Prevalence of low vitamin B12 and high homocysteine in serum in an elderly male population: association with atrophic gastritis and Helicobacter pylori infection.

BACKGROUND: Deficiency of vitamin B12 raises the serum and tissue levels of homocysteine. Atrophic corpus gastritis results in impaired secretion of intrinsic factor and may lead to malabsorption of vitamin B12 in the intestine. We examined how common an undiagnosed vitamin B12 deficiency is among elderly men in the general population and, in particular, how often this deficiency is related to atrophic corpus gastritis. METHODS: The serum level of pepsinogen I (S-PGI) was assayed in a population-based sample of 12,252 men (age 51-65 years) from two cities in Finland. In this sample, all 635 men with S-PGI < 25 microg/l formed Series A ('males with atrophic corpus gastritis'). Series C (controls--'males without atrophic corpus gastritis)' with a non-atrophic gastric corpus was formed as a random sample of men (n = 402) with S-PGI > or = 50 microg/l. Serum levels of vitamin B12 (S-B12), folate (S-Fol), total homocysteine (S-Hcy) and Helicobacter pylori antibodies (S-HpAb) were assayed in all, or in large subsamples, of the men in Series A and C. RESULTS The men in Series A had significantly lower S-B12 and S-Fol levels than those in Series C. In Series A, 172 of 613 men tested (28%) had S-B 12 < 170 pmol/ 1, and 133 men (22%) had S-B 12 in the range 170-219 pmol/l. The corresponding prevalences were 7% (P < 0.001) and 17% (P < 0.001) in Series C, respectively. The mean S-Hcy was significantly higher in Series A in men with low S-B12 than the mean S-Hcy in Series C in men with normal S-B12. The prevalence of S-Hcy > 15 ,micromol/l was 27% in Series A and 15% in Series C (P < 0.05; chi2 = 4.63). Among subjects with S-B 12 < 220 pmol/l, 46% (104 of 226 men tested) in Series A and 16% (16 of 99) in Series C had S-Hcy > or = 15 micromol/l (P < 0.001). The mean S-Hcy was significantly (P < 0.001) higher in men with S-B12 in the range 170-219 pmol/l in Series A (mean 14.6 +/- 5.0 micromol/l) than in Series C (11.3 +/- 3.0 micromol/l). It was extrapolated that 2.5% of men in the age group 51-65 years in the present study population had a low S-B12 (< 220 pmol/l) level that associated with atrophic corpus gastritis. Of these men, 72% (128 of 179 tested) had an elevated S-HpAb level. CONCLUSIONS: Low S-B12 related to atrophic corpus gastritis is relatively common (prevalence 2.5%) among elderly males in the general population. An ongoing H. pylori infection occurs in three-fourths of these cases.

Increased risk of developing atrophic gastritis in patients infected with CagA+ Helicobacter pylori.

BACKGROUND: To clarify the possible role of CagA positive (CagA+) Helicobacter pylori strains in the development of atrophic gastritis, the prevalence of antibodies to H. pylori and CagA (120 kD protein) was studied among subjects with atrophic and non-atrophic gastritis. METHODS: The study population was randomly selected among 12,252 Finnish men who were screened for atrophic corpus gastritis with serum pepsinogen I-assay (S-PGI). S-PGI level was used as a selection criterion. Group A consisted of 295 subjects with S-PGI <25 microg/l (low), group B of 320 subjects with S-PGI 25-100 microg/l (normal) and group C of 338 subjects with S-PGI >100 microg/l (high). Antibodies to H. pylori were measured with EIA and immunoblot analysis and antibodies to CagA with immunoblot analysis. Endoscopical and histological examinations were performed for 203 patients from group A. RESULTS: The prevalence of antibodies to H. pylori was significantly lower in group B than in groups A or C (P < 0.0001, chi-squared test). There was a significant association between the prevalence of antibodies to CagA and the lowered level of S-PGI (P < 0.0001, Jonckheere-Terpstra trend test). There was also a linear decrease in the prevalence of antibodies to CagA as the atrophic corpus gastritis became more severe (P < 0.0001, linear-by-linear trend test). CONCLUSION: The presence of antibodies to CagA seems to be associated with development of atrophic corpus gastritis.

