Showing papers on "Chronic gastritis published in 2000"

Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer.

Abstract: The role and significance of microsatellite instability (MSI) in gastric carcinogenesis remain unknown. This study determined the chronology of MSI in gastric carcinogenesis by examining intestinal metaplasia (IM) from patients with and without gastric cancer. DNA was obtained from gastric specimens of 75 patients with gastric IM (30 cancer, 26 peptic ulcer, and 19 chronic gastritis patients) and was amplified with a set of eight microsatellite markers. Eight (26.7%) tumors and seven (9.3%) IM samples (three from cancer-free patients) displayed high-level MSI (three or more loci altered). Low-level MSI (one or two loci altered) was detected in 50. of the tumors, in 40% of IM samples coexisting with cancer, and in 38% of IM tissues of cancer-free individuals. Among the 30 cancer patients, microsatellites were more frequently altered in IM coexisting with tumors that showed MSI ( P = 0.003). In addition, patients with low-level MSI in the tumor tissues were more likely to have active Helicobacter pylori infection than those with stable tumors ( P = 0.02). In conclusion, this study indicates that MSI occurs not only in gastric IM of patients with gastric carcinoma, but also in IM of cancer-free individuals. These data suggest that the progressive accumulation of MSI in areas of IM may contribute to gastric cancer development, representing an important molecular event in the multistep gastric carcinogenesis cascade.

GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population.

Abstract: Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic compounds. The homozygous deletions or null genotypes of GSTT1 (theta class) and GSTM1 (mu class) genes may be associated with an increased risk of cancer. Few studies have evaluated the relationship between GSTT1, GSTM1 and the risk of gastric cancer, as well as the potential interactions between these genetic markers and other risk factors of gastric cancer in the Chinese population. We conducted a case-control study with 143 cases with gastric cancer, 166 chronic gastritis (CG) cases and 433 cancer-free population controls from Yangzhong County, China. The epidemiological data were collected by a standard questionnaire for all of the subjects, and blood samples were obtained from 91 gastric cancer cases, 146 CG cases, and 429 controls. GSTT1 and GSTM1 genotypes were assayed by the PCR method, and Helicobacter pylori infection was measured by the ELISA method. Using logistic regression model in SAS, we assessed the independent effects of GSTT1 and GSTM1 null genotypes on the risk of gastric cancer and their potential interactions with other factors. The prevalence of GSTM1 null genotype was 48% in gastric cancer cases, 60% in CG patients, and 51% in controls. The prevalence of GSTT1 null genotype was 54% in gastric cancer cases, 48% in CG patients, and 46% in controls. After controlling for age, gender, education, pack-years of smoking, alcohol drinking, body mass index, H. pylori infection, and fruit and salt intake, the adjusted odds ratio (OR) for GSTT1 and gastric cancer was 2.50 (95% confidence interval (CI), 1.01-6.22). When gastric cancer cases were compared with CG patients, the adjusted OR for GSTT1 was 2.33 (95% CI, 0.75-7.25). However, GSTT1 null genotype was not associated with the risk of CG when using population controls. No obvious association was found between GSTM1 and the risk of both gastric cancer and CG. Our results suggest that GSTT1 null genotype may be associated with an increased risk of gastric cancer in a Chinese population.

Effect of Helicobacter pylori eradication on chronic gastritis during omeprazole therapy.

Abstract: BACKGROUND We have previously observed that profound acid suppressive therapy in Helicobacter pylori positive patients with gastro-oesophageal reflux disease is associated with increased corpus inflammation and accelerated development of atrophic gastritis. AIM To investigate if H pylori eradication at the start of acid suppressive therapy prevents the development of these histological changes. PATIENTS/METHODS In a prospective randomised case control study, patients with reflux oesophagitis were treated with omeprazole 40 mg once daily for 12 months. H pylori positive patients were randomised to additional double blind treatment with omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily or placebo for one week. Biopsy sampling for histology, scored according to the updated Sydney classification, and culture were performed at baseline, and at three and 12 months. RESULTS In the persistently H pylori positive group (n=24), active inflammation increased in the corpus and decreased in the antrum during therapy (p=0.032 and p=0.002, respectively). In contrast, in the H pylori positive group that became H pylori negative as a result of treatment (n=33), active and chronic inflammation in both the corpus and antrum decreased (p⩽0.0001). The decrease in active and chronic inflammation in the corpus differed significantly compared with the persistently H pylori positive group (both p=0.001). For atrophy scores, no significant differences were observed between H pylori eradicated and persistently H pylori positive patients within one year of follow up. No changes were observed in the H pylori negative control group (n=26). CONCLUSIONS H pylori eradication prevents the increase in corpus gastritis associated with profound acid suppressive therapy. Longer follow up is needed to determine if H pylori eradication prevents the development of atrophic gastritis.

