Relationship among serum pepsinogens,serum gastrin,gastric mucosal histology and H. pylori virulence factors in a paediatric population

Objective. Serum pepsinogens and gastrin have been proposed as markers of gastritis, but have seldom been studied in children. In this study the aim was to identify host- and Helicobacter pylori-related factors linked to variations in serum gastrin, PGI, PGII, and to evaluate the potential of these biomarkers for diagnosing gastritis, whether H. pylori-associated or not. Material and methods. Ninety-two dyspeptic children referred for endoscopy (peptic ulcer exclusion) were included in the study. H. pylori status (urease, culture, histology) was assessed, and genotype determined (PCR) in H. pylori-positive subjects. Serum gastrin, PGI and PGII levels were measured by standard radioimmunoassay (RIA). Results. PGI and PGII levels were significantly higher in H. pylori-positive subjects (p=0.007; p=0.012, respectively). Gastrin levels were significantly higher in H. pylori-negative subjects (p=0.035). PGI and PGII were associated significantly with higher antrum inflammation scores (p=0.002; p=0.016, respectively); only PGI was associated with age, after controlling for inflammation (p=0.033) and for activity (p=0.037). The contribution of virulence factors could not be assessed owing to the low number of virulent strains. After multivariate analysis, only antrum inflammation was independently associated with PGI level (p=0.012). Receiver operating characteristic (ROC) analysis showed a low PGI and PGII discriminant power for predicting antrum inflammation. Conclusions. Pepsinogen levels as measured in this study seem predominantly to reflect antral inflammation, but they are not an effective screening test for gastritis (H. pylori-positive or -negative) in dyspeptic children.     

Serum pepsinogen concentration as a marker of <Emphasis Type="Italic">Helicobacter pylori </Emphasis>infection and the histologic grade of gastritis; evaluation of gastric mucosa by serum pepsinogen levels

Background: Helicobacter pylori infection and associated gastritis are well-known significant factors in many gastrointestinal diseases, and evaluation of these conditions is important for health evaluation. We investigated the utility of serum pepsinogen (PG) concentrations for the diagnosis of H. pylori infection and evaluation of the grade of histologic gastritis. Methods: The subjects consisted of 283 individuals (147 men and 136 women; mean age, 44.0 years). Biopsy specimens were obtained from the gastric antrum and body to assess grade of inflammation and atrophy and histologic evidence of H. pylori infection. H. pylori infection was judged by Giemsa staining and serum IgG antibodies against H. pylori. PG concentrations were determined by radioimmunoassay. Results: In subjects with H. pylori infection, serum PGII concentrations were increased, and the PGI/PGII ratio (I/II ratio) was decreased. In patients with marked atrophy or intestinal metaplasia, both serum PGI and the I/II ratio were decreased. When PGII concentrations of 12 ng/ml or more, or a I/II ratio of 4.0 or less were used as the cutoff points for the diagnosis of H. pylori infection, the sensitivity and specificity of diagnosis were 90.0% and 93.5%, respectively. All subjects with serum PGI concentrations of 85 or more ng/ml, or serum PGII concentrations of 15 or more ng/ml were H. pylori-positive and all subjects with a I/II ratio of more than 6.5 were H. pylori-negative. Conclusions: These results suggest that H. pylori infection, gastritis, and glandular atrophy of the stomach can be evaluated via serum PG concentrations, allowing the evaluation of gastric mucosal integrity. Received: April 1, 2002 / Accepted: September 6, 2002 Acknowledgments. The authors thank Goro Kajiyama, M.D., Ph.D., and Koji Sumii, MD., PhD. (First Department of Internal Medicine, Hiroshima University School of Medicine) for helpful advice and supervision. This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan. Reprint requests to: M. Yoshihara     