Implications of serum pepsinogen I in early endoscopic diagnosis of gastric cancer and dysplasia. Helsinki Gastritis Study Group.

BACKGROUND AND AIMS: The risk of gastric cancer (GCA) is increased in atrophic gastritis. A low serum pepsinogen group I (SPGI) level is a good serologic indicator of atrophic gastritis of the gastric corpus and fundus, and can be used for diagnosis of subjects with atrophic gastritis and of increased risk for GCA. The present study was undertaken to investigate whether SPGI assay and a diagnostic gastroscopy could enable the diagnosis of GCA at an early stage. MATERIAL AND METHODS: The study was carried out as part of the Alpha-Tocopherol, Beta-Carotene Cancer prevention study (ATBC study) in Finland, in which 22,436 male smokers aged 50-69 years were screened by SPGI. Low SPGI levels (< 25 microg/l) were found in 2196 (9.8%) men. Upper GI endoscopy (gastroscopy) was performed in 1344 men (61%) and 78% of these had moderate or severe atrophic corpus gastritis in endoscopic biopsies. A control series of 136 men from the ATBC study cohort with abdominal symptoms, but with SPGI > or = 50 microg/l were similarly endoscopied, and 2.2% of these had corpus atrophy. RESULTS: Neoplastic alterations were found in 63 (4.7%; 95% CI: 3.6%-5.8%) of the 1344 endoscopied men with low SPGI levels. Of these, 42 were definite dysplasias of low grade, 7 dysplasias of high grade, 11 invasive carcinomas, of which 7 were 'early' cancers, and 3 carcinoid tumors. In the control series, 1 man (0.7%) of the 136 men had a definite low-grade dysplasia. Thus, 18 (1.3%; 95% CI 0.7%-2.0%) cases with 'severe' neoplastic lesions (4 advanced cancers, 7 early cancers and 7 dysplasias of high grade) were found in the low SPGI group, but there were none in the control group. All four patients with advanced cancer died from the malignancy within 5 years (mean survival time 2.5 years), whereas surgical treatment in all those with early cancer or high-grade dysplasia was curative. One of the seven patients with early cancer and two of the seven with high-grade dysplasia died within 5 years, but none died from the gastric cancer. Thus, curative treatment was given to 14 of 18 men in whom a malignant lesion was found in gastroscopy. This is about 15% of all gastric cancer cases (92 cases) which were diagnosed within 5 years after SPGI screening in the 22,436 men. Among the gastric cancer cases of the main ATBC study, the 5-year survival rate was 33% (85% of the non-survivors died from gastric cancer). CONCLUSIONS: We conclude that assay of SPGI followed by endoscopy is an approach which can enable the early diagnosis of gastric cancer at a curable stage.

Gastric cancer and premalignant lesions in atrophic gastritis: a controlled trial on the effect of supplementation with alpha-tocopherol and beta-carotene. The Helsinki Gastritis Study Group.