Relationship of Blood Group Determinants on Helicobacter pylori Lipopolysaccharide with Host Lewis Phenotype and Inflammatory Response

Abstract: As Lewis a (Lea) and Lewis b (Leb) blood group antigens are isoforms of Lewis x (Lex) and Lewis y (Ley) and are expressed in the gastric mucosa, we evaluated whether the patterns of expression of Lex and Ley on Helicobacter pylori lipopolysaccharides reflected those of host expression of Lea and Leb. When 79 patients (secretors and nonsecretors) were examined for concordance between bacterial and host Le expression, no association was found (χ2 = 5.734, 3 df, P = 0.125), nor was there a significant difference between the amount of Lex or Ley expressed on isolates from ulcer and chronic gastritis patients (P > 0.05). Also, the effect of host and bacterial expression of Le antigens on bacterial colonization and the observed inflammatory response was assessed. In ulcer patients, Lex expression was significantly related to neutrophil infiltration (rs = 0.481, P = 0.024), whereas in chronic gastritis patients significant relationships were found between Lex expression and H. pylori colonization density (rs = 0.296, P = 0.03), neutrophil infiltrate (rs = 0.409, P = 0.001), and lymphocyte infiltrate (rs = 0.389, P = 0.002). Furthermore, bacterial Ley expression was related to neutrophil (rs = 0.271, P = 0.033) and lymphocyte (rs = 0.277, P = 0.029) infiltrates. Thus, although no evidence of concordance was found between bacterial and host expression of Le determinants, these antigens may be crucial for bacterial colonization, and the ensuing inflammatory response appears, at least in part, to be influenced by Le antigens.

Detection of circulating gastric carcinoma‐associated antigen MG7‐Ag in human sera using an established single determinant immuno‐polymerase chain reaction technique

Abstract: BACKGROUND In 1994, a novel sensitive method termed immuno-polymerase chain reaction (PCR) for the detection of the gastric carcinoma-associated antigen MG7-Ag in the gastric carcinoma cell line KATO III was reported. Compared with the enzyme-linked immunoadsorbent assay, the single determinant immuno-PCR technique could allow for as few as 20 cells to be detected and was found to show an approximately 10,000-fold enhancement in sensitivity of the detection limit. The current study clinically evaluated the significance of serum MG7-Ag detection in gastric carcinoma patients. METHODS The sera of patients were immobilized on wells and a specific DNA molecule, which could be amplified by PCR, was employed as a marker. The biotinylated monoclonal antibody against gastric carcinoma was added to bind the antigen immobilized on the wells. After the biotinylated antibody was bound to the antigen, free avidin was used to attach a biotinylated monoclonal antibody and biotinylated DNA molecule. The biotinylated DNA complexed with antigen-antibody-avidin was amplified by PCR and the PCR products were analyzed by agarose gel electrophoresis. In the current study this method was used to detect circulating MG7-Ag in the sera of patients with gastric carcinoma and other various malignancies. For comparison, carcinoembryonic antigen, CA 50, CA 19-9, and TAG-72 were quantitated by radioimmunoassay and immunoradiometric assay using the relevant commercial kits in the same sera samples from 86 patients with pathologically confirmed gastric carcinoma and 83 patients with relevant benign diseases of the stomach. In addition, the semiquantitative analysis of PCR products among gastric carcinoma patients with or without metastasis was performed to compare the intensity of DNA band amplification. RESULTS Using the immuno-PCR assay, positive results were obtained in 164 of 198 patients with gastric carcinoma (82.8%). The rates of positivity in other malignancies were 17.4% for esophageal carcinoma (15 of 86 patients), 44.4% for colonic carcinoma (40 of 90 patients), 0% for liver carcinoma (none of 84 patients), 2.2% for ovarian carcinoma (1 of 45 patients), 0% for uterine carcinoma (none of 27 patients), and 6.1% for lung carcinoma (4 of 66 patients). The positive results obtained from those patients with benign diseases were: 7.7% for peptic ulcer (6 of 78 patients), 5.9% for chronic gastritis (7 of 118 patients), 3.3% for chronic colitis (2 of 60 patients), and 0.8% for healthy blood donors (2 of 236 patients). In addition, the semiquantitative analysis of PCR products showed that the intensity of DNA band amplified from the PCR products of those patients with metastasis was much higher than that of patients without metastasis or those with early stage tumors (1.94 ± 0.03 vs. 1.28 ± 0.02). In comparative studies of immuno-PCR and commercial assays for tumor-associated antigens the sensitivity of immuno-PCR was 81.4% and pseudopositivity was lower (8.4% vs. 7.2–12.0% with radioimmunoassay or immunoradiometric assay). CONCLUSIONS The results of the current study demonstrate that introducing PCR into the indirect determination of tumor-associated antigen in the serum can improve the sensitivity of detection greatly. This novel assay also might be used to monitor the circulating amount of tumor-associated antigen after gastrectomy and provide information regarding recurrence or metastasis, as well as for screening elderly patients who have no indications for endoscopy and those with precancerous conditions. The application of immuno-PCR in the serologic diagnosis of carcinoma has significant advantages including ready application in the clinical setting as well as use as a potential screening tool in mass surveys of high risk populations with gastric carcinoma. Cancer 2000;88:280–5. © 2000 American Cancer Society.

