K. Varis

Relationships Among Serum Pepsinogen I, Serum Pepsinogen II, and Gastric Mucosal Histology: A Study in Relatives of Patients with Pernicious Anemia

To examine the possible effect of gastritis on the endocrine component of pepsinogen secretion, we determined relationships among gastric mucosal histologic characteristics and serum levels of pepsinogen I and pepsinogen II in 170 first-degree relatives of patients with pernicious anemia. Sixtyfour had normal fundic gland mucosa, 66 had superficial gastritis, 17 had mild or moderate atrophic gastritis, and 23 had severe atrophic gastritis. In superficial gastritis, serum pepsinogen I and pepsinogen II were both significantly higher than normal, but the percentage rise in pepsinogen II was significantly greater than the rise in pepsinogen I. In mildl moderate atrophic gastritis, pepsinogen I did not differ from normal, but pepsinogen II was significantly elevated, while in severe atrophic gastritis, pepsinogen II did not differ from normal, but pepsinogen I was significantly decreased. The nonparallel changes in serum pepsinogen I and pepsinogen II levels resulted in a decrease in the pepsinogen I to pepsinogen II ratio from 6.2 ± 0.2 in subjects with normal fundic gland mucosa to 4.3 ± 0.2, 2.9 ± 0.4, and 0.7 ± 0.2, respectively, in those with superficial gastritis, mild to moderate atrophic gastritis, and severe atrophic gastritis. The pepsinogen I to pepsinogen II ratio in combination with the absolute level of serum pepsinogen I correctly predicted the histologic status of the gastric mucosa in 119 of the 170 subjects, 70.0%. The results indicate that (a) increasing severity of gastritis is associated with nonparallel alterations in serum levels of pepsinogen I and pepsinogen II, (b) that these changes lead to a progressive decrease in the pepsinogen I to pepsinogen II ratio, and (c) that the pepsinogen I to pepsinogen II ratio, in combination with pepsinogen I, is predictive of the histologic status of the gastric mucosa.

Cumulative 10-Year Risk of Symptomatic Duodenal and Gastric Ulcer in Patients with or without Chronic Gastritis: A Clinical Follow-up Study of 454 Outpatients

The cumulative rate of symptomatic peptic ulcer (PU) was examined in a 10-year clinical follow-up study of 454 consecutive outpatients who had undergone diagnostic gastroscopy, from whom routine biopsy specimens were taken from the antral and corpus mucosa, and who were found to be ulcer-free before and at the time of this initial gastroscopy. During the follow-up period 34 (11%) of 321 patients who showed gastritis in the biopsy specimens at the initial gastroscopy had contracted symptomatic PU (18, 5, 7, and 4 cases of duodenal, pyloric, antral, and angular or corpus ulcer, respectively), which was verified by endoscopy. Only 1 (0.8%) of 133 patients with normal antral and corpus mucosa had contracted PU. It was calculated that the 10-year cumulative probability of PU was 10.6% (95% confidence interval (CI95), 7.2-14.0%) in the patients with gastritis, whereas this probability was only 0.8% (0-2.2%) in the patients who had normal antral and corpus mucosa in the initial specimens. The cumulative probability of PU was found to be highest, 27.3% (1.0-53.6%), in middle-aged men (41-60 years of age) who had chronic antral gastritis or chronic pangastritis (gastritis in both antrum and corpus). It is concluded that chronic gastritis precedes the appearance of PU and that the cumulative 10-year risk of PU is very low when both antral and corpus mucosa are normal but may be high if chronic gastritis is present.

Serum Pepsinogen I and Serum Gastrin in the Screening of Severe Atrophic Corpus Gastritis

The possibilities to screen atrophic corpus gastritis with serum pepsinogen I (S-PGI) and serum gastrin (S-gastrin) concentrations have been studied in 774 subjects: 71 index subjects selected from a general population at random, 353 of their first-degree relatives, 276 first-degree relatives of patients with gastric cancer, 53 patients with pernicious anaemia, and 21 of their relatives. Discrimination function analysis was calculated from members of random and gastric carcinoma families. S-PGI less than 30 ng/ml had a high sensitivity for severe diffuse atrophic corpus gastritis (SDAG) alone (89.5%) and SDAG + severe patchy atrophic corpus gastritis (SPAG) (89.1%). Respective figures for specificity were 91.5% and 94.8%. The discriminatory power of S-PGI less than 30 ng/ml and S-PGI less than 25 ng/ml was of the same order. The sensitivity of low S-PGI decreased sharply in detection of slighter forms of atrophic corpus gastritis. The sensitivity of S-gastrin greater than 100 pmol/l to discriminate SDAG was 57.9% and SDAG+SPAG 58.7%. Respective figures for specificity were 90.2% and 92.2%. Diffuse and patchy atrophic changes behaved similarly regarding S-PGI and S-gastrin mean concentrations. Accordingly, the biopsy specimen with the severest atrophic changes indicates the degree of atrophy, which associates closely with the changes in S-PGI and S-gastrin. In conclusion, severe atrophic (diffuse or patchy) corpus gastritis may be screened from a general population with high sensitivity and specificity by low S-PGI less than 30 ng/ml, whereas an increased level of S-gastrin is too insensitive for this.

