-19 patients reported more frequently PLID than patients who were intubated for other conditions. Full article

Purpose: The diagnosis of laryngopharyngeal reflux (LPR) is commonly based on non-specific symptoms and findings and a positive response to an empirical therapeutic trial. The therapeutic response is, however, unpredictable, and many patients need pH-impedance monitoring to confirm the diagnosis. Methods: A review of the recent literature was conducted in PubMED, Scopus, and Embase about the pH-study features of LPR patients. A summary of last evidence was proposed. Results: The awareness of otolaryngologists about indications and interpretation of pH-impedance monitoring is low. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) is the most reliable examination determining the type and composition of hypopharyngeal reflux events (HRE) and the LPR features. The use of HEMII-pH is important to confirm the diagnosis in selected patients because non-specificity of symptoms and findings. There are no international consensus guidelines for the LPR diagnosis at the HEMII-pH. However, most studies supported the occurrence of >1 acid/weakly acid/nonacid HRE as diagnostic threshold. HREs are more frequently gaseous, weakly/nonacid compared with reflux events of gastroesophageal reflux. HREs occurred as daytime and upright, which does not support the value of double proton pump inhibitors or bedtime alginate. Oropharyngeal pH-monitoring is another approach reporting different sensitivity and specificity outcomes from HEMII-pH. The use of Ryan score for the LPR diagnosis at the oropharyngeal pH monitoring may be controversial regarding the low consideration of alkaline HREs. Conclusions: The awareness of otolaryngologists about HEMII-pH indication, features, and interpretation is an important issue regarding the high prevalence of LPR in outpatients consulting in otolaryngology. The HEMII-pH findings may indicate a more personalized treatment considering type and occurrence time of HREs. Full article