Body Mucosa Research Articles

Chronic gastritis and gastroduodenal ulcer: a case control study on risk of coexisting duodenal or gastric ulcer in patients with gastritis.

Chronic (atrophic) gastritis (AG) is common in active duodenal (DU) and gastric ulcer (GU) disease. In this case control study in consecutive prospective outpatients (571 cases and 1074 controls) who had undergone diagnostic upper gastrointestinal endoscopy and routine biopsies from both antral and body mucosa, we calculated the risk of coexisting active DU and/or GU in different gastritis of the antrum or body and according to grade (superficial gastritis, mild, moderate or severe atrophic gastritis). The risk of coexisting active gastroduodenal ulcer (ulcer in duodenum and/or stomach), as well as the risk of DU or GU, was dependent upon the presence and grade of gastritis in antrum and body mucosa. The risk of coexisting ulcer, as expressed as an age adjusted relative risk (RR) and calculated as odds ratio of gastritis in cases and controls, was significantly increased in the presence of superficial antral and body gastritis (RR = 8.5 (7.0-20.0) in men; RR = 5.8 (3.3-10.2) in women), as compared with the risk of ulcer in subjects with histologically normal mucosa (RR = 1). The risk of ulcer, and the risk of GU in particular, increased further with increasing severity of antral gastritis. In such patients with moderate or severe atrophic antral gastritis the RR of coexisting ulcer even exceeded 20 in men and 10 in women (RR = 25.6 (9.0-72.7) in men; RR = 11.7 (5.9-23.0) in women). On the other hand, the RR of ulcer, and the RR of DU in particular, was below 1 in the presence of atrophic gastritis in the gastric body, irrespective of the grade of gastritis in the antrum. We conclude that the type and grade of gastritis strongly predicts the risk of coexisting peptic ulcer, and that the risk of coexisting DU or GU increases with an increase in grade of AG of the antrum but decreases with an increase in grade of AG of the gastric body.

Atrophic gastritis as a premalignant condition.

Chronic (atrophic) gastritis is a progressive disease which in a small proportion of patients leads to severe (total) atrophy (severe grade of chronic gastritis) of the antral or body mucosa or both. Chronic gastritis is a premalignant condition which favours the development of gastric cancer. Chronic gastritis precedes gastric cancer and shows a severalfold increase in the risk of gastric cancer compared to subjects with histologically normal stomach. Several tentative modifications to the estimate of the risks may be presented: (i) a severe risk of developing gastric cancer is restricted to subjects with a severe grade of chronic gastritis (ii) the risk of gastric cancer is increased in subjects who have either severe antral or body chronic gastritis, the risk being approximately three to five times higher in the antral chronic gastritis (B-type of gastritis) than in the body chronic gastritis (A type of gastritis); (iii) the antral and body chronic gastritis are independent risk factors for gastric cancer, the joint risks being multiplicands of the marginal risks i.e., the estimated risk is highest in those subjects who show severe chronic gastritis in both the antrum and the body (AB type of gastritis); (iiii) the chronic gastritis mediated gastric cancer risk is limited to gastric cancers of the intestinal type, and thus covers only a proportion of all cases of gastric cancer. In the highest risk groups it may be estimated that the probability of a subject developing gastric cancer in subsequent decades is up to 30% if the subject is a young man who has severe chronic gastritis in his antrum, or who has it coexistently in the antrum and body.

Prostaglandin effect on the enzymatic sulfation of mucus glycoprotein in gastric mucosa

The effect of 16,16-dimethyl prostaglandin E 2 (DMPGE 2 on the sulfation of mucus glycoprotein in gastric mucosa was investigated. The enzymatic activity which catalyzes the transfer of the sulfate ester group from 3'-phosphoadenosine-5'-phosphosulfate to gastric mucus glycoprotein was located in the detergent extracts of Golgi-rich membrane fraction of antral and body mucosa of rat stomach. The sulfotransferase activity of this fraction from body mucosa, however, was 35% higher than that from the antrum. The enzyme exhibited optimum activity at pH 6.8 using 0.5% Triton X-100 and 30 mM NaF. The apparent K m of the enzyme for sulfation of mucus glycoprotein was 10.5 μM, and the sulfate ester was found incorporated into the carbohydrate chains of the glycoprotein. Introduction of DMPGE 2 to the reaction mixtures led to an enhancement in the rate of mucus glycoprotein sulfation. The rate of enhancement was proportional to the concentration of DMPGE 2 up to 1.0 × 10 −4 M and was of the competitive type, with an apparent K m value of 6.7 μM. Since sulfated mucins play an important role in gastric mucosal defense and the increase in their sulfation occurred at levels of prostaglandin present in gastric mucosa, the observed effect may be of significance to gastric mucosal defense in vivo.

