Reflux Esophagitis Patients Research Articles

The study on the function of gastrointestinal autonomic nerve in reflux esophagitis patients

Objective To explore the features of autonomic nerve function in reflux esophagitis (RE) patients, and the role of abnormal function in the pathogenesis of RE. Methods Twenty RE patients (RE group) and 18 healthy controls (HS group) all underwent heart rate variability (HRV) with meal stimulation to test the function of autonomic nerve. At same time, the endoscopic Los Angeles (LA) Classification, RE symptom score, Gastroesophageal reflux disease-health related quality of life (GERD-HRQL), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were evaluated in the RE patients. Of those, 12 RE patients were re-examined the function of autonomic never after 2 to 4 months [mean (3.7±0.8) months] of proton pump inhibitors (PPI) treatment. Results In fasting state, the sympathetic activity was higher in RE group than in HS group, while the parasympathetic activity was lower in HS group (P=0.022 and 0.034). Postprandial, the trend of autonomic functional change was the same in RE group and HS group. Postprandial, the sympathetic activity was negatively correlated with symptom score in RE patients; however, the parasympathetic activity was positively correlated with RE symptom score. The influence of meal on the balance of sympathetic and parasympathetic was negatively correlated with RE symptom score (r=-0.48, P=0.022). The influence of meal on the parasympathetic nerve was positively correlated with RE symptom score and GERD-HRQL score. After PPI treatments, RE symptom score, GERD-HRQL score, SAS score and SDS score were all significantly decreased in RE patients. There was no significant difference in autonomic nerve function before and after PPI treatment. Conclusions There is abnormal autonomic nerve function in RE patients, characterized by higher sympathetic activity and lower parasympathetic activity in fasting state. The autonomic nerve function is correlated with RE symptom score. The abnormal autonomic nerve function may be one of the causes of RE. Key words: Esophagitis, peptic; Autonomic path ways; Gastrointestinaltract

Vitamin D, calcium and dairy intake, and risk of oesophageal adenocarcinoma and its precursor conditions

Evidence is accumulating that vitamin D may be protective against carcinogenesis, although exceptions have been observed for some digestive tract neoplasms. The aim of the present study was to explore the association between dietary vitamin D and related nutrients and the risk of oesophageal adenocarcinoma and its precursor conditions, Barrett's oesophagus and reflux oesophagitis. In an all-Ireland case-control study conducted between March 2002 and July 2005, 218 oesophageal adenocarcinoma patients, 212 Barrett's oesophagus patients, 208 reflux oesophagitis patients and 252 population-based controls completed a 101-item FFQ, and provided lifestyle and demographic information. Multiple logistic regression analysis was applied to examine the association between dietary intake and disease risk. Oesophageal adenocarcinoma risk was significantly greater for individuals with the highest compared with the lowest tertile of vitamin D intake (OR 1·99, 95 % CI 1·03, 3·86; P for trend = 0·02). The direct association could not be attributed to a particular vitamin D food source. Vitamin D intake was unrelated to Barrett's oesophagus and reflux oesophagitis risk. No significant associations were observed for Ca or dairy intake and oesophageal adenocarcinoma, Barrett's oesophagus or reflux oesophagitis development. High vitamin D intake may increase oesophageal adenocarcinoma risk but is not related to reflux oesophagitis and Barrett's oesophagus. Ca and dairy product intake did not influence the development of these oesophageal lesions. These findings suggest that there may be population subgroups at an increased risk of oesophageal adenocarcinoma if advice to improve vitamin D intake from foods is implemented. Limited work has been conducted in this area, and further research is required.

The effect and their mechanism of acid pocket in reflux esophagitis

Objective To investigate the function of acid pocket in reflux esophagitis. Methods The 15 healthy controls and 24 reflux esophagitis patients were identified by reflux disease questionnaire (RDQ) and gastric endoscopy. The location of subjects' lower esophageal sphincter (LES) was determined by 4 channel esophageal manometry system. Then a single-channel pH electrode was positioned 1 cm below the distal border of the LES to monitor fasting pH for half an hour. After a standard meal, the pH was continuously measured for two hours. Then the electrode was moved to 5 cm above the proximal border of the LES to monitor the dynamic pH for 24 h.Results Acid pocket was found in 16 cases of reflux esophagitis patients(66.67%) and 10 cases of healthy individuals (10/15). Acid pocket occurred earlier in reflux esophagitis group than healthy controls [11.00(4.25-17.00) min vs 30.00(15.50-54.25) min, P＜0.05], and the average pH value was lower [1.84(1.59-2. 19) vs 2.32 (1.96-2.71), P＜0.05]. There was no statistic difference in mean pH value of gastroesophageal junction and the duration of acid pocket before the meal.Conclusion There is abnormal acid reflux in reflux esophagitis patients, and acid pocket with earlier occurrence and lower pH value may relevant to esophageal mucosal impairment. Key words: Acid pocket; Gastroesophageal reflux disease; Reflux esophagitis

