Helicobacter pylori cagA polymorphism and gastric inflammation: an international comparison between Japanese and Brazilian patients.

OBJECTIVE: Gastritis induced by Helicobacter pylori can cause the onset of gastric cancer, and H. pylori cytotoxin associated gene A (cagA) is considered to be an important factor for its development. We investigated the relationship between the grades of gastritis and cagA phenotype in Japanese and Brazilian patients. MATERIAL AND METHODS: We studied 47 Brazilian and 47 age-, gender-matched Japanese patients. Status of H. pylori infection, the degree of histologic gastritis, and the levels of serum pepsinogen levels were evaluated. DNA was extracted from paraffin-embedded sections and a portion of the cagA gene was amplified using the polymerase chain reaction, followed by direct sequencing of the fragment. We investigated the cagA subtype using a newly developed restriction fragment length polymorphism (RFLP) system. RESULTS: In H. pylori-positive patients, the grades of histological and serological gastritis were more prominent in the Japanese subjects than their Brazilian counterparts, although no difference was detected in the H. pylori-negative subjects. According to cagA phenotype analysis, our RFLP system was helpful for evaluating cagA phenotype, and we found that the prevalence of the East Asia subtype was significantly higher in the Japanese subjects than in the Brazilian. CONCLUSION: Infection with H. pylori possessing the East Asian cagA gene contributes to the progression of gastritis.

Plaunotol induces a comparative increase of acidic mucin fraction in gastric juice.

BACKGROUND/AIMS: Gastric mucus protects the gastric mucosa. Plaunotol, a gastroprotective agent, has been shown to increase mucus production in animal models. However, it is unclear whether plaunotol benefits human gastric mucus secretion. METHODOLOGY: Twenty-five patients with atrophic gastritis were studied. All patients underwent gastroendoscopy and gastric juice was collected before and after plaunotol treatment for 3 months. Gastric juice mucin was examined by gel filtration as well as anion-exchange chromatography. The identification of each fraction was examined by enzyme-linked immunosorbent assay (ELISA) with the use of HGM75 and HIK1083, antibodies against mucin from surface mucus cells and from gastric glandular mucus cells, respectively. RESULTS: Plaunotol significantly increased the total gastric juice volume (7.8mL before vs. 10.7mL, after administration; p=0.03). By anion exchange chromatography, we detected three mucin fractions (Fr I-III). Fr I strongly reacted with HGM75 but did not react with HIK1083. The other fractions (Fr II, III) reacted with HIK1083 but weakly reacted with HGM75. After administration of plaunotol, a significant increase in Fr III (acidic mucin) was observed (p=0.02). CONCLUSIONS: Long-term administration of plaunotol changes the composition of gastric juice mucin, including a significant increase in the proportion of acidic mucin fraction.

Helicobacter pylori dupA and gastric acid secretion are negatively associated with gastric cancer development.

Few reports have described the cancer prevalence of peptic ulcer patients with long-term follow-up studies. We have conducted a long-term retrospective cohort study of Japanese peptic ulcer patients and evaluated the risk factors for the occurrence of gastric cancer (GCa). A total of 136 patients diagnosed with peptic ulcers from 1975 to 1983 were enrolled. These 136 cases [102 males and 34 females; 69 gastric ulcer (GU) and 67 duodenal ulcer (DU) patients at the time of enrollment; mean follow-up period of 14.4 years (range 1-30 years)] after being matched with a tumour registry database in Hiroshima prefecture were surveyed for GCa. We investigated Helicobacter pylori duodenal ulcer promoter gene A (dupA) using paraffin-embedded gastric biopsy specimens in 56 cases. Gastric acid secretion and basal acid output (BAO) in 40 cases, and maximal acid output in 68 cases, had been measured at first diagnosis of peptic ulcers. GCa was detected in 24 patients (17 with GU, 7 with DU) during the follow-up. The prevalence of GCa was significantly higher in GU patients than in DU patients (log-rank test P<0.05). dupA-positive H. pylori was detected not only in DU patients (9/20) but also in GU patients (9/36). Gastric acid output was significantly larger in quantity in patients with dupA-positive H. pylori than in those with dupA-negative H. pylori (P<0.05). The occurrence of GCa was significantly lower in patients with dupA-positive H. pylori and a high BAO level (log-rank test P<0.05). DUs, higher acid output and dupA-positive H. pylori were negatively associated with GCa.

Little necessity of acid inhibition against proton pump inhibitor rebound effects and prior helicobacter pylori eradication therapy in gastric ulcer patients: a randomized prospective study.

