M. Kekki

Chronic Gastritis: Dynamic and Clinical Aspects

A simple method for grading gastritis is to assess the severity of round cell infiltration and the loss of normal glands, and this may be applied to both antral and body changes. However, there is, as yet, no satisfactory classification of gastritis. In population samples, gastritis shows a linear increase in age-specific prevalence so that the annual increase in the body atrophic gastritis pool up to geriatric age is constant (1.5%). In the elderly, there appears to be a retardation of the process, particularly in the antral mucosa, where some healing trend is demonstrable. This dynamic behaviour is qualitatively similar in all population samples collected in Finland and Estonia. On the other hand, the dynamic behaviour of gastritis in different subpopulations differs markedly from that in the population at large. In pernicious anemia patients and their first-degree relatives, the progression of body atrophic gastritis in its final stages is about 20 times more rapid than in a general population, while, simultaneously, antral gastritis displays a distinct healing tendency. A behaviour opposite to that in pernicious anemia is seen in patients with active or healed duodenal ulcer disease and in duodenitis: antral gastritis behaves, on the whole, similarly to that in the general population, but in the body mucosa there occurs virtually no progression with age, and the mucosa generally remains normal or at the stage of superficial gastritis. However, after antrectomy body gastritis progresses rapidly in the remnant at first, but it slows down later and then closely resembles that in the general population.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

The sequelae and course of chronic gastritis during a 30- to 34-year bioptic follow-up study.

Three hundred and seventy-seven subjects with different conditions of the gastric body mucosa have been followed up for 30-34 years, first by the blind suction biopsy method and since 1973-1976 by the direct-vision endoscopic method. Body gastritis revealed a distinct worsening trend during the whole follow-up period. However, during the last follow-up period some slowing down of the process was also discernible. In the antrum there was a distinct healing trend during that period. Thus all cases of distinct atrophic gastritis limited to the antrum and found at the re-examination in 1973-1976 had disappeared during the last follow-up period owing to regression of the antral or continuation of the body process. On the other hand, a considerable proportion of cases of diffuse antrofundal atrophic gastritis found in 1973-1976 appeared in 1983-1984 in the pure body atrophic gastritis group, obviously due to regression of the antral process. This indicates the existence of an alternative pathway via diffuse antrofundal atrophic gastritis for the development of atrophic gastritis limited to the body area. The occurrence of parietal cell antibodies was on the whole a poor indicator of the progression of atrophic gastritis. However, the development of the end-stage (severe) atrophic gastritis was significantly associated with their presence. Atrophic changes of the body mucosa were not found in 1983-1984 in any cases of duodenal ulcer disease, whereas in patients with gastric polyps atrophic gastritis affecting only the body was, as a rule, present. No case of gastric carcinoma was detected during the last follow-up examination.

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.

Decreased Incidences of Intestinal and Diffuse Types of Gastric Carcinoma in Finland during a 20-Year Period

The incidence of gastric carcinoma (GCA) has decreased throughout the world. This decrease is attributed to a decline in incidence of the intestinal type of GCA (IGCA), whereas the diffuse (DGCA) type of GCA is considered to be endemic in nature and more stable in incidence. In the present study we have estimated how much the incidences of IGCA and DGCA have decreased in percentage in Finland from 1952-61 to 1972-81. Our calculations are based on the Finnish Cancer Registry data of new GCA cases, on population statistics in Finland, and on the percentage distribution of GCA subtypes in three consecutive samples of GCA patients collected in the time periods 1952-61 (reference series) and 1972-81 (two separate samples: series A and B). The samples totaled 1837 GCA cases. We calculated that the incidence of IGCA had decreased from 1952-61 to 1972-81 by 62-71% (reference series versus series A - reference series versus series B) among men and by 69-70% among women. Correspondingly, the incidence of DGCA was calculated to have decreased by 30-39% among men and 37-42% among women. We conclude that not only has the incidence of IGCA decreased in percentage approximately twice as much as the incidence of DGCA but DGCA has also distinctly decreased in incidence in Finland from 1952-61 to 1972-81.

Progression of antral and body gastritis in patients with active and healed duodenal ulcer and duodenitis

The dynamics of the antral and body mucosa has been studied in biopsy specimens obtained during endoscopy of patients with duodenal ulcer (103 cases), patients with duodenal ulcer scars (108 cases), and patients with duodenitis (44 cases). A representative Finnish population sample consisting of 434 subjects was used as reference material. The antral mucosa of all patient series showed an increase in the severity and prevalence of gastritis similar to that of the general population, whereas virtually no progression of gastritis with age was seen in the body mucosa, which remained normal or at the stage of superficial gastritis up to geriatric age. In contrast, in the present controls and in all earlier population samples studied by us so far, there was a significant and steady increase in the severity and prevalence of body gastritis with age. It is concluded that the age behavior of the antral and body mucosa was in duodenal ulcer scars and duodenitis similar to that of patients with active duodenal ulcer. The persistence of normal conditions in the acid-secreting area may serve as one explanation of the strong tendency of the disease to recur. In addition, it is tentatively concluded that in duodenal ulcer disease there are factors that have a protecting influence on the body glands and which are abolished by antrectomy, according to our earlier studies.