Gastroesophageal reflux disease: An Asian perspective

The prevalence of gastroesophageal reflux disease (GERD) ranges from 2.5% to 7.1% in most population‐based studies in Asia. There is evidence that GERD and its complications are rising, coinciding with a decline in Helicobacter pylori (H. pylori) infection. Asian GERD patients share similar risk factors and pathophysiological mechanisms with their Western counterparts. Possible causes for the lower prevalence of GERD include less obesity and hiatus hernia, a lesser degree of esophageal dysmotility, a high prevalence of virulent strains of H. pylori, and low awareness. Owing to the lack of precise translation for ‘heartburn’ in most Asian languages, reflux symptoms are often overlooked or misinterpreted as dyspepsia or chest pain. Furthermore, a symptom‐based diagnosis with a therapeutic trial of the proton pump inhibitor (PPI) may be hampered by the high prevalence of H. pylori‐related disease. The risk stratification for prompt endoscopy, use of a locally‐validated, diagnostic symptom questionnaire, and response to H. pylori‘test and treat’ help improve the accuracy of the PPI test for diagnoses. PPI remain the gold standard treatment, and ‘on‐demand’ PPI have been shown to be a cost‐effective, long‐term treatment. The clinical course of GERD is benign in most patients in Asia. The risk of progression from non‐erosive reflux disease to erosive esophagitis is low, and treatment response to a conventional dose of PPI is generally higher. Although H. pylori eradication may lead to more resilient GERD in a subset of patients, the benefits of H. pylori eradication outweigh the risks, especially in Asian populations with a high incidence of gastric cancer.     

Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology

BACKGROUND Helicobacter pylori(H.pylori)infection is known to prevent the occurrence of gastroesophageal reflux disease(GERD)by inducing gastric mucosal atrophy.However,little is known about the relationship between atrophic gastritis(AG)and GERD.AIM To confirm the inverse correlation between AG and the occurrence and severity of GERD.METHODS Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included.The grade of reflux esophagitis was evaluated according to the Los Angeles classification.Endoscopic AG(EAG)was categorized into six grades.Serologic AG(SAG)was defined as pepsinogen I≤70 ng/m L and pepsinogen I/II ratio≤3.0.The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis.RESULTS In total,4684 individuals with GERD were compared with 21901 healthy controls.In multivariate logistic regression analysis,advanced age,male sex,body mass index>23 kg/m2,presence of metabolic syndrome,current smoking,and alcohol consumption were associated with an increased risk of GERD.Seropositivity for H.pylori immunoglobulin G antibodies was associated with a decreased risk of GERD.There was an inverse correlation between the extent of EAG and occurrence of GERD:Odds ratio(OR),1.01[95%confidence interval(CI):0.90-1.14]in C1,0.87(0.78-0.97)in C2,0.71(0.62-0.80)in C3,0.52(0.44-0.61)in O1,0.37(0.29-0.48)in O2,and 0.28(0.18-0.43)in O3.Additionally,the extent of EAG showed an inverse correlation with the severity of GERD.The presence of SAG was correlated with a reduced risk of GERD(OR=0.49,95%CI:0.28-0.87,P=0.014).CONCLUSION The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD.AG followed by H.pylori infection may be independently protect against GERD.     

Prevalence and determinants of histological abnormalities of the gastric cardia in volunteers

Objective. The findings of studies examining the prevalence and major risk factors of histological abnormalities of the gastric cardia have been inconsistent. Selection bias was possible in these studies depending on whether patients were referred for ulcer or gastroesophageal reflux disease (GERD). There have been no studies on non-patient populations. The aim of this study was to mitigate the potential effects of selection bias. Material and methods. In a study comprising health-care workers, we distributed symptom questionnaires and invitations to undergo upper endoscopy. A single endoscopist performed standard endoscopy and biopsy examinations (2 antral, 2 corporal, and 2 cardiac biopsies). Staining was done using triple stain. Two pathologists, who were blinded to the results of the questionnaires and endoscopy, interpreted and recorded the histological findings. Results. A total of 226 participants underwent endoscopy. Gastric cardia, as defined by the presence of mucous glands, was identified in 191 subjects; mean age of the subjects was 45 years, 117 (61%) were women, and 49% were black. Active gastritis of the cardia was present in 58 (30.4%), chronic gastritis in 133 (69.6%), intestinal metaplasia (IM) in 29 (15.2%), and pancreatic metaplasia in 25 (13%). Direct (organisms) or indirect evidence (active anywhere or chronic gastritis in antrum or corpus) for Helicobacter pylori was present in all participants with active gastritis, 60% of subjects with chronic gastritis, and approximately half of those with IM of the cardia. Approximately 15% with chronic carditis had neither H.pylori nor GERD symptoms. There were also no significant differences in the prevalence of heartburn or acid regurgitation, or the use of histamine-2-receptor antagonists (H₂RAs) or proton-pump inhibitors (PPIs) between groups with and without active or chronic gastritis, IM, or pancreatic metaplasia, whereas active or chronic gastritis in the antrum or corpus and H. pylori infection were more frequent (1.5- to 2-fold) among those with histological abnormalities of the cardia. Conclusions. Active and chronic gastritis as well as intestinal metaplasia of the gastric cardia are relatively common in health-care worker volunteers. Although GERD symptoms are not significantly associated with these abnormalities, H. pylori infection is a strong risk factor. However, a considerable number of participants with chronic gastritis of the cardia have neither H. pylori nor GERD.     

