Spectrum Of Gastroesophageal Reflux Disease Research Articles

The Clinical Spectrum of Gastroesophageal Reflux Disease: Facts and Fictions

<b><i>Background:</i></b> This review addresses the intricate spectrum of gastroesophageal reflux disease (GERD), a condition affecting 10–30% of the Western population. GERD is characterized by the backflow of gastric contents into the esophagus, causing typical and atypical symptoms. Its pathophysiology involves various factors such as hiatal hernia, esophageal motor disorders, and dietary triggers. The review explores the complexities of GERD spectrum, including nonerosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). <b><i>Summary:</i></b> The diagnostic process for GERD, based on the Lyon Consensus 2.0 criteria, encompasses clinical evaluation, endoscopy, and functional tests, including pH-impedance and wireless-pH monitoring. NERD, a significant subset of GERD, is defined by reflux symptoms and abnormal reflux burden without mucosal damage. RH, classified under functional esophageal disorders by Rome IV criteria, presents with typical esophageal symptoms associated with reflux but lacks of structural, inflammatory, or motor causes. FH is identified by heartburn with normal endoscopy, reflux testing, and esophageal manometry results. The management of RH and FH, focusing on reducing esophageal hypersensitivity, varies from standard GERD treatments. <b><i>Key Messages:</i></b> The review emphasizes the necessity of personalized treatment strategies due to the complexity and overlap of GERD subtypes. It highlights the importance of a multidisciplinary approach, involving gastroenterologists, psychologists, and other specialists, to improve patient outcomes and quality of life. The article underscores that understanding the distinctions and overlaps among NERD, RH, and FH is crucial for effective management, and the need for innovative approaches in diagnosis and treatment to address the unique challenges of each subtype.

Association of self-reported and objective sleep disturbance with the spectrum of gastroesophageal reflux disease.

The relationship between obstructive sleep apnea (OSA) and gastroesophageal reflux disease (GERD) is complex. We aimed to determine the association of self-reported and objective sleep parameters with diverse manifestations of the GERD spectrum. We prospectively recruited 561 individuals who underwent an electrocardiogram-based cardiopulmonary coupling for OSA screening during a health check-up. All participants received the Reflux Disease Questionnaire and an upper endoscopy to determine the presence of troublesome reflux symptoms and erosive esophagitis (EE). Sleep quality was evaluated by the Pittsburgh Sleep Quality Index and sleep dysfunction was defined as a Pittsburgh Sleep Quality Index score > 5. OSA was defined as a cardiopulmonary coupling-derived apnea-hypopnea index exceeding 15 events/h. Comparisons were made between participants on the GERD spectrum with respect to their various self-reported and objective sleep parameters. Among the 277 patients with GERD (49.4%), 198 (35.3%) had EE. Patients with GERD had higher PSQI scores (6.99 ± 3.97 vs 6.07 ± 3.73, P = .005) and a higher prevalence of sleep dysfunction (60.6% vs 49.6%, P = .009). Patients with EE had a higher prevalence of OSA (42.9% vs 33.9%, P = .034). Along the GERD spectrum, symptomatic patients with EE had the highest PSQI scores and prevalence of sleep dysfunction (70.7%), while asymptomatic patients with EE had the highest prevalence of OSA (44%). Our findings indicate a high prevalence of sleep dysfunction among individuals with GERD. Furthermore, patients on the GERD spectrum are prone to experiencing a range of self-reported and objective sleep disturbances. Hu K-Y, Tseng P-H, Hsu W-C, etal. Association of self-reported and objective sleep disturbance with the spectrum of gastroesophageal reflux disease. J Clin Sleep Med. 2024;20(6):911-920.

