Clinical and morphofunctional characteristics of the gastrointestinal zone in atrophic gastritis and gastric adenocarcinoma

The dissertation is devoted to the study of the clinical, morphological and functional features of the gastrointestinal zone in patients with atrophic gastritis and gastric adenocarcinoma. The work was carried out on the material of examination of several patient groups, including patients with primary gastric adenocarcinoma, patients with a three-year recurrence-free postoperative course of the disease, patients with atrophic gastritis, and practically healthy individuals who formed the control group. Clinical and laboratory, enzyme immunoassay, radioimmunoassay and histochemical methods of investigation were applied, along with methods of mathematical statistics.

Particular attention is given to the analysis of the level of blood biogenic amines (serotonin and neurotensin), the state of Helicobacter pylori infection of the gastric mucosa, including that of the gastric stump after surgical treatment, and the morphofunctional activity of APUD cells and mast cells of the gastrointestinal zone. The results obtained are aimed at improving the diagnosis of precancerous diseases and early stages of gastric cancer, as well as at assessing the risk of postoperative recurrence of adenocarcinoma.

The annual incidence of gastric carcinoma in Russia remains high: on average, more than 25,917 people [6; 124]. At the same time, in most developed countries of Europe and the United States by the end of the twentieth century a downward trend in gastric cancer incidence has been recorded: from 20 cases per 100,000 population in the early 1930s to 5 per 100,000 at present [124; 127; 130; 163].

It should also be emphasized that gastric carcinoma in Russia affects, in a significant percentage of cases, patients of working age [6; 43; 81].

Given the late diagnosis of gastric carcinoma, mortality from this disease also remains high. The ratio of those who died to those who fell ill with gastric adenocarcinoma in such a large industrial center as Yekaterinburg remains high, amounting to 68.25% [15].

Until now, the diagnosis and treatment of patients with gastric adenocarcinoma, both in the pre- and postoperative periods, have been carried out predominantly by oncological surgeons [8; 15; 18; 38; 39]. At the same time, the low effectiveness of the work of physicians of therapeutic specialties in the early diagnosis of gastric cancer is noted. This is evidenced by the fact that 96% of patients with advanced gastric cancer, prior to verification of the diagnosis by an oncologist, repeatedly sought help from district therapists and gastroenterologists.

The continuing aging of the Russian population should also be noted, which in itself may lead to an increase in the oncological morbidity.

Therefore, the involvement of therapists in the search for additional criteria for early cancer and its postoperative recurrence appears to be an important factor in organizing effective prevention and detection of early forms of this disease.

The solution to the problem of successful treatment of gastric adenocarcinoma and the associated increase in the life expectancy of patients in this category is undoubtedly related to the identification of risk factors, prevention and timely diagnosis of early stages of the disease.

The age structure of the population, the character and manifestations of many non-neoplastic gastric diseases (primarily due to changes in modern medicinal preparations) that have changed in recent decades require the study of the manifestations of "today's" gastric cancer.

In this regard, the search for new diagnostic criteria, both for precancerous diseases and conditions, primarily atrophic gastritis, and for early stages of gastric cancer, is of scientific and practical interest.

At present, much is known about the risk factors, precancerous diseases and conditions of the gastric mucosa. Thus, the role of Helicobacter pylori infection [10; 155; 185]; multifocal chronic gastritis [19; 45]; genetically determined disturbance of the regulation of proliferative processes of the gastric mucosa [31; 55] in the development of primary gastric adenocarcinoma has been studied in sufficient detail. However, the issue of Helicobacter pylori infection of the gastric stump after surgical treatment of the disease remains insufficiently studied.

There are extremely few data in the literature on the role of the gastroenteropancreatic endocrine system in the implementation of the oncological process.

The gastroenteropancreatic endocrine system, represented by APUD cells (cells performing the uptake, decarboxylation and secretion of biogenic amine precursors) and mast cells, largely determines the morphofunctional state of the mucosa of the gastrointestinal zone, and the majority of gastrointestinal hormones are biogenic amines [48; 177; 180; 184].

