AGA clinical practice update on the diagnosis and management of Atrophic Gastritis: expert review

The purpose of this Clinical Practice Update Expert Review is to provide clinicians with guidance on the diagnosis and management of atrophic gastritis, a common preneoplastic condition of the stomach, with a primary focus on atrophic gastritis due to chronic Helicobacter pylori infection-the most common etiology-or due to autoimmunity. To date, clinical guidance for best practices related to the diagnosis and management of atrophic gastritis remains very limited in the United States, which leads to poor recognition of this preneoplastic condition and suboptimal risk stratification. In addition, there is heterogeneity in the definitions of atrophic gastritis, autoimmune gastritis, pernicious anemia, and gastric neoplasia in the literature, which has led to confusion in clinical practice and research. Accordingly, the primary objective of this Clinical Practice Update is to provide clinicians with a framework for the diagnosis and management of atrophic gastritis. By focusing on atrophic gastritis, this Clinical Practice Update is intended to complement the 2020 American Gastroenterological Association Institute guidelines on the management of gastric intestinal metaplasia. These recent guidelines did not specifically discuss the diagnosis and management of atrophic gastritis. Providers should recognize, however, that a diagnosis of intestinal metaplasia on gastric histopathology implies the diagnosis of atrophic gastritis because intestinal metaplasia occurs in underlying atrophic mucosa, although this is often not distinctly noted on histopathologic reports. Nevertheless, atrophic gastritis represents an important stage with distinct histopathologic alterations in the multistep cascade of gastric cancer pathogenesis. The Best Practice Advice statements presented herein were developed from a combination of available evidence from published literature and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out. These statements are meant to provide practical advice to clinicians practicing in the United States. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Atrophic gastritis is defined as the loss of gastric glands, with or without metaplasia, in the setting of chronic inflammation mainly due to Helicobacter pylori infection or autoimmunity. Regardless of the etiology, the diagnosis of atrophic gastritis should be confirmed by histopathology. BEST PRACTICE ADVICE 2: Providers should be aware that the presence of intestinal metaplasia on gastric histology almost invariably implies the diagnosis of atrophic gastritis. There should be a coordinated effort between gastroenterologists and pathologists to improve the consistency of documenting the extent and severity of atrophic gastritis, particularly if marked atrophy is present. BEST PRACTICE ADVICE 3: Providers should recognize typical endoscopic features of atrophic gastritis, which include pale appearance of gastric mucosa, increased visibility of vasculature due to thinning of the gastric mucosa, and loss of gastric folds, and, if with concomitant intestinal metaplasia, light blue crests and white opaque fields. Because these mucosal changes are often subtle, techniques to optimize evaluation of the gastric mucosa should be performed. BEST PRACTICE ADVICE 4: When endoscopic features of atrophic gastritis are present, providers should assess the extent endoscopically. Providers should obtain biopsies from the suspected atrophic/metaplastic areas for histopathological confirmation and risk stratification; at a minimum, biopsies from the body and antrum/incisura should be obtained and placed in separately labeled jars. Targeted biopsies should additionally be obtained from any other mucosal abnormalities. BEST PRACTICE ADVICE 5: In patients with histology compatible with autoimmune gastritis, providers should consider checking antiparietal cell antibodies and anti-intrinsic factor antibodies to assist with the diagnosis. Providers should also evaluate for anemia due to vitamin B-12 and iron deficiencies. BEST PRACTICE ADVICE 6: All individuals with atrophic gastritis should be assessed for H pylori infection. If positive, treatment of H pylori should be administered and successful eradication should be confirmed using nonserological testing modalities. BEST PRACTICE ADVICE 7: The optimal endoscopic surveillance interval for patients with atrophic gastritis is not well-defined and should be decided based on individual risk assessment and shared decision making. A surveillance endoscopy every 3 years should be considered in individuals with advanced atrophic gastritis, defined based on anatomic extent and histologic grade. BEST PRACTICE ADVICE 8: The optimal surveillance interval for individuals with autoimmune gastritis is unclear. Interval endoscopic surveillance should be considered based on individualized assessment and shared decision making. BEST PRACTICE ADVICE 9: Providers should recognize pernicious anemia as a late-stage manifestation of autoimmune gastritis that is characterized by vitamin B-12 deficiency and macrocytic anemia. Patients with a new diagnosis of pernicious anemia who have not had a recent endoscopy should undergo endoscopy with topographical biopsies to confirm corpus-predominant atrophic gastritis for risk stratification and to rule out prevalent gastric neoplasia, including neuroendocrine tumors. BEST PRACTICE ADVICE 10: Individuals with autoimmune gastritis should be screened for type 1 gastric neuroendocrine tumors with upper endoscopy. Small neuroendocrine tumors should be removed endoscopically, followed by surveillance endoscopy every 1-2 years, depending on the burden of neuroendocrine tumors. BEST PRACTICE ADVICE 11: Providers should evaluate for iron and vitamin B-12 deficiencies in patients with atrophic gastritis irrespective of etiology, especially if corpus-predominant. Likewise, in patients with unexplained iron or vitamin B-12 deficiency, atrophic gastritis should be considered in the differential diagnosis and appropriate diagnostic evaluation pursued. BEST PRACTICE ADVICE 12: In patients with autoimmune gastritis, providers should recognize that concomitant autoimmune disorders, particularly autoimmune thyroid disease, are common. Screening for autoimmune thyroid disease should be performed.