Exploration of esophageal hypervigilance and anxiety status in patients with symptomatic gastroesophageal reflux disease: A single‐center study in Taiwan

AbstractThe esophageal hypervigilance and anxiety scale (EHAS) is a valuable cognitive‐affective evaluation of visceral sensitivity, which has been demonstrated to associate with gastroesophageal reflux disease (GERD) symptom severity and psychological stress. We aimed to obtain the values for EHAS in the setting of patients who underwent esophagogastroduodenoscopy (EGD) without GERD symptoms and investigate potential clinical factors contributing level of EHAS in symptomatic patients. Patients scheduled EGD with or without GERD symptoms were prospectively enrolled for assessing patient‐reported outcomes, including EHAS and GERD questionnaire (GERDQ). Patients without GERD symptoms had GERDQ ≤8 were classified as controls. Potential factors influencing the level of EHAS were identified via generalized linear model. We enrolled 534 patients, aged 20 to 84 years (mean, 52.78), of whom 54.2% were female; 110 had GERD symptoms, and 418 were controls. Patients with GERD symptoms had higher EHAS levels than controls (28.7 vs 10.2, P < .001). On generalized linear model GERDQ scores and female gender positively correlated with EHAS (GERDQ, β = 2.254, P < .001; female, β = 3.828, P = .001). In summary, our study suggests that greater esophageal hypervigilance and anxiety are associated with reflux symptoms burden across the spectrum of GERD, and correlate with female gender too.

A Study on the Correlation Between Endoscopic Findings and Symptoms of Gastroesophageal Reflux Disease (GERD).

BackgroundGastroesophageal reflux disease is a common disorder affecting a large section of the community. In addition, the numerous complications of chronic gastroesophageal reflux disease (GERD) necessitate adequate diagnosis and treatment of this common entity. Thus, to analyze the spectrum of GERD on the basis of symptoms and endoscopic findings along with the contributory effects of various risk factors including obesity, this specific study has been carried out.Study designA descriptive type of observational study was conducted on the patients visiting the outpatient department (OPD) at Acharya Vinoba Bhave Rural Hospital (AVBRH), affiliated with Datta Meghe Institute of Medical Sciences (DMIMS), Wardha, Maharashtra. The clinical symptoms, suspected risk factors, and endoscopic findings of the patients were studied, assessed, and correlated.Methods and materialPatients, more than 18 years of age complaining of a minimum of two typical symptoms of GERD for at least one month, were included in the study. Demographic data, clinical symptomatology, and personal history of the patients were noted. All the patients were subjected to esophagogastroduodenoscopy, and findings were recorded. Correlation and analysis were done on clinical and endoscopic findings.Statistical analysisThis descriptive study has been conducted after the approval of the Ethics Committee Department of Medical Education, Jawaharlal Nehru Medical College, Deemed University, Sawangi (DMIMS(DU)/IEC/Sept-2019/8403). The outcomes were recorded and analyzed at the end of the study using a Microsoft Excel Spreadsheet (version 16.40, Microsoft Corporation, Redmond, Washington, USA).Results and conclusionA total of 100 patients were included in the study. A number of male patients (58%) were more than that of female patients. Most of the patients were in the age group of 30-60 years (70%). The most common symptoms were epigastric pain (78%), regurgitation (71%), and heartburn (63%). Forty-five percent of the patients had erosive lesions suggestive of reflux esophagitis on endoscopic evaluation.

Current advances in the diagnosis and management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is very common and defined as troublesome symptoms owing to excessive acid reflux. The spectrum of GERD is broad, including not only erosive esophagitis and Barrett's esophagus but also nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. Patients with reflux symptoms despite normal endoscopy remain common clinical presentation, can be heterogeneous overlapping with functional gastrointestinal disorders. Ambulatory esophageal pH monitoring with and without impedance helps the diagnosis of NERD. Metrics such as baseline impedance and postreflux swallow induced peristaltic wave enhance diagnostic accuracy in patients with inconclusive diagnoses. The major treatment of all manifestations of GERD is acid suppression with proton pump inhibitors, while other therapies, such as reflux-reducing agents and adjunctive medications, can be individualized where the response to traditional management is incomplete. GERD patients often need long-term treatment due to frequent relapses. Anti-reflux surgery can be effective too. Endoscopic therapies have some promising results, but long-term outcomes remain to be determined.

Impact of Participation of Surgeons in Diagnostic Studies of Gastroesophageal Reflux Disease on Completion of Workup and Utilization of Antireflux Surgery.