Enzymatic sulfation of mucus glycoprotein in gastric mucosa. Effect of ethanol.

A sulfotransferase activity that catalyzes the transfer of sulfate ester group from 3'-phosphoadenosine 5'-phosphosulfate to carbohydrate chains of gastric mucus glycoprotein has been demonstrated in the antral and body mucosa of rat stomach. Subcellular fractionation studies revealed that the enzyme is associated with Golgi-rich membrane fraction. The sulfotransferase activity of this fraction in antral mucosa was about 35% lower than that in the body. Optimum enzyme activity was obtained with 0.5% Triton X-100 and 30 mM NaF at a pH of 6.8 using desulfated mucus glycoprotein substrate. The enzyme was equally capable of sulfation of the proteolytically degraded and reduced forms of the desulfated glycoprotein, but the acceptor capacity of the intact mucus glycoprotein was about 60% lower than that of the desulfated preparation. The enzyme preparation also catalyzed the transfer of sulfate to galactosylceramide. The sulfation of mucus glycoprotein, however, was not affected by the presence of this glycolipid, suggesting that the sulfotransferase involved in mucus glycoprotein sulfation is different from that responsible for the synthesis of sulfatoglycosphingolipid. The mucus glycoprotein sulfotransferase activity was inhibited by ethanol. The rate of inhibition was proportional to the concentration of ethanol up to 0.3 M and was of the competitive type. The apparent Km value of the enzyme for mucus glycoprotein was 10.5 X 10(-6) M (21 mg/ml), and the KI in the presence of ethanol was 4.7 x 10(-1) M. The 35S-labeled mucus glycoprotein product of the enzyme reaction gave in CsCl density gradient a band in which the 35S label coincided with the glycoprotein. Alkaline borohydride reductive cleavage of this glycoprotein led to the liberation of the label into reduced acidic oligo-saccharide fraction. Most of the label was found incorporated in three oligosaccharides. These were identified as tri-, tetra-, and pentasaccharides, each carrying a labeled sulfate ester group on the terminal N-acetyl-glucosamine residue. Based on the results of structural analyses, the most abundant oligosaccharide was characterized as SO3H----6GlcNAc beta 1----3Gal beta 1----3GalNAc-ol.

Reduced thickness of gastric mucosa and retarded progression of chronic gastritis in patients with renal failure.

Conflicting results are reported in the literature on the structure and function of gastric mucosa in patients with chronic renal failure (CRF). In the present endoscopic study of 68 CRF patients on conservative treatment (regular dialyses or transplantations had not yet been undertaken), we sought to clarify whether CRF leads to hypertrophic or hypotrophic phenomena in gastric mucosa, as interpreted by the presence and grade of gastritis and by the thickness of the gastric mucosa. We found that the mean progression of gastritis in both antrum and body was significantly slower than expected in CFR patients, and that the thickness of both antral and body mucosa was significantly lower in CFR patients than in non-CRF controls. Furthermore, although the thickness of the oxyntic body mucosa in CRF showed a positive correlation to serum gastrin (SeGa) levels and even though 12 of the patients showed high SeGa levels corresponding to those seen in the Zollinger-Ellison synbdrome (300-1500 ng/l), the thickness of the oxyntic body mucosa in CRF patients did not exceed that seen in control subjects with normal SeGa. We conclude that CRF exerts inhibitory effects on the gastric mucosa resulting in retardation in the progression of chronic gastritis and hypotrophy of the gastric mucous membrane.

Campylobacter pylori in a sample of Finnish population: relations to morphology and functions of the gastric mucosa.