Randomised clinical trial: efficacy of the addition of a prokinetic, mosapride citrate, to omeprazole in the treatment of patients with non-erosive reflux disease - a double-blind, placebo-controlled study

Proton pump inhibitors (PPIs) are less effective in non-erosive reflux disease (NERD) patients than in reflux oesophagitis patients. Whether the addition of prokinetics to PPIs improves NERD patients' symptoms remains unknown. To evaluate the efficacy of mosapride in NERD patients when used with PPI. A total of 200 NERD patients were randomised to one of two arms: omeprazole (10 mg once daily) plus mosapride citrate (5 mg three times a day) (treatment arm) and omeprazole plus placebo (placebo arm). The primary endpoint was the rate of responders [visual analogue scale (VAS) was zero or <1 cm] after 4 weeks of treatment. The secondary endpoints were changes in the VAS score and the safety profile. There was no significant difference between the rates of responders in both arms in intent-to-treat (ITT) and per-protocol (PP) analysis. The change in the VAS score in treatment arm was significantly better than placebo arm in PP analysis (-4.0 ± 0.2 and -3.3 ± 0.2, mean ± S.E.M.) (N.S. in ITT analysis). The rate of adverse events was similar in both groups. The addition of mosapride to omeprazole was not more effective than omeprazole alone.

Fibroblast-derived HB-EGF promotes Cdx2 expression in esophageal squamous cells

The molecular basis of attaining columnar phenotype in Barrett’s esophagus is poorly understood. One hypothesis states that factors locally produced by cells of mesenchymal origin in chronic reflux esophagitis induce metaplastic transformation. This study was performed to elucidate the factors secreted from fibroblasts that cause columnar phenotype in adjacent squamous epithelium. Human fibroblast cells were exposed to acidified medium for 20 min, followed by medium neutralization for 2 h, and then total RNA was hybridized to Sentrix Human-6 Expression BeadChips. Furthermore, esophageal mucosal biopsy specimens from reflux esophagitis patients were examined for HB-EGF expression using immunohistochemistry. In addition, cells from the human esophageal squamous epithelial cell line HET1A were treated with recombinant HB-EGF, and changes in expressions of Cdx2 and columnar markers were analyzed. The gene expression profile revealed significant upregulation of a variety of growth factors and inflammatory chemokines in response to acid exposure. Among them, HB-EGF was upregulated more than 10-fold. Biopsy specimens from reflux esophagitis patients showed a strong expression of HB-EGF in fibroblast cells underlying the damaged epithelium. Furthermore, in vitro stimulation of HET1A cells with HB-EGF increased Cdx2 in dose-dependent manners. Functional analysis of human Cdx2 promoter also revealed its upregulation by HB-EGF stimulation, showing the role of potential responsive elements (AP-1 and NF-κB) for its transcriptional activation. Moreover, the columnar markers cytokeratin 7 and villin were also upregulated by HB-EGF stimulation. HB-EGF induces several genes characteristics of columnar phenotypes of esophageal squamous epithelium in a paracrine manner.

Persistent Reflux Symptoms in the Proton Pump Inhibitor Era: The Changing Face of Gastroesophageal Reflux Disease

Given the widespread use of potent acid suppressive therapies and primary caregivers’ increasing comfort with prescribing these medications at high doses, the patient population presenting to gastroenterologists for symptoms of gastroesophageal reflux disease (GERD) has changed. Whereas previous consultation often revolved around the control of erosive disease and other mucosal manifestations of GERD, and terminated with the prescription of proton pump inhibitor (PPI) therapy, gastroenterologists often now only enter the scene after failure of PPI therapy, for symptoms either resistant or only partially responsive to these medications. Because of the high proportion of subjects with esophagitis who are healed with PPI, 1,2 upper endoscopy of such individuals is low yield, 3 with only a small minority demonstrating erosive disease. The care of such patients is challenging. High-quality evidence supporting useful diagnostic testing or alternative effective therapies is largely lacking. However, the number of subjects with GERD symptoms incompletely or nonresponsive to PPI therapies is high, and their utilization of healthcare resources is substantial. The purpose of this mini-review is to examine the definition and epidemiology of esophageal GERD symptoms incompletely responsive to PPI therapy, the potential pathophysiologic mechanisms behind these symptoms, the differential diagnosis and evaluation of such patients, and current and developing therapeutic options.