Introduction. Patients presenting with symptoms of gastroesophageal reflux disease (GERD) are usually evaluated by gastroenterologists who perform the diagnostic workup and determine when to refer for surgical consideration. The multiple diagnostic studies can be overwhelming, and this leads to dropouts. In a rural setting, without gastroenterology services, the surgeon can diagnose GERD and perform antireflux procedures. This study aimed to assess the completion of the required diagnostic studies and progression to surgical intervention. Methods. This is a retrospective chart review of patients who presented with GERD symptoms between August 2015 and January 2018. Standardized workup included the upper gastrointestinal study and esophagogastroduodenoscopy with concomitant wireless pH placement. High-resolution impedance manometry and the gastric emptying scan were selectively utilized. Results. 429 patients were evaluated. Proton pump inhibitors were used by 82.2% of patients. The required diagnostic workup was completed by 92.7% of all patients. Nearly 75% were suitable candidates for antireflux surgery. Approximately 2/3 of these patients proceeded with antireflux surgery. Discussion. The lack of gastroenterology services in rural hospitals provides a unique opportunity for general surgeons to diagnose and treat GERD patients locally. This avoids fragmentation of care and enables the surgeon to evaluate the entire spectrum of GERD. This structured approach results in increased completion of multiple diagnostic studies. Moreover, surgical candidates are likely to proceed with surgical intervention. Conclusion. A surgical antireflux program with diagnostic and therapeutic capabilities results in increased completion of diagnostic workup and utilization of antireflux surgery.

Distinct Microbiota Dysbiosis in Patients with Non-Erosive Reflux Disease and Esophageal Adenocarcinoma.

Non-erosive reflux disease (NERD) and esophageal adenocarcinoma (EAC) are often regarded as bookends in the gastroesophageal reflux disease spectrum. However, there is limited clinical evidence to support this disease paradigm while the underlying mechanisms of disease progression remain unclear. In this study, we used 16S rRNA sequencing and mass-spectrometer-based proteomics to characterize the esophageal microbiota and host mucosa proteome, respectively. A total of 70 participants from four patient groups (NERD, reflux esophagitis, Barrett’s esophagus, and EAC) and a control group were analyzed. Our results showed a unique NERD microbiota composition, distinct to control and other groups. We speculate that an increase in sulfate-reducing Proteobacteria and Bacteroidetes along with hydrogen producer Dorea are associated with a mechanistic role in visceral hypersensitivity. We also observed a distinct EAC microbiota consisting of a high abundance of lactic acid-producing bacteria (Staphylococcus, Lactobacillus, Bifidobacterium, and Streptococcus), which may contribute towards carcinogenesis through dysregulated lactate metabolism. This study suggests the close relationship between esophageal mucosal microbiota and the appearance of pathologies of this organ.

New evidence defining the pathology and pathogenesis of lower esophageal sphincter damage

SummaryBackgroundPresent diagnosis and management of gastroesophageal reflux disease (GERD) has resulted in a dramatic increase in the incidence of esophageal adenocarcinoma. This is due to failure to identify pathologic changes of early GERD; at present, pathology is limited to management of Barrett esophagus (BE).MethodsConvincing evidence have confirmed that cardiac mucosa distal to the squamocolumnar junction in the endoscopically normal person is a metaplastic GERD-induced esophageal epithelium, and not a normal proximal gastric epithelium.ResultsWhen cardiac mucosa is recognized as a metaplastic esophageal epithelium, it becomes self-evident that the present endoscopic definition of the gastro-esophageal junction is incorrect, and there exists a dilated distal esophagus (DDE) in what is incorrectly termed the “gastric cardia” presently mistaken for proximal stomach. It also becomes clear that the length of the DDE correlates with the presence and severity of GERD and represents the pathology of the entire spectrum of GERD. Further, it allows recognition that the DDE, measured as the gap between esophageal squamous epithelium and gastric oxyntic mucosa that is composed of cardiac mucosa, represents the pathologic anatomy of damage to the abdominal segment of the lower esophageal sphincter (LES).ConclusionThe new understanding of the significance of cardiac mucosa provides a new and highly accurate histologic method of assessment of LES damage, the primary cause of GERD. This opens a new door to complete histologic assessment of GERD from its etiologic standpoint and to new research that permit early diagnosis of GERD at its outset. Ultimately, such early diagnosis has the potential to reverse the increasing trend of esophageal adenocarcinoma.

