Gastric metaplasia

C.M. Leys, S. Nomura, E. Montogomery, and J.R. Goldenring, Tissue microarray evaluation of prothymosin as a biomarker for human gastric metaplasia and neoplasia. J. Surg. Res. 121, 327-328 (2004). 

Gastric metaplasia is found in 90% of H pylori-infected DU patients and about 60% of non-DU patients with increased acid secretory levels. The induction of gastric acid causes se-vae inflammation and increases the areas of... 

Jonkets D, Houben G, de Bruine A, et al. Prevalence of gastric metaplasia in the duodenal bulb and distribution of Helicobacter pylori in the gastric mucosa. A clinical and histopath-ological smdy in 96 consecutive patients. Ital J Gastroenterol Hepatol. 1998 30 481-483. 

Gastric metaplasia in the duodenum is a prerequisite for H. pylori colonization... 

As in the stomach, chronic inflammation follows colonization of islands of duodenal gastric metaplasia by K pylori and the inflamed duodenal mucosa becomes increasingly vulnerable to peptic acid attack and exposed to subsequent ulceration [31] (Fig. 1). Although H. pylori infection can be eradicated successfully, gastric metaplasia may persist or regress only partially [28, 32]. There is no continued increased risk for further duodenal ulcer relapse once H. pylori is eradicated. 

Noah LA, Rolf TM, Bosma NB et al (1993) Gastric metaplasia and Helicobacter pylori infection. Gut 34 1510... 

Carrick J, Lee A, Hazell S, Ralston M, Daskalopoulos G (1989) Campylobacter pylori, duodenal ulcer and gastric metaplasia possible role of functional heterotopic tissue in ulcerogenesis. Gut 3 790-797... 

Khulusi S, Badve S, Patel P, Lloyd R, Marrero JM, Finlayson C, Mendall M, A., North-field TC (1996) Pathogenesis of gastric metaplasia of the human duodenum role of Helicobacter pylori, gastric acid and ulceration. Gastroenterology 110 452-458... 

Gastric metaplasia appears as a slightly elevated irregularity of the base of the duodenal bulb and consists of gastric body mucosa harbouring both parietal and goblet cells. 

There is also evidence to suggest that the visual appearances of lymphoid hyperplasia, gastric metaplasia, and Brunner s glandhyperplasia (Fig. 4.31a,b) are easier to differentiate with barium radiology than at endoscopy without biopsy. 

Fig. 4.31a,b. Duodenal nodules. The different causes all show very distinct patterns that are easy to confuse at endoscopy, a Follicular lymphoid hyperplasia, b gastric metaplasia ( spilling out of the pylorus )... 

Alterations in other gastric secretions, such as pepsinogens and blood group substances also take place in chronic atrophic gastritis. The secretion of pepsinogen I has been used as an indicator of intestinal metaplasia and gastric cancer (21, 22). 

The process, once initiated, is self-sustaining and may become more accelerated with time because the atrophy and intestinal metaplasia are progressive lesions and lead to further loss of parietal cells and incrased bacterial colonization of the mucosa. The initial mutations transform gastric cells into mature intestinal-type cells. Further superimposed mutations transform metaplastic cells into progressively dysplastic cells and eventually into neoplastic cells. This is a process of loss of differentiation which implies a multihit phenomenon which could be explained on the basis of continued formation of minute amounts of nitroso compounds over many years. 

The incomplete (less differentiated) foci of metaplasia surround foci of cancer, suggesting progressive loss of differentiation (16, 19). High nitrite levels in the gastric cavity have been associated with acceleration of the gastric cancer induction with MNNG in experimental animals (26). Gastric cancer has been induced in experimental animals with products derived from nitro-sated fish (32). 

Prolonged hypergastrinemia leading to the development of colonic polyps and potentially adenocarcinoma in rats was a concern that has proven to be unfounded with long-term use in humans.19 The FDA has stated that there is insufficient evidence linking PPI use to atrophic gastritis, intestinal metaplasia, or gastric cancer.20... 

Hirayama F, Takagi S, Kusuhara H, Iwao E, Yokoyama Y, Ikeda Y. (1996) Induction of gastric ulcer and intestinal metaplasia in Mongolian gerbils infected with Helicobacter pylori. J Gastroenterol 31 755-757. 

Patients with healed GERD were treated for up to 40 months with rabeprazole and monitored with serial gastric biopsies. Approximately 4% of patients had intestinal metaplasia at some point during follow-up, but no consistent changes were seen. Hepatic effects In patients with various degrees/types of hepatic disease, the AUC was prolonged (lansoprazole, esomeprazole, rabeprazole, pantoprazole), half-life was prolonged (lansoprazole, omeprazole, rabeprazole, pantoprazole), increased bioavailability was observed (omeprazole), decreased clearance with rabeprazole and increased maximum pantoprazole concentrations. 

Among patients infected with H pylori, long-term acid suppression leads to increased chronic inflammation in the gastric body and decreased inflammation in the antrum. Concerns have been raised that increased gastric inflammation may accelerate gastric gland atrophy (atrophic gastritis) and intestinal metaplasia—known risk factors for... 

Repeated dosing of rats at 3.4 g/kg/day or higher caused gastrointestinal hemorrhaging in rats that died in a chronic oral-dosing study (Van Miller et al. 1977). Metaplasia of the gastric mucosa was found in rhesus monkeys exposed to 0.1 g/kg/day of 2,3,7,8-TCDD for 3 weeks (McNulty 1984), and gastric... 

Of 33 patients with severe reflux esophagitis prospectively followed up for 5-8 years six were positive for H. pylori (16). There was no evidence of significant enterochromaffin-hke cell hyperplasia, gastric atrophy, intestinal metaplasia, dysplasia, or neoplastic changes during 185 patient foUow-up years during which 137 gastric biopsies were taken. 

There has been concern about the potential for proton pump inhibitors to cause enterochromaffin-hke cell hyperplasia, gastric carcinoid tumors and gastric cancers, colorectal polyps and adenocarcinoma, atrophic gastritis, and intestinal metaplasia in patients with H. pylori infection, and bacterial overgrowth. 

There is very limited evidence for CYP expression in the human stomach. Furthermore, it is difficult to propose any function for gastric CYPs because the gastric epithelium secretes rather than absorbs. However, the potential of those CYPs expressed in the stomach to play roles in stomach cancer has been investigated in cases of intestinal metaplasia of the stomach. Intestinal metaplasia of the stomach, which involves the replacement of the gastric mucosa with a small intestine-like epithelium (100), is considered to be a precancerous lesion (101). A combination... 

Similar results were obtained with immunoblot and RT-PCR probes for CYP1A1 and 1A2 (103). CYP1A1 and 1A2, as well as CPR, were reported to be detected in human gastric mucosa with intestinal metaplasia and in pyloric gland cells. Mi-crosomes prepared from these cells activated BaP and 2-amino-2-methy limidazole [4,5-f]quinoline. 

---