Incidence and risk factor of fundic gland polyp and hyperplastic polyp in long-term proton pump inhibitor therapy: a prospective study in Japan

To investigate the development of fundic gland polyp (FGP) and gastric hyperplastic polyp (HPP) during long-term proton pump inhibitor (PPI) therapy and risk factors of each polyp via patient status in a multicenter prospective study. The risk of developing FGP may increase during long-term PPI therapy. However, the association with PPI-induced hypergastrinemia is unclear. Helicobacter pylori (Hp) infection (which there is a high rate of in Japan) may influence the development of HPP. Reflux esophagitis patients on PPI maintenance therapy were enrolled. At baseline, the presence of protruding lesion (gastric polyps) and mucosal atrophy was examined endoscopically. The serum gastrin level (SGL) and Hp infection status were noted. The patients took rabeprazole 10 mg/day for 104 weeks and endoscopy was performed at weeks 24, 52, 76, and 104 to check for newly developed FGPs and HPPs. The hazard ratios (HRs) of risk factors were calculated. 191 patients were analyzed. The distribution of patients with baseline SGLs (pg/mL) of <200, >or=200 to <400, and >or=400 was 118 (61.8%), 51 (26.7%), and 22 (11.5%), respectively. 78 (40.8%) patients were Hp-positive, and gastric polyps were found in 70 (36.6%) patients. By the end of rabeprazole therapy, 26 (13.6%) and 17 (8.9%) patients had developed new FGPs and HPPs. In terms of risk factors, Hp-positive was significantly lower (HR=0.288; 95% CI, 0.108-0.764) for FGP while SGL>or=400 pg/mL was significantly higher (HR=4.923; 95% CI, 1.486-16.31) for HPP. During long-term PPI therapy, FGP development was associated with absence of Hp infection. Meanwhile, Hp infection and high SGL may influence HPP development.

A false sense of security; symptom control does not predict healing of oesophagitis on proton pump inhibitors

Sirs, The study by Labenz et al. attempted to determine the factors associated with resolution of heartburn in patients with reflux oesophagitis treated with proton pump inhibitor.1 Certainly, effective control of heartburn symptoms is crucial in treating patients with reflux oesophagitis; however, it is not the only goal. We suggest that treatment of the symptoms is but one part of the paradigm of treating reflux oesophagitis; the other therapeutic goals should include healing the oesophagitis, maintaining remission, prevention of complications and improvement in quality of life.2 Our study agreed with the findings of Labenz et al. that greater age was associated with a greater likelihood of heartburn resolution during proton pump inhibitor therapy. However, our study did not find any association between Helicobacter pylori status, male gender and symptoms resolution. Labenz J. et al. conclude that the results of their study should help physicians categorize reflux oesophagitis patients as likely to be ‘treatment responsive’ or ‘treatment refractory’; we feel this is worrisome on two grounds. First, our study found that symptom resolution on proton pump inhibition does not predict healing of oesophagitis. In fact, whilst 75.8% of our study patients had complete resolution of their symptoms, only 48% had complete healing of the oesophagitis at endoscopy after 8 weeks of proton pump inhibition.2 Secondly, it remains uncertain as to the long-term sequelae of mild oesophagitis; some studies have found very low rates of gastro-oesophageal reflux-related complications3, 4 including strictures and Barrett’s oesophagus, whereas other studies have suggested a higher rate of GERD-related complications.5, 6 Treatment of symptoms is critical in the management of patients with reflux oesophagitis, but until there is unequivocal evidence that mild oesophagitis has little by the way of long-term sequelae, it is important not to be lulled into a false sense of security in patients who are proton pump inhibitor ‘treatment responsive’ symptom wise, as resolution of symptoms does not necessarily mean the resolution of oesophagitis. Declaration of personal and funding interests: None.