Glucocorticoids and Androgens Protect From Gastric Metaplasia by Suppressing Group 2 Innate Lymphoid Cell Activation.

BACKGROUND & AIMS: The immune compartment is critical for maintaining tissue homeostasis. A weak immune response increases susceptibility to infection, but immune hyperactivation causes tissue damage, and chronic inflammation may lead to cancer development. In the stomach, inflammation damages the gastric glands and drives the development of potentially preneoplastic metaplasia. Glucocorticoids are potent anti-inflammatory steroid hormones that are required to suppress gastric inflammation and metaplasia. However, these hormones function differently in males and females. Here, we investigate the impact of sex on the regulation of gastric inflammation. METHODS: Endogenous glucocorticoids and male sex hormones were removed from mice using adrenalectomy and castration, respectively. Mice were treated with 5α-dihydrotestosterone (DHT) to test the effects of androgens on regulating gastric inflammation. Single-cell RNA sequencing of gastric leukocytes was used to identify the leukocyte populations that were the direct targets of androgen signaling. Type 2 innate lymphoid cells (ILC2s) were depleted by treatment with CD90.2 antibodies. RESULTS: We show that adrenalectomized female mice develop spontaneous gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM) but that the stomachs of adrenalectomized male mice remain quantitatively normal. Simultaneous depletion of glucocorticoids and sex hormones abolished the male-protective effects and triggered spontaneous pathogenic gastric inflammation and SPEM. Treatment of female mice with DHT prevented gastric inflammation and SPEM development when administered concurrent with adrenalectomy and also reversed the pathology when administered after disease onset. Single-cell RNAseq of gastric leukocytes revealed that ILC2s expressed abundant levels of both the glucocorticoid receptor (Gr) and androgen receptor (Ar). We demonstrated that DHT treatment potently suppressed the expression of the proinflammatory cytokines Il13 and Csf2 by ILC2s. Moreover, ILC2 depletion protected the stomach from SPEM development. CONCLUSIONS: Here, we report a novel mechanism by which glucocorticoids and androgens exert overlapping effects to regulate gastric inflammation. Androgen signaling within ILC2s prevents their pathogenic activation by suppressing the transcription of proinflammatory cytokines. This work revealed a critical role for sex hormones in regulating gastric inflammation and metaplasia.

Inflammation-Associated Senescence Promotes Helicobacter pylori-Induced Atrophic Gastritis.