Screening of atrophic gastritis and gastric cancer by serum pepsinogen, gastrin-17 and Helicobacter pylori immunoglobulin G antibodies

OBJECTIVE: Currently the screening and diagnosis of gastric cancer and atrophic gastritis are mainly made by endoscopy and biopsy. The aim of this study was to evaluate the use of serum tests: serum pepsinogen I (PGI pepsinogen I/II ratio (PGR), gastrin‐17 (G‐17) and H. pylori‐immunoglobulin G (IgG) antibodies to screen atrophic gastritis and gastric cancer. METHODS: A total of 458 patients were recruited, and each underwent endoscopy with biopsies before the serum tests were performed. These patients were divided into five groups based on the endoscopic and histological findings: 92 patients in the atrophic gastritis group, 58 in the gastric ulcer group, 90 in the duodenal ulcer group, 141 in the gastric cancer group (40 early gastric cancer and 101 advanced gastric cancer) and 77 (including mild non‐atrophic gastritis) served as a control group. Serum samples for PGI and II, G‐17, and H. pylori‐IgG antibodies estimation were analyzed by ELISA. RESULTS: PGI and PGR values decreased significantly both in atrophic gastritis and gastric cancer groups (P < 0.01). For the best discrimination of atrophic gastritis, the cut‐off values of PGI and PGR were 82.3 µg/L and 6.05, respectively. The PGI, PGR and G‐17 values were related significantly with the grades and/or sites of atrophic gastritis (P < 0.01). Patients with atrophic corpus gastritis had low PGI and PGR values and high G‐17 level, and patients with atrophic antral gastritis had low G‐17 level. G‐17 increased significantly in the gastric cancer group (P < 0.01). PGI and PGR values were significantly lower in patients with advanced gastric cancer than in patients with early gastric cancer, while there was no difference in G‐17 level between them. The positivity rate of H. pylori‐IgG antibodies was 54.55% in the control group. The PGI level was higher in H. pylori positive patients than in H. pylori negative ones (P < 0.001), while there was no difference in G‐17 level between them. The positivity rates of H. pylori‐IgG antibodies were over 85% in all other four groups. CONCLUSIONS: Low serum PGI, PGR and G‐17 values are biomarkers of atrophic antral gastritis. Atrophic corpus gastritis can be screened by lower serum PGI, PGR and high G‐17 values. [Correction added after online publication on 2 February 2007: the preceding sentence has replaced one that read ‘Atrophic be screened by serum PGI and PGR values’]. Gastric cancer can be screened on the basis of increased serum G‐17 and remarkedly low serum PGI and PGR values. The H. pylori infection is related to the change of PG level.     

Does <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection protect against esophageal diseases in Asia?

The speculations on the protective role of Helicobacter pylori against gastroesophageal reflux disease (GERD) originated from epidemiological observations. These studies have shown that the rising trend of GERD is coincident with declining prevalence of H. pylori and peptic ulcer disease in Asia. Furthermore, most case–control and population-based studies suggest a negative association between H. pylori infection and GERD. It is generally believed that the preponderance of cagA+ and vacA+ virulent strains and proinflammatory interleukin-1 beta polymorphism increase the risk of hypochlohydria and protects against the development of GERD in Asian population. Recovery of gastric acid secretion and emergence of reflux esophagitis has been reported after H. pylori eradication in patients with corpus gastritis and atrophic gastritis. Recent studies have also reported that H. pylori eradication leads to recovery of ghrelin secreting cells in the gastric corpus and a rise in plasma ghrelin levels, which may contribute to obesity through its appetite-stimulating action and predispose to GERD. The prevalence of H. pylori infection is generally lower in younger Asians who enjoy improved socioeconomic status and sanitation compared with their older counterparts. The Asian population is probably facing a rising generation with high gastric acid and ghrelin secretion rates. These physiological changes may contribute to increased dietary calorie intake, obesity and increased prevalence of GERD.     