The occurrence of Campylobacter pylori (CP) was examined in 179 subjects representing a sample collected from the population of South Finland. In a normal antral and body mucosa CP was present in 5% and 11% and in superficial gastritis (SG) in 71% and 91% of subjects, respectively. In atrophic gastritis (AG) of antrum and body the prevalence of CP decreased significantly with an increasing degree of atrophy, so that CP was not found in severe body AG. Different combinations of antral and body gastritis revealed a characteristic pattern. Campylobacter pylori was lacking when antral and body mucosa were normal, but was present in 41% when normal mucosa was associated with gastritis in the opposite area. In SG affecting diffusely antrum and body, the bacterium was present in every case, but when SG was associated with AG in the opposite area it was lacking in 29% of the subjects. When SG affecting both areas was compared with SG accompanied by different degrees of AG in the body, there was a highly significant decrease of the prevalence of CP in antrum and body along with an increasing degree of AG in the body. This decrease showed a highly significant positive correlation with the acid output. On the whole, acid output correlated well with the occurrence of CP in both antrum and body. Thus the prevalence of CP was 10% in achlorhydria and rose up to 100% in cases with acid output above 30 mmol/h. The presence of CP did not correlate with signs of acute inflammation, but correlated significantly with those of chronic inflammation. No correlation was found in the antrum and a significant negative one in the body, between CP infestation and the extension of intestinal metaplasia. It is concluded that increased pH of gastric contents and mucus secreted by intestinalised glands may create unfavourable conditions for survival of the bacteria and might explain the decrease in the prevalence of CP in the more severe degrees of AG. The present results, however, give no definite answer to the question of the pathogenic significance of CP in the development of chronic gastritis.

Campylobacter pylori: prospective analysis of clinical and histological factors associated with colonization of the upper gastrointestinal tract

The association of Campylobacter pylori (C.p.) colonization of the upper gastrointestinal tract with five predefined anamnestic variables, seven symptoms of dyspepsia, and various blindly evaluated histological criteria, was prospectively investigated in a consecutive series of 149 patients submitted to upper gastrointestinal tract endoscopy. Colonization was determined by biopsy urease tests and histological searches. Significant differences (P less than 0.05) between C.p.-positive and C.p.-negative patients were found for smoker status and the frequency of therapy with ulcer-healing drugs (positive association with C.p.) and antibiotics (negative association), but not for any other of the anamnestic data or symptoms. These data were further submitted to stepwise multiple logistic regression analyses. Concerning histological findings, C.p. colonization was significantly associated with the degree of antrum and body gastritis (P less than 0.01), and also with lymphocellular infiltration in antrum and body biopsies and neutrophil cellular grading in gastric antra. We conclude that C.p. colonization of the upper gastrointestinal tract is associated with gastritic change of the antrum and, albeit to a lesser extent, of the body mucosa. However, a specific pattern of symptoms to predict C.p. colonization could not be established.

Campylobacter pylori is associated with chronic gastritis but not with active peptic ulcer disease.

Campylobacter pylori is supposed to be involved in the pathogenesis of gastroduodenal peptic ulcer diseases and chronic gastritis. In order to study whether the Campylobacter pylori in the stomach of peptic ulcer patients is related to ulcer itself or to a co-existing chronic gastritis, we examined the frequency of the bacteria in Giemsa stained histological sections of biopsy specimens from a series of patients with active peptic ulcer and from series of non-ulcer control subjects. We found no difference in the frequency of Campylobacter- positive cases between ulcer patients and non-ulcer controls when the comparison was done within the same category of chronic gastritis; e.g., within the category of chronic superficial gastritis 74% and 78% of cases showed the bacteria in antral biopsies from ulcer patients and from non-ulcer controls, respectively. In both ulcer patients and control subjects, in similar way in both antral and body mucosa, the Campylobacter pylori was strongly associated with chronic superficial gastritis but was more weakly associated with chronic atrophic gastritis, and the bacteria were only occasionally seen in normal mucosa. We conclude that Campylobacter pylori is associated with chronic gastritis in peptic ulcer patients but is not related to active ulcer.