BACKGROUND & AIMS: The association between cellular senescence and Helicobacter pylori-induced atrophic gastritis is not clear. Here, we explore the role of cellular senescence in H pylori-induced atrophic gastritis and the underlying mechanism. METHODS: C57BL/6J mice were infected with H pylori for biological and mechanistic studies in vivo. Gastric precancerous lesions from patients and mouse models were collected and analyzed using senescence-associated beta-galactosidase, Sudan Black B, and immunohistochemical staining to analyze senescent cells, signaling pathways, and H pylori infection. Chromatin immunoprecipitation, luciferase reporter assays, and other techniques were used to explore the underlying mechanism in vitro. RESULTS: Gastric mucosa atrophy was highly associated with cellular senescence. H pylori promoted gastric epithelial cell senescence in vitro and in vivo in a manner that depended on C-X-C motif chemokine receptor 2 (CXCR2) signaling. Interestingly, H pylori infection not only up-regulated the expression of CXCR2 ligands, C-X-C motif chemokine ligands 1 and 8, but also transcriptionally up-regulated the expression of CXCR2 via the nuclear factor-κB subunit 1 directly. In addition, CXCR2 formed a positive feedback loop with p53 to continually enhance senescence. Pharmaceutical inhibition of CXCR2 in an H pylori-infected mouse model attenuated mucosal senescence and atrophy, and delayed further precancerous lesion progression. CONCLUSIONS: Our study showed a new mechanism of H pylori-induced atrophic gastritis through CXCR2-mediated cellular senescence. Inhibition of CXCR2 signaling is suggested as a potential preventive therapy for targeting H pylori-induced atrophic gastritis. GEO data set accession numbers: GSE47797 and GSE3556.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Effectiveness of Helicobacter pylori eradication in preventing metachronous gastric cancer and preneoplastic lesions. A systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori is a significant risk factor for gastric cancer. Recent trials show eradication decreases the incidence of gastric cancer in patients with early-stage gastric cancer. However, data on gastric cancer prevention are inconsistent for patients with precancerous lesions such as atrophic gastritis and intestinal metaplasia. AIM: The aim of the study is to assess the efficacy of H. pylori eradication in gastric cancer prevention in patients with varying risk factors for gastric cancer at baseline. METHODS: A systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Medline, and Google Scholar were searched from inception through March 2019 for randomized controlled trials (RCTs) studying H. pylori eradication on gastric cancer prevention. We estimated the odds ratio (OR) with 95% confidence interval (CI) for each outcome using a random-effects model. P values of less than 0.05 were considered significant. RESULTS: Nine RCTs with total of 6967 patient were included in the analysis. There was significant reduction in gastric cancer incidence in the H. pylori group for patients with early gastric cancer status post endoscopic mucosal resection OR, 0.47; 95% CI, 0.33-0.67; P < 0.0001; I = 0%. There was no difference in gastric cancer incidence in patients with atrophic gastritis and intestinal metaplasia at baseline for H. pylori arm OR, 0.67; 95% CI, 0.42-1.07; P = 0.09; I = 0%). Atrophic gastritis and intestinal metaplasia improved from baseline in the H. pylori arm compared to placebo OR, 2.61; 95% CI, 1.41-4.81; P = 0.002; I = 88 and OR, 2.61; 95% CI, 1.66-4.11; P ≤ 0.0001; I = 0%, respectively. CONCLUSIONS: H. pylori eradication is associated with reduced gastric cancer incidence in patients with early-stage gastric cancer and improvement in atrophic gastritis and intestinal metaplasia. There was no difference in gastric cancer incidence in patients with atrophic gastritis and intestinal metaplasia at baseline.

Therapeutic assessment of fractions of Gastrodiae Rhizoma on chronic atrophic gastritis by 1H NMR-based metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. AIM OF THE STUDY: To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. MATERIALS AND METHODS: The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. RESULTS: The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. CONCLUSION: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.

Nuclear magnetic resonance-based metabolomics approach to evaluate preventive and therapeutic effects of Gastrodia elata Blume on chronic atrophic gastritis.

Chronic atrophic gastritis (CAG) is one of the most common digestive system diseases worldwide which defined by WHO as initial step of cancer. Gastrodia elata Blume (GEB) is a traditional herbal with multiple pharmacological activities which was widely used in Asian countries. This study aims to explore the preventive and therapeutical effects of Gastrodia elata Blume on auto-immune induced CAG in rats. Tissues of stomachs were collected and submitted to 1H NMR-based metabolomics analysis and histopathological inspection. The biochemical indexes of MDA, SOD, GSH, NO and XOD were measured. Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and the biochemical parameters, enhance gastric acid secretion, and significantly relieve the inflammation of the stomach. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles and correlation network analysis revealed that Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti-oxidation and anti-inflammation effects.

Host Nonresponsiveness Does not Interfere With Vaccine-Mediated Protection Against Gastric Helicobacter Infection.

BACKGROUND: Helicobacter pylori pathogenesis results from the inflammation induced by chronic infection. CBA mice are nonresponsive to gastric Helicobacter infection, providing a useful model for examining host regulation of Helicobacter-induced gastritis. We examined whether gastric Helicobacter nonresponsiveness impacts upon vaccine efficacy and whether immune-mediated protection could occur in the absence of inflammation. METHODS: Mice were vaccinated prior to challenge with Helicobacter felis or H. pylori. Gastritis and H. felis colonization was evaluated histologically. H. pylori colonization was quantified by colony-forming assay. RESULTS: Immunizations protected CBA mice against challenge with either H. felis or H. pylori. Protection against H. felis was marked by a loss of nonresponsiveness and development of an atrophic gastritis with mucus metaplasia. However, vaccine-induced protection against H. pylori was only associated with cell infiltration into the gastric mucosa. CONCLUSIONS: Nonresponsiveness to gastric Helicobacter infection did not interfere with vaccination-induced protection. Vaccine-induced protective immunity against H. pylori was linked with the induction of cellular infiltration, but importantly not atrophic gastritis.