BACKGROUND: Vitamin E and beta-carotene are considered to decrease the risk of gastric cancer both in humans and in laboratory animals. We studied the effect of dietary supplementation with alpha-tocopherol and beta-carotene on the end-of-trial prevalence of premalignant and malignant lesions of the stomach in older men with atrophic gastritis. METHODS: The study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC study) in Finland, in which 29,133 male smokers aged 50-69 years were randomly assigned to receive daily 50 mg alpha-tocopherol, 20 mg beta-carotene, both of these agents, or placebo, for 5-8 years. Serum pepsinogen was determined at base line and after 3 years' supplementation to find men with atrophic gastritis. A low serum pepsinogen I level, indicating atrophic gastritis of the corpus area of the stomach, was found in 2132 men. These men were invited to have upper gastrointestinal endoscopy (gastroscopy), which was performed on 1344 subjects after a median supplementation time of 5.1 years. RESULTS: Neoplastic alterations were found in 63 of the men (4.7%): 42 with definite dysplasias of low grade (moderate dysplasia), 7 with definite dysplasias of high grade (severe dysplasia), 11 with carcinomas (of which 7 were 'early' cancers), and 3 with carcinoid tumors. Neither alpha-tocopherol (relative risk, 0.98; 95% confidence interval, 0.57-1.69) nor beta-carotene (relative risk, 1.13; 95% confidence interval, 0.65-1.95) supplementation had any association with end-of-trial prevalence of gastric neoplasias after adjustment for other possible risk factors. The effect was not modified by base-line serum level or dietary intake of vitamins, prevalence of Helicobacter pylori infection, or other covariates. CONCLUSIONS: We thus conclude that supplementation with alpha-tocopherol or beta-carotene for 5 years has no major impact on the occurrence of neoplastic changes of the stomach in older male smokers with atrophic gastritis.

Risk of gastric carcinoma in patients with mucosal dysplasia associated with atrophic gastritis: a follow up study.

AIMS: To assess the risk of gastric carcinoma in patients with histologically verified dysplasia and atrophic gastritis of the stomach. METHODS: One hundred and one patients with mild (n = 84), moderate (n = 14), or severe (n = 3) dysplasia among 359 elderly men who smoked underwent gastroscopy because of low serum pepsinogen. Patients with dysplasia were prospectively followed up for an average of four years with repeated gastroscopies and multiple biopsies. RESULTS: Four of the 84 (4.8%) cases of mild dysplasia had progressed to moderate dysplasia during the follow up. Most of the cases of mild dysplasia had resolved spontaneously. No surgical intervention was required. Three of the 14 (21%) cases of moderate dysplasia had progressed to severe dysplasia, but no carcinomas were observed during follow up. Five moderately dysplastic lesions were removed surgically or endoscopically. In two of these five cases, moderate or severe dysplasia recurred. Two of the three severe dysplasias progressed to carcinoma. CONCLUSIONS: In atrophic gastritis progression of mild and moderate dysplastic lesions seems to be a slow process and is rare in mild dysplasia. However, severe dysplasia is highly predictive of subsequent cancer. It is suggested that a five year follow up interval is sufficient in cases with mild dysplasia and two years in those with moderate dysplasia. Local removal of moderate dysplasia is indicated but does not guarantee that the lesion will not progress. Severe dysplasia requires immediate surgical intervention.

An aseptic inflammation of the clavicle in a patient with Crohn's disease. A potential manifestation of the SAPHO syndrome.

A female patient with Crohn's disease developed an septic osteoarticular involvement of the left clavicle and sterno- and acromioclavicular regions. Repeated surgical revisions combined with a broad-spectrum antimicrobial treatment could not prevent the progress of the disease. However, the patient started to improve after the diagnosis of the SAPHO (synovitis, acne, pustulosis, hyperostosis and osteomyelitis) syndrome was made and the dose of her immunosuppressive therapy increased. This patient reminds of the existence of extraintestinal aseptic infections in association with inflammatory bowel disease (IBD). Moreover, it may provide further evidence on the significant association between SAPHO and IBD.

Helicobacter pylori infection and fasting serum gastrin levels in a series of endoscopically diagnosed gastric polyps.