Morphological, Functional and Immunological State of the Gastric Mucosa in Gastric Carcinoma Families: Comparison with a Computer-matched Family Sample

Three hundred and one first-degree relatives (series) of 73 gastric carcinoma patients and 358 control relatives (controls) of 73 computer-matched probands from a general population were studied by direct-vision gastric biopsy and functional and immunological examinations. The controls were representative of the series with respect to age, sex, birth and dwelling place, and relationship of the relatives. Series and controls behaved similarly as to total prevalence of gastritis, age and sex distribution of gastritis, serum gastrin level, and circulating gastric antibodies. On the other hand, the total prevalence of hyperplastic polyps, atrophic gastritis of the body and antrum, severe atrophic gastritis of the body, intestinal metaplasia, epithelial atypia, and achlorhydria was significantly higher in the series than in the controls. In subjects below 50 years of age the prevalence of severe atrophic gastritis of the body, intestinal metaplasia, and epithelial atypia was also significantly higher in the series. In addition, the mean age of the subjects with atrophic gastritis, intestinal metaplasia, epithelial atypia, and achlorhydria was lower in the series than in controls; however, significant differences were found only in female subjects with epithelial atypia and atrophic gastritis of the body. The results suggest that the prevalence of signs often considered premalignant is significantly higher in carcinoma relatives than in controls and that these signs show a trend to occur at an earlier age in carcinoma relatives. This could explain the significantly higher than expected death rate from gastric carcinoma in close relatives with this disease, found in the present and in other series.

An appraisal of tests for severe atrophic gastritis in relatives of patients with pernicious anemia.

The sensitivities, specificities, and predictive values of parietal cell antibody, serum gastrin, and serum pepsinogen I (PG I) for severe atrophic gastritis of the oxyntic gland mucosa have been determined in 171 first-degree relatives of 62 patients with pernicious anemia. Parietal cell antibody had the lowest sensitivity (65%), specificity (87%), and predictive value (44%). A low serum PG I and a high serum gastrin had identical specificities (97%), and similar predictive values (84 vs 83%), but the sensitivity of a low serum PG I was greater than that of a high serum gastrin (91 vs 83%). Parietal cell antibody was found in 19 of 148 relatives without severe atrophic gastritis and occurred as an isolated finding in 17. In contrast, 14 of the 15 relatives with severe atrophic gastritis who had parietal cell antibody also had a high serum gastrin and a low serum PG I. A high serum gastrin together with a low serum PG I had a specificity of 100%. The results recommend serum PG I and serum gastrin, but not parietal cell antibody, as tests for severe atrophic gastritis in relatives of patients with pernicious anemia.

Gastric Morphology, Function, and Immunology in First-degree Relatives of Probands with Pernicious Anemia and Controls

Gastric morphology, function, and immunology was studied in 68 patients with pernicious anemia (PA), 183 of their first-degree relatives, and 354 control subjects. The PA relatives and controls were comparable in age and sex distribution. In both groups, mean gastric acid output decreased and mean fasting serum gastrin levels and the prevalence of atrophic gastritis increased with age. The total prevalence of chronic gastritis was similar in the two groups, but severe atrophic gastritis of the body of the stomach (AGB), achlorhydria, parietal cell antibodies, and a raised fasting serum gastrin level were significantly more common in PA relatives than in controls. Of the PA relatives 23 had severe AGB which was indistinguishable from the gastric mucosal lesion found in PA probands and was, as a rule, accompanied by several other characteristics of type A gastritis. These included a normal antrum (78%), slight or absent inflammatory cell infiltration in the gastric mucosa (70%), achlorhydria (91%), high fasting serum gastrin level (83%), parietal cell antibodies (65%), and intrinsic factor antibodies (22%). The mean age and the proportion of subjects with slight and moderate AGB of all AGB subjects was significantly lower in PA relatives than in controls. This suggests an early onset and a rapid progression from mild to severe AGB in PA relatives. Thus, the PA relatives appear to consist of two populations, one with a high and one with little or no proneness to severe AGB. This bimodal distribution suggests the participation of a single major factor, probably genetic, in the pathogenesis of severe AGB in PA relatives.

