Esophageal Reflux Hypersensitivity: A Comprehensive Review

Reflux hypersensitivity (RH) is one of the phenotypes of gastroesophageal reflux disease. The latest Rome IV defines RH as a condition with typical reflux symptoms and positive reflux-symptom association despite normal acid exposure. Subsequently, the Lyon consensus proposed detailed cutoff values for the criteria on the basis of experts’ consensus. Rome IV brought a clear-cut perspective into the pathophysiology of gastroesophageal reflux disease and the importance of esophageal hypersensitivity. This perspective can be supported by the fact that other functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia often overlap with RH. Although several possible pathophysiological mechanisms of esophageal hypersensitivity have been identified, there is still unmet medical needs in terms of treatment for this condition. This review summarizes the current knowledge regarding RH.

High expression of folate receptor alpha is associated with poor prognosis in patients with cervical cancer / 부인종양

Objective@#Folate receptor α (FRα) is a membrane protein expressed in various solid tumors but has limited expression in normal cells. Therefore, FRα is an attractive target for cancer treatment. This study aimed to investigate the relationship between FRα expression and the clinicopathological characteristics and survivals of cervical cancer. @*Methods@#This retrospective study included patients with cervical cancer who underwent primary surgery between 2000 and 2020 at our institution. Immunohistochemical staining of FRα was performed using an anti-folate-binding protein/FBP antibody. FRα-positive staining was defined as ≥5% of tumor staining and FRα-high as ≥50% tumor staining with ≥2+ intensity. The association between FRα expression and survival was assessed using multivariate Cox regression analysis, adjusting for established prognostic factors. @*Results@#Overall, 123 patients were identified, and 140 tumor samples, including 17 paired primary and metastatic samples, were evaluated. As histological types, 67 patients had squamous cell carcinoma (SCC), and 56 patients had non-SCC. All primary tumors were FRα-positive. High FRα expression was observed in 25% of the cases and differed according to histology (SCC vs. non-SCC, 14.9% vs. 37.5%, p=0.004). FRα expression was significantly higher in metastatic tumors than in primary (170 [IQR, 140–205] vs. 125 [IQR, 110–150], p=0.0006). High FRα expression was significantly associated with worse overall survival (hazard ratio, 6.73; 95% confidence interval, 2.21–20.53; p=0.001). @*Conclusion@#In cervical cancer, FRα expression was elevated in metastatic tumors and high expression was associated with a worse prognosis. Our study supports the development of FRα-targeted therapy for advanced cervical cancer.

Heartburn, Functional Dyspepsia, Anxiety/Depression, and Sleep Disturbances Are Associated With Clinically Significant Belching

Background/Aims@#Belching is the act of expelling gas from the stomach or esophagus noisily through the oral cavity. Although it is a physiological phenomenon, belching may also be a symptom of upper gastrointestinal diseases such as reflux esophagitis and functional dyspepsia (FD). A detailed epidemiology of belching has not yet been reported. The aim of this study is to examine the prevalence and clinical characteristics of clinically significant belching (CSB) in adults. @*Methods@#We analyzed 1998 subjects who visited the hospital for annual health checkups. Belching was evaluated by a simple question “Do you burp a lot?” and scored as 0 (never), 1 (occasionally), 2 (sometimes), 3 (often), or 4 (always). Subjects with CSB were defined ashaving scores ≥ 3. We also collected the clinical parameters, endoscopic findings, and data according to the Athens Insomnia Scale, Rome IV questionnaire, and Hospital Anxiety and Depression Scale (HADS). @*Results@#Of the 1998 subjects, 121 (6.1%) had CSB. Subjects with CSB had FD more commonly than reflux esophagitis, but presence of heartburn was high (10.7% vs 3.1%). In addition, the HADS and Athens Insomnia Scale scores in subjects with CSB were significantly higher than those in subjects without CSB. Presence of heartburn (OR, 2.07; 95% CI, 1.05-4.09), presence of FD (OR, 2.12; 95% CI, 1.33-3.36), anxiety/depression (OR, 2.29; 95% CI 1.51-3.45), and sleep disturbances (OR, 1.73; 95% CI, 1.14-2.61) were significantly associated with CSB. @*Conclusion@#The detailed epidemiology of belching in the general adult population was clarified.