The few publications available in the literature, mainly of an experimental character, indicate the involvement of the APUD system of the gastrointestinal zone in the pathological process in adenocarcinomas of the gastrointestinal tract [195; 203].

Given the significance of biogenic amines produced by the endocrine system of the gastrointestinal zone in motor and trophic changes of the stomach, an investigation of the levels of serotoninemia and neurotensinemia in patients with gastric adenocarcinoma in the pre- and postoperative periods, as well as in multifocal atrophic gastritis (as a precancerous disease), would evidently expand the possibilities for diagnosing early forms of gastric cancer and its postoperative recurrence.

Thus, the medico-social and scientific relevance of the work is determined by the following:

1. High incidence, late diagnosis, and, as a consequence, the preservation of high morbidity and mortality from gastric cancer in Russia and, in particular, in Yekaterinburg.

2. The presence of a large contingent of patients with atrophic gastritis, which is a precancerous disease requiring dynamic follow-up, primarily by therapists and gastroenterologists, for the purpose of prevention and diagnosis of early stages of gastric cancer.

3. The lack of analysis of Helicobacter pylori infection (as a known risk factor for the development of adenocarcinoma) of the gastric stump after surgical treatment of the disease.

4. An insufficiently complete understanding of the participation of gastrointestinal hormones in the development of gastrointestinal and extra-abdominal manifestations of gastric adenocarcinoma.

5. Insufficient understanding of the morphofunctional state of the endocrino-paracrine system of the gastrointestinal zone and its role in the oncogenesis of patients with gastric adenocarcinoma.

Based on the above, the aim of the present work was: the improvement of diagnosis of precancerous diseases and gastric cancer through the identification of patterns of clinical manifestations of the disease, the level of blood biogenic amines and the morphofunctional state of the gastrointestinal zone.

Achievement of this aim required the solution of the following tasks:

1. To study the clinical manifestations of "modern" gastric cancer.

2. To analyze the level of blood biogenic amines (serotonin and neurotensin) in patients with gastric adenocarcinoma, with a three-year recurrence-free postoperative course of the disease, and in atrophic gastritis as a precancerous disease.

3. To investigate the correlation between the clinical manifestations of gastric adenocarcinoma and the level of blood biogenic amines in the studied groups of patients.

4. To evaluate the inflammatory and atrophic changes in the gastrointestinal zone in patients with gastric adenocarcinoma.

5. To study the features of Helicobacter pylori infection of the gastrointestinal zone not only in patients with primary gastric adenocarcinoma, but also in the gastric stump after surgical treatment of the disease.

6. To carry out a morphofunctional analysis of gastroenteropancreatic endocrine cells (ECn-, ECL- and F-mast cells) in patients with gastric adenocarcinoma, with a three-year recurrence-free postoperative course of the disease, and with atrophic gastritis.

Scientific novelty of the research:

- For the first time, a comparative analysis of the levels of serotoninemia and neurotensinemia was performed in patients with gastric adenocarcinoma, with a three-year recurrence-free course of the disease, and in atrophic gastritis, which made it possible to reveal a significant increase in the levels of blood biogenic amines in patients with gastric adenocarcinoma.

The correlations between the clinical manifestations of adenocarcinoma, atrophic gastritis and the level of blood biogenic amines (serotonin and neurotensin) have been refined.

A detailed characterization of Helicobacter pylori infection of the gastrointestinal zone in patients with gastric adenocarcinoma has been provided not only before, but also after surgical treatment.

The morphofunctional activity of APUD cells and mast cells of the gastrointestinal zone in patients with gastric adenocarcinoma, with a three-year recurrence-free course of the disease, and with a precancerous disease (atrophic gastritis), has been analyzed.

The practical significance of the work is determined by the fact that: the diagnostic criteria for the precancerous disease (atrophic gastritis) and gastric cancer have been refined and supplemented; the role of blood biogenic amines (serotonin and neurotensin) in the realization of certain clinical manifestations of gastric adenocarcinoma and atrophic gastritis has been clarified; the necessity of investigating gastric mucosal biopsy specimens for Helicobacter pylori infection has been shown not only in patients with active gastritis, but also in patients with gastric adenocarcinoma both before and after surgery; the morphofunctional criteria of the state of APUD cells and mast cells in gastric adenocarcinoma and precancerous disease (atrophic gastritis) have been studied, which on the whole will expand the diagnostic algorithm for these diseases.