Histochemische Untersuchungen an Magenbiopsien des Menschen unter besonderer Berücksichtigung von Hydrolasen

Peptidases, phosphatases, glycosidases, non-specific esterases, succinate dehydrogenase, cholinesterases, and carbohydrate components were studied in bioptic material of the normal and diseased human stomach using well established older, modified older, and new qualitative histochemical methods. For the first time, an enzyme pattern is reported for all regions of the human mucosa. Local and regional enzyme histochemical differences existed between the cardiac, fundic, body, and pyloric mucosa. Differences were absent, however, in the same region, and no differences were found between the anterior and posterior wall and the large and small curvature of the stomach. In cases of histologically less severe gastritis as a rule, enzyme histochemical changes were not found. They were numerous, however, in biopsies of patients with severe gastritis; only amino-peptidases A and M were unchanged. Dipeptidyl peptidase IV was absent; gamma-glutamyl transpeptidase exhibited individual differences. Alkaline phosphatase occurred in the pericapillary stroma and adenosine phosphates were not hydrolysed in atrophic glandular epithelia. Activity increases of lysosomal dipeptidyl peptidase I and beta-D-glucuronidase were typical for inflammatory infiltration processes of the gastric mucosa. Severe atrophy was accompanied by an activity decrease of glandular non-specific esterases, dipeptidyl peptidase II, and beta-N-acetyl-D-glucosaminidase and an activity decrease of the stromal peptidases and glycosidases. Enzyme activity was absent in the gastric glands proper in cases of total atrophy. An increase in macrophage number was primarily linked with an increase in acid phosphatase activity. Alkaline phosphatase, aminopeptidase M and gamma-glutamyl transpeptidase activities were enhanced in malignant neoplasms. High activities of all peptidases and alkaline phosphatase were found in the brush border of surface epithelial cells in cases of intestinal metaplasia. Except for dipeptidyl peptidase I and II, the enzyme pattern corresponds to that of small intestinal enterocytes. Compared with histological routine procedures for gastric diagnosis and assessment of the course enzyme histochemical methods deliver additional information; practically, however, the enzyme histochemical analysis of gastric biopsies are only useful in special cases.

Local immune defence in relation to gastritis in Billroth-II-resected stomachs.

Biopsy specimens from Billroth-II-resected stomachs obtained endoscopically 28-32 years after the operation were subjected to an immunohistochemical study by two-colour immunofluorescence staining. The epithelial distribution of immunoglobulin A (IgA), secretory component (SC), lysozyme (Ly), and lactoferrin (Lf) was evaluated, and IgA-, IgM-, and IgG-producing cells were quantified in the lamina propria. Gastric body mucosa excised from resected stomachs obtained from patients with duodenal ulcer was used as control and showed considerably less extensive gastritis than the stump mucosa. Both specimen categories showed enhanced expression of epithelial IgA, SC, Ly, and Lf associated with severe gastritis, except for areas with intestinal metaplasia, which lacked Ly and Lf. The number of IgA-, IgM-, and IgG-producing cells was significantly increased with increasing degree of gastritis, particularly so for IgG cells on a relative basis. After partial gastrectomy, therefore, the stump mucosa generally responds with activation of local immune mechanisms; this response is principally similar to that seen in simple gastritis of comparable severity.

Synaptophysin immunoreactivity and small clear vesicles in neuroendocrine cells and related tumours

Synaptophysin (protein p38) immunoreactivity has been detected immunohistochemically in neuroendocrine cells of the human adrenal medulla, carotid body, skin, pituitary, thyroid, lung, pancreas and gastrointestinal mucosa as well as in 87 out of 93 neuroendocrine tumours investigated, including pheochromocytomas, chromaffin and non-chromaffin paragangliomas, ganglioneuromas, pituitary adenomas, thyroid medullary carcinomas, parathyroid adenomas, lung carcinoids and neuroendocrine carcinomas, pancreatic and gut endocrine tumours and cutaneous merkelomas. Parallel ultrastructural investigation of synaptophysin-reactive cells and tumours revealed the presence, in addition to dense-cored, secretory granules, of a population of pleomorphic, small, clear vesicles resembling synaptic vesicles of nerve terminals as well as the synaptophysin immunoreactive vesicles already described in rat adrenal medullary and pituitary cells. 21 Synaptophysin immunoreactivity showed several differences in its distribution among tumour and non-tumour endocrine cells when compared to chromogranin A immunoreactivity, a well known marker of the core of endocrine granules. Synaptophysin represents a reliable general marker of neuroendocrine cells and tumours, which may be useful in diagnostic histopathology.

Chronic gastritis in cholecystectomized patients.