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) eradication therapy increases acid secretion and promotes the development of gastroesophageal reflux disease (GERD) and reflux esophagitis (RE). Rebound acid hypersecretion develops after the use of proton pump inhibitors (PPI). We examined the clinical necessity of acid inhibitors to prevent GERD or RE caused by PPI rebound phenomenon and prior H. pylori eradication therapy. METHODOLOGY: We enrolled 39 patients who underwent successful H. pylori eradication therapy prior to endoscopic mucosal resection of gastric cancer. After 8-week rabeprazole treatment for iatrogenic ulcer, they were randomly divided into two groups (who took nizatidine (group N) and sofalcone (group S)), and took each for 16 weeks, we compared RE/GERD symptoms with the baseline by endoscopy and QUEST score. RESULTS: All patients had corpus atrophy in which there was no difference between the two groups. Only 1 patient in group S (5.9%) developed symptomatic GERD, and 1 patient in group N (4.5%) developed RE. CONCLUSIONS: In severe atrophic gastritis patients, there is little clinical necessity of acid inhibitors to prevent GERD/RE caused by PPI rebound and prior H. pylori eradication therapy.

Clinical prevention of gastric cancer by Helicobacter pylori eradication therapy: a systematic review.

Helicobacter pylori (H. pylori) infection plays an important role in gastric carcinogenesis. We conducted a systematic review concerning gastric cancer development after H. pylori eradication therapy. In total 15 papers matched our criteria, the results were reviewed. The H. pylori eradication therapy statistically diminished the prevalence of clinical gastric cancer by approximately one-third. The studies from Japan supported this conclusion; however, studies from overseas reported conflicting results. The differences in these conclusions lie in the diagnostic ability of endoscopic examination, since the clinical stage was quite different between these studies. Gastric cancer that developed after eradication revealed a mainly intestinal type histology and depressed-type appearance. The following are possible reasons for reduced gastric cancer: (1) eradication therapy inhibits the new occurrence of gastric cancer, (2) eradication regresses or inhibits the growth of gastric cancer, and (3) eradication interferes with the discovery of gastric cancer. Considering the biological nature of cancer cell proliferation, a sufficiently long-term follow-up may clarify the effect of eradication therapy on inhibition of the development (not discovery) of gastric cancer and reduction of gastric cancer-related mortality.

Evaluation of gastric cancer risk using topography of histological gastritis: a large-scaled cross-sectional study.

We evaluated the topography of histological gastritis, which may be risk factors for gastric cancer (GCa). A total of 530 Helicobacter pylori-positive patients underwent diagnostic upper-gastrointestinal endoscopy. Biopsy specimens were obtained from the gastric antrum and body to assess the grade of gastritis. Subjects were divided into four groups by the topography of active gastritis (antrum predominant gastritis, AP; pan-gastritis with or without corpus atrophy, Pan-1 and Pan-2; and corpus predominant gastritis, CP). A higher prevalence of GCa followed the order of Pan 2-->CP-->Pan 1-->AP. The age of patients decreased in the same order. When we set Pan 2 and CP as a high-risk group, the sensitivity and specificity for GCa detection were 77.3 and 54.7%, which were superior to the serum criteria using pepsinogens. These suggest that topography of histologic gastritis is an important marker to identify the high-risk group.

Role of Helicobacter pylori infection and chronic inflammation in gastric cancer in the cardia.

BACKGROUND: Helicobacter pylori-induced gastritis is an important factor for gastric carcinogenesis. However, it is still controversial whether it is also applicable for cardiac cancer development. Recently, we reported that H. pylori is an important factor for the induction of cardiac inflammation. We examined the status of H. pylori-induced gastritis in patients with cardiac cancer. METHODS: Seventy-five Japanese patients (58 men; mean age, 64.2 years) with cardiac cancer were studied. Cardiac cancer was defined as that mainly located within 2 cm from the squamo-columnar junction (SCJ). Histological gastritis including the cardiac region was evaluated using the biopsy or surgically resected sections. Cardiac inflammation was evaluated at 1 cm distal from SCJ in lesser curvature. Sera were collected and several markers were evaluated. The status of H. pylori infection was evaluated by histology and serum antibodies. Expressions of cytokeratins were examined by immunohistochemical analysis. RESULTS: Out of 75 patients with cardiac cancer, H. pylori was positive in 71 (95%) patients. The cardiac inflammation was examined in 30 patients (26 with H. pylori and four without H. pylori infection) and we found cardiac inflammation was present in all cases with H. pylori infection. Histologically, H. pylori-related gastritis was also found in the gastric corpus and antrum. Serological data were consistent with the presence of chronic atrophic gastritis. Intestinal metaplasia was found in 18 cases in the cardiac mucosa, and their cytokeratin 7/20 pattern was judged as a gastric pattern in all cases. CONCLUSION: H. pylori infection is closely associated with cardiac cancer.