Systematic Endoscopy 5Years After Sleeve Gastrectomy Results in a High Rate of Barrett's Esophagus: Results of a Multicenter Study.

Recent evidence has indicated an increased risk of Barrett's esophagus (BE) in the long term after sleeve gastrectomy (SG). The aim of the study is to investigate the spectrum of gastroesophageal reflux disease (GERD) symptoms as well as the prevalence of BE, at minimum 5years after SG in patients who underwent SG in different bariatric centers of two countries: France and Italy. Five high volume outpatient centers dedicated to bariatric surgery that routinely perform upper GI endoscopy before any bariatric procedures were invited to participate in the study. From January 2017 to June 2018, each center during scheduled postoperative evaluation after surgery asked a minimum 10 consecutive patients, which had performed SG at least 5years before and with no evidence of BE preoperatively, to undergo another upper GI endoscopy. Ninety (66 F) consecutive patients were enrolled. The mean follow-up was 78 ± 15months, and the mean total body weight loss was 25 ± 12%. The prevalence of BE was 18.8% with no significant difference among centers. Weight loss failure was significantly associated with BE (p < 0.01). The prevalence of GERD symptoms, erosive esophagitis, and the usage of PPIs increased from 22%, 10%, and 22% before the SG to 76%, 41%, and 52% at the time of follow-up, respectively (p < 0.05). This multicenter study show a high rate of BE at least 5years after SG. Weight loss failure was significantly associated with BE. We suggest to provide systematic endoscopy in these patients to rule out this condition.

Complexity and diversity of gastroesophageal reflux disease phenotypes.

Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms, impairs quality of life, or leads to mucosal damage or complications. There are two main phenotypic presentations of GERD, the erosive (ERD) and non-erosive reflux disease (NERD), with the latter one representing up to 70% of GERD spectrum. Moreover, patients with GERD can be clinically subdivided into two distinct syndromes: patients with esophageal and extraesophageal symptoms. The diagnosis of NERD should be supported by the evidence that symptoms are due to reflux episodes on the basis of an excess of acid into the esophagus or a positive correlation between symptoms and acid and/or weakly acidic reflux episodes as evidenced by 24-hour impedance-pH monitoring. Patients with normal esophageal acid exposure and no correlation between heartburn and any kind of chemical reflux are considered affected by functional heartburn and do not pertain to the realm of NERD. They do not usually respond to PPI therapy as further empirical criterion and are included in the large group of functional digestive disorders with the expression of altered generation or perception of symptoms at the esophageal level and can often overlap with functional dyspepsia and irritable bowel syndrome.

Critical appraisal of Rome IV criteria: hypersensitive esophagus does belong to gastroesophageal reflux disease spectrum.

The Rome IV Committee introduced a major change in the classification of functional gastrointestinal disorders, proposing a more restrictive definition of gastroesophageal reflux disease (GERD). It was suggested that hypersensitive esophagus (HE) may sit more firmly within the functional realm. It was suggested that GERD diagnosis should be based upon abnormal acid exposure time (AET) only, implying no advantage of impedance-pH over pH monitoring. Symptom association probability (SAP), symptom index (SI) and heartburn relief with proton pump inhibitor (PPI) therapy were regarded as unreliable, whereas a lack of response to PPI was considered as evidence of functional heartburn. These assumptions are contradicted by numerous studies showing the clinical relevance of weakly acidic refluxes and the diagnostic utility of SAP, SI and new impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI). The PSPW index and MNBI provide significant diagnostic advantage, particularly in patients with normal AET who can be classified as HE when both parameters are abnormal, even though SAP and SI are negative. Visceral pain modulators are recommended by the Rome IV Committee despite scanty evidence of efficacy, but a positive outcome with medical or surgical anti-reflux treatment has been reported by several studies of HE patients. Therefore, we believe that patients with endoscopy-negative heartburn should be investigated by means of impedance-pH monitoring with analysis of PSPW index and MNBI: such an approach provides accurate identification of HE cases, who remain, in our opinion, within the realm of GERD and should be treated accordingly.

Review of Clinical Spectrum of Gastroesophageal Reflux Disease in a General Population; A Study from South-East Iran.

