Gastritis results from multifactorial gastric mucosal injury. Helicobacter pylori (Hp) is the main cause, and associated diseases have typical underlying patterns of gastritis. Gastric ulcer and gastric cancer (GC) develop from chronic atrophic corpus gastritis (CAG) which therefore represents the most important pattern. GC incidences in East Asia are substantially higher than elsewhere, and this should be also reflected by higher prevalences of CAG and characteristic differences in pathophysiology compared to the West.

The few available comparative studies of gastritis in Eastern and Western patients are summarized. The main pathogenic factors of gastritis are discussed together with their limitations to explain local differences in disease outcome. Emphasis was put to also include less well-established pathogenic host and environmental factors of possible impact.

CAG is more prevalent in East Asian areas with high GC incidences than the West. Geographic heterogeneity of associated diseases is due to differences in Hp prevalence and virulence as well as modulating host and environmental factors. The following may contribute to the higher burden of CAG in the East: ABD type of CagA with vacA s1 and babA2 alleles of Hp, host Lewis(b) expression in sej/sej nonsecretors, H. heilmannii, low parietal cell mass, high sodium and nitrate intake, preferences in vegetable and fruit consumption, cigarette smoking, air pollution, alcohol. Conversely, green tea, nonfermented soy products and rice may confer protective effects. Hp is on the decline, but also in a world cleared from this bacterium, differences in host genetics will continue to modify gastric disease outcome together with maintained customs as part of cultural diversity.

Autoimmune gastritis is a chronic progressive inflammatory condition that results in the replacement of the parietal cell mass by atrophic and metaplastic mucosa. A complex interaction of autoantibodies against the parietal cell proton pump and sensitized T cells progressively destroy the parietal cells, inducing hypochlorhydria and then achlorhydria, while autoantibodies against the intrinsic factor impair the absorption of vitamin B₁₂. The resulting cobalamin deficiency manifests with megaloblastic anaemia and neurological and systemic signs and symptoms collectively known as pernicious anaemia. Previously believed to be predominantly a disease of elderly women of Northern European ancestry, autoimmune gastritis has now been recognized in all populations and ethnic groups, but because of the complexity of the diagnosis no reliable prevalence data are available. For similar reasons, as well as the frequent and often unknown overlap with Helicobacter pylori infection, the risk of gastric cancer has not been adequately assessed in these patients. This Review summarizes the epidemiology, pathogenesis and pathological aspects of autoimmune metaplastic atrophic gastritis. We also provide practical advice for the diagnosis and management of patients with this disease.

Early gastric cancer is defined as adenocarcinoma confined to the mucosa or submucosa irrespective of lymph node involvement. In Japan, mucosal high-grade neoplasia is diagnosed as intramucosal early gastric cancer. Some early gastric cancers progress to advanced gastric cancer after several years of follow-up. Image-enhanced endoscopy (chromoendoscopy), narrow-band imaging, and magnifying endoscopy increase the diagnostic yield in characterizing early gastric cancer. Endoscopic resection of intramucosal early gastric cancer with endoscopic mucosal resection or endoscopic submucosal dissection is currently performed in East Asian countries to prevent the development of advanced gastric cancer and preserve patients' quality of life after treatment.

The relationship between Helicobacter pylori infection and metabolic syndrome is not well understood. Adiponectin is an adipose-derived protein considered to play a significant role in the development of metabolic syndrome. The aim of this study was to clarify the influence of H. pylori infection on circulating adiponectin in humans.

In a prospective study, 456 patients underwent endoscopy and H. pylori testing. All of the 338 H. pylori -positive patients received eradication therapy. Treatment was successful in 241 patients. Circulating adiponectin and other metabolic parameters were measured at baseline in all patients and 12 weeks after eradication therapy in those initially positive for H. pylori.

Circulating adiponectin levels were not different between H. pylori -positive and H. pylori -negative patients. In the group with successful eradication, levels of total adiponectin and each multimer form were significantly increased after therapy. Conversely, the levels of total adiponectin and high-molecular-weight adiponectin, but not middle-molecular-weight and low-molecular-weight adiponectin, were increased in the group with unsuccessful eradication after the therapy.

Eradication therapy of H. pylori increased circulating adiponectin levels in Japanese individuals and could be beneficial for preventing metabolic syndrome conditions.

B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.