Helicobacter pylori Protection Against Reflux Esophagitis

Background and Aim

Negative association has been reported between presence of Helicobacter pylori and developing gastroesophageal reflux disease (GERD) and its complications. The aim of this study was to determine whether H. pylori (HP) can be protective against GERD in an African American (AA) population.

Methods

From 2004 to 2007, we studied 2,020 cases; esophagitis (58), gastritis (1,558), both esophagitis and gastritis (363) and a normal control group (41). We collected their pathology and endoscopy unit reports. HP status was determined based on staining of gastric biopsy.

Results

HP data was available for 79 % (1,611) of the cases. The frequency of HP positivity in gastritis patients was 40 % (506), in esophagitis patients 4 % and in normal controls 34 % (11), while HP was positive in 34 % of the patients with both esophagitis and gastritis. After adjusting for effects of age and sex, odds ratio of HP was 0.06 (95 % CI 0.01–0.59; P value = 0.01) for the esophagitis group versus the normal group.

Conclusions

Our results show H. pylori has a significant negative association with esophagitis in AAs which may point to a protective role of H. pylori in the pathogenesis of esophagitis. In addition, H. pylori may be the reason for the low GERD complications in AAs.     

Relationship of sliding hiatus hernia to gastroesophageal reflux disease: a possible role for Helicobacter pylori infection?

Sliding hiatal hernia is a common endoscopic finding with a prevalence that increases with the age of patients. Although nearly all patients with GERD have HH, only a minority of patients with hernia reports reflux symptoms. Our hypothesis is that H. pylori infection may be responsible for the high number of asymptomatic hernias. After exclusion of patients with peptic ulcer, 507 patients with an endoscopic diagnosis of hernia were considered. Patients were divided into three groups: A, 45 years, 141 patients; B, 46–60 years, 144 patients; and C, 61 years, 222 patients. Presence of reflux symptoms (questionnaire) and esophagitis, H. pylori status, and gastric histology were recorded. The prevalence of hernia in the total series was 11% in group A, 23% in B, and 38% in C. Aging was associated with a significant increase in H. pylori prevalence and corpus gastritis scores, and a parallel decrease of GERD symptom prevalence, which was 66.6% in group A, 52.1% in B, and 46.8% in C (P < 0.01). Taking the three groups together, prevalence of H. pylori infection was higher in patients without GERD than with GERD (66.4 vs 57.3%, P < 0.05), and higher in patients with nonerosive GERD than erosive GERD (62.8 vs 48.6%, P = 0.02); corpus gastritis scores were significantly higher in patients without GERD than those with GERD and in those with nonerosive than erosive GERD. In conclusion, H. pylori infection protects against development of GERD in subjects with hiatus hernia. This effect is significantly more evident in the elderly where, in spite of the high prevalence of hernia, only a small number of individuals develop GERD. The development of a corpus-predominant gastritis is probably responsible for this effect.     

A 12-Year Follow-up Study of Chronic Gastritis and Helicobacter pylori in a Population-Based Random Sample

Background: The study is a 12-year endoscopic follow-up investigation on the course of chronic gastritis and Helicobacter pylori infection in a sample of 81 Estonian people. Methods: The series is a subset from a random sample of 227 subjects in whom a gastroduodenal endoscopy had been done. The grade of superficial gastritis (SG), atrophy, and colonization of the mucosa by H. pylori was evaluated in biopsy specimens from both antrum and corpus in accordance with the principles of the Sydney System. Resufrs: The healing rate of the H. pylori and gastritis was 0.3% (3 of 81); H. pylori colonization with gastritis developed in 5 of 81 during the follow-up. The mean prevalence of atrophic gastritis (AG) was three times more common in the corpus than in the antrum on the average. The formation of new cases of AG and the disappearance of AG were quite equal during the follow-up, and the overall changes in the grade of SG and atrophy were slow. The mean life span of corpus AG was nearly three times as long as that of antrum AG. In the antrum the grade of chronic inflammation correlated positively with the grade of H. pylori colonization. In cases of SG a low grade of colonization of H. pylori in the antral mucosa in connection with moderate inflammation predicted a reduction or even a healing of gastritis in the long term. Conclusions: New H. pylori infections with subsequent gastritis may occur in adulthood; a healing of gastritis occurs but is a quite rare event in the course of the 12-year follow-up. Further, in the present random sample of Estonian people atrophic corpus gastritis did not show an overall progression, in contrast to our earlier findings.     