BACKGROUNDGastroesophageal reflux disease (GERD) is one of the most common gastrointestinal problems worldwide. The aim of this study was to evaluate the clinical spectrum, prevalence, and some of the variables that are supposed to be the risk factors of this chronic disorder.METHODSThis population- based cross-sectional study was conducted in a one-stage randomized clustered sample of adult inhabitants in Kerman city in 2011-2012. A total of 2265 subjects with age range of 15-85 years were enrolled. Face to face interview was performed for all the subjects. GERD was defined as at least weekly heart burn and/or acid regurgitation during the past year. Association of GERD with factors like demographic variables, medical condition, diet and life habits were analyzed.RESULTS A total of 2265 subjects including 988 (43.8%) male and 1275 (56.3%) female patients were evaluated. The prevalence of GERD was 28%. The prevalence was higher in female patients and with aging. There was also a significant association between GERD and the following risk factors: lower educational level (p <0.0001), higher body mass index (p =003), presence of depression(p<0.0001), and anxiety (p <0=0001). CONCLUSIONGERD as a common disorder in our region was seen more in elderly and female patients and was associated with some anthropometric, metabolic, medical conditions, and behavioral habits.

Prevalence of gastroesophageal reflux disease in Moscow.

Limited data exist to determine the prevalence and clinical spectrum of gastroesophageal reflux disease (GERD) in the Russian population, which might be different from those in Western countries. This study was performed in Moscow on randomized 1065 adults aged ≥ 15 years. A validated reflux questionnaire comprising 72 questions and an additional 29 sub-questions were used. The questions assessed (heartburn and regurgitation) and related (dyspepsia, dysphagia, odynophagia and chest pain) symptoms, the triggering factors of these symptoms, family history and data on demographic and socioeconomic features. GERD was defined as heartburn and/or regurgitation once a week or common. Of the 1065 participants, 42.1% were male and 57.9% were female. The prevalences of frequent and occasional symptoms were 17.6 and 22.1% for heartburn and 17.5 and 21.8% for regurgitation, respectively, over the last 12 months. The prevalence of GERD was found to be 23.6%. The rate of GERD was significantly higher in females than in males (15.4 vs. 29.5%, P < 0.001) and significantly increased as the age of the participants increased (P = 0.011). GERD was present in 20.4% of smokers, 24.2% of coffee drinkers, 21.5% of alcohol consumers and 45.9% of stressed participants. Although the rate of alcohol consumers was lower in those with GERD compared with those without GERD, the rate of coffee drinkers and stressed participants was higher among those with GERD. The rate of additional symptoms was higher even in participants complaining of regurgitation/heartburn rarely, compared with those without complaints. Using the same questionnaire, which makes it possible to compare the present results with those from different countries, we found the prevalence of GERD in Moscow to be 23.6%, one of highest in the Western populations. The rates of heartburn and regurgitation were found to be similar, which constitutes a different result than has been found in similar studies. Additional symptoms should be assessed, in all GERD patients even in the presence of rare complaints of regurgitation/heartburn.

Gender difference in gastro-esophageal reflux diseases.

The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett's esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.

Estrogen Enhances Esophageal Barrier Function by Potentiating Occludin Expression.

We recently demonstrated that a female sex hormone, estrogen, suppressed esophageal epithelial injury in a reflux esophagitis model of rat, suggesting that estrogen may play an important role in controlling the progress of the gastro-esophageal reflux disease spectrum. However, the precise mechanism of the action is unclear. To investigate the potential role of estrogen in the esophageal barrier function. Male rabbits were pretreated with either continuous release 17β-estradiol or placebo, and the excised esophageal mucosa was subjected to Ussing chamber experiments after the 2-week pre-treatment. The mucosal side of the chamber was perfused with luminal irritants (HCl or acidified sodium nitrite), while the basal side was perfused by modified Krebs buffer. The epithelial barrier function was evaluated by the transmembrane resistance and the epithelial permeability. The intercellular space of the epithelium was investigated with transmission electron microscopy and the expression of tight junction protein, occludin, claudin-1, and claudin-4, with immunoblotting. Estrogen pre-treatment significantly attenuated the decrease in the transmembrane resistance and the increase in the epithelial permeability induced by luminal irritants. Furthermore, the dilation of the intercellular space induced by luminal HCl was significantly alleviated by 17β-estradiol administration. The baseline occludin expression was significantly potentiated by 17β-estradiol administration. This is the first study showing an enhancement of the esophageal barrier function by 17β-estradiol administration. The lack of the protective effect of estrogen could be responsible for the male predominance of erosive reflux esophagitis.