Regression of colonic low grade B cell lymphoma of the mucosa associated lymphoid tissue type after eradication of Helicobacter pylori

Abstract: BACKGROUND Lymphoma of the mucosa associated lymphoid tissue (MALT) arising in the stomach has been shown to be related to Helicobacter pylori infection, and total regression of gastric lymphoma after successful eradication of H pylori has consistently been reported. MALT-type lymphoma at other localisations, however, has to our knowledge not been linked to H pylori , and eradication of the bacteria has not been studied for management of such lymphomas. PATIENT/METHOD A 67 year old man was diagnosed with MALT-type lymphoma simultaneously involving the stomach and the colon descendens. In addition to the presence of MALT-type lymphoma, H pylori associated chronic gastritis was diagnosed, and treatment with clarithromycin, metronidazole, and omeprazole was initiated, resulting in its successful eradication. RESULTS Follow up performed four months later showed regression of the colonic manifestation, whereas the gastric lymphoma did not respond to antibiotic treatment, as assessed by regular follow up for 14 months, in spite of its restriction to mucosa and submucosa. The patient was therefore treated with oral cyclophosphamide (100 mg a day) resulting in partial remission after seven months of continuous treatment. Because of the presence of residual lymphoma, additional irradiation was performed, which led to complete remission of the gastric lymphoma. The patient remains in complete remission 40 months after diagnosis and 26 months after initiation of treatment. CONCLUSION In the case of concurrent gastric and intestinal low grade MALT-type lymphoma, H pylori eradication may cause regression of the intestinal lesion.

Prevalence of gastroduodenitis and Helicobacter pylori infection in a general population sample relations to symptomatology and life-style.

Abstract: Some benign and malignant diseases develop on the background of chronic gastritis or duodenitis. The present study was performed in order to determine the magnitude of these background changes with relations to symptomatology and life style in the general population. Examinations were performed in 501 volunteers (age 35–85 years). Fifty percent had gastritis; this was associated with H. pylori in 87%. H. pylori-negative gastritis was associated with regular use of NSAIDs [odds ratio 3.8 (1.6–9.9)]. Duodenitis, observed in 32%, was associated with H. pylori infection [odds ratio 2.3 (1.3–4.6)], previous cholecystectomy [odds ratio 3.6 (1.1–16.1)], and regular use of NSAIDs [odds ratio 3.0 (1.4–7.1)]. Neither gastritis nor duodenitis was associated with smoking or alcohol consumption. The rate of digestive symptoms did not differ between subjects with and without uncomplicated gastritis or duodenitis. In conclusion, half of this adult population had gastritis strongly associated with H. pylori infection. Gastritis without H. pylori infection was frequently associated with regular NSAID intake. One third had duodenitis, which was associated with H. pylori infection as well as with regular use of NSAIDs and previous cholecystectomy. Digestive symptoms were not overrepresented in uncomplicated gastritis or duodenitis.

Helicobacter pylori infection in recurrent abdominal pain.