Duodenogastric reflux is considered to be a possible cause of chronic gastritis. This reflux, however, is reported to be common after cholecystectomy. In the present investigation we have studied the possible relation between chronic gastritis and prior cholecystectomy in 106 symptomatic outpatients with prior cholecystectomy and in 131 controls without cholecystectomy. We surveyed their endoscopic biopsy specimens from antral, body, and esophageal mucosa. We found that the mean score and prevalence of chronic antral and body gastritis in cholecystectomized patients was the same as or slightly lower than that in controls. The mean progression of gastritis, when compared with the progression of gastritis in the general population, was slightly slower than expected in the cholecystectomized patients. This slow progression was seen in body gastritis in cholecystectomized patients with a coexisting esophagitis. We conclude that there is no positive correlation between chronic gastritis and prior cholecystectomy. In contrast, this correlation may be negative, especially in patients with esophagitis, in whom an association of the postcholecystectomy state and a possible duodenogastric reflux with normal, nongastritic and nonatrophic body mucosa may facilitate mechanisms favoring the pathogenesis of esophagitis.

Campylobacter-like organisms and gastritis: histopathology, bile reflux, and gastric fluid composition.

We studied a prospective series of 107 randomly chosen dyspepsia patients without gastric ulcer for the association of spiral Campylobacter-like organisms (CLO) with features of antral and fundal gastritis and duodenogastric reflux. CLO were observed in 38% of the patients. The scores for all classes of inflammatory cells in both antral and body mucosa were significantly higher in the CLO-positive patients than in the CLO-negative ones (p less than 0.001), and foveolar hyperplasia was also associated with CLO (p less than 0.05). Metaplasia and glandular atrophy in the antral mucosa were significantly commoner in the CLO-positive group (p less than 0.05 and p less than 0.01, respectively). The body gastritis score correlated significantly with age in the CLO-negative patients (R = 0.33, p less than 0.01) but not in the CLO-positive ones. There were no significant differences between the groups with regard to duodenogastric reflux or intragastric pH. The results confirm that CLO are associated with gastritis, most notably superficial gastritis in the body and atrophic gastritis in the antrum, but their aetiological significance remains to be proved.

Prepyloric erosions: an entity of its own among erosive gastric lesions. A morphologic and dynamic study of gastric mucosa in patients with gastric erosions.

The morphology and dynamics of the gastric mucosa were examined in 130 patients with gastric mucosal erosions by using mathematical methods based on stochastic principles. The results were compared with those of controls representative of the general population. The progression of antral gastritis was less rapid in erosion patients than in the controls (p less than 0.001), but body gastritis increased with age, as expected. In patients with prepyloric erosions body gastritis showed less rapid progression with age than in the controls (p less than 0.01) or in other erosion patients (p less than 0.05). Antral gastritis increased, as in the controls, and more rapidly than in other erosion patients (p less than 0.01). The preservation of the body mucosa in patients with prepyloric erosions despite ageing is similar to that seen in patients with duodenal ulcer disease, suggesting a common acid-related pathogenesis.

Flow cytometric DNA studies in human gastric cancer and polyps.

Flow cytometric DNA studies were performed on cell suspensions of biopsy specimens from gastric tumors and neutral gastric mucosa in 18 patients with gastric cancer and 9 patients with gastric polyps. In cancer, aneuploidy was found in two tumors in the antral and five in the body part of the stomach (39%). The mean DNA index for aneuploid cancers was 1.57. In patients with aneuploid carcinomas three biopsy specimens from uninvolved mucosa also showed aneuploidy. In diploid carcinomas in the antral part of the stomach, the proliferative index (PI) was increased when compared with that of antral mucosa in controls (p less than 0.05). Increased PI was found in uninvolved mucosa in aneuploid carcinomas of the body part of the stomach when compared with that in diploid carcinomas (p less than 0.001). In uninvolved body mucosa in aneuploid carcinomas of the body part significantly reduced levels of acid-beta-glucuronidase (p less than 0.0001) were found when compared with diploid carcinomas. No polyps showed aneuploidy, and the PI in biopsy specimens from patients with gastric polyps did not differ from that in controls.

Sensitivity of gastric acid secretion in patients with chronic renal failure.

