This study was designed and carried out according to the updated Declaration of Helsinki, in a group of 169 dyspeptic patients (58 males, 111 females; mean age: 66.44 ± 10.22 years) with atrophic gastritis who were diagnosed by endoscopy and the Kimura-Takemoto visual endoscopic classification system. This work was performed in accordance with the Declaration of Helsinki (2000) of the World Medical Association. This study also received approval by the Ethical Committee of North Caucasian State Academy (Minutes No. 14/20 dated 29.06.2020). All patients provided informed written consent to the examination. Any patients who had been treated with proton pump inhibitors, H2 antagonists and nonsteroidal anti-inflammatory drugs (commonly known as NSAIDs) at least one month before the study were excluded. Assessment of the type of mucosal atrophy, according to Kimura-Takemoto’s grading (i.e., visual endoscopic classification), was as follows: C-0, absence of atrophy; C-1, atrophy exclusively in the antrum; C-2, border of atrophy on the lesser curvature in the lower third of the gastric corpus; C-3, border of atrophy on the lesser curvature in the middle third of the gastric corpus; O-1, boundary between the lesser curvature and the anterior wall of the gastric corpus; O-2, border of atrophy within the anterior wall of the gastric corpus; and O-3, boundary between the posterior wall of the gastric corpus and large curvature. Biopsies were taken in addition to the visual assessment of atrophic gastritis and comprised six samples subsequently assessed by Kimura-Takemoto grading (C1, C2, C3, O1, O2, O3)[18,19].

Biopsy specimens were fixed in 10% formalin, embedded in paraffin, cut into sequential 5-μm sections, and stained with hematoxylin and eosin, PAS/alcian blue (pH = 2.5), and Giemsa stain. The grade of stomach mucosal atrophy was estimated from mild to severe, according to the Houston visual analogous scale[20]. In total, 169 persons underwent serological noninvasive screening for atrophic gastritis. The GastroPanel^® (Biohit Plc, Helsinki, Finland) assay kit was used to identify parameters of postprandial G17 and pepsinogen-1 (PG1) in the fasting state. The levels of serological markers of mucosal atrophy (mild, moderate, and severe) were assessed according to levels of G17 in the antrum (mild, from 7 to 10 pmol/L; moderate, from 4 to 7 pmol/L; severe, from 0 to 4 pmol/L) and PG1 in the corpus (mild, from 15 to 25 μg/L; moderate, from 9 to 15 μg/L; severe, from 0 to 9 μg/L)[21].

In accordance with the purpose and objectives of the study, sensitivity indicators were used to perform comparative evaluations. For analyses of the various groups of mild, moderate and severe atrophy of atrophic gastritis, the percentage of each group among the total population was used. The threshold value of P ≤ 0.05 was set as statistical significance. Given these criteria, differences were identified among patients groups. To assess the relationship between the groups, we applied the nonparametric Spearman correlation coefficient.

Stomach corpus mucosa biopsy specimens were subjected to histological analysis, with each designated as С2, С3, О1, О2, or О3. Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. Four patients did not show histological evidence of atrophy in any biopsy specimen. One hundred and twenty-one patients had at least one of their five biopsy specimens show severe histological mucosal atrophy. The serological markers of gastric corpus mucosal atrophy have known limitations for assessment because the area of the corpus of the stomach is greater than the area of the antrum. The histological atrophy of the gastric corpus was evaluated in five biopsies (C2, C3, O1, O2, O3) of the Kimura-Takemoto classification and was considered as the reference standard for comparison with serological markers. The severity of histological atrophy in every biopsy was evaluated in four grades, namely no atrophy and mild, moderate or severe atrophy. The findings were compared with patient-correspondent PG1 serum levels. The correlation coefficient was determined between the severity of histological atrophy and the serum levels of PG1 (Table 1).

No strong negative correlation has been observed between the severity of histological atrophy in biopsy specimens of the gastric corpus and serological marker PG1 level. This underlies a low eligibility of the serological marker PG1 in the assessment of the severity of gastric corpus atrophy. Thus, statistical comparison of the serological marker PG1 of atrophy in the gastric corpus using the morphological standard according to the Kimura-Takemoto classification (five biopsies from the gastric corpus) is much more correct than using the updated Sydney system (two biopsies from the gastric corpus). This can explain the low level of correlation of severity of mucosal atrophy between PG1 and the histological standard of five biopsies of the gastric corpus (C2, C3, O1, O2, O3 according to the Kimura-Takemoto classification). We, thereafter, evaluated the serological marker of atrophy, G17, to detect the severity of mucosal atrophy of the gastric corpus based on a comparison with the histological standard of five biopsies according to the Kimura-Takemoto classification. Table 2 presents the data on PG1 and G17.

PG1 detection yielded 84.3% false-negative results upon comparison with the Kimura-Takemoto histological standard. G17, in contrast, yielded only 6.6% false-negative results. In the previous part of the study, we had analyzed the comparison of serological markers with histological multifocal severe atrophic gastritis of the gastric corpus in five biopsy specimens (C2, C3, O1, O2, O3). Next, we analyzed comparisons of serological markers with histological monofocal severe atrophic gastritis of the gastric corpus. Results of that analysis are presented in Table 3.