Associations of Circulating Gut Hormone and Adipocytokine Levels with the Spectrum of Gastroesophageal Reflux Disease

ObjectiveThe pathogenesis of gastroesophageal reflux disease (GERD) is complex and poorly understood. We aim to investigate the association of various circulating peptide hormones with heterogenous manifestations of GERD.MethodsOne hundred and four patients that had experienced typical GERD symptoms (heartburn and/or acid regurgitation) for at least 3 episodes per week in the past 3 months were enrolled. All patients received a baseline assessment of symptom severity and frequency with the Reflux Disease Questionnaire and an upper endoscopy to classify GERD into erosive esophagitis (EE, n = 67), non-erosive esophagitis (NE, n = 37), and Barrett’s esophagus (BE, n = 8). Fifty asymptomatic subjects with an endoscopically normal esophagus were recruited as the control group. Complete anthropometric measures and blood biochemistry were obtained and fasting serum levels of adipocytokines (adiponectin and leptin) and gut hormones (ghrelin and peptide YY (PYY)) were determined by enzyme-linked immunosorbent assay in all subjects.ResultsAll circulating peptide hormone levels were not statistically different between the GERD and control groups. However, GERD patients appeared to have lower PYY levels [median (25th-75th percentile), 80.1 (49.8–108.3) vs. 99.4 (65.8–131.9) pg/ml, p = 0.057] compared with control subjects. Among the GERD patients, ghrelin levels were inversely associated with the frequency and severity of acid regurgitation. In male GERD patients, EE was associated with significantly higher PYY levels [107.0 (55.0–120.8) vs. 32.8 (28.7–84.5) pg/ml, p = 0.026] but lower adiponectin levels [6.7 (5.6–9.3) vs. 9.9 (9.6–10.6) μg/ml, p = 0.034] than NE. Patients with BE had significantly lower adiponectin levels [6.0 (5.1–9.2) vs. 9.2 (7.1–11.2) μg/ml, p = 0.026] than those without BE.ConclusionsHumoral derangement of circulating peptide hormones might participate in inflammation and symptom perception in patients suffering from GERD. Further studies to clarify the exact role of these hormones in the pathogenesis of GERD are warranted.

Spectrum of GastroEsophageal Reflux Disease (GERD) in Systemic Sclerosis (SSc)-Associated Esophageal Dysmotility as Defined by High Resolution Esophageal Manometry (HREM)

Introduction: The worsening esophageal dysmotility and incompetent lower esophageal sphincter(LES) are major contributors of GERD in patients with SSc. The spectrum of GERD can vary from nonerosive disease to severe esophagitis with stricturing. Our aim was to see if degree of esophageal dysmotility as defined by HREM correlated with the severity of GERD in SSc patients. Methods: This is a retrospective chart review of all SSc patients who underwent HREM at our institution from January 2008 to October 2014. The following data were collected: demographic features (age, gender, and race), medications, tobacco and alcohol use, esophagogastroduodenoscopy(EGD) findings, pH studies, and barium esophagogram results. All HREM were reinterpreted using the Chicago Classification of Esophageal Motility Disorders, v3.0 criteria. Data are reported as mean ± standard deviation, median, or frequency (percent). For univariate analyses, we used analysis of variance(ANOVA), non-parametric Kurksal-Wallis, Pearson's chi-square, or Fisher's Exact tests, where appropriate. Results: A total of 122 patients with SSc underwent HREM of which 73 had absent contractility(AC), 22 had ineffective esophageal motility(IEM), and 23 had a normal study. On upper endoscopy, erosive esophagitis, hiatal hernia and esophageal strictures were more common in AC than in other two groups. There were no statistically significant differences in other endoscopic findings in all three groups (Table 1). On barium esophagogram, esophageal dysmotility and dilated esophageal lumen were more prevalent in AC group. Of note, 6 out of 78 patients had barium esophagograms suggestive of achalasia but HREM showed AC with low LES pressure. Conversely, one patient had Type II Achalasia on HREM but the barium esophagogram showed normal primary peristalsis with retrograde escape and impediment to passage of 13 mm barium tablet at gastroesophageal junction. Esophageal pH testing showed no association with severity of esophageal dysmotility.Table 1: Esophageal Testing in SSc hiaConclusion: In this large cohort of SSc patients who underwent HREM, the severity of GERD related endoscopic and barium esophagogram findings correlated with the degree of esophageal dysmotility. However, a similar association was not observed between esophageal dsymotility and pH study results in patients with SSc.