The occurrence of H. pylori infection and the levels of fasting serum gastrin (SEGA) were examined in 97 patients with different morphological types of endoscopically diagnosed gastric polyps. According to the histology of the polyps the series was divided into three groups: inflammatory polyps (43 cases), polyps with foveolar hyperplasia (25 cases), and hyperplastic polyps including adenomas (29 cases). The prevalence of H. pylori infection was significantly lower in patients with hyperplastic polyps (45%) and foveolar hyperplasia (48%) than in the group with inflammatory polyps (81%). SEGA levels were higher in patients with hyperplastic polyps (mean +/- sd: 335 +/- 298 pmol/l) and foveolar hyperplasia (183 +/- 216) than in patients with inflammatory polyps (89 +/- 127). Signs of so-called "autoimmune" gastric, i.e. corpus atrophy and presence of parietal cell antibodies, were commonly found in patients with hyperplastic polyps and foveolar hyperplasia, but rarely in patients with inflammatory polyps. These results suggest that the polyps with hyperplastic changes (hyperplastic polyps and foveolar hyperplasia) are in some of the cases closely related to autoimmune gastritis. The presence of corpus atrophy, hypoacidity and various types of metaplasia, which characterizes autoimmune gastritis, could explain the low prevalence of H. pylori and the high SEGA levels found in these patients.

Sucralfate as maintenance treatment for the prevention of duodenal ulcer recurrence.

Eighty-eight patients with endoscopically proven and healed duodenal or pyloric ulcer were randomly allocated into a double-blind, placebo-controlled, 12-month maintenance trial to determine whether sucralfate, 1 g twice daily, can be used to prevent a recurrence of ulceration. The patients were assessed endoscopically at three, six, and 12 months, or earlier if a symptomatic relapse occurred. Serum aluminum levels were also monitored. Sixteen patients were excluded from the study during the follow-up: nine of 41 in the sucralfate group, and seven of 47 in the placebo group. The groups did not differ with respect to age, sex, or smoking. The cumulative relapse rates in the sucralfate group were 28 percent after three months, 33 percent after six months, and 45 percent after 12 months, as compared with 49 percent (p less than 0.05), 64 percent (p less than 0.01), and 68 percent (p less than 0.05), respectively, in the placebo group. It is concluded that 1 g sucralfate twice daily is more effective than a placebo and is safe for the maintenance treatment of duodenal and pyloric ulcer disease.

Gastric ulcer and gastritis: results of short-term follow-up examinations.

A hundred and one cases of gastric ulcer were examined in Poland by direct-vision endoscopic biopsy obtained from the antrum, angulus and body far outside the ulcer area, and from the edge of the ulcer. A simple mean score of gastritic changes and of intestinal metaplasia (IM) was calculated for each area, as also a mean score of IM for the mucosa around the ulcer. Two re-examinations were performed, one on average 2 months and the other on average 4.5 years, after the first examination. On the whole, gastritic changes and IM behaved as expected from earlier studies. The most striking finding was the high mean score of the angular mucosa in the case of more proximally situated ulcers. This angular peak was present at all examinations and both in patients healed during the follow-up and those in whom the disease remained active. A corresponding peak of gastritic changes and IM at the angulus was not found in more comprehensive Finnish control material, but was present in another smaller outpatient series, although the differences between the angulus and surrounding tissues were insignificant. At the first examination the mean scores of gastritis and of IM outside and around the ulcer were higher in patients with proximal ulcers in whom the ulcer healed during the observation period than in those, in whom it remained active. This difference was found at the first and at all subsequent examinations, and some of the differences were statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric carcinoma and pernicious anaemia in long-term endoscopic follow-up of subjects with gastric polyps.

The starting material consisted of 357 subjects with gastric polyps found at endoscopy. Histologically, these cases were divided in four groups: adenoma, 8%; hyperplastic polyp, 34%; foveolar hyperplasia, 21%; and inflammatory polyp, 36%. Of these 210 patients were for various reasons no longer available for follow-up study. Endoscopic follow-up study for about 8 years (range, 5-15.5 years) was performed in 147 patients. At the follow-up examination, in 103 patients morphologic signs and in 92 of these immunological and functional signs of pernicious anaemia were examined. The prevalences of severe atrophic gastritis affecting mainly the body mucosa (26%), parietal cell and/or intrinsic factor blocking antibodies (25%), low serum vitamin B12 levels (8%), and overt pernicious anaemia (treated and new cases, 11%) were significantly higher than in equal numbers of age- and sex-matched controls examined in a similar manner. Gastric cancer was found in 3 (2%) cases followed up for more than 5 years. This is seven times the expected incidence, with a 95% confidence interval of the risk ratio (1.5-20.9). The high frequency of gastric cancer and pernicious anemia emphasizes the importance of long-term endoscopic follow-up study of patients with gastric polyps.