Clinical trial: factors associated with freedom from relapse of heartburn in patients with healed reflux oesophagitis ‐ results from the maintenance phase of the EXPO study

Ability to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients. To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis. This post-hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH-NEG-0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once-daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse. Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P < 0.0001). Other factors significantly associated with freedom from heartburn relapse were Helicobacter pylori infection, greater age, non-obesity, absence of epigastric pain at baseline, pre-treatment nonsevere heartburn and GERD symptom duration < or =5 years. Several factors predict freedom from heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long-term symptom management in reflux oesophagitis patients.

H. pylori Eradication Prevents the Progression of Gastric Intestinal Metaplasia in Reflux Esophagitis Patients Using Long-Term Esomeprazole

This study aimed to determine whether Helicobacter pylori eradication limits the progression of precancerous changes, manifested as intestinal metaplasia (IM), in patients with reflux esophagitis using long-term esomeprazole. Three hundred twenty-five reflux esophagitis patients were enrolled and randomly assigned to (i) the H. pylori-positive eradication group receiving 1-week triple therapy (n=105); (ii) H. pylori-positive non-eradication controls (n=105); and (iii) H. pylori-negative controls (n=115). All the patients received continuous esomeprazole until sustained symptomatic response, and when possible, shifted to on-demand therapy (ODT) thereafter. Serial gastroscopy was scheduled on enrollment and at the end of the first and second years to assess the prevalence and progression or regression of gastric atrophy (AT) and IM. There were 93 patients in the H. pylori-eradication group, 83 in the non-eradication controls, and 100 in the negative controls to complete the study. The negative controls had no progression of AT and IM during follow-up. For the H. pylori-positive eradication group, there was significant regression of AT and IM during follow-up (P<0.05). In the H. pylori-positive non-treated controls, the prevalence rates of AT and IM were significantly greater on the second year than on enrollment (P<0.05). During the second-year follow-up, the patients in the eradication group achieved more regression and less development of AT and IM than did the non-eradication controls (P<0.001). In patients using long-term esomeprazole for reflux esophagitis, screening for and eradicating H. pylori infection are necessary in order to limit the progression or cause the regression of gastric precancerous changes.

Helicobacter pylori eradication may induce de novo, but transient and mild, reflux esophagitis: Prospective endoscopic evaluation

The effect on reflux esophagitis of eradicating Helicobacter pylori is variable and not fully defined. We previously reported that in patients who have reflux esophagitis associated with duodenal ulcer, a significant improvement in the pre-existing reflux esophagitis occurred after H. pylori was eradicated. In the present study, we asked whether H. pylori eradication leads to de novo development of reflux esophagitis in peptic ulcer patients. Prospective post-eradication evaluations were conducted in 1195 H. pylori-positive patients with peptic ulcer diseases who were confirmed not to have reflux esophagitis by endoscopic examination before eradication therapy. After eradication therapy, endoscopy and a urea breath test were performed yearly. A total of 1187 patients were followed for up to 10.0 years (a mean of 3.6 years). Reflux esophagitis developed in 279 of 1000 patients cured of infection and in 26 of 187 patients who had persistent infection (P < 0.0001, Fisher's exact test). The esophagitis was mild (Los Angeles grade A) in most patients, transient in approximately one-half, and rarely necessitated long-term medication for the condition. Cure of infection, alcohol consumption, younger age, and high body mass index were identified as significant factors for the risk of developing non-transient reflux esophagitis. Cure of H. pylori infection may increase the risk of developing reflux esophagitis in patients with peptic ulcer, but the esophagitis is mostly mild and transient, and long-term medication is rarely required. Thus, H. pylori eradication therapy need not be withheld for fear of provoking reflux esophagitis.

Gastro-esophageal reflux disease: the recent trend in Japan.

Gastro-esophageal reflux disease (GERD) has increased in Japan, as in other countries. This is probably due to increased acid secretion among Japanese due to Westernized foods and lifestyle as well as decreased prevalence of Helicobacter pylori infection. Proton pump inhibitor (PPI) is mainly used for treatment of this condition. PPI has recently been approved for treatment of nonerosive reflux disease (NERD) in Japan. NERD is known to have different characteristics to GERD, and effectiveness of PPI in NERD patients is lower than that in reflux esophagitis patients. Regarding therapeutic benefit of treatment, a recent study showed that PPI improved quality of life (QOL) of GERD patients also in Japan. For diagnosis of reflux esophagitis in Japan, we use a unique classification, a modified Los Angeles (LA) classification, which includes minimal change (grade M esophagitis) as one distinct criteria. However, recent studies from Japan showed poor interobserver agreement in diagnosis of grade M, although excess acid reflux in minimal change was shown in another study. Our definition of Barrett's esophagus is also different from that in the West. Nationwide consensus on diagnosis of reflux esophagitis and Barrett's esophagus should be achieved in Japan, preferably consistent with world standard.