Nonerosive Reflux Disease

Nonerosive reflux disease (NERD) is a distinct presentation of gastroesophageal reflux disease (GERD). NERD is commonlydefined as the presence of classical GERD symptoms in the absence of esophageal mucosal erosions/breaks on upper endoscopy. Within the spectrum of GERD, the pathophysiological and clinical characteristics distinguishing NERD and erosive esophagitis remaina matter for debate. Recent research on NERD has focused on understanding the pathophysiology and natural history. Giventhe increased incidence of NERD in Korea, we reviewed the concept of NERD and its relationship to GERD and functional gastrointestinaldisorders.

Time series analysis of gastric acid secretion over a 20-year period in normal Japanese men.

The gastric acid secretion level is an important determinant for the manifestation of the gastroesophageal reflux disease spectrum, finally leading to the development of esophageal adenocarcinoma (EAC). Although the incidence of EAC has remained low in Asia, understanding the recent trend in gastric acid secretion should be helpful in estimating future incidences of EAC in that area. We investigated the latest chronological change (1995-2014) in gastric acid secretion in normal Japanese patients. A total of 307 asymptomatic Japanese men who attended the clinic for annual endoscopic checkups from 1995 to 2014 were enrolled in this analysis. Gastrin-stimulated gastric acid secretion was estimated with the endoscopic gastrin test. The association between gastric acid secretion and chronological period was assessed with a multivariate linear regression analysis. Overall gastric acid secretion gradually increased over the 20-year period in the entire cohort in the unadjusted analysis (p < 0.05). However, the apparent increase was largely related to the relative decreasing rate of H. pylori infection, which profoundly inhibited gastric acid secretion. Gastric acid secretion did not change over the 20-year period in H. pylori-negative subjects, and it showed only a mild increase during this period in H. pylori-positive subjects. Considering that gastric acid secretion remained unchanged in H. pylori-negative Japanese men over a 20-year period at a level much lower than that in Occidental subjects, upper gastrointestinal disease profiles in the Japanese population will differ from those in Western countries in the post-H. pylori era.

Involvement of luminal nitric oxide in the pathogenesis of the gastroesophageal reflux disease spectrum

Over the last 3 decades, the incidence of esophageal adenocarcinoma has dramatically increased in Western countries; a similar increase may be observed in Asian countries in the near future. Esophageal adenocarcinoma arises from a sequential gastroesophageal reflux disease (GERD) spectrum from reflux erosive esophagitis, to Barrett's esophagus, and finally to esophageal adenocarcinoma. At present, gastric acid and bile are assumed to be primarily involved in the etiology of the GERD spectrum. We reported in 2002 that, at the gastroesophageal junction in humans, abundant amounts of nitric oxide (NO) are generated luminally through the entero-salivary re-circulation of dietary nitrate. Since then, we have carried out a series of experiments to demonstrate that NO diffuses into the adjacent epithelium at cytotoxic levels. This diffusion results in disruption of the epithelial barrier function, exacerbation of inflammation, acceleration of columnar transformation in the esophagus (Barrett's esophagus) via the induction of caudal-type homeobox 2, and the shifting of carcinogenic N-nitroso compound formation from the luminal to epithelial compartment. These results suggest that, in addition to conventionally recognized causative factors, luminal NO could also be involved in the pathogenesis of the GERD spectrum. In addition, we recently showed that there is a prominent gender-related difference in NO-related cytotoxicity in the esophagus and that estrogen attenuated the esophageal tissue damage via the estrogen receptor in female rats. The role of estrogen in attenuating the esophageal tissue damage in NO-related esophageal damage could explain the well-recognized male predominance in the GERD spectrum in humans.