Abstract: Background Helicobacter pylori is associated with chronic gastritis and peptic ulcer in adults and in children. The purpose of the present study was to analyze the association of recurrent abdominal pain and H. pylori infection in children and to evaluate the efficacy of antimicrobial treatment in patients with evidence of infection. Methods The clinical and histopathologic findings in children who underwent diagnostic upper endoscopy for recurrent abdominal pain were analyzed retrospectively. Patients with evidence of infection with H. pylori were treated with a combination of omeprazole, amoxicillin, and clarithromycin. Efficacy of treatment was assessed using the 13C-urea-breath test. Results H. pylori was found in histopathologic sections of 29 (40%) of 73 patients undergoing diagnostic endoscopy for recurrent abdominal pain. Five children (17%) were of Swiss ethnic origin, and 24 (83%) were non-Swiss. All the infected patients had chronic gastritis and 4 (14%) had ulcerations in the duodenum. Treatment with omeprazole, amoxicillin, and clarithromycin resulted in eradication of the infection in all and in resolution of the clinical symptoms in 15 (80%) of 19 patients who had a follow-up examination. Conclusions The presented data suggest that gastritis induced by H. pylori may be associated with recurrent abdominal pain and that in Switzerland infections with H. pylori primarily involve persons who are non-Swiss. A combined therapy results in eradication of the bacterium and in improvement of the clinical symptoms in a significant majority of the patients.

Relationship between Ethanol-Induced Gastritis and Gastric Ulcer Formation in Rats

Abstract: Background/Aims: Patients with peptic ulcer diseases have a high prevalence of coexisting chronic gastritis. The mechanism of how gastritis leads to gastric ulcer formation is yet t

Helicobacter pylori. One bacterium and a broad spectrum of human disease! An overview.

Abstract: Since the historical rediscovery of gastric spiral Helicobacter pylori in the gastric mucosa of patients with chronic gastritis by Warren and Marshall in 1983, peptic ulcer disease has been largely viewed as being of infectious aetiology. Indeed, there is a strong association between the presence of H. pylori and chronic active gastritis in histology. The bacterium can be isolated in not less than 70% of gastric and in over 90% of duodenal ulcer patients. Eradication of the organism has been associated with histologic improvement of gastritis, lower relapse rate and less risk of bleeding from duodenal ulcer. The bacterium possesses several virulence factors enabling it to survive the strong acid milieu inside the stomach and possibly damaging host tissues. The sequence of events by which the bacterium might cause gastric or duodenal ulcer is still not fully elucidated and Koch's postulates have never been fulfilled. In the majority of individuals, H. pylori infection is largely or entirely asymptomatic and there is no convincing data to suggest an increase in the prevalence of peptic ulcer disease among these subjects. An increasingly growing body of literature suggests an association between colonization by H. pylori in the stomach and a risk for developing gastric mucosa-associated lymphoid tissue (MALT), MALT lymphoma, gastric adenocarcinoma and even pancreatic adenocarcinoma. The bacterium has been implicated also in a number of extra-gastrointestinal disorders such as ischaemic heart disease, ischaemic cerebrovascular disease, atherosclerosis, and skin diseases such as rosacea, but a causal role for the bacterium is missing. Eradication of H. pylori thus seems to be a beneficial impact on human health. Various drug regimens are in use to eradicate H. pylori involving the administration of three or four drugs including bismuth compounds, metronidazole, clarithromycin, tetracyclines, amoxycillin, ranitidine, omeprazole for 1-2 weeks. The financial burden, side effects and emergence of drug resistant strains due to an increase in the use in antibiotics for H. pylori eradication therapy need further reconsideration.

Expression of Cdc2 and Cyclin B1 in Helicobacter pylori-Associated Gastric MALT and MALT Lymphoma : Relationship to Cell Death, Proliferation, and Transformation