This study was performed to assess the affects of age, sex, and Helicobacter pylori status on pepsinogen testing for atrophic gastritis and to establish the clinical implications of pepsinogen test results and H. pylori serology in a Korean population presenting for a health check-up.

Serum pepsinogen (PG) I and PG II, and H. pylori IgG were measured in 1485 adults. The PG values were analyzed based on age, sex, and H. pylori status, and the cutoff value for atrophic gastritis was determined.

Serum PG I (sPGI) and sPGII were higher in H. pylori positive than in H. pylori negative individuals (sPGI, 56.3 vs. 42.2 microg/l, P<0.001; sPGII, 17.5 vs. 8.0 microg/l, P<0.001). The PG I/II ratio was lower in H. pylori positive than in H. pylori negative individuals (3.7 vs. 6.0, P<0.001). The sPGII and PG I/II ratio had a positive (r=0.132, P<0.001) and negative correlation with age (r=-0.229, P<0.001), respectively. Men had a higher sPGI (54.7 microg/l) than did women (48.4 microg/l) (P<0.001) but the PG I/II ratio was not statistically different and neither the atrophic gastritis. The PG I/II cutoff value for atrophic gastritis was 6.0 for H. pylori negative and 3.0 for H. pylori positive individuals. sPGI and sPGII were, however, not specific for atrophic gastritis.

The H. pylori IgG status, age, and sex were associated with the serum PG levels. To increase the efficacy of the PG I/II ratio for the detection of atrophic gastritis, the cutoff value of the PG I/II ratio should be stratified according to the H. pylori IgG status in the Korean population presenting for a health check-up.

Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG). A large variety of definitions of CAG have been used in epidemiologic studies in the past. The aim of this work was to systematically review and summarize estimates of the association between H. pylori infection and CAG according to the various definitions of CAG. Articles on the association between H. pylori infection and CAG published until July 2007 were identified. Separate meta-analyses were carried out for studies defining CAG based on gastroscopy with biopsy, serum pepsinogen I (PG I) only, the pepsinogen I/pepsinogen II ratio (PG I/PG II ratio) only, or a combination of PG I and the PG I/PG II ratio. Numbers of identified studies and summary odds ratios (OR) (95% confidence intervals) were as follows: gastroscopy with biopsy: n = 34, OR = 6.4 (4.0-10.1); PG I only: n = 13, OR = 0.9 (0.7-1.2); PG I/PG II ratio: n = 8, OR = 7.2 (3.1-16.8); combination of PG I and the PG I/PG II ratio: n = 20, OR = 5.7 (4.4-7.5). Studies with CAG definitions based on gastroscopy with biopsy or the PG I/PG II ratio (alone or in combination with PG I) yield similarly strong associations of H. pylori with CAG. The association is missed entirely in studies where CAG is defined by PG I only.

Chronic atrophic gastritis (CAG), a precursor of intestinal gastric cancer, is mostly ascertained noninvasively by serum pepsinogens in epidemiologic studies. However, serological definitions vary widely. We aimed to investigate the impact of this variation on estimated prevalence of CAG and its association with its main risk factors, age and Helicobacter pylori infection. Serum pepsinogen I and II and antibodies against H. pylori were measured by ELISA among 9,444 women and men aged 50-74 years in a population-based cohort study in Saarland/Germany. Application of the various definitions resulted in a wide range of prevalence estimates of CAG prevalence (2.1%-8.2%, with an outlier of 18.8% for one particular definition) and its associations with age and H. pylori infection (age adjusted odds ratios, OR, for CagA positive H. pylori infection: 0.98-4.48). Definitions of CAG based on both pepsinogen I and the pepsinogen I/II ratio or on the pepsinogen I/II ratio only revealed much clearer associations with both age and H. pylori infection than definitions of CAG based on pepsinogen I only (ORs for H. pylori infection: 1.45-4.48 and 0.86-1.30, respectively). Epidemiologic findings on CAG lack comparability due to the heterogeneity in serologic definitions of CAG. The association of age and H. pylori infection with CAG may be strongly underestimated in studies in which CAG is defined by pepsinogen I only.

Epidemiological data on chronic atrophic gastritis from general population samples are sparse in Germany.

To assess prevalence of chronic atrophic gastritis according to potential risk factors and clinical outcomes in a large-scale population-based study.