The reliability of the obtained results is ensured by the execution of the work on a sufficiently large material (45 patients with gastric adenocarcinoma; 35 patients with a three-year recurrence-free course of the disease; 40 patients with atrophic gastritis; 37 practically healthy individuals, as a control group); as well as by the use of modern methods of enzyme immunoassay and radioimmunoassay of biogenic amines (serotonin, neurotensin in the blood), histochemical methods of investigation of gastroenteropancreatic endocrine cells, and the application of reliable methods of mathematical statistics.

Main propositions of the dissertation submitted for defense:

1. The severity of gastrointestinal and extra-abdominal clinical symptoms in gastric adenocarcinoma and atrophic gastritis is interrelated with the level of biogenic amines in the blood (in particular, serotonin).

2. The high level of Helicobacter pylori colonization of the gastric mucosa in patients with adenocarcinoma significantly exceeds that in HP-associated gastritis, which confirms the role of HP in oncogenesis at this tumor localization.

3. Significant Helicobacter pylori colonization of the gastric stump (the absence of reliable differences in the score characteristics of Helicobacter pylori infection before surgery and in the mucosa of the gastric stump) should be considered as a factor preserving the risk of developing postoperative recurrence of adenocarcinoma.

4. Gastric adenocarcinoma is characterized by increased morphofunctional activity of gastroenteropancreatic endocrine cells (APUD cells and mast cells), which is preserved even after radical surgical treatment with a three-year recurrence-free course of the disease.

5. The level of blood biogenic amines and the morphofunctional changes in APUD cells of the gastrointestinal zone can serve as one of the diagnostic criteria of the precancerous disease (atrophic gastritis) and the risk of postoperative recurrence of gastric adenocarcinoma.

Implementation of the results into practice:

The results of the work have been implemented into the practice of the Gastroenterological Department of City Clinical Hospital No. 40 in Yekaterinburg and of the Regional Oncological Dispensary of Yekaterinburg.

Approbation of the work: the results of the work were presented in the materials of the 6th and 7th Russian Gastroenterological Week and of the All-Russian Congress of Oncologists with international participation in 2000.

- Publications: the main propositions of the dissertation are presented in 6 publications, including 3 in central press.

Structure and scope of the work: the content of the work is set out on pages of computer typescript and consists of an introduction, a review of the literature, a chapter on materials and methods of the study, two chapters of original research, a conclusion, conclusions, practical recommendations, and a bibliography comprising 206 sources, including 125 domestic and 81 foreign authors.

The work is illustrated with 32 figures (including 12 photographs of histological sections), 13 tables; two case histories are presented.

The work was carried out at the Departments of Internal Diseases No. 1 (Head of the Department — Corresponding Member of the RANS, Professor P. A. Sarapultsev), Oncology (Head of the Department — Professor S. A. Berzin), and the Central Research Laboratory (Head — Professor G. Ya. Lipatov) of the State Educational Institution of Higher Professional Education "Ural State Medical Academy of the Ministry of Health of the Russian Federation" (Rector — Corresponding Member of the RAMS, Professor A. P. Yastrebov).

Clinical investigations were conducted on the basis of the departments of the Municipal Institution "City Clinical Hospital No. 40" in Yekaterinburg (Chief Physician — Doctor of Medical Sciences F. I. B adaev) and of the Regional Oncological Dispensary (Chief Physician — Candidate of Medical Sciences V. B. Shamansky).

Enzyme immunoassay and radioimmunological investigations were carried out on the basis of the City Center for Laboratory Diagnostics of Maternal and Child Diseases of Yekaterinburg (Head — Professor Ya. B. Beykin).

Analysis of histological sections was performed in the Morphological Department of the Central Research Laboratory of the USMA (Head — Candidate of Medical Sciences S. Yu. Medvedeva).