Abstract: Mucosa-associated lymphoid tissue (MALT) may accumulate within gastric mucosa as a result of long standing Helicobacter pylori infection, and this acquired MALT may eventually develop into low-grade B-cell MALT lymphoma. To determine the possible association of cell cycle regulatory proteins and apoptotic cell death in the transformation of H. pylori gastritis to MALT lymphoma, the extent of cell proliferation, cell viability, expression of Cdc2/Cdk1 and cyclin B in gastric mucosal from patients with H. pylori -positive chronic gastritis ( n = 7), MALT ( n = 12), or MALT lymphoma ( n = 12) were undertaken. Control tissue was obtained from H. pylori - negative patients ( n = 5). Proliferating cell nuclear antigen (PCNA), Cdc2, and cyclin B1 were examined in paraffin embedded tissue by immunohistochemistry, while the apoptotic index (AI) was determined using the TUNEL assay. H&E staining for histology and modified Giemsa staining for the detection of H. pylori was conducted simultaneously. When compared to chronic gastritis tissue, those with MALT or MALT lymphoma had an increase in PCNA labeling index of 3.3- and 2.7-fold, while that for Cdc2/Cdk1 increased 2.3- and 3.1-fold, respectively. cyclin B1 labeling was 1.9 and 3.0 fold, while the AI was 3.4. and 1.4-fold higher in MALT and MALT lymphoma tissue, respectively, in the same comparison. On the other hand, the AI index of MALT lymphoma was 2.5-fold lower than that for MALT tissues. The labeling scores for Cdc2/Cdk1 and cyclin B1 were significantly higher in the germinal center when compared to the mantle and marginal zones of MALT tissues. Using χ 2 and Pearson/Spearman's rho correlation coefficient with regression analyses, there was an inverse correlation between the AI and Cdc2/Cdk1 or cyclin B1 in MALT and MALT lymphoma tissues. There was no correlation between AI and PCNA labeling in any of the tissues. These results suggest that Cdc2/Cdk1 and cyclin B1 expression may be actively associated in the modulation of cellular death by apoptosis, as well as cellular proliferation and transformation during the evolution of H. pylori -associated gastritis to MALT lymphoma. Subclassification of high labeling score (≥40) for Cdc2/Cdk1 and cyclin B1 and low labeling index ( H. pylori -associated MALT may help in identifying a population of patients with an increased risk of developing MALT lymphoma.

Ascorbic acid and intestinal metaplasia in the stomach: a prospective, randomized study.

Abstract: Background: Intestinal type metaplasia plays a role in intestinal type gastric carcinoma development. Ascorbic acid demonstrates a protective effect against gastric carcinogenesis, due to its ability to inactivate oxygen free-radicals as well as its nitrite-scavenging effects. Aim: To assess whether long-term ascorbic acid administration following Helicobacter pylori eradication could affect intestinal metaplasia regression in the stomach. Methods: Sixty-five patients were included in the study. The inclusion criterion was the presence of intestinal metaplasia on the gastric mucosa after H. pylori eradication. An upper gastrointestinal endoscopy was performed and 3 biopsy specimens were taken in the antrum, 3 in the gastric body, and 2 in the incisura angularis. Patients were randomized to receive 500 mg of ascorbic acid o.d., after lunch (32 patients) for 6 months or no treatment (33 patients). All patients underwent to endoscopic control at the end of the 6 months. Results: H. pylori infection recurrence was detected in 6 (9.4%) patients (three from each group), and these patients were excluded from further analysis. We were unable to find evidence of intestinal metaplasia in any biopsied site of the gastric mucosa in 9/29 (31%) patients from the ascorbic acid group and in 1/29 (3.4%) of the patients from the control group (P=0.006). Moreover, a further six (20.7%) patients from the ascorbic acid group presenting chronic inactive pangastritis with widespread intestinal metaplasia at entry, showed less extensive antritis with intestinal metaplasia at control, whilst a similar finding was only seen in one patient from the control group (P=0.051). Conclusion: The administration of ascorbic acid significantly helps to resolve intestinal metaplasia of the gastric mucosa following H. pylori eradication, and its use as a chemoprevention treatment should be considered.

gastric α-tocopherol and β-carotene concentrations in association with helicobacter pylori infection