In the baseline examination of ESTHER, a population-based cohort study conducted in Germany, serological measurements of pepsinogen (PG) I and II and Helicobacter pylori antibodies were taken in 9444 women and men aged 50-74 years. Information on potential risk factors and medical history were obtained by questionnaire.

With the definition used in the EUROGAST study (PG I < 25 ng/mL), prevalence of chronic atrophic gastritis increased from 4.8% in age group 50-54 to 8.7% in age group 70-74. An alternative definition of chronic atrophic gastritis (PG I < 70 ng/mL and PG I/PG II < 3), used in multiple studies from Japan, revealed a greater increase with age (from 2.7% to 9.1%) and a strong association with H. pylori infection (adjusted odds ratio: 2.9, 95% confidence interval: 2.4-3.7). With both definitions, a strong inverse association with heartburn was observed.

Overall chronic atrophic gastritis prevalence is low among older adults in Germany, but it strongly increases with age and H. pylori infection.

The current status of gastric cancer screening, worldwide, as well as in Japan, using the serum pepsinogen test method, was reviewed. We performed a metaanalysis of sensitivity and specificity results from 42 individual studies (27 population-based screening studies: n = 296 553 and 15 selected groups: n = 4 385). Pooled pairs of sensitivity and false-positive rates (FPr) for pepsinogen I level < or = 70 ng/ml; pepsinogen I/II ratio < or = 3, had a sensitivity of 77%/FPr27%. The positive predictive value varied between 0.77% and 1.25%, and the negative predictive value varied between 99.08% and 99.90%. Therefore, we concluded that the definition of the pepsinogen test should include the pepsinogen I/II ratio, as consistency was obtained for both the population-based studies and the selected groups for those studies that used pepsinogen I serum levels together with the pepsinogen I/II ratio for screening for gastric cancer in high-incidence regions other than Japan. Individuals testing positive for extensive atrophic gastritis by serum pepsinogen levels undergo endoscopic examination to test for the presence of gastric cancer. We should increase the efficacy and cost-effectiveness of the gastric cancer screening system, by the identification of groups, at low-risk, as well as those at high-risk, of developing gastric cancer, using a combination of assays of serum Helicobacter pylori antibody titers and the concentration of pepsinogen I and II. In conclusion, the pepsinogen test method can be used as a screening test for high-risk subjects, rather than as a tool for screening for cancer itself. I hope that this pepsinogen test method will become a world standard for gastric cancer prevention in the near future, in other countries, as well as in Japan.

Chronic atrophic gastritis (CAG) is a well-established precursor of intestinal gastric cancer, but epidemiologic data about its occurrence are sparse. We provide an overview on studies that examined the prevalence of CAG in different parts of the world. Articles containing data about the prevalence of chronic atrophic gastritis in unselected population samples and published until November 2005 were identified by searching the MEDLINE database. Furthermore, the references in the identified publications were screened for additional suitable studies. Studies comprising at least 50 subjects were included. Forty-one studies providing data on the prevalence of CAG in unselected population samples could be identified. CAG was determined by gastroscopy in 15 studies and by pepsinogen serum levels in 26 studies. Although results are difficult to compare due to the various definitions of CAG used, a strong increase with age, the lack of major gender differences, and strong variations between populations and population groups (in particular, relatively high rates in certain Asian populations) could be observed quite consistently. We conclude that CAG is relatively common among older adults in different parts of the world, but large variations exist. Large-scale international comparative studies with standardized methodology to determine CAG are needed to provide a coherent picture of the epidemiology of CAG in various populations. Noninvasive measurements of CAG by pepsinogen levels may be particularly suited for that purpose.