[To the problem of evaluation of public health: screening for gastroduodenal pathology on the example of atrophic gastritis in mass medical examination of the population].

Assessment of health status of the population - the most important issue in preventive medicine. The objective of this work - to determine the possibility of nonendoscopic screening for gastroduodenal pathology, by the example of atrophic gastritis, in mass medical examinations of working residents in Moscow. Minimally invasive diagnostic test system GastroPanel ("Biohit", Finland) has been used. It allows with the ELISA method to determine both serum indicators of the function of the stomach -pepsinogen 1, gastrin 17 and the presence of H. pylori infection. 758 persons have been examined. The performed study confirms the possibility with the use of a set of mentioned indicators to identify individuals suspected for the presence of gastroduodenal disorders, especially atrophic gastritis, recognized as a precancerous condition. The use in preventive medicine complex diagnostic system, firstly, will make assessment of the health of the population more correct, increase the effectiveness of preventive measures and quality of life, and secondly, will contribute to the diagnosis of diseases of the stomach and duodenum in the early stages.

Gastric type I carcinoid: a pilot study with human G17DT immunogen vaccination.

CONTEXT: Gastric type I carcinoid is a rare neoplasm, deriving from enterochromaffin-like cells (ECL), mainly affecting women with autoimmune gastritis. The approach to treatment, either endoscopic, medical or surgical, is not well defined, particularly in multifocal tumours or carcinoids with rapid growth/frequent recurrence. OBJECTIVE: To determine whether an anti-G17 vaccination might interfere on the natural history of gastric type I carcinoid. SETTING: Padua teaching Hospital, outpatient clinic. DESIGN AND PATIENTS: Three patients with type I gastric carcinoid in autoimmune gastritis were administered, after informed consent and ethic committee approval, with a vaccine against gastrin 17 (G17), a synthetic peptide that stimulates specific and high-affinity anti-G17 antibodies, and followed up endoscopically and clinically for a mean of 36 months. MAIN OUTCOME MEASURES: Gastric histology and specifically carcinoid growth/recurrence and trend in time in gastrin, G17, pepsinogens, chromogranin A and clinical parameters. RESULTS: Following vaccination, carcinoid regression was observed in 2/3 patients and, in one of the patients, even the disappearance of ECL hyperplasia, with a reduced ECL cells stimulation, confirmed by a significant reduction in chromogranin A levels. Regression was observed in the two patients that showed a more clear local response to the vaccine. Increased autoantibody titre was observed, but no appearance of new autoimmune diseases. CONCLUSIONS: Anti-G17 vaccination induced regression of type I gastric carcinoid and could be considered for the treatment of this tumour, when endoscopic removal is not indicated.

High-protein diet suppresses corpus atrophic gastritis in Helicobacter pylori infected Mongolian gerbils.

To investigate the effect of a high-protein diet on corpus atrophic gastritis in Helicobacter pylori-infected Mongolian gerbils, H. pylori was administered orally to 5-wk-old Mongolian gerbils; and the animals were then fed a control diet (Group C); a high-fat diet (Group F: 40% fat); a high-protein diet (Group P: 32% protein); or a high-fat, high-protein diet (Group FP: 40% fat, 32% protein) for 50 wk beginning at 7 wk of age. In uninfected animals, the mucosal thickness of the corpus was significantly greater in Group P and Group FP than in Group C (P < 0.05). In infected animals, the serum gastrin level was significantly decreased in Group FP and marginally significantly decreased in Group P (P = 0.057) in comparison to Group C. The mucosal thickness of the corpus was significantly greater in Group P and Group FP than in Group C (P < 0.05). Mean inflammation and atrophy scores in the corpus were significantly lower in the high-protein groups (Groups P and FP) than in the control groups (Groups C and F; both inflammation and atrophy: P < 0.05). In conclusion, long-term administration of a high-protein diet suppresses corpus atrophic gastritis in H. pylori-infected Mongolian gerbils.