The demographic characteristics and health-related quality of life in a large cohort of reflux esophagitis patients in Japan with reference to the effect of lansoprazole: the REQUEST study

Patients with reflux esophagitis (RE) in Western countries have impaired health-related quality of life (HRQOL). However, few data are available concerning HRQOL in Asian patients with RE. To determine the demographic characteristics, HRQOL, and the impact of lansoprazole treatment in a large cohort of RE patients in Japan. Patients with RE were enrolled. Lansoprazole was administered for 8 weeks and HRQOL assessed using the SF-8 and a newly developed questionnaire for RE-specific HRQOL (RESQ) at baseline and after 4 and 8 weeks of treatment. Among enrolled patients, 2320 patients with the Los Angeles classification grade A to D esophagitis at enrollment to the study were analyzed. A higher proportion of older women was observed (in the group of patients aged >or=60 years, 61.3% were women). Prevalence of obesity was 4.7%. At baseline, HRQOL scores of RE patients were well below the mean for the Japanese general population in all domains of the SF-8. After 8 weeks of treatment with lansoprazole, these scores significantly improved to the levels of the general population (P < 0.01). Scores of RESQ also significantly improved (P < 0.01). Demographically, RE patients in Japan differ from those in Western countries with an increased proportion in older women and lower prevalence of obesity. RE has a marked negative impact on HRQOL, which is significantly improved by treatment with lansoprazole.

Increased COX-2 Expression of Esophageal Squamous Epithelium in the Patients with Reflux Esophagitis

Background/Aims: Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Previous studies have suggested that increased expression of COX-2 is important in the genesis of esophageal adenocarcinoma. The aim of this study was to compare the COX-2 expression of distal esophageal squamous epithelium between the patients with reflux esophagitis and normal controls. Methods: Biopsies of the distal esophageal squamous mucosa were taken 3 cm above the squamocolumnar junction in 19 reflux esophagitis patients and 21 normal controls. The expression of COX-2 was confirmed by immunohistochemistry using monoclonal antibodies. The staining index was obtained by adding up the scores for staining intensity with the staining area, which ranged from 0 to 6. Results: COX-2 expression in the squamous epithelium from paraffin embedded biopsies in patients with reflux esophagitis was significantly increased compared to controls (31.6% vs. 0%, P = 0.038). The mean COX-2 expression score was 2.2 in the reflux esophagitis patients with positive COX-2 expression. Conclusions: It suggests that the changes in COX-2 expression occur before any metaplastic changes in the esophageal squamous epithelium of the patients with reflux esophagitis.

Reflux oesophagitis in Italy (Diomede project)

Aims A multicentric observational study was performed to update the available information on reflux oesophagitis in Italy. Methods In phase I, the number and severity of reflux oesophagitis diagnosed in 1 year (2003) were reported together with the associated endoscopic findings. In phase II, oesophagitis patients consecutively referred in a 3-month period were analysed. A multivariate analysis was used to identify the risk factors for severe oesophagitis. Results 253,992 upper endoscopies were collected. The overall prevalence of oesophagitis was 14.8% and the endoscopic findings associated with oesophagitis were hiatus hernia (46.3%), duodenal ulcer (10.7%), gastric ulcer (3.6%) and Barrett's oesophagus (2.9%). In phase II, 1542 reflux oesophagitis patients were analysed (60.3% males; mean age 50.7 ± 16.6 years). Only 53.4% of patients reported heartburn and/or regurgitation as main complaint. Severe symptoms, age >50 years, hiatus hernia and male gender were identified as independent predictors of severe oesophagitis. Conclusions Oesophagitis is the most frequent among the peptic diseases of the upper gastro-intestinal tract. Only half of the oesophagitis patients reported typical reflux symptoms as dominant. Advanced age, male gender, severe symptoms and hiatus hernia were independent risk factors for severe disease.