The current status of gastric cancer screening, worldwide, as well as in Japan, using the serum pepsinogen test method, was reviewed. We performed a metaanalysis of sensitivity and specificity results from 42 individual studies (27 population-based screening studies: n = 296 553 and 15 selected groups: n = 4 385). Pooled pairs of sensitivity and false-positive rates (FPr) for pepsinogen I level < or = 70 ng/ml; pepsinogen I/II ratio < or = 3, had a sensitivity of 77%/FPr27%. The positive predictive value varied between 0.77% and 1.25%, and the negative predictive value varied between 99.08% and 99.90%. Therefore, we concluded that the definition of the pepsinogen test should include the pepsinogen I/II ratio, as consistency was obtained for both the population-based studies and the selected groups for those studies that used pepsinogen I serum levels together with the pepsinogen I/II ratio for screening for gastric cancer in high-incidence regions other than Japan. Individuals testing positive for extensive atrophic gastritis by serum pepsinogen levels undergo endoscopic examination to test for the presence of gastric cancer. We should increase the efficacy and cost-effectiveness of the gastric cancer screening system, by the identification of groups, at low-risk, as well as those at high-risk, of developing gastric cancer, using a combination of assays of serum Helicobacter pylori antibody titers and the concentration of pepsinogen I and II. In conclusion, the pepsinogen test method can be used as a screening test for high-risk subjects, rather than as a tool for screening for cancer itself. I hope that this pepsinogen test method will become a world standard for gastric cancer prevention in the near future, in other countries, as well as in Japan.

Although previous studies have indicated that serum pepsinogen I levels, as well as the pepsinogen I/II ratio, were positively correlated with maximal gastric output, the relationship may be different between Helicobacter pylori-negative and -positive subjects. The aim of this study was to investigate the relation between serum pepsinogen concentrations and gastric acid secretion in H. pylori-positive and -negative subjects separately.

The presence of H. pylori infection, the serum pepsinogen concentrations, and gastric acid secretion were investigated in 182 subjects without localized lesions in the upper gastrointestinal tract. Serum pepsinogen concentration was measured by radioimmunoassay, and maximal gastric acid output was estimated by an endoscopic gastrin test, as we have previously shown.

In H. pylori-positive subjects, serum pepsinogen I levels and the pepsinogen I/II ratio were significantly correlated with gastric acid secretion, although the latter showed a better correlation (r=0.40 and 0.53, respectively). On the other hand, in H. pylori-negative subjects, serum pepsinogen concentrations were well correlated with acid secretion (r=0.57), but there was no relation between the pepsinogen I/II ratio and acid secretion.

The correlations between serum pepsinogens and gastric acid secretion differ, depending on the presence or absence of H. pylori infection. With the use of serum pepsinogens as a simple measure of gastric acid secretion, therefore, consideration of H. pylori infection status is needed. Because the determination of the acid secretory level has some clinical implications in both H. pylori-positive and -negative subjects, its estimation by serum pepsinogen concentrations can be of practical use.

Elevated serum gastrin and a low pepsinogen A/C ratio are well-recognized markers for atrophic body gastritis (ABG). We have shown that the presence of body atrophy is also associated with elevated serum pro-inflammatory cytokines. This study tested the hypothesis that serum cytokines provide additional information to gastrin and pepsinogens in screening for ABG.

Two hundred and twenty-six consecutive patients were investigated on referral for upper gastrointestinal endoscopy: 150 were patients with gastro-oesophageal reflux disease, receiving acid inhibitory medication either with proton pump inhibitors (n = 113) or with histamine2-receptor antagonists (n = 37), and 76 were nontreated controls, who had normal endoscopic findings. Gastric mucosal biopsies were sampled for histological examination (Sydney classification). Serum samples were analyzed for gastrin, chromogranin A (CgA), and pepsinogens A and C by RIA, and for the interleukins (IL)-1beta, IL-6, and IL-8 by ELISA.

Subjects with ABG had significantly higher serum gastrin (P < 0.01) and serum CgA (P < 0.01) levels and significantly lower pepsinogen A/C ratios (P < 0.001) than those without ABG. Additionally, serum IL-1beta, IL-6 and, especially, IL-8 levels were significantly higher in the subjects with than in those without ABG (P < 0.0001, for all cytokines). To optimize the detection of body atrophy we defined the ABG index: the ratio between the simultaneously measured IL-8 and pepsinogen A/C. The area under the ROC curve for the ABG index was significantly greater than that for serum gastrin and for serum pepsinogen A/C alone (0.91 +/- 0.029 vs. 0.72 +/- 0.042, and vs. 0.83 +/- 0.031, P = 0.018 and P = 0.049). Using the ABG index at a cut-off value of 1.8 pg mL-1, 91% of the cases were classified correctly.

The ratio between serum IL-8 and pepsinogen A/C accurately predicts the presence of ABG. We therefore propose the ABG index as a noninvasive screening test for ABG in population-based studies.