Abstract: OBJECTIVE The effects of Helicobacter pylori infection and its associated gastric histology on alpha-tocopherol and beta-carotene concentrations in serum, gastric juice and antral mucosa were investigated in patients undergoing routine gastroscopy for investigation of dyspepsia. METHOD Eighty-six patients were studied. High-performance liquid chromatography was used to measure alpha-tocopherol and beta-carotene concentrations. H. pylori infection was assessed by histology, bacterial culture, rapid urease test and serology. RESULTS No obvious association was found between age, sex, smoking or endoscopic diagnosis and alpha-tocopherol or beta-carotene concentrations in serum, gastric juice and antral mucosa. However, alcohol drinkers had significantly lower antral mucosal and gastric juice beta-carotene concentrations compared to non-drinkers. Gastric juice beta-carotene concentration was markedly lower in patients infected with H. pylori than uninfected controls (2.9 nmol/l (interquartile range 0.3-4.3) versus 4.6 nmol/l (interquartile range 3.5-7.6), P = 0.01), but there was no significant difference in serum or gastric mucosal beta-carotene concentrations between the two patient groups. The presence of gastric atrophy and intestinal metaplasia was significantly associated with reduced mucosal alpha-tocopherol and beta-carotene concentrations. Furthermore, antral mucosal alpha-tocopherol concentrations decreased progressively as antral mucosal histology changed from normal to chronic gastritis alone and finally to atrophy and intestinal metaplasia. CONCLUSION Gastric alpha-tocopherol and beta-carotene concentrations are affected by H. pylori-associated gastric histological changes, and these findings suggest that H. pylori infection may not only impair the protective role of vitamin C, but also of alpha-tocopherol and beta-carotene in the stomach.

Role of apoptosis in gastric epithelial turnover.

Abstract: Gastric epithelial turnover is a dynamic process. It is characterized by continuous cell proliferation, which is counterbalanced by cell loss. The biological principle that mediates the homeostasis of epithelium is programmed cell death, or apoptosis. Currently, several subtypes of apoptosis are distinguished, which are mediated by different mechanisms. Various subtypes of apoptosis also occur in the gastric epithelium under various conditions. In the normal stomach, apoptosis due to cell isolation (anoikis) mediates the physiological epithelial turnover. Albeit rarely seen in routine histology, approximately 2% of epithelial cells in the normal stomach are apoptotic. In Helicobacter pylori-induced gastritis, apoptosis and epithelial proliferation are moderately increased, with approximately 8% apoptotic epithelial cells. In gastritis, factors such as CD95 ligand or tumor necrosis factor (TNF) alpha act as death factors. They bind to specific receptors, CD95 and TNF-R, which are induced either by other cytokines, such as interferon gamma, or by Helicobacter pylori itself. In addition to CD95, H.pylorican also induce upregulation of CD95 ligand expression. Taken together, the upregulated expression of CD95, and the presence of CD95L in the close proximity to apoptotic gastric epithelial cells suggest a functional role of the CD95-CD95L system in the induction of apoptosis in H.pylori-gastritis. The role of other pathways to apoptosis is currently under study. Apart from being a biological phenomenon, apoptosis in the stomach may also have direct clinical consequences. An extreme example is given in gastric graft-vs.-host disease when epithelial denudement occurs.

Clinical usefulness of microsatellite instability for the prediction of gastric adenoma or adenocarcinoma in patients with chronic gastritis.

Abstract: To assess a role of microsatellite instability (MSI) in the development of gastric adenocarcinoma or adenoma from chronic gastritis, we analysed mutations of five microsatellite loci in gastritis, adenoma and adenocarcinoma retrospectively. Gastric mucosa was biopsied from the same area in each patient at different periods and examined for MSI. Only one of 55 patients with chronic gastritis revealed MSI-H phenotype and the other 54 patients showed microsatellite stable (MSS) phenotypes. In six of 17 patients with gastric adenoma or well-differentiated adenocarcinoma, MSI-positive phenotypes were demonstrated. Interestingly, all of six patients showing MSI, including three high-level MSI (MSI-H) cases and three low-level (MSH-L) cases, had already revealed MSI at the stage of chronic gastritis. In two of three MSI-H cases, the identical MSI patterns had been observed at the stage of gastritis 1.5–7 years before the final diagnosis of adenocarcinoma. The adjacent gastritis mucosa within 10 mm from the carcinoma demonstrated MSI as well. MSI was not found in any of 35 patients with Helicobacter pylori infection, but found in one of 30 patients without infection. Moreover, two of three cases of gastric adenoma or well-differentiated adenocarcinoma with MSI-H at the stage of chronic gastritis showed no evidence of Helicobacter pylori infection throughout the observation periods. These results indicate that MSI in biopsy specimens at the stage of chronic gastritis may predict the risk of the progression to adenoma and well-differentiated adenocarcinoma, and that Helicobacter pylori infection itself may not induce MSI directly in the gastric mucosa. © 2000 Cancer Research Campaign

Proliferation and apoptosis in gastric antral epithelial cells of patients infected with Helicobacter pylori.