Presence of Vertebral Fractures is Highly Associated with Hiatal Hernia and Reflux Esophagitis in Japanese Elderly People

Recent studies have shown the correlation between vertebral fractures (VFs) and gastrointestinal disorders in postmenopausal women. The aim of this study was to assess the association between VFs and hiatal hernia (HH) and/or reflux esophagitis (RE) in our patient population of both men and women. We analyzed retrospective data of 280 patients aged 60 years or older (140 men and 140 women, mean +/- SD 73.5 years +/-7.05) who had undergone upper gastrointestinal endoscopy and chest X-rays in our hospital from August 2005 to February 2006. We analyzed the correlation between the presence of VFs and the presence of HH and/or RE. The incidence of RE in this study was 13.9% (39/280) and that of HH was 30.0% (84/280). Among these patients, 12.1% (41/280) had VFs. The incidence of RE in patients with VFs was 24.4% (10/41) and without VFs was 12.1% (29/239), with the difference being significant between those with and without VFs (p<0.05). The incidence of HH in patients with VFs was 43.9% (18/41) and in those without VFs was 27.6% (66/239), p<0.05. We subdivided subjects into four groups: HH only group, RE only group, HH/RE group and neither condition present group. We compared the incidence of VFs among these groups. VFs were observed in 16.4% (11/67) of the HH only group, 13.6% (3/22) of the RE only group, 41.2% (7/17) of the HH/RE group and 11.5% (20/174) in the neither condition present group. There was a significant difference in the incidence of VFs between the HH/RE group and neither condition present group (p<0.05). The presence of VFs was significantly associated with the presence of either RE or HH. This association became more significant when HH and RE were present together in elderly Japanese people.

Clinical and endoscopic features of Chinese reflux esophagitis patients

To analyze the clinical and endoscopic features of Chinese patients with reflux esophagitis (RE). A total of 1405 RE patients were analyzed retrospectively. Data on gender, age, presence/absence of H pylori infection and associated esophageal hiatal hernia were collected. Esophagitis was divided into different grades according to Los Angeles Classification. Of 18823 patients, 1405 were diagnosed as RE. The ratio of male to female patients was 1.75:1 (P < 0.01). The mean age of male and female patients was significantly different (P = 0.01). The peak age at onset of the disease was 40-60 years. According to Los Angeles Classification, there were significant differences in the age of patients with grades A and B compared to patients with grades C and D (P < 0.01). Two hundred and seventy-seven patients were infected with H pylori, the infection rate was low (P < 0.01). Complication of esophageal hiatal hernia was found to be significantly associated with the severity of esophagitis and age in 195 patients (P < 0.01). Esophageal mucosa damages were mainly located at the right esophageal wall. The peak age of onset of RE is 40-60 years and higher in males than in females. The mean age of onset of RE is lower in males than in females. The infection rate of H pylori is significantly decreased in patients with esophagitis. Old age and esophageal hiatal hernia are associated with more severe esophagitis. Right esophageal mucosal damage can occur more often in RE patients.

Endoscopic reflux esophagitis in patients with upper abdominal pain‐predominant dyspepsia

Reflux symptom assessment had reliable accuracy in the diagnosis of gastroesophageal reflux disease (GERD). However, patients may recognize heartburn or regurgitation as dyspepsia because of inaccurate understanding or atypical presentation. The aim of the present study was to estimate endoscopic reflux esophagitis in patients with upper abdominal pain as a predominant symptom in the absence of heartburn or regurgitation. Two hundred and sixty-three consecutive patients presenting dyspepsia without heartburn or regurgitation were enrolled. Patients with heartburn or regurgitation were excluded using the symptom interviewer method. Dyspepsia was categorized into pain-predominant or dysmotility-predominant groups according to the Rome II proposal. Endoscopic reflux esophagitis was graded using the Los Angeles classification. One hundred and five patients were included in the pain-predominant group and 119 in the dysmotility-predominant group. Reflux esophagitis was found in 18.8% (42/224) of all dyspeptic patients. Grade A esophagitis was noted in 27.6% (29/105) of the pain-predominant group and in 7.6% (9/119) of the dysmotility-predominant group. Grade B was noted in two patients in each group. A total of 29.5% (31/105) and 9.3% (11/119) had reflux esophagitis, respectively (P < 0.001). Comparing patients with or without reflux esophagitis, there was no difference in body mass index, smoking habit, alcohol consumption, or Helicobacter pylori infection status. A significant proportion of patients presenting dyspepsia, especially pain-predominant dyspepsia, have endoscopic reflux esophagitis. In view of GERD, pain-predominant dyspepsia should be investigated and managed differently from dysmotility-predominant dyspepsia.