Migrant communities constitute a possible target population for primary prevention of Helicobacter pylori-related complications in low incidence countries.

OBJECTIVE: Pre-selection of individuals with epidemiological risk factors for Helicobacter pylori infection and atrophic gastritis could increase the efficiency of serologic screening to prevent peptic ulcer disease and gastric cancer in Western countries. The aim of this study was to determine the prevalence of and risk factors for H. pylori infection and atrophic gastritis in a migrant community in The Netherlands. MATERIAL AND METHODS: Inhabitants from an urban district in Rotterdam, The Netherlands with a large proportion of immigrants were randomly selected. Information was collected on demographic factors, socio-economic status, lifestyle, history of dyspeptic symptoms and medication use. In addition, serologic H. pylori and CagA status and the presence of atrophic gastritis were evaluated. RESULTS: In total, 288 subjects were included. Surinamese or Antillean, Turkish, Cape Verdian and Moroccan subjects were H. pylori-infected in 65%, 82%, 86% and 96% of cases, respectively, whereas the infection rate in Dutch subjects was 46% (all p<0.05). Within multivariate logistic regression analysis, ethnicity and number of persons in a household were identified as independent risk factors for H. pylori infection. In addition, mean pepsinogen I level and pepsinogen I/II ratio were significantly lower in subjects of non-Dutch origin as compared to Dutch subjects (both p<0.001). No Dutch subjects suffered from atrophic gastritis, as compared with 12 subjects of non-Dutch origin (p=0.13). CONCLUSIONS: The prevalence of H. pylori is high in migrant populations in The Netherlands. Furthermore, markers of atrophic gastritis are increased in subjects of foreign origin. Therefore, these migrant communities may constitute a target group for serologic screening to prevent H. pylori-related complications in Western countries.

Effects of Helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia: a 3-year follow-up study.

AIM: To investigate the effect of H pylori eradication on atrophic gastritis and intestinal metaplasia (IM). METHODS: Two hundred and fifty-nine patients with atrophic gastritis in the antrum were included in the study, 154 patients were selected for H pylori eradication therapy and the remaining 105 patients served as untreated group. Gastroscopy and biopsies were performed both at the beginning and at the end of a 3-year follow-up study. Gastritis was graded according to the updated Sydney system. RESULTS: One hundred and seventy-nine patients completed the follow-up, 92 of them received H pylori eradication therapy and the remaining 87 H pylori-infected patients were in the untreated group. Chronic gastritis, active gastritis and the grade of atrophy significantly decreased in H pylori eradication group (P<0.01). However, the grade of IM increased in H pylori -infected group (P<0.05). CONCLUSION: H pylori eradication may improve gastric mucosal inflammation, atrophy and prevent the progression of IM.

[Mechanism of isinglass in prevention and treatment of chronic atrophic gastritis in rats].

OBJECTIVE: To investigate the mechanism of isinglass in the prevention and treatment of chronic atrophic gastritis (CAG) in rats. METHOD: Animal models of SD rats with CAG were made in accordance with the previous experience of combined administration of 60% ethanol, 20 mmol x L(-1) sodium deoxycholate and 0.1% ammonia water. In prevention groups, sucralfate and isinglass were used as preventive therapy while CAG rat model was being made. In the reverse groups, sucralfate and isinglass were used to treat rats after establishment of CAG rat model. Finally all the rats were executed. Then the length of the proliferation zone of the gastric mucosa and serum epidermal growth factors (EGF) and growth hormones (GH)level were studied. RESULT: In isinglass prevention groups and high dose isinglass reverse group, the length of the proliferation zone of the gastric mucosa was very close to that in normal control group (P > 0.05), much better than model control group (P < 0.01). In low dose isinglass reverse group, it was lower than that in normal control group (P < 0.01), but much better than model control group (P < 0.01). In both prevention and reverse groups, serum EGF level was higher than that in normal (P < 0.01) and model control group (P < 0.05). Serum GH level was the same in every group (P > 0.05). CONCLUSION: The mechanism of isinglass in the prevention and treatment of CAG rats lies in revitalizing and proliferating gastric mucosal cells by stimulating endogenous EGF secretion.

Broccoli consumption and chronic atrophic gastritis among Japanese males: an epidemiological investigation.