Abstract: We measured cell proliferation and apoptosis in the antral epithelial cells of Helicobacter pylori-infected and H. pylori-uninfected persons, and examined these processes in relation to diagnosis and the histologic parameters of inflammation to investigate their role in cellular turnover in diseases of the upper gastrointestinal tract. The subjects were: 25 patients with antral gastric cancers, 20 with antral gastric ulcers, 18 with duodenal ulcers, and 28 with chronic gastritis, and 4 subjects with normal gastric mucosa. Seventy-two subjects were infected with H. pylori, and 23 subjects, including the 4 with normal gastric mucosa, were uninfected. H. pylori infection was associated with increased apoptosis and cell proliferation in the gastric mucosa, which correlated with the degree of acute inflammation and the density of H. pylori, and these latter two factors correlated with each other. Intestinal metaplasia and glandular atrophy were significantly higher in gastric cancers and gastric ulcers than in duodenal ulcers. Cell proliferation was significantly lower in gastric cancers than in gastric ulcers, but the apoptotic count did not show a significant differenence between these diseases. This decreased proliferation in the adjacent mucosa in gastric cancers compared with findings in the other diseases is thought to be closely related to the relatively decreased acute inflammation, which may, partly, contribute to glandular atrophy in the adjacent mucosa of gastric cancer.

The relationship between persistent secretion of RANTES and residual infiltration of eosinophils and memory T lymphocytes after Helicobacter pylori eradication

Abstract: Helicobacter pylori (HP)-infected gastric mucosa displays a conspicuous infiltration of mononuclear cells as well as neutrophils. RANTES is a potent chemoattractant peptide for memory T lymphocytes and eosinophils. RANTES protein concentration and the numbers of RANTES-, CD45RO-, and major basic protein (MBP)-positive cells were therefore evaluated in the gastric mucosa from 51 patients with HP-positive chronic gastritis before and after HP eradication and from 22 HP-negative healthy volunteers. RANTES protein concentration was significantly elevated in HP-positive cases and remained high after HP eradication. The numbers of RANTES-, CD45RO-, and MBP-positive cells were significantly increased in HP-positive cases and were well correlated with RANTES protein levels. All tended to decrease after HP eradication, but did not reach the level of HP-negative cases, even at 24 months after HP eradication. It was concluded that persistent expression and secretion of RANTES were closely related to residual infiltration of memory T lymphocytes and eosinophils, for a prolonged period after HP eradication. This seems to be an important mechanism of prolonged gastric mucosal immune response against HP infection, even after HP eradication, and of persistent mucosal damage and atrophy.

Role of Helicobacter pylori gastritis in gastric atrophy, intestinal metaplasia, and gastric neoplasia.

Abstract: Helicobacter pylori is the major cause of chronic gastritis worldwide. With an estimated rate of infection of over one half of the world's population, it is responsible for extensive morbidity and mortality. Infection with this organism does not appear to spontaneously resolve. Instead it reaches a chronic stage from which a number of outcomes are possible. This article reviews those outcomes that have been linked to H. pylori and explores the pathogenesis while attempting to resolve the discrepant paths infection can take. The associations include duodenal and gastric ulcers and the majority of gastric lymphomas of B-cell type derived from the mucosa-associated lymphoid tissue (MALT). Chronic gastritis has also been shown to evolve into atrophy with intestinal metaplasia in certain populations. This change in the gastric epithelium has been linked with an increased risk of gastric adenocarcinoma. Microsc. Res. Tech. 48:313-320, 2000. Published 2000 Wiley-Liss, Inc.

Patterns of inflammation linked to ulcer disease

Abstract: Peptic ulcers are accompanied by different patterns of chronic gastritis and duodenitis that generally run parallel to the topography of colonization by Helicobacter pylori (H. pylori). Duodenal ulcers arise on a background of a gastroduodenitis; the gastritis is antrum-predominant while the duodenitis requires acid-induced gastric metaplasia in the duodenal mucosa before bacterial colonization can occur. The colonized and inflamed metaplastic areas in the duodenum (and inflamed pre-pyloric antrum) are the initial sites of ulceration. Proximal gastric ulcers arise in a diffuse (pan-) gastritis or a corpus-predominant H. pylori gastritis when the weakened gastric mucosa (especially in the antrum-body transitional zone) is susceptible to ulceration even in the presence of subnormal acid production. These distinctive patterns of gastritis are sufficiently consistent for them to be used to predict ulcer risk.