Mechanisms of Acid Gastroesophageal Reflux in the Japanese Population

In contrast to Western countries, reflux esophagitis is considered to be less common in the Orient, including Japan. Transient LES relaxation (TLESR) is a major mechanism of gastroesophageal reflux (GER); however, there are no data on the mechanisms of GER in Japanese people. In addition, it is unclear whether or not the rate of TLESRs, in the sitting position, is higher in reflux esophagitis patients than in healthy subjects. The aim of this study is to determine the mechanisms of acid reflux and the rate of TLESRs, and to compare the rate of acid reflux during TLESRs between healthy volunteers and patients with reflux esophagitis in Japan. Preprandial and postprandial esophageal manometry and pH monitoring were performed in the sitting position in ten healthy volunteers and ten patients with reflux esophagitis of Los Angeles grade C. The energy level of the meal was 692 kcal and consisted of 33% fat. In healthy volunteers, 100% (median) of the acid reflux episodes occurred during TLESRs compared with 55.0% in patients with esophagitis. The remaining reflux episodes in the esophagitis patients were related to straining (12.8%) and absent basal LES pressure (19.5%). The rate of TLESRs in patients with esophagitis was 4.7 h(-1) (3.3-5.7) [median, (interquartile range)] and did not vary significantly from that in healthy volunteers [5.0 h(-1) (4.3-6.3)] 3 h postprandially. The rate of acid reflux during TLESRs in patients with esophagitis (42.7%, median) 3 h postprandially was significantly higher than in healthy volunteers (9.2%). In Japan, the mechanisms of GER in both groups are similar to those reported in Western countries. The rate of acid reflux during TLESRs in patients with reflux esophagitis is significantly higher than in healthy volunteers; however, compared to rates reported in Western countries these rates are very low for both groups.

The roles of Helicobacter pylori and pattern of gastritis in the pathogenesis of reflux esophagitis

Comparing the infection rates and density of Helicobacter pylori (H. pylori) and the patterns of gastritis in reflux esophagitis (RE) and non-erosive reflux disease (NERD) patients to investigate the role of H. pylori in the pathogenesis of RE. Two hundred and twenty-three out-patients with typical gastroesophageal reflux symptoms who consecutively visited the hospital underwent ambulatory 24-hour pH monitoring and gastroscopy, and biopsy of the gastric mucosa. RE and NERD were diagnosed based on the presentation of endoscopy. Gastritis was divided into four different patterns: chronic non-atrophic antritis (CNAA); chronic non-atrophic pan-gastritis (CNAG); chronic atrophic antritis (CAA); and chronic atrophic pan-gastritis (CAG). H. pylori infection was evaluated by Warthin-Starry staining. DeMeester score > or = 15 was considered as pathological acid reflux. Sixty-two patients (27.8%) were found to have RE, 161 (72.2%) were found to have NERD. Totally, 67 patients had H. pylori infection (30.0%). There was no significant difference in H. pylori infection rate between the RE and NERD groups (25.8% vs. 31.5%, P > 0.05). 45 of the 223 patients were diagnosed as with CNAA (20.2%), 88 (39.5%) with CNAG, 65 (29.2%) with CAA, and 25 (11.2%) with CAG. The CAG rates in the RE and NERD groups were 6.5% and 13.0% respectively (P > 0.05). There were no differences in abnormal pH monitoring rate and DeMeester score among the different patterns of gastritis. In the sixty-seven H. pylori-positive GERD patients, the 24 h pH monitoring positive rate of the moderate-severe H. pylori colonization density group was 46.4%, significantly higher than that of the mild H. pylori colonization density group (73.5%, P < 0.05); and the mean intra-gastric pH value during 24 hours of the moderate-severe H. pylori colonization density group was 2.3 +/- 0.8, significantly higher than that of the mild H. pylori colonization density group (2.0 +/- 1.1, P < 0.05). H. pylori infection is associated with the pattern of gastritis, but shows no relationship to the incidence of RE. High density of H. pylori colonization in gastric corpus may reduce the esophageal acid exposure. Diffuse atrophic gastritis may protect the patients from RE.