Age- and Sex-Related Behaviour of Gastric Acid Secretion at the Population Level

Pentagastrin-stimulated gastric acid output and the histology of the antral and body mucosa were examined in 72 computer-selected probands and their 365 relatives, altogether 437 cases. The frequencies of upper abdominal complaints, peptic ulcer and hiatal hernia, and blood group distribution were comparable with those of the population at large. Acid output, expressed as mmol/h, mmol/h/kg of total body weight (TBW), mmol/h/kg of lean body mass (LBM), and mmol/h/kg of fat-free body weight (FFB), correlated with the changes in the body mucosa but not with those in the antrum. Acid output was lower in females than in males when expressed as mmol/h or mmol/h TBW but not when expressed in terms of FFB, which better than LBM accounts for the variation in the gastric surface area and, in this manner, for that of the parietal cell mass. This suggests that the lower acid output in females is due to a smaller gastric surface area and correspondingly smaller parietal cell mass rather than to a lower reactivity of the cells to stimulation. Acid output decreased with increasing age in both sexes, and this was due to a concomitant increase in the incidence and severity of atrophic changes in the body mucosa. An age-related decrease in acid output was not seen in males with a normal body mucosa. In females with a normal body mucosa, however, output expressed in terms of FFB showed a significant increase with age. The reason for this increase is not clear. In males and females with superficial gastritis of the body mucosa acid output decreased with increasing age regardless of the formulation used.

Serum pepsinogen I and serum gastrin in the screening of atrophic pangastritis with high risk of gastric cancer.

Serum pepsinogen I (S-PGI) and serum gastrin (S-gastrin) were examined in the screening of three types of atrophic gastritis with inherent high risk of gastric cancer: in 102 cases with severe atrophic corpus gastritis (SACG), in 5 cases with severe atrophic antrum gastritis (SAAG), and in 15 cases with severe atrophic pangastritis (SAPG) (atrophy both in corpus and in antrum) found among 916 subjects from three family series (265 from gastric cancer families, 425 from randomly selected control families and 226 from pernicious anaemia families). There is no way to screen directly atrophic gastritis restricted to the antral mucosa. In pangastritis atrophy of antral glands causes a failure of the hypergastrinemic reaction of achlorhydria. The combination of S-PGI less than 25 micrograms/l + S-gastrin less than 200 pmol/l detected 80.0% of our cases with SAPG, and only 17 subjects of 794 (2.1%) were false positives i.e. who had not advanced atrophic gastritis. The risk of gastric cancer may be significantly higher in SAPG than in SACG. The estimated prevalence of SAPG was 3% in random-family members over 60 years. The combination of S-PGI and S-gastrin is recommended when the cost/benefit ratio in the screening program of gastric cancer is considered and people from a general population are selected for endoscopic studies.

Changed Profile of Peptic Ulcer Disease in Hospital Patients during 1969–1984 in Finland

The annual number of hospital discharges for peptic ulcer decreased in Finland from 1969 to 1974, mainly because of a smaller number of men with uncomplicated peptic ulcer disease. After the mid-1970s the number of hospital admissions remained stable, whereas the number of elderly patients increased. From 1979 to 1984 the number of hospitalizations for perforated ulcers remained stable, whereas those for ulcer haemorrhages increased, the increase being most marked in the older age groups. The age-specific mortality from peptic ulcer remained stable from 1969 to 1984 and rose thereafter among old patients. The risk of death from peptic ulcer was about 10-fold higher in patients over 75 years old than in younger age groups, and about half of the deaths caused by peptic ulcer occurred in patients over 75 years old. The men to women ratio among hospitalized patients decreased from 3.5 in the late 1960s to 2.1 in the 1980s, and the gastric ulcer to duodenal ulcer ratio was about 1.1 throughout the observation period.

Course of antrum and body gastritis in pernicious anemia families

The course of antrum and body gastritis was studied using an essentially linear multicompartmental model in pernicious anemia probands, their first-degree relatives, and controls consisting of a representative family sample of a large Finnish population. Our earlier dynamic approach showed that progression of body gastritis was virtually identical in a series followed up with biopsies and in cross-comparison analyses, indicating that cross-sectional data can be used for dynamic analyses at a population level. The collected data fitted a model which consisted of stepwise progression of body gastritis to severe atrophy, of corresponding progressive steps for antral gastritis, and of regression of the antral changes after the end-stage of the body process had been reached. In addition, acceleration of the progression of gastritis in older subjects had to be taken into account in the model construction. The main findings which characterized pernicious anemia probands and their close relatives were: (1) a rapid overall progression of body gastritis particularly after 50 years of age; (2) a very rapid progression of body atrophy in its final stages, which was unrelated to age; (3) the occurrence of juvenile severe body atrophy; and (4) the healing of antral gastritis which was most marked at the stage of superficial gastritis. These results may offer a dynamic explanation for the occurrence of severe body atrophy in association with a normal or slightly altered antral mucosa in pernicious anemia and the prepernicious anemia state.