If severe histological mucosal atrophy was present in only one of five biopsy specimens (C2, C3, O1, O2, O3), then it was considered as monofocal atrophic gastritis of the gastric corpus. We have always rated such gastritis as severe corpus atrophic gastritis because it has a high risk of gastric cancer[22]. The postprandial G17 serological marker was used to detect monofocal severe atrophic gastritis of the gastric corpus. Analysis of these results is presented in Table 4. Receiver-operating characteristic - analysis for multifocal atrophic gastritis is shown in Figure 1.

Open in New Tab   Full Size Figure   Download Figure

Figure 1 Receiver-operating characteristic - analysis of serological marker (gastrin-17 from 0 to 10 pmol/L) for severe multifocal atrophic gastritis. TPR: True positive rate; FPR: False positive rate; AUC: Area under the receiver-operating characteristic curve.

Postprandial G17 is the best marker of severe monofocal corpus atrophic gastritis, indicating such in the range of 0-10 pmol/L. It has a sensitivity of 100%, supported by the complete absence of false-negative results. When the range of 0-4 pmol/L was considered, however, the sensitivity dropped to 62.2%. We did not find a strong correlation between severe intestinal metaplasia and severe dysplasia using the Kimura-Takemoto histological classification (correlation coefficient = 0.53; P > 0.05) (Table 5).

History of present illness: A 63–year–old man in 2017 underwent serological screening by means of a laboratory test panel “Gastropanel” with a preventive purpose for early detection of precancerous pathology of the stomach. The patient had no complaints.

Personal and family history: The patient’s father died of pancreatic cancer in 2014 at the age of 85. The patient’s mother died of breast cancer in 2013 at the age of 85.

Results of serological screening in 2017: Testing for anti-H. pylori immunoglobulin G (IgG): Positive, G17 postprandial: 7.2 pmol/L, PG1: 90 mkg/L. The results for anti-H. pylori IgG: Positive and G17 postprandial: 7.2 pmol/L were considered as H. pylori-associated, antrum-atrophic gastritis mild according to serological criteria by Kotelevets and Chekh[23]. Additional studies were prescribed.

Physical examination: On physical examination, the vital signs were as follows: Body mass index, 22.5; body temperature, 36.3 °C; blood pressure, 120/78 mmHg; heart rate, 62 beats per min; respiratory rate, 12 breaths per min; the abdomen is soft and painless.

Laboratory examinations: Antibodies to gastric parietal cells: Negative, vitamin B12: 227 pg/mL.

Esophagogastroduodenoscopy: Endoscopic symptoms of diffuse atrophic gastritis. Biopsy and morphological examination in accordance with the Sydney system are presented in Tables 6 and 7.

Final diagnosis:H. pylori-associated, multifocal atrophic gastritis mild.

Treatment: 14 - daily quadruple therapy: (1) Omeprazole 20 mg twice a day; (2) Bismuth tripotassium dicitrate (de-nol) 240 mg twice a day; (3) Tetracycline 500 mg four times a day; (4) Metronidazole 500 mg twice a day; and (5) Probiotic. After the eradication treatment, the gastroprotection was appointed: De-nol 240 mg twice a day in two weeks; after de-nol sucralfate 1 g three times a day for a month; after sucralfate taking medication plantaglucid (Plantago major) 1 g three times a day for a 6 month.

Outcome and follow-up: A year after serological screening and diagnostic procedures, the following examinations were repeated: Esophagogastroduodenoscopy with biopsy in accordance with the Sydney System and histological examination of biopsies with an assessment on a visual analog scale; G17 postprandial; three tests for H. pylori (anti-H. pylori IgG, C13 urease breath test, histological test).

Summary for 2018: As a result of anti-H. pylori therapy, effective eradication of H. pylori was obtained, which was confirmed by three tests (anti-H. pylori IgG, C13 urease breath test, histological test). The dynamics of multifocal atrophy of the gastric mucosa was absent after effective eradication and cytoprotective therapy. The results are presented in Tables 6 and 7.

After a dynamic examination in 2018, patient underwent gastrocytoprotective treatment with Rebagit (PRO.MED.CS Praha, a.s.) at a dose of 100 mg three times a day for four months. A year after the start of this treatment, a control annual examination was performed: Esophagogastroduodenoscopy with biopsy in accordance with the Sydney system and histological examination of biopsies with an assessment on a visual analog scale; G17 postprandial; three tests for H. pylori (anti-H. pylori IgG, C13 urease breath test, histological test). The results are presented in Tables 6 and 7.

Summary for 2019: The dynamics of multifocal atrophy of the gastric mucosa was absent after the four-month gastrocytoprotective therapy with Rebagit (PRO.MED.CS Praha, a.s.). After a dynamic examination in 2019, patient was started prolonged courses of atrophic gastritis replacement therapy with rennet received from baby calves and lambs. This therapy is similar to Abomin therapy, which the authors published in 2020[8]. The course of treatment continued for five months.

Summary for 2020-2023: Morphological dynamics of multifocal atrophy of the gastric mucosa was absent after five months of rennet replacement therapy. There is a pronounced positive long–term dynamics of the serological marker of atrophy – postprandial G17, after five months of rennet replacement therapy (Table 6). Normalization of the production of postprandial G17 indicates the restoration of the function of G-cells of the gastric antrum. Postprandial G17 is an earlier marker of regression of atrophic gastritis than morphological examination of gastric biopsy according to the Sydney system.