Characteristics of Gastric Mucosa Which Precede Occurrence of Gastric Malignancy: Results of Long-Term Follow-up of Three Family Samples

The aim of the study was to evaluate what family characteristics and what morphological, functional and immunological changes of the gastric mucosa precede the development of gastric malignancy in a follow-up of 11-14 years. The material consisted of 301 first-degree relatives of gastric carcinoma patients, 183 relatives of pernicious anaemia patients, and of 358 control relatives of probands computer matched from the general population by age and sex for the carcinoma probands. All subjects were endoscopically examined in 1973-1976 and followed up to the end of 1987. According to cancer registry data, 11 cases of malignant gastric tumours (9 carcinomas, one carcinoid tumour and one anaplastic tumour with suspicion of Hodgkins disease) had been diagnosed during the follow-up: 6 belonged to gastric carcinoma, 2 to pernicious anaemia and 3 to control families. The occurrence of malignancy was significantly related to the presence of advanced gastritis with atrophy and of intestinal metaplasia before the start of the follow-up. In relatives with achlorhydria and low serum pepsinogen I levels the incidence of malignancy did not significantly differ from that in controls of similar age and sex distribution. The risk of getting malignancy was about four-fold in female members of gastric carcinoma and pernicious anaemia families but was not increased in control families. The risk was increased only in female members and concerned only gastric malignancy being the expected one or even lower than the expected in regard to malignancies of other location.

Increase of Serum Pepsinogen I with Age in Females with Normal Gastric Mucosa but not in Males, Possibly Due to Increase in Acid-Pepsin Secreting Area

The mean pepsinogen I (PG I) level in a Finnish family sample was different in males and females and the difference was statistically significant. After exclusion of subjects with gastritis there remained 67 females and 68 males with morphologically completely normal antral and corpus mucosa. In females there was a significant increase of PG I with advancing age, the regression coefficient being 0.37 and statistically significant (p less than 0.01). In males no such increase was found, and individual cases revealed an almost random distribution with age. A similar increase with age has been noted in gastric acid output in females but not in males. Assuming that there is a linear relationship between PG I levels and the total chief cell mass, the PG I level would be determined by three main variables: thickness of the glandular layer, density of chief cells, and area occupied by chief cells. Of these variables the thickness and chief cell density showed neither in females nor in males any statistically significant increase with age, leaving the area as the variable which would account for the increase of PG I.

Enrichment of Combined Antral and Corpus Atrophic Gastritis (“Combined AG”) in Sibs of Gastric Carcinoma Patients

The occurrence of different combinations of antral and corpus atrophic gastritis (AG) was studied in 127 sibs and 159 children of 73 gastric carcinoma patients. Seventy-three control probands, age- and sex-matched for the carcinoma probands, and their 379 first-degree relatives were used as controls. Sibs of gastric carcinoma patients revealed a significant enrichment of AG affecting simultaneously both antrum and corpus (combined AG), while no such enrichment could be demonstrated in children, who behaved on the whole similarly to the controls. In addition, sibs of gastric carcinoma patients showed a significant aggregation of combined AG also when compared with children of similar age. This suggests that genetic factors in addition to environmental ones participate in the accumulation of combined AG in sibs. The lack of phenotype AB in children excludes the possibility of dominant Mendelian inheritance, but leaves the possibility of a recessive autosomal or multigenetic inheritance. The enrichment of combined AG in sibs of gastric carcinoma patients could be one of the factors involved in the increased liability of close relatives of gastric carcinoma patients to contract gastric malignancy.

Hypersecretion of Gastric Acid in a Representative Finnish Family Sample

To evaluate the family behaviour of acid secretion and particularly of hypersecretion, we have examined by pentagastrin test and direct vision gastric biopsy 342 subjects with a normal mucosa or superficial gastritis of the body mucosa, collected from a large family sample of the Finnish population. Acid output (AO) was expressed in terms of fat-free body weight (FFB), which eliminates the sex factor found by other expressions of AO. Subjects with values above 1.0 mmol/h/FFB were considered hypersecretors (14 subjects, or 4% of the whole sample). They differed from the whole sample with regard to a high prevalence of signs of duodenal ulcer disease, of high serum pepsinogen, and of blood group O and lack of gastric antibodies and of high serum gastrin levels. The Fisher distribution test showed a significant family aggregation of AO values. In addition, at low AO levels there were subgroups with distinct gaps between them. This finding suggests the effect of genetic variation rather than of a common family environment. The occurrence of higher AO values in sibs but not in children of hypersecretors seems to rule out the possibility of a dominant Mendelian inheritance. These present results are considered to be best compatible with a multigenetic mode of inheritance of gastric hypersecretion.