Host factors contributing to the discovery of gastric cancer after successful eradication therapy of Helicobacter pylori: preliminary report.

BACKGROUND AND AIM: Clinical features of patients who develop gastric cancer after successful eradication of Helicobacter pylori are still unclear. We attempted to identify host factors associated with the discovery of gastric cancer, including changes in the background gastric mucosa in patients with atrophic gastritis. METHODS: We enrolled 101 patients (59 men, 42 women; mean age 56.0 years) who underwent successful eradication therapy. All patients had no neoplastic lesion in the stomach and were diagnosed with corpus atrophic gastritis histologically before the eradication therapy. After successful eradication, these patients were followed up by an annual endoscopic examination (mean follow-up time 63.2 months; range 12-157 months). Fasting sera were obtained before and after eradication therapy and the serum levels of gastrin/pepsinogens were evaluated. RESULTS: Gastric cancer occurred during follow-up in eight of the 101 patients (7.9%). We compared the host features between the cancer-discovered group (n = 8) and the non-discovered group (n = 93). We found no difference in gender, history of previous treatment of gastric cancer, and serum pepsinogen/gastrin levels at entry between them. The trends in alterations of serum markers did not differ between the two groups. However, gastric cancer was more frequently found in older patients (>54 years at eradication) than in others (P < 0.05). CONCLUSION: Improvement of gastric inflammation did not correlate with the discovery of gastric cancer after eradication; however, age at the time of eradication seemed to be important. Strict follow-up after eradication is needed in older patients with atrophic gastritis.

The effect of Helicobacter pylori eradication therapy on gastric ulcer healing after endoscopic mucosal resection.

BACKGROUND AND AIM: It remains unclear whether Helicobacter pylori eradication therapy accelerates the healing of acute gastric ulcer after endoscopic mucosal resection (EMR) of gastric tumor. We examined the effect of H. pylori eradication therapy on ulcer healing after EMR. METHODS: Twenty-six patients who underwent successful H. pylori eradication therapy before EMR were followed prospectively. Patients underwent endoscopic examination 1 or 2 months after EMR, during which the ulcer status and reduction rate were assessed. The effect of H. pylori eradication on the quality of ulcer healing was also evaluated. Six patients in whom eradication therapy failed and 26 patients who underwent EMR without eradication therapy served as control subjects. RESULTS: Endoscopically, 18 (75%) of 24 ulcers in the eradication group were at the healing stage 1 month after EMR. The ulcer reduction rates were 85.0 +/- 2.6% and 96. 9 +/- 1.1% at 1 and 2 months after EMR, respectively. Ulcer stage and reduction rate did not differ significantly between the eradication group and control group. However, we frequently observed a better quality of ulcer healing in the eradication group than in the control groups (P < 0.01). CONCLUSION: H. pylori eradication therapy does not accelerate ulcer healing after EMR but may improve the quality of ulcer healing of gastric ulcer after EMR.

A combination of the Helicobacter pylori stool antigen test and urea breath test is useful for clinical evaluation of eradication therapy: a multicenter study.

BACKGROUND: Helicobacter pylori stool antigen (HpSA) test is a new tool for evaluating the H. pylori infection. The present study was carried out to investigate the clinical usefulness of the HpSA test in the evaluation of eradication therapy by comparing it with the (13)C-urea breath test (UBT). METHODS: One hundred and five patients received eradication therapy for H. pylori. After more than 8 weeks, the success of the therapy was evaluated by the HpSA test and the UBT. Concordant results were regarded as a final diagnosis, but when the results were discordant, histological examination was carried out. RESULTS: Of the 105 patients receiving eradication therapy for H. pylori, 25 patients were regarded as H. pylori positive by the UBT and and 20 patients were regarded as H. pylori positive by the the HpSA test. Nine patients (8.6%) showed discordant results (seven cases with UBT(+) and HpSA(-), and two with UBT(-) and HpSA(+)). Five cases out of nine were ultimately judged as having a false-positive result of the UBT, and in these cases the UBT values were relatively low (below 10 per thousand). The final diagnostic accuracies of the UBT and the HpSA test were 94.3% (88.0-97.9%; 95% CI) and 97.1% (91.9-99.4%), respectively. When we used the HpSA test in cases with weakly positive UBT values, we were able to diagnose the correct status of H. pylori infection after eradication in 99% of all patients (94.8-100.0%). CONCLUSION: The HpSA test is a useful tool for the evaluation of eradication therapy and a combination of the HpSA test and UBT is clinically recommended.