The natural course of Helicobacter pylori gastritis may vary between different ethnic groups. Gastric histopathology and the occurrence of H. pylori organisms in the stomach were investigated in healed duodenal (DU) and gastric (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial.

In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological gastritis variables and H. pylori were assessed from biopsy specimens obtained using a specific sampling protocol and interpreted according to guidelines of the updated Sydney grading system.

The ratio of GU:DU was observed to be very different between the recruited Japanese (39:55) and Swedish (0:109) patients. A comparison of data from SDU and JDU showed that the prevalence of H. pylori infection and the antral predominant gastritis demonstrated by both SDU and JDU were essentially identical. A comparison of data from JDU and JGU demonstrated a greater prevalence of H. pylori infection in the antrum, but not corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all patients.

The site specified biopsy methodology and standardized interpretation criteria utilized in this study clearly show that the histotopographic profile of Swedish and Japanese DU patients is essentially the same.

Biopsy sampling of the gastric mucosa at diagnostic endoscopy provides information that cannot be obtained otherwise. The most common indication for gastric biopsy is the need to know whether the patient is infected with Helicobacter pylori or not and whether the stomach is gastritic or not. Microscopic examination of gastric biopsy specimens gives, in addition to H. pylori status, information about the grade, extent, and topography of gastritis- and atrophy-related alterations in the gastric mucosa. This information provides further possibilities for the assessment of risk and likelihood of various gastric disorders. The presence of atrophy (loss of mucosal glands) results in failures in secretory functions of the corresponding mucosa and leads to errors in the homeostasis of normal gastric physiology. The grade of atrophy of the corpus mucosa linearly correlates with peak and maximal output of acid. The presence of advanced (moderate or severe) corpus atrophy indicates an extremely hypochlorhydric or achlorhydric stomach in which, for example, ordinary peptic ulcer is unlikely or impossible in spite of a possible H. pylori infection. Some well characterized and common topographic phenotypes of H. pylori gastritis and atrophic gastritis can be delineated as follows: Predominance or restriction of the H. pylori-related inflammation in antrum, in association with a nonatrophic corpus mucosa--of which phenotype is the most common--and with an increased risk of peptic ulcer disease, duodenal ulcer in particular ("duodenal ulcer phenotype" of gastritis); the presence of atrophic gastritis in corpus of the stomach ("corpus predominant gastritis"), which indicates a low risk of peptic ulcer and a reduction in the capacity of the patient to secrete acid; the occurrence of advanced atrophic gastritis and intestinal metaplasia multifocally in the stomach (advanced "multifocal atrophic gastritis"), which are features of a gastritis type and which also indicate a low acid secretion capacity and an increased risk of gastric neoplasias ("gastric cancer phenotype of gastritis"), suggesting a need for a careful exclusion of concomitant presence of small focal neoplastic or dysplastic lesions; and the presence of normal and healthy gastric mucosa, which indicates an extremely low risk of both peptic ulcer disease or gastric cancer and, therefore, is a finding of high clinical relevance. The presence of duodenal or gastric ulcer in conjunction with normal, healthy gastric mucosa suggests either aspirin or nonsteroidal antiinflammatory drugs to be the most likely cause of the ulcer.

Helicobacter pylori infection is the cause of chronic gastritis that progresses to atrophic gastritis over years and decades in more than half of affected individuals. H. pylori gastritis and, particularly, subsequent atrophic gastritis increase the risk for gastric cancer on multifactorial basis. Largely unknown cascades of manifold reactions result in gene errors of epithelial cells in gastric and atrophic stomach, which raise the likelihood of gastric neoplasias and cancer among people infected by H. pylori. The prevalences and incidences of gastric cancer and H. pylori are similarly decreased during the past decades in western countries, supporting the view that H. pylori infection is a key event and a trigger of the phenomena that result in cancer in some of the infected subjects.

Nocturnal gastric acid breakthrough is defined as night-time periods when gastrin pH falls below 4.0 for greater than 1h during administration of a proton pump inhibitor. This phenomenon is a serious problem for patients who require strict control of their gastric acid secretions.

To investigate the prevalence of nocturnal gastric acid breakthrough in Japanese subjects during administration of rabeprazole, and to clarify the relationship between Helicobacter pylori infection and nocturnal gastric acid breakthrough.