Cystic 'hamartomatous' gastric polyps: a disorder of oxyntic glands.

In 1977, Elster et al. described gastric polyps of a new type. These polyps were formed of fundic glandular cysts in otherwise normal gastric mucosa. In this paper a series of 52 cases of this type of polyp are presented. In addition to cysts, polyps contained deformed oxyntic glands and areas where the formation of secondary irregular glands occurred from cysts and from the existing glands. However, all glands and cysts in polyps were composed of normal, but intermixed cells of oxyntic type, suggesting that deranged differentiation of otherwise normal oxyntic glands is the basic mechanism in the pathogenesis of these polyps. Based on these observations, the polyps were considered most likely to be epithelial hamartomas. In agreement with the findings of Elster et al., the present cases showed typical clinical characteristics: three-quarters of patients were females with a peak prevalence in the fifth and sixth decades. Polyps were most often multiple and occurred only in the oxyntic mucosa of the stomach.

The gastric mucosa in stomachs with polyps: morphologic and dynamic evaluation.

Biopsy specimens from the antral and body mucosa of 183 patients with gastric polyps (adenoma, 4; hyperplastic polyp (HP), 52; foveolar hyperplasia (FH), 49; and inflammatory polyp (IP), 78 cases) have been examined. The prevalence of gastritis in the series was compared with that in 183 age- and sex-matched controls. The dynamics (progression) of gastritis was evaluated by means of an age-adjusted gastritic score. In the HP and FH groups the prevalence and progression of body gastritis were significantly higher and more rapid (p less than 0.001) while the prevalence of antral gastritis was lower (p less than 0.05) and its progression less rapid (p less than 0.001) than in controls. It is concluded that the pernicious anaemia type of gastritis (A-type gastritis) is closely related to gastric polyps of hyperplastic origin. The progression of this gastritis type seemed to increase in the order IP, FH, and HP. In addition, we observed an increase in the prevalence of intestinal metaplasia (p less than 0.001) and marked epithelial dysplasia (0.1 greater than p greater than 0.05; chi-square = 3.75) in stomachs with polyps as compared with in controls.

Gastric polyps; their morphological and endoscopical characteristics and relation to gastric carcinoma.

In 13 200 consecutive gastroscopies polyp-like lesions were found in 454 patients and of these 425 were examined histologically. Tumours other than polyps were excluded and there remained 357 cases which were divided in four groups: adenoma (8%), hyperplastic polyp (34%), foveolar hyperplasia (21%) and inflammatory polyp (36%). Transitional forms between different groups were seen and sometimes characteristics of different polyptypes could be seen within one and same polyp. In addition, the mean age of the patients increased in order: inflammatory polyp, foveolar hyperplasia, hyperplastic polyp and adenoma, suggesting that the different groups are not separate entities but represent related stages in the morphogenesis of gastric polyps. 219 cases out of 357 patients were re-examined endoscopically on average 2.5 years after the first examination. This examination revealed new polyps in 26% of all cases and spontaneous disappearance of the polyps in 14% of cases suggesting that gastric polyps, particularly those of the hyperplastic and inflammatory type are in a dynamically labile state. Gastric carcinoma was found in 27 (8%) of patients with polyps. In 4 of these cases the carcinoma was found at the re-examination (which in 3 cases was performed within 0.5 and in 1 case within 1.5 year). In 14 cases carcinoma was found inside the polyps and in 6 of these carcinoma was "early" in its growth. In 13 cases carcinoma was found outside the polyps and in all of these carcinoma was "advanced". Carcinoma was found in 38% of adenoma cases and in 5% of cases with polyps other than adenomas.