Risk factors for erosive and non-erosive gastroesophageal reflux disease and Barrett's esophagus in Nothern Sardinia

Objective: Gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma have been increasing. We studied the relationship of conventional risk factors and Helicobacter pylori infection in patients with erosive and non-erosive GERD and Barrett’s esophagus.

Materials and methods: This was a retrospective study of dyspeptic patients undergoing upper endoscopy between 2002 and 2013. Following endoscopy, those with previously undiagnosed GERD were sub-grouped into non-erosive GERD (NERD), erosive GERD (eGERD), or Barrett's esophagus. H. pylori status was confirmed by 2 positive tests.

Results: About 5156 patients were included, GERD was present in 65.6% including 1992 with NERD and 1392 with eGERD. About 1772 dyspeptic patients without symptoms of reflux and/or esophagitis served as controls. A hiatal hernia increased the risk of both eGERD and NERD. eGERD was more prevalent among the obese (OR =1.72, p?p?Helicobacter pylori infection was significantly more common among those with NERD (OR =1.17 versus 1.01, p?=?0.046). Logistic regression analysis for eGERD and NERD using age, gender, body mass index, H. pylori infection, hiatal hernia, and smoking showed that overweight and hiatal hernia were significant risk factors for eGERD, and female gender for NERD. Male gender, eGERD and age?>50 years were the major risk factors for Barrett’s esophagus.

Conclusions: The epidemiology of eGERD and NERD suggests differences in pathogenesis, and prevention and treatment strategies should be separately examined in men and women.     

Relationship of Sliding Hiatus Hernia to Gastroesophageal Reflux Disease: A Possible Role for Helicobacter pylori Infection?

Sliding hiatal hernia is a common endoscopic finding with a prevalence that increases with the age of patients. Although nearly all patients with GERD have HH, only a minority of patients with hernia reports reflux symptoms. Our hypothesis is that H. pylori infection may be responsible for the high number of asymptomatic hernias. After exclusion of patients with peptic ulcer, 507 patients with an endoscopic diagnosis of hernia were considered. Patients were divided into three groups: A, 45 years, 141 patients; B, 46–60 years, 144 patients; and C, 61 years, 222 patients. Presence of reflux symptoms (questionnaire) and esophagitis, H. pylori status, and gastric histology were recorded. The prevalence of hernia in the total series was 11% in group A, 23% in B, and 38% in C. Aging was associated with a significant increase in H. pylori prevalence and corpus gastritis scores, and a parallel decrease of GERD symptom prevalence, which was 66.6% in group A, 52.1% in B, and 46.8% in C (P < 0.01). Taking the three groups together, prevalence of H. pylori infection was higher in patients without GERD than with GERD (66.4 vs 57.3%, P < 0.05), and higher in patients with nonerosive GERD than erosive GERD (62.8 vs 48.6%, P = 0.02); corpus gastritis scores were significantly higher in patients without GERD than those with GERD and in those with nonerosive than erosive GERD. In conclusion, H. pylori infection protects against development of GERD in subjects with hiatus hernia. This effect is significantly more evident in the elderly where, in spite of the high prevalence of hernia, only a small number of individuals develop GERD. The development of a corpus-predominant gastritis is probably responsible for this effect.     

