Endoscopic findings of the gastric mucosa during long-term use of proton pump inhibitor - a multicenter study.

BACKGROUND AND AIM: It is clinically important to diagnose drug-induced gastric lesions correctly. Recently, the use of proton pump inhibitors (PPI) has increased worldwide. The histological features induced by PPI have been reported; however, few reports have described endoscopic findings induced by PPI. Therefore, we aimed to clarify the characteristic endoscopic features in PPI users and associated pathogenic factors. METHODS: We prospectively registered 1007 consecutive participants (70 PPI users and 937 nonusers) who underwent endoscopic examination for cancer screening in three hospitals/clinics. Clinical data and endoscopic findings were recorded in the registration forms. We compared the endoscopic features between the two groups and evaluated contributing factors via univariate and multivariate analyses. RESULTS: Multiple white elevated lesions (MWEL) and cobblestone-like mucosa (CLM) were more commonly observed in PPI users compared with nonusers (p < .01). Foveolar hyperplastic polyps were also frequently observed in PPI users but were not statistically significantly different (p = .06). MWEL and CLM were more frequently observed in older patients than in younger patients. MWEL was more frequently observed in female patients than in male patients; however, CLM was predominantly observed in male patients. CONCLUSION: MWEL and CLM are characteristic endoscopic features in PPI users. A gender-associated difference was noted in terms of the frequency of these lesions.

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.

Serological comparison of serum pepsinogen and anti-parietal cell antibody levels between Japanese and German patients.

BACKGROUND: Atrophic gastritis is more common in Japan than in Germany. The expression of anti-parietal cell antibody has been implicated in the genesis of atrophic gastritis associated with Helicobacter pylori infection. OBJECTIVE: We investigated the difference in serum levels of pepsinogens and in anti-parietal cell antibody expression between Japanese and German patients. METHODS: We recruited 102 Japanese and 46 German patients with dyspepsia. Endoscopic examination detected no localized lesions in the upper gastrointestinal tract of any patients. Anti-parietal cell antibody was investigated by enzyme-linked immunosorbent assay with the purified porcine H+,K+-ATPase fraction and immunohistochemistry. H. pylori infection was diagnosed by the presence of anti-H. pylori antibody, by using the urease test and by histological examination. Serum levels of pepsinogen I and II and of gastrin were measured by a modified radioimmunoassay. RESULTS: Seventy-one Japanese (70%) and 17 Germans (37%) were positive for H. pylori. Serum levels of anti-parietal cell antibody were not significantly different between Japanese and Germans in both H. pylori negative and positive groups. The serum pepsinogen I/II ratio and gastrin levels were altered by H. pylori infection in both populations. Moreover, anti-parietal cell antibody levels were higher in H. pylori-positive patients with low pepsinogen levels than in those with high pepsinogen levels in both populations. CONCLUSIONS: The levels of anti-parietal cell antibody do not differ statistically between Japanese and Germans. Anti-parietal cell antibody might play a role in the progression of atrophic gastritis in both Japanese and German patients.

[Differential diagnosis of GERD].

It was widely accepted that the prevalence of GERD is lower in Oriental countries compared to Western countries. But the incidence of GERD has recently increased in Japan. The most commonly recognized manifestation of GERD is heartburn or a substernal burning sensation in the chest. Most patients with reflux esophagitis complain of typical symptoms such as heartburn, regurgitation or dysphagia. However, some patients complain of atypical symptoms such as hoarse voice, chronic cough, adult-onset asthma or vocal cord polyps. It is not always easy to diagnose atypical symptomatic patients as GERD. If patients who complain of these atypical symptoms have not improved with common medical treatment, GERD should be the consideration in its differential diagnosis.

Basis of decreased risk of gastric cancer in severe atrophic gastritis with eradication of Helicobacter pylori.

Helicobacter pylori infection induces chronic gastritis and lowers gastric juice ascorbic acid concentrations. We investigated how H. pylori eradication affected multiple variables that could prevent or delay development of new or occult gastric cancer in patients with early gastric cancer treated by endoscopic mucosal resection. Gastric juice pH, nitrite concentrations, and total vitamin C concentrations, serum concentrations of vitamin C and specific H. pylori antibody, and intensity of neutrophil infiltration in gastric mucosa were determined before and after successful H. pylori eradication. Successful eradication increased acid output and ascorbic acid secretion into gastric juice, accompanied by disappearance of polymorphonuclear infiltration from the surface epithelium and decreased gastric juice nitrite concentrations. Our data suggest that H. pylori eradication decreases the nitrosation rate as the ratio of vitamin C to nitrite increases. This decreases reactive oxygen species and nitric oxide, eliminating their damaging effect on DNA and reducing cell turnover.