Previous in vitro and animal experiments have shown that sulforaphane, which is abundant in broccoli, inhibits Helicobacter pylori (H. pylori) infection and blocks gastric tumor formation. This suggests that broccoli consumption prevents chronic atrophic gastritis (CAG) introduced by H. pylori infection and, therefore, gastric cancer. For an epidemiological investigation of the relationship between the broccoli consumption and CAG, a cross-sectional study of 438 male employees, aged 39 to 60 years, of a Japanese steel company was conducted. CAG was serologically determined with serum cut-off values set at pepsinogen I < or = 70 ng/ml and a ratio of serum pepsinogen I/pepsinogen II < or = 3.0. Broccoli consumption (weekly frequency) and diet were monitored by using a 31-item food frequency questionnaire. The prevalence of CAG among men who ate broccoli once or more weekly was twice as high as that among men who consumed a negligible amount (P < 0.05). Multiple logistic regression analysis indicated that broccoli consumption once or more weekly significantly increased the risk for CAG (odds ratio, 3.06; 95% confidence interval, 1.12-8.38; P < 0.05), after controlling for age, education, cigarette smoking, and alcohol consumption. The present study failed to show an expected association between frequent broccoli consumption and a low prevalence of CAG.

Prevention by bovine milk against Helicobacter pylori-associated atrophic gastritis through its adherence inhibition.

BACKGROUND/AIMS: The effects of Helicobacter pylori infection on the development of atrophic gastritis and intestinal metaplasia in relation to lifestyle and diet and the effect of the bovine milk on H. pylori adherence to gastric antral mucosa were investigated. METHODOLOGY: H. pylori infection was investigated in 63 patients without endoscopic evidence of gastroduodenal disease. Presence of H. pylori infection was assessed by culture and histologic examination of antral and corpus biopsy samples. Grades of atrophic gastritis and intestinal metaplasia were judged with chromoendoscopy (Congo red-methylene blue test). Adherence of H. pylori was evaluated with scanning electron microscopic examination of antral mucosa in Mongolian gerbils. RESULTS: Cross-sectional analysis of lifestyle and diet showed that a high intake of bovine milk was significantly related to prevention of H. pylori infection and the developments of atrophic gastritis and intestinal metaplasia. H. pylori adherence to the gastric mucosa was inhibited by bovine milk in a dose-dependent manner. CONCLUSIONS: Bovine milk prevents the development of atrophic gastritis and intestinal metaplasia through its defense mechanisms against the attachment of H. pylori to the gastric mucosa.

Cure of Helicobacter pylori infection in patients with reflux oesophagitis treated with long term omeprazole reverses gastritis without exacerbation of reflux disease: results of a randomised controlled trial.

BACKGROUND: Helicobacter pylori gastritis may progress to glandular atrophy and intestinal metaplasia, conditions that predispose to gastric cancer. Profound suppression of gastric acid is associated with increased severity of H pylori gastritis. This prospective randomised study aimed to investigate whether H pylori eradication can influence gastritis and its sequelae during long term omeprazole therapy for gastro-oesophageal reflux disease (GORD). METHODS: A total of 231 H pylori positive GORD patients who had been treated for > or =12 months with omeprazole maintenance therapy (OM) were randomised to either continuation of OM (OM only; n = 120) or OM plus a one week course of omeprazole, amoxycillin, and clarithromycin (OM triple; n = 111). Endoscopy with standardised biopsy sampling as well as symptom evaluation were performed at baseline and after one and two years. Gastritis was assessed according to the Sydney classification system for activity, inflammation, atrophy, intestinal metaplasia, and H pylori density. RESULTS: Corpus gastritis activity at entry was moderate or severe in 50% and 55% of the OM only and OM triple groups, respectively. In the OM triple group, H pylori was eradicated in 90 (88%) patients, and activity and inflammation decreased substantially in both the antrum and corpus (p<0.001, baseline v two years). Atrophic gastritis also improved in the corpus (p<0.001) but not in the antrum. In the 83 OM only patients with continuing infection, there was no change in antral and corpus gastritis activity or atrophy, but inflammation increased (p<0.01). H pylori eradication did not alter the dose of omeprazole required, or reflux symptoms. CONCLUSIONS: Most H pylori positive GORD patients have a corpus predominant pangastritis during omeprazole maintenance therapy. Eradication of H pylori eliminates gastric mucosal inflammation and induces regression of corpus glandular atrophy. H pylori eradication did not worsen reflux disease or lead to a need for increased omeprazole maintenance dose. We therefore recommend eradication of H pylori in GORD patients receiving long term acid suppression.