Is the course of gastroesophageal reflux disease progressive? A 21-year follow-up

Abstract

Objective. We re-evaluated a cohort of patients referred for reflux symptoms and objectively diagnosed with pathological reflux, with the purpose of clarifying the course of conservatively treated gastroesophageal reflux disease (GERD). Material and methods. All consecutive patients with GERD diagnosed between 1984 and 1988 showing pathologic 24-h pH-metry in the interval 3.8–10% and without any previous surgery in the gastroesophageal tract were assessed for further follow-up. A total of 40 evaluable patients were followed in the years 2007–08 with endoscopy, manometry, 24-h pH-metry, Helicobacter pylori assessment and the self-administered questionnaires the GERD Impact Scale, the Reflux Disease Questionnaire, the Quality of Life in Reflux and Dyspepsia and the Medical Outcome Study Short Form-36 Health Survey. Baseline data from the 1980s were retrieved and compared with the evaluations conducted at follow-up. Results. At follow-up 20.7 years (range 18.8–23.5 years) after referral, the study population showed more use of acid suppressants (p = 0.007) and increasing prevalences of esophagitis (p = 0.001) and Barrett's esophagus (p = 0.002). Esophagitis was seen in 16/40 patients (40%) at baseline and in 29/40 (72.5%) at follow-up. No significant deterioration was seen at follow-up in manometry data and in most pH data. Patients with esophagitis (ERD) were less likely to have a positive H. pylori test (hazard ratio 0.054; p = 0.002) than non-erosive (NERD) patients. Symptom evaluations showed significantly lower quality of life in the ERD group. Conclusions. After 20 years a considerable part of the cohort still experienced symptoms of reflux and showed endoscopic progression, although no significant deteriorations were seen in manometry data and in most pH-metry data. H. pylori infection was inversely associated with erosive esophagitis and this supports the hypothesis that H. pylori colonization is a protective factor against GERD.     

Helicobacter pylori Infection,Pattern of Gastritis,and Symptoms in Erosive and Nonerosive Gastroesophageal Reflux Disease

Background: The aim of this study was to evaluate the prevalence of Helicobacter pylori infection and the characteristics of gastritis and symptoms of patients with erosive and nonerosive gastroesophageal reflux disease (GERD). Methods: We studied 202 consecutive patients with a diagnosis of GERD (symptoms score and endoscopy): group A (n = 110), erosive GERD; group B (n = 92), nonerosive GERD; 200 patients with upper abdominal complaints without abnormalities at endoscopy (functional dyspepsia, group C); and 200 asymptomatic controls tested for H. pylori serum antibody (group D). Antral and body biopsy specimens were taken for histology and the rapid urease test in groups A, B, and C. Results: The prevalence of H. pylori infection was higher in groups B and C (62% and 55%, respectively) than in A and D (36% and 40%) (P &lt; 0.05). In positive patients H. pylori colonization and gastritis grade scores in the gastric body were higher in nonerosive than in erosive GERD and functional dyspepsia (P &lt; 0.05). No differences in H. pylori colonization or gastritis grades were found in the antrum. Fifty-nine patients with nonerosive GERD (64%) and 42 with erosive GERD (38%) showed other dyspeptic symptoms associated with reflux symptoms (P &lt; 0.05). Conclusions: H. pylori prevalence is higher in patients with nonerosive GERD than in normal subjects and in patients with erosive GERD and similar to that of patients with dyspepsia. Patients with nonerosive GERD often show dyspeptic symptoms and higher H. pylori colonization and inflammation grades in the proximal stomach. Our data support the hypothesis that in GERD H. pylori gastritis may, on the one hand, protect against the development of esophageal erosions and, on the other, contribute to the esophageal hypersensitivity to acid which is a feature of GERD.     

AN ENDOSCOPIC AND MAGNIFYING ENDOSCOPIC STUDY OF ESOPHAGEAL CARDIAC GLAND: WHAT ROLE DOES ESOPHAGEAL CARDIAC GLAND PLAY AT THE ESOPHAGO‐GASTRIC JUNCTION?