Heartburn, Functional Dyspepsia, Anxiety/Depression, and Sleep Disturbances Are Associated With Clinically Significant Belching

Background/Aims@#Belching is the act of expelling gas from the stomach or esophagus noisily through the oral cavity. Although it is a physiological phenomenon, belching may also be a symptom of upper gastrointestinal diseases such as reflux esophagitis and functional dyspepsia (FD). A detailed epidemiology of belching has not yet been reported. The aim of this study is to examine the prevalence and clinical characteristics of clinically significant belching (CSB) in adults. @*Methods@#We analyzed 1998 subjects who visited the hospital for annual health checkups. Belching was evaluated by a simple question “Do you burp a lot?” and scored as 0 (never), 1 (occasionally), 2 (sometimes), 3 (often), or 4 (always). Subjects with CSB were defined ashaving scores ≥ 3. We also collected the clinical parameters, endoscopic findings, and data according to the Athens Insomnia Scale, Rome IV questionnaire, and Hospital Anxiety and Depression Scale (HADS). @*Results@#Of the 1998 subjects, 121 (6.1%) had CSB. Subjects with CSB had FD more commonly than reflux esophagitis, but presence of heartburn was high (10.7% vs 3.1%). In addition, the HADS and Athens Insomnia Scale scores in subjects with CSB were significantly higher than those in subjects without CSB. Presence of heartburn (OR, 2.07; 95% CI, 1.05-4.09), presence of FD (OR, 2.12; 95% CI, 1.33-3.36), anxiety/depression (OR, 2.29; 95% CI 1.51-3.45), and sleep disturbances (OR, 1.73; 95% CI, 1.14-2.61) were significantly associated with CSB. @*Conclusion@#The detailed epidemiology of belching in the general adult population was clarified.

Liquid-containing Refluxes and Acid Refluxes May Be Less Frequent in the Japanese Population Than in Other Populations: Normal Values of 24-hour Esophageal Impedance and pH Monitoring

BACKGROUND/AIMS: Twenty-four-hour esophageal impedance and pH monitoring allows detection of all types of reflux episodes and is considered the best technique for identifying gastroesophageal refluxes. However, normative data for the Japanese population are lacking. This multicenter study aimed to establish the normal range of 24-hour esophageal impedance and pH data both in the distal and the proximal esophagus in Japanese subjects. METHODS: Forty-two healthy volunteers (25 men and 17 women) with a mean ± standard deviation age of 33.3 ± 12.4 years (range: 22–72 years) underwent a combined 24-hour esophageal impedance and pH monitoring. According to the physical and pH properties, distal or proximal esophageal reflux events were categorized. RESULTS: Median 45 reflux events occurred in 24 hours, and the 95th percentile was 85 events. Unlike previous reports, liquid-containing reflux events are median 25/24 hours with the 95th percentile of 62/24 hours. Acidic reflux events were median 11/24 hours with the 95th percentile of 39/24 hours. Non-acidic gas reflux events were median 15/24 hours with the 95th percentile of 39/24 hours. Proximal reflux events accounted for 80% of the total reflux events and were mainly non-acidic gas refluxes. About 19% of liquid and mixed refluxes reached the proximal esophagus. CONCLUSIONS: Unlike previous studies, liquid-containing and acidic reflux events may be less frequent in the Japanese population. Non-acidic gas reflux events may be frequent and a cause of frequent proximal reflux events. This study provides important normative data for 24-hour impedance and pH monitoring in both the distal and the proximal esophagus in the Japanese population.

Overlap in Patients With Dyspepsia/Functional Dyspepsia

Patients with dyspepsia/functional dyspepsia (FD) show frequent overlapping of other gastrointestinal (GI) diseases, such as irritable bowel syndrome, and non-GI diseases, in addition to internal subgroup overlapping. These overlap patients have more frequent or more severe symptoms, poorer health-related quality of life and higher somatization scores, and they are more likely to experience anxiety, depression or insomnia compared to non-overlap patients. The higher prevalence of overlap in patients with dyspepsia/FD is not by chance, indicating common pathogeneses, including visceral hypersensitivity, altered GI motility, infection, and stressful early life events. There are few clinical trials targeting overlap in patients with dyspepsia/FD, and no therapeutic strategy has been established. Further studies in this research area are needed. In this review, we describe the epidemiology, pathogenesis and treatment of overlap in patients with dyspepsia/FD.