By means of a dose-response secretion test the sensitivity of gastric acid secretion was investigated in 85 patients with chronic renal failure and in 85 age- and sex-matched controls. The renal patients were also gastroscoped, with biopsy specimens taken from the gastric body. The examinations were repeated on 18 patients undergoing regular dialysis and 8 patients after successful transplantation. The acid secretion sensitivity of the stomach among the non-dialyzed patients was decreased when compared with the controls (p less than 0.01) but tended to normalize during the intermittent dialysis treatment (p less than 0.05) and particularly after transplantation (p less than 0.01). The low secretion responses were independent of gastric body histology and were also seen in patients with normal body mucosa. The maximum theoretic acid output did not differ significantly from that of the controls. It is concluded that there is an inhibition of gastric acid secretion in chronic renal failure. This inhibition depends on the decreased sensitivity to stimulation and is diminished by treatment of renal failure by dialysis or transplantation.

Pernicious anaemia and mucosal endocrine cell proliferation of the non-antral stomach.

There is a recognised association between pernicious anaemia and the development of gastric carcinoma, endocrine cell hyperplasia, and carcinoid tumour. Multiple endoscopic biopsies from the body mucosa of seven patients with pernicious anaemia showed small intestinal metaplasia with varying degrees of inflammation, fibrosis, and expansion of the lamina propria. Using conventional silver and lead stains, endocrine cells were inconspicuous. Staining for the general neural and neuroendocrine markers NSE and PGP 9.5 revealed a proliferation of endocrine cells in the epithelium and isolated clumps of endocrine cells in the lamina propria. The clumps were composed of two cell types, either small or large. Some of these endocrine cells showed gastrin, 5HT, VIP and substance P immunoreactivity of varying intensity. Ultrastructurally nine morphologically distinct types of granules were found some of which correlated with the immunohistochemistry. Some separate islands were composed solely of endocrine cells while others had a definite neural component, suggesting that the former arise from 'budding off' of enteroendocrine cells and the latter originate from the neuroendocrine cells of the lamina propria plexus. Thus there may be a dual origin of carcinoid tumours. Carcinoid tumours associated with pernicious anaemia tend to be multifocal and are infrequent. Less than 50 such cases have hitherto been reported. Our findings of endocrine cells proliferations in seven cases of pernicious anaemia indicate that this may be an adaptive change that occurs frequently and provides the basis on which carcinoids, less frequently, develop.

Quantitative distribution of immunoglobulin-producing cells in gastric mucosa: relation to chronic gastritis and glandular atrophy.

Immunoglobulin (Ig)-producing immunocytes were quantified by paired immunofluorescence staining in specimens of gastric antral (n = 52) and body (n = 117) mucosa obtained from 45 patients with various gastrointestinal disorders. Enumerations were carried out in a 500 micron wide zone from the muscularis mucosae to the lumen ('tissue unit'). The specimens were divided into three categories according to the degree of inflammation, and each specimen received a grade for atrophy (0-2). The total number of IgA-, IgM- and IgG-producing cells per tissue unit increased strikingly with increasing degree of inflammation, both in antral and body mucosa. IgA immunocytes predominated (61-91%) in all specimens, but the IgG isotype showed the largest relative increase (four to 17-fold), particularly in the basal part of the mucosa. In this layer of the gastric body the proportion of IgG cells was also significantly raised in association with atrophy, irrespective of degree of inflammation. Locally produced IgG may be of protective significance in terms of internal (or 'second line') defence but may at the same time maintain immunopathological mechanisms contributing to the chronicity of gastritis.

舌神経切断後の舌粘膜の変化に関する実験的研究

舌神経切断後の舌粘膜の変化に関する実験的研究

Nodular hyperplasia of Brunner's glands

A clinical, endoscopic, and histological study of 206 cases of nodular hyperplasia of Brunner's glands was carried out. Firm nodules with a reddened surface due to hyperplastic Brunner's glands were limited mainly to the first part of the duodenum and affected almost exclusively male patients. Gastric acid secretion after pentagastrin stimulation was significantly increased compared to normal. In most cases, biopsies of the nodule center revealed spreading of Brunner's glands from within the lamina propria to the surface epithelium, whereas in biopsies performed between nodules, Brunner's glands were limited to the deeper part of the mucosa. Thirty-six nodules completely removed by diathermy were composed almost entirely of Brunner's glands. The frequent association with duodenal ulcer, chronic gastric erosions, and cobblestone pattern of the gastric body mucosa, as well as the significant hypersecretory state, suggest that hyperacidity plays a role in the pathogenesis of nodular hyperplasia of Brunner's glands.