Association of Helicobacter pylori-dependent gastritis with gastric carcinomas in young Japanese patients: histopathological comparison of diffuse and intestinal type cancer cases.

Abstract: Aims : The causal relationship of H. pylori gastric colonization with gastric cancer development has not as yet been fully elucidated. The prevalence of H. pylori infection increases with age in the asymptomatic population in Japan, and reaches a high plateau in those older than 40 years. The objective of this study was to assess the link between H. pylori and gastric carcinomas in patients younger than 40 years. Methods and results : Detection of H. pylori and assessment of background mucosa based on the Sydney system was performed histopathologically for 40 Japanese gastric cancer cases younger than 40 years and compared with 40 age- and sex-matched controls. H. pylori infection in gastric mucosa was detected significantly more frequently (P < 0.001) in patients with cancer (29/40; 72.5%) than in controls (11/40; 27.5%). Additionally, by histopathological comparison between intestinal (18 cases) and diffuse (70 cases) types of young gastric cancer patients, mucosal atrophy and intestinal metaplasia were found to coexist with acute and chronic inflammation in the background mucosa of both intestinal and diffuse types, being significantly more prevalent than in young controls. Conclusions : As well as the high prevalence of H. pylori in young subjects with gastric cancer, it is clear that persistent infection induces mucosal damage, resulting in atrophy and intestinal metaplasia. Thus, acute/chronic gastritis could play an essential role in the early development of neoplasia in the stomach.

Expression of human telomerase catalytic subunit gene in cancerous and precancerous gastric conditions

Abstract: Background and Aims: Telomerase activity is thought to be necessary for cellular immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic subunit (hTERT) has recently been identified, and expression of hTERT mRNA is thought to regulate activation of telomerase. To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia. Methods: Using reverse transcription-polymerase chain reaction, hTERT gene expression was investigated in 18 gastric cancers and 60 specimens of chronic gastritis. Telomerase activity was evaluated using telomeric repeat amplification protocol. Results: Sixteen of 18 (89%) gastric carcinomas expressed hTERT mRNA, and this expression was unrelated to histological type or depth of invasion. Telomerase activity was found in seven of eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and was most prominent in seven of 15 (47%) specimens of gastric mucosa with intestinal metaplasia. Expression of the hTERT gene was significantly more frequent in chronic gastritis with intestinal metaplasia than in gastritis without intestinal metaplasia (P = 0.030). In addition, hTERT gene expression was not correlated with age, sex, biopsy site, histological grade of inflammatory cells, glandular atrophy and lymph follicles, or infection with Helicobacter pylori. None of eight normal gastric mucosa expressed hTERT mRNA. Conclusions: Our results indicate that hTERT mRNA is expressed in precancerous conditions as well as in gastric cancer, and that hTERT gene expression is induced at an early stage of gastric carcinogenesis.

Clarithromycin-resistance and point mutations in the 23S rRNA gene in Helicobacter pylori isolates from Japan.

Abstract: Background: Resistance of Helicobacter pylori to clarithromycin is mostly due to the point mutations in the 23S rRNA. In Japan, however, the frequency of these mutations has not been fully investigated. Furthermore, no study has used gastric biopsy specimens to detect these point mutations. Methods: The frequency of primary clarithromycin-resistant H. pylori was examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Eighty-two strains (42 isolated from patients with gastric cancer and 40 isolated from patients with chronic gastritis) were examined. Two biopsy specimens obtained from patients in whom eradication therapy including clarithromycin had failed were also studied. Results: Either A2143G or A2144G point mutation was detected in 90% of clarithromycin-resistant H. pylori strains. Eight out of 82 strains (9.8%) had either A2143G or A2144G point mutation. Only one out of 42 strains in patients with gastric cancer had A2143G mutation, whereas five strains had A2144G and two had A2143G mutations in 40 strains isolated from control subjects. The proportion was significantly lower in patients with early gastric cancer (P < 0.05). This PCR-RFLP was also applicable for DNA samples extracted from biopsy specimens and infection of clarithromycin-resistant H. pylori was observed. Conclusion: The results suggest that the point mutation in the 23S rRNA gene is commonly seen in clarithromycin-resistant H. pylori and it contributes to the treatment failure in Japan. The PCR-RFLP system is a sensitive method by which to diagnose H. pylori infection as well as a simple method for detecting clarithromycin resistance without bacterial culture.