The purpose of this study was to ascertain whether areas of yellow elevated change in the distal squamous epithelium represent esophageal cardiac gland and to further assess the features of the exposed esophageal cardiac gland in the magnified view. In addition, the relationship between the columnar‐lined esophagus, gastro‐esophageal reflux disease (GERD), reflux esophagitis, and H. pylori infection was also assessed. Fifty patients (28 men, 22 women; median age 61 years) underwent elective upper GI endoscopy. The distal margin of the squamo‐columnar junction was observed to ascertain whether a yellow elevated lesion was present. When such a lesion was observed, this area was studied using magnifying endoscopy with acetic acid and a biopsy specimen was taken. Furthermore, biopsy specimens of the cardia, antrum, and body were taken for biopsy specimen to check for the presence of carditis, gastritis, and H. pylori. Of 38 patients showing the yellow elevated change, all showed exposed columnar epithelium and 30 patients proved to have esophageal cardiac gland tissue in biopsy specimens. Of 31 patients with H. pylori infection, all had carditis and the yellow elevated lesion. Of 19 patients with a H. pylori‐negative normal stomach, none had carditis and seven patients had the yellow elevated change which was ascertained to be esophageal cardia by biopsy. The yellow elevated change at the distal squamo‐columnar junction was revealed to be esophageal cardiac gland and exposed esophageal cardiac gland was visible in all cases by magnifying endoscopy with acetic acid.     

Circulating Ghrelin Levels in Patients with Various Upper Gastrointestinal Diseases

The stomach is the main source of circulating ghrelin. Plasma concentrations of this hormone in patients with various upper gastrointestinal diseases remain undetermined. Thus we measured plasma ghrelin levels by radioimmunoassay in 225 subjects, including 134 Helicobacter pylori-infected and 91 uninfected subjects. They included 67 patients with chronic gastritis (CG), 26 with benign gastric polyp (BGP), 24 with gastric ulcer (GU), 24 with reflux esophagitis (RE), 18 with duodenal ulcer (DU), 28 with acute gastritis (AG), 23 with gastric cancer (GC), and 39 who had normal mucosa on upper endoscopy (N). Plasma pepsinogen I and II levels were also measured. The extent of gastritis was assessed endoscopically. Ghrelin levels differed significantly among the different disease groups. Plasma ghrelin concentrations were lowest in the CG group, followed by the GU group, and highest in the AG patients. There was a significant difference in the levels between differentiated and undifferentiated GC. Ghrelin concentrations in BGP, RE, and DU patients were comparable to those in the N group. Ghrelin circulating levels were lower in H. pylori-positive than –negative individuals, but the significant differences among disease groups were still observed in H. pylori-infected and uninfected populations. Ghrelin concentrations correlated positively with plasma pepsinogen I levels and I/II ratios and inversely with the extent of H. pylori-related gastritis. Plasma ghrelin levels varied widely in diverse conditions of the upper digestive tract, reflecting the inflammatory and atrophic events of the background gastric mucosa. Further investigation is warranted to unravel the mechanisms of the high circulating ghrelin levels in certain upper gastrointestinal diseases.     

Helicobacter Pylori and Precancerous Gastric Lesions

Background: To determine the relationship between Helicobacter pylori (H. pylori) infection and the precancerous gastric lesions: atrophic gastritis (AG) and intestinal metaplasia (IM) and dysplasia. Methods: A total of 347 dyspeptic patients, including 141 H. pylori‐positive patients and 206 H. pylori‐negative patients, were studied alongside age‐ and sex‐matched controls. The patients underwent gastroscopy and endoscopic biopsy for detection of H. pylori, and histological examinations. Helicobacter pylori was detected by a urease test (CLO; Delta West; Bentley, Australia), by histology (H&E stain, Giemsa) and by serology (BioSig; BioMeditech, NJ, USA). Atrophic gastritis, IM and dysplasia were detected by histological examination (Giemsa, H&E stain). Results: There is a higher rate of atrophic gastritis in H. pylori‐positive than in H. pylori‐negative patients (46 vs 13.5%, odds ratio (OR) = 5.4; P < 0.01). Gastritis in H. pylori‐positive patients also has a higher rate of activity than in H. pylori‐negative patients. The rate of IM is higher in H. pylori‐positive patients than in H. pylori‐negative patients (35 vs 11%; OR = 4.3; P < 0.01). Metaplasia is more often diffuse in H. pylori‐positive than in H. pylori‐negative patients. Dysplasia is more common in H. pylori‐positive than in H. pylori‐negative patients (12 and 3.8%; OR = 3.3; P < 0.01). Conclusions: This study supports the suggestion of a relationship between H. pylori infection and precancerous gastric lesions. Wherever H. pylori is present, the precancerous lesions are more common and more severe.     