Thirty-one normal male volunteers were examined by ambulatory 24 h gastric pH monitoring four times: without medication, after a morning or an evening dose of 20 mg rabeprazole, and after administration of an H2-receptor antagonist at bedtime, in addition to the morning dose of rabeprazole. H. pylori infection was determined by the 13C-urea breath test and an assay for serum anti-H. pylori antibody.

Nocturnal gastric acid breakthrough was observed in 12 patients (39%) after the morning dose of 20 mg rabeprazole. In all cases, nocturnal gastric acid breakthrough was inhibited completely by administration of the H2-receptor antagonist at bedtime. Only one patient with nocturnal gastric acid breakthrough had H. pylori infection.

The absence of H. pylori infection appears to be closely related to the occurrence of nocturnal gastric acid breakthrough during dosing with a proton pump inhibitor.

To determine the clinical significance of Helicobacter pylori seropositivity and seronegativity in healthy blood donors, we carried out a serological evaluation of Helicobacter pylori status and endoscopy in a healthy blood donors population. In all, 1010 donors were screened for Helicobacter pylori by IgG ELISA and assessed for pepsinogen I and gastrin levels by RIA; 298 IgG seropositive and 61 seronegative subjects underwent endoscopy with biopsies. Of 359, 165 were also tested for CagA by western blotting. Of the 298 IgG seropositives, 274 were shown to be infected on biopsy testing. Endoscopy revealed 70 peptic ulcers, 41 cases of erosive duodenitis, and two gastric cancers. In all 105 seropositive donors were tested for CagA and 69 were CagA positive [34/58 gastritis (58.6%), 24/35 duodenal ulcer (68.6%) and 11/12 gastric ulcer (91.6%)]. Histologically active/chronic gastritis was associated with CagA: 88.4% vs 50% (CagA seropositive vs seronegative). Of the 61 IgG seronegatives, 59 were negative on biopsy testing. At endoscopy three had duodenitis. Of the 60/61 IgG seronegatives tested for CagA, one had a moderate reaction. Duodenal ulcer donors showed higher pepsinogen I levels than donors without duodenal ulcers (97.7 microg/ml vs 80.9 microg/ml respectively). Screening for Helicobacter pylori and anti-CagA seropositivity and pepsinogen I can identify individuals likely to have gastroduodenal pathology even in the absence of symptoms.

elucidate the mechanisms that lead to severe hypergastrinaemia during long-term omeprazole therapy for gastro-oesophageal reflux disease (GERD).

A total of 26 GERD patients were studied during omeprazole maintenance therapy. Twelve patients with severe hypergastrinaemia (gastrin > 400 ng/L) were compared with 14 control patients (gastrin < 300 ng/L). Helicobacter pylori serology and a laboratory screen were obtained in all patients. Gastric emptying was scored by the evidence of food remnants upon endoscopy 12 h after a standardized meal. Gastric antrum and corpus biopsies were analysed for histological parameters, as well as somatostatin and gastrin concentrations. All patients underwent a meal-stimulated gastrin test and the hypergastrinaemia patients also underwent a vagal nerve integrity assessment by pancreatic polypeptide testing (PPT).

Severe hypergastrinaemia patients had a longer duration of treatment (80 vs. 55 months; P = 0.047) and were characterized by a higher prevalence of H. pylori infection (9/12 vs. 2/14, P = 0.004), corpus mucosal inflammation and atrophic gastritis (P < 0.04). This was reflected in lower serum pepsinogen A concentrations (mean +/- S.E.M. 53.6 +/- 17.9 vs. 137 +/- 16.0 mg/L, P = 0.03), pepsinogen A/C ratio (1.8 +/- 0.3 vs. 4.1 +/- 0.6, P = 0.005) and mucosal somatostatin concentrations (2.75 +/- 0.60 vs. 4.48 +/- 1.08 mg/g protein, P = 0.038). Two patients in the hypergastrinaemia group had signs of delayed gastric emptying, but none in the normogastrinaemia group did (P = N.S.). In addition, both groups had a normal meal-stimulated gastrin response.

Severe hypergastrinaemia during omeprazole maintenance therapy for GERD is associated with the duration of therapy and H. pylori infection, but not with abnormalities of gastric emptying or vagal nerve integrity.