Clinical characteristics and natural history of patients with low-grade reflux esophagitis.

BACKGROUND AND AIM: Although the incidence of reflux esophagitis (RE) has recently increased in Japan, the majority of these cases are mild (Los Angeles classification grades A and B). In order to consider therapy for these patients, it is important to understand the natural history of mild RE. There is little information concerning the natural course of RE, particularly low-grade disease. The goal of this study is to elucidate the natural course of patients with mild RE and to identify specific prognostic indicators associated with a poor outcome. METHODS: One hundred and five patients with mild RE were followed, without medical treatment, by endoscopy in addition to a questionnaire regarding symptomatology, for a mean of 5.5 years (range, 2.0-8.8 years) after initial diagnosis. Factors associated with the development of severe esophagitis were analyzed. RESULTS: Endoscopically, 11 patients (10.5%) progressed to more severe forms of RE (recurrent progressive (RP) group), 60.0% of patients relapsed without disease progression (recurrent non-progression group), and the remaining 29.5% of patients had no further episodes of RE (isolated episode group). Risk factors for progressive disease were increased age, female sex, the presence of symptoms at initial diagnosis by endoscopy, presence of a hiatal hernia, absence of atrophic gastritis, and absence of Helicobacter pylori infection. Despite having all risk factors, there were six patients who did not progress to more severe forms of RE. The primary esophageal peristaltic amplitude in these patients was significantly higher than in the RP group. CONCLUSIONS: Among patients with mild RE, only 10.5% progressed to more severe forms of RE. The patients with risk factors are candidates for aggressive therapy in order to prevent the progression of the RE disease process.

Mucin phenotype and background mucosa of intramucosal differentiated-type adenocarcinoma of the stomach.

OBJECTIVES: Gastric carcinomas have been divided into differentiated (intestinal) and undifferentiated (diffuse) types. Recently, classification studies based on mucin expression have revealed that some differentiated-type carcinomas are of a gastric phenotype. In this study, we investigated the clinicopathological features of differentiated-type adenocarcinomas and evaluated the background mucosa of the stomach based on mucin expression by the tumors. METHODS: Seventy-six intramucosal differentiated-type adenocarcinomas of the stomach were evaluated macroscopically and histologically. The mucin expression of tumor cells was examined by immunohistochemical staining with monoclonal antibodies against human gastric mucin (45M1), class III mucin (HIK1083), small intestinal mucinous antigen (SIMA-4D3), and MUC2 (Ccp58). Tumors were classified by phenotype as gastric (G-type), intestinal (I-type), mixed (M-type), or null (N-type). Not only the clinicopathological features but also the background mucosa of the stomach of G-type and I-type carcinomas were compared histologically and serologically. RESULTS: Seventeen tumors (22.4%) were classified as G-type, 31 (40.8%) as I-type, 22 (28.9%) as M-type, and 6 (7.9%) as N-type. The frequencies of elevated type tumors and papillary adenocarcinomas and the ratio of moderately/well-differentiated adenocarcinomas were higher in G-type than in I-type carcinomas. The scores for glandular atrophy and intestinal metaplasia were higher and the scores for chronic inflammation, polymorphonuclear neutrophil activity, and the density of Helicobacter pylori were lower in G-type than in I-type tumors. The serum level of pepsinogen I and the pepsinogen I/II ratio were significantly lower in G-type than in I-type tumors. CONCLUSIONS: G-type carcinoma is the predominant phenotype of papillary adenocarcinoma. The background mucosa of G-type carcinoma is associated with glandular atrophy and intestinal metaplasia, whereas that of I-type carcinoma is associated with active and chronic inflammation induced by H. pylori infection.

Helicobacter pylori infection influences expression of genes related to angiogenesis and invasion in human gastric carcinoma cells.

Infection with Helicobacter pylori (H. pylori) is considered a risk factor for gastric carcinoma. The purpose of this study was to clarify whether H. pylori infection plays a role in progression of gastric carcinoma. We examined the expression of genes encoding angiogenic factors and proteases by human gastric carcinoma cell lines (MKN-1 and TMK-1) co-cultured with or without H. pylori by cDNA microarray analysis. Co-culture with H. pylori increased expression of mRNAs encoding interleukin (IL)-8, vascular endothelial growth factor (VEGF), angiogenin, urokinase-type plasminogen activator (uPA), and metalloproteinase (MMP)-9 by gastric carcinoma cells. Up-regulation of these genes at the mRNA and protein levels was confirmed by Northern blot analysis, semi-quantitative RT-PCR analysis, and ELISA. In vitro angiogenic and collagenase activities of conditioned medium from the gastric carcinoma cells were also stimulated by co-culture with H. pylori. These results indicate that H. pylori infection may regulate angiogenesis and invasion of human gastric carcinoma.