Helicobacter pylori infection correlates with severity of reflux esophagitis: with manometry findings

The role of Helicobacter pylori infection in the development and exacerbation of reflux esophagitis was investigated. The prevalence of Helicobacter pylori infection, the severity of atrophic gastritis, and esophageal motility (determined by esophageal manometry by an infusion catheter method) were assessed in patients with mild (n = 46) and severe (n = 27) reflux esophagitis and subjects without reflux (n = 28). Compared with the prevalence of Helicobacter pylori infection in the non-reflux group, the prevalence in the mild and severe reflux groups (60.7%, 47.8%, and 14.8%, respectively) was significantly (P < 0.05) lower. Atrophic gastritis was milder in both reflux groups than in the non-reflux group. The degree of gastritis was also milder in the severe reflux group than in the mild reflux group. The esophageal sphincter pressure was significantly (P < 0.05) lower in the reflux groups than in the non-reflux group, and the amplitude of primary peristalsis was significantly (P < 0.05) lower in the severe reflux group than in the non-reflux group. There were no significant differences between reflux patients with and without Helicobacter pylori infection in the parameters of esophageal manometry. These data imply that a low prevalence of Helicobacter pylori infection may result in a milder grade of atrophic gastritis, and consequently, exacerbate reflux esophagitis. Received: July 21, 1998 / Accepted: April 28, 1999     

Prospective evaluation of a new stool antigen test for the detection of Helicobacter pylori, in comparison with histology, rapid urease test, (13)C-urea breath test, and serology

Background and Aims: This study aimed to evaluate the efficacy of a new polyclonal enzyme immunoassay for the detection of Helicobacter pylori (H. pylori) antigen in stool by determination of the optimal cut‐off value in the screening population. Methods: A consecutive 515 patients undergoing a routine health check‐up were prospectively enrolled. H. pylori infection was defined if at least two of four tests (histology, rapid urease test, ¹³C‐urea breath test, and serology) were positive. A stool antigen test (EZ‐STEP H. pylori) was performed for the detection of H. pylori. The optimal cut‐off value was determined by the receiver–operator characteristic curve. The diagnostic performance of each test was evaluated with regard to the histological diagnosis of atrophic gastritis (AG)/intestinal metaplasia (IM), degree of AG/IM, and old age. Results: Sensitivity, specificity, positive and negative predictive values, and accuracy of the stool antigen test were 93.1%, 94.6%, 95.1%, 92.3%, and 93.8%, respectively. The sensitivity of histology, rapid urease test, and the ¹³C‐urea breath test ranged from 89.1% to 97.6%, and their specificity was > 98%, while serology had high sensitivity, but low specificity. The accuracy of the stool antigen test was comparable to that of other methods (93.6–95.9%), whereas it was higher than that of serology. The stool antigen test still showed good diagnostic performance in the setting of progression of AG/IM and in patients over 40 years. Conclusions: The performance of a new stool antigen test was comparable to that of other methods in the diagnosis of H. pylori infection for the screening population, even with the presence of AG/IM.     

Expression of COX‐1, COX‐2 and inducible nitric oxide synthase in superficial gastritis,mucosal dysplasia and gastric carcinoma

OBJECTIVE : To investigate the significance of the expression of cyclooxygenase‐1 (COX‐1), cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) in superficial gastritis, gastric mucosal dysplasia and gastric carcinoma, and to study the relationship between COX‐2, iNOS, gastric carcinoma and Helicobacter pylori infection. METHODS : Polyclonal antibodies to COX‐1, COX‐2 and iNOS were used detect their expression and the status of H. pylori infection in 92 specimens of paraffin‐embedded gastric tissue. Of the 92 patients, 33 had superficial gastritis, 30 had gastric mucosal dysplasia and 29 had gastric cancer. Helicobacter pylori was detected by toluidine blue staining. RESULTS : Expression of COX‐2 and iNOS in gastric cancer (65.5%, 62.1%) was significantly higher than that in gastritis (18.2%, 18.2%; P < 0.01). Expression of COX‐2 and iNOS in gastritis with H. pylori infection was higher than that in gastric mucosal dysplasia with H. pylori infection. The expression of COX‐2 and iNOS occurred concomitantly in gastritis, dysplasia and gastric cancer. CONCLUSION : Inflammation and H. pylori infection may be able to stimulate the expression of COX‐2 and iNOS, which might be involved in gastric carcinogenesis.