Helicobacter pylori is the causative agent of type B chronic gastritis, and plays a major role in the pathogenesis of gastroduodenal ulcer and gastric cancer. Because gastric cancer has been the leading cause of cancer mortality in Japan and Korea, we conducted a seroepidemiological study to estimate the prevalence of H. pylori infection in Japan and Korea in order to explain the current change in the gastric cancer incidences between two countries.

Samples used for this study included 1204 sera from Chinju, Korea and 580 sera from Fukuoka, Japan. Immunoblotting, using a sonicated crude H. pylori antigen and 1:5 dilution of serum, was performed, considering the immunoblot shows reactivity to the 120 Kd antigen of H. pylori as a specific marker of H. pylori infection.

Seroepidemiology data from Fukuoka, Japan showed a prevalence of H. pylori infection of 20% before school age, 40% by teenage years, and over 80% beyond 20 years of age. Seroepidemiology data from Chinju, Korea, showed a 50% infection rate in preschool ages, and over 80% prevalence rate after 7 years of age.

Lower rates of childhood H. pylori infection in Fukuoka may explain the recent decline and shift in the incidence of stomach cancer in Japan, supporting the hypothesis that H. pylori is a major determinant in the pathogenesis of stomach cancer.

Gastric acid secretion in Japanese subjects decreases with aging. One of the possible causative mechanisms of this attenuated acid secretion is speculated to be a Helicobacter pylori induced chronic gastritis. The infection rate of this microorganism has decreased recently in Japan.

To investigate whether gastric acid secretion has altered over the past 20 years, and if so, what the influence of H pylori infection might be in the Japanese population.

Gastric acid secretion, serum gastrin and pepsinogen I and II concentrations, and H pylori infection were determined in 110 Japanese subjects in both the 1970s and 1990s.

Basal acid output as well as maximal acid output have greatly increased over the past 20 years, not only in individuals with H pylori infection but also in those without infection. Furthermore, subjects with H pylori infection tended to show decreased gastric acid secretion in comparison with those without infection, particularly in geriatric subjects. There was a positive correlation between gastric acid secretion and serum pepsinogen I concentrations.

In Japan, both basal and stimulated gastric acid secretion have increased over the past 20 years; some unknown factors other than the decrease in H pylori infection may play an important role in this phenomenon.

There have been many studies on gastric carcinoma in populations with contrasting cancer risks. We aimed to find out whether the criteria for the histological diagnosis of early gastric carcinoma were comparable in Western countries and Japan.

Eight pathologists from Japan, North America, and Europe individually reviewed 35 microscope slides: 17 gastric biopsy samples and 18 endoscopic mucosal resections taken from 17 Japanese patients with lesions ranging from early gastric cancer to adenoma, dysplasia, and reactive atypia. The pathologists were given a list of pathological criteria and a form on which they were asked to indicate the criteria on which they based each diagnosis.

For seven slides most Western pathologists diagnosed low-grade adenoma/dysplasia, whereas the Japanese diagnosed definite carcinoma in four slides, suspected carcinoma in one, and adenoma in only two. Of 12 slides with high-grade adenoma/dysplasia according to most Western pathologists the Japanese gave the diagnosis of definite carcinoma in 11 and suspected in one. Of six slides showing high-grade adenoma/dysplasia with suspected carcinoma according to most Western pathologists the Japanese diagnosed definite carcinoma in all. There were no major differences in the diagnoses of three slides showing reactive epithelium and seven slides with clearly invasive carcinoma. When the opinion of the majority of the pathologists was taken as the final diagnosis there was agreement between Western and japanese in 11 of the 35 slides (kappa coefficient 0.15 [95% CI 0.01-0.29]). Presence of invasion was the most important diagnostic criterion for most Western pathologists whereas for the Japanese nuclear features and glandular structures were more important.

In Japan, gastric carcinoma is diagnosed on nuclear and structural criteria even when invasion is absent according to the Western viewpoint. This diagnostic practice results in almost no discrepancy between the diagnosis of a superficial biopsy sample and that of the final resection specimen. This may also contribute to the relatively high incidence and good prognosis of gastric carcinoma in Japan when compared with Western countries.

To clarify the roles of Helicobacter pylori cytotoxin in gastric atrophy, the cytotoxin positive rate and cytotoxin activity in Fukui and Okinawa, where the prevalence of atrophic gastritis and gastric cancer risk are quite different, were studied.

