Bile acid promotes intestinal metaplasia and gastric carcinogenesis.

BACKGROUND: Bile acid and Helicobacter pylori (H. pylori) are important toxic factors for gastric mucosal injury. We examined the role of bile acid in promoting histologic gastritis and gastric carcinoma in Japanese patients. METHODS: A total of 767 patients (452 men, mean age 51.1 years) were studied. Gastric juice was collected by gastro-endoscopic examination, and the bile acid concentration was examined by enzymatic method. The grade of histologic gastritis was evaluated by gastric biopsies, and the relationship between the bile acid concentration and the gastritis score was examined. The occurrence of gastric cancer was examined by a retrospective cohort study. CDX2/CINC1 expression in RGM-1 cells was evaluated by real-time PCR. RESULTS: In H. pylori-positive patients, we found significant positive correlation between the bile acid concentration and the grades of atrophy/intestinal metaplasia (P < 0.01). However, we found significant negative associations between the bile acid concentrations and the histologic scores of mononuclear cell/neutrophil infiltrations (P < 0.01). Patients with a high concentration of bile acid developed gastric cancer more frequently than those with a low concentration (P < 0.05). Cholic acid treatment significantly increased CDX2 expression in RGM-1 cells. CINC1 expression in RGM-1 cell was significantly induced by coculture with H. pylori, and the induction was reduced by glycochenodeoxycholic acid treatment. CONCLUSION: The bile acid in gastric juice contributes to the progression of histologic atrophy and intestinal metaplasia without inflammatory cell infiltration, followed by carcinogenesis in H. pylori-positive patients. IMPACT: Bile acid promotes intestinal metaplasia and gastric carcinogenesis without inflammatory cell infiltration.

Gastric cancer development after Helicobacter pylori eradication therapy: a new form of gastric neoplasia.

BACKGROUND AND AIM: Along with the widespread use of eradication for Helicobacter pylori (H. pylori), the incidence of gastric cancer after eradication has also been increasing. There is a need for clarification of the clinical and biological characteristics of these neoplasms. PATIENTS AND METHODS: We studied 27 cases of gastric cancer that developed after eradication (group AE). Out of the 27, we selected 26 with early-stage gastric cancer and compared them with 78 age-matched gastric cancer patients with H. pylori infection (group Pos) and 20 patients without H. pylori (group Neg). The patient with autoimmune gastritis was not included. Clinicopathological features, mucus patterns and Wnt5a expressions were compared among these groups. RESULTS: Among group AE patients, there were more males than females, and the tumor histology was mainly intestinal type, a significant difference from group Neg. In contrast, macroscopically, the tumors were predominantly of the flat-depressed type, a feature similar to that of group Neg but significantly different from that of group Pos. MUC2 and Wnt5a expression was significantly lower in group AE than in group Pos. CONCLUSION: Gastric cancer development after eradication may have a carcinogenic pathway similar to that in cancer with H. pylori infection, though macroscopic/biological features may be modified by eradication therapy.

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.

Role of the gastrin-gastrin receptor system in the expansive growth of human gastric neoplasms.

BACKGROUND AND AIM: Gastrin is one of the most important gut hormones. However, the role of the gastrin-gastrin receptor (GR) system in the growth of gastric tumors is still unclear. METHODS: We examined serum gastrin levels in 957 patients with early gastric carcinoma. Next, we raised antibody against the GR and examined GR expression in 5 gastric carcinoma cell lines and 48 human gastric tumor tissues. In 28 cases, Helicobacter pylori eradication therapy was performed and morphological tumor changes were examined. RESULTS: Serum gastrin levels were significantly higher in patients with elevated tumors than in patients with depressed tumors (p = 0.02). All gastric carcinoma cell lines expressed GR. Thirty-one of 48 (65%) gastric tumors expressed GR, and its expression was prominent in elevated-type tumor with an intestinal histologic feature. Of 28 patients who underwent eradication therapy, 9 showed gastric tumors that became flat or depressed. In these 9 cases, GR expression was detected in all tumors, and the decrease in gastrin levels was more prominent than in those without morphological change (p = 0.01). CONCLUSION: The gastrin-GR system plays an important role in the elevated morphology of gastric tumors.

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.

A case of congenital absence of the portal vein.

We experienced a girl with congenital absence of the portal vein. She was examined by computed tomography (CT), three-dimensional computed tomographic angiography (3DCTA), digital subtraction angiography and liver biopsy. Nodular regenerative hyperplasia of the liver was detected, presumably due to an abnormal hepatocellular response to absent portal flow. 3DCTA showed that the splenic vein and superior mesenteric vein joined to form a common trunk, which directly entered the right atrium. 3DCTA may be a valuable noninvasive tool for identifying portal malformations.