Seventy three strains from Fukui and 51 from Okinawa were examined.

The validation of atrophy was done by endoscopy, being confirmed with histology. The supernatant of liquid H pylori culture media was concentrated 20-fold, serially diluted, using doubling dilutions, and scored from 1 to 8. The semi-quantitated cytotoxin activity was expressed as the maximum dilution score yielding > 50% A431 cell vacuolation, being standardised with bacterial density.

The cytotoxin activity of the strains from Fukui was highly diverse compared with that from Okinawa, although the cytotoxin positive rate was not different. In Fukui strains, the grade of atrophy and the cytotoxin activity were correlated (p < 0.05). In addition, the cytotoxin activity of the strains from all patients in Okinawa, most of whom showed closed-type/mild atrophy, was significantly lower than that of the strains from the patients with open-type/severe atrophy in Fukui (6.46 (5.53) v 9.76 (8.80), p < 0.05), (mean (SEM)).

The difference in profile of the cytotoxin activity in the two areas was related to the difference in the prevalence of atrophic gastritis.

Helicobacter pylori, non-steroidal anti-inflammatory drugs, family history, blood group O, hyperpepsinogenaemia A, alcohol and smoking have been reported to be risk factors for peptic ulcer disease. The strength of causal risk factors may differ in different populations. In 215 Japanese and 493 Dutch employees of similar age, gender and type of occupation, a structured history was obtained using a questionnaire and fasting serum samples were analysed for IgG antibodies to H. pylori and pepsinogen A all in the same laboratory. A past ulcer history was verified through case notes. We found that H. pylori seropositivity, a high serum pepsinogen A and a family history of ulcer disease were significant and independent risk factors for peptic ulcer disease. For H. pylori seropositivity there was a 20-fold increased risk among the Dutch and an eight-fold increased risk among the Japanese. The seroprevalence of H. pylori was 90% in 20 Dutch subjects with a verified ulcer history and 95% in 41 Japanese ulcer subjects; it was 29% in Dutch non-ulcer subjects and 70% in Japanese non-ulcer subjects. The cumulative difference in risk to develop peptic ulcer disease at the age of 48 years between H. pylori-infected and -uninfected subjects was 24.5-3.0 = 21.5% for the Japanese and 11.8-0.5 = 11.3% for the Dutch. Duodenal ulcer disease was associated with a high coffee consumption only among the Japanese population, where this habit was much less prevalent than among the Dutch. In conclusion, the characterization of peptic ulcer risk factors as weak or strong has no universal basis: the present study shows that from a diagnostic point of view H. pylori appears to be a weaker risk factor for peptic ulcer disease in a society with a higher seroprevalence. However, from an aetiological point of view, H. pylori has an even greater impact on ulcer morbidity in the Japanese than in the Dutch population.

In a Dutch working population, the apparent association between dyspeptic symptoms and Helicobacter pylori infection was found to be entirely due to subjects with an ulcer history. In general populations with a much higher prevalence of H. pylori infection and peptic ulcer disease, such as in Japan, the relationship between dyspepsia and H. pylori has yet to be clarified. A questionnaire on ulcer history and dyspeptic symptoms during the preceding 3 month period was obtained from apparently healthy Japanese employees who underwent a periodic medical examination. In addition, serum samples were analysed for anti-H. pylori IgG antibodies. A total of 196 men and 35 women, aged 23-71 years, participated in the study. Seven women (20%) and 49 men (25%) had a diagnosis of peptic ulcer disease. Among 41 subjects with verified duodenal (26) and/or gastric (17) ulcer, 95% were H. pylori positive while 32% had had frequent dyspeptic symptoms in the 3 months prior to the study (29% of the 35 men and 50% of the 6 women). Among the 147 men and 28 women without an ulcer history, the 3 month period prevalence of frequent dyspepsia was 14 and 32%, respectively. The rate of H. pylori positivity was 80% in non-ulcer dyspeptics and 68% in all other non-ulcer subjects (95% confidence intervals: 61-92 and 61-76%, respectively). Significant differences in symptoms between H. pylori positive and negative subjects could not be detected, neither in the whole population nor in the non-ulcer group. In conclusion, in this Japanese working population, no association was found between dyspeptic symptoms and H. pylori infection, irrespective of the inclusion of subjects with a peptic ulcer history.