Clinical and morphological characteristics of functional dyspepsia in the conditions of the North

The dissertation is devoted to the study of the clinical and morphological features of the functional dyspepsia syndrome in residents of the Republic of Sakha (Yakutia). The work is based on a comprehensive examination of indigenous and non-indigenous inhabitants of the region using clinical, endoscopic, and histological methods, as well as on the diagnosis of Helicobacter pylori infection and 24-hour monitoring of intragastric acidity. Particular attention is paid to comparing clinical variants of dyspepsia with morphological changes in the gastric mucosa and the state of gastric acid production. The study aims to substantiate a differentiated approach to prescribing anti-Helicobacter and antisecretory therapy in the conditions of the North, where the prevalence of dyspeptic disorders and chronic gastritis has regional characteristics. The results obtained expand the understanding of the role of H. pylori in the pathogenesis of functional dyspepsia and are of importance for the prevention of precancerous conditions of the stomach in the population of Yakutia.

Relevance of the study. One of the pressing problems of modern medicine is the problem of functional diseases of the gastrointestinal tract. The interest in functional dyspepsia (FD) that has increased in recent years is due primarily to the fact that this pathology, along with other functional disorders of the digestive organs, causes considerable economic damage to society, occupying the second place in the list of the main causes of temporary disability after acute respiratory infections [16; 18; 23; 25]. The frequency of dyspepsia syndrome in the population amounts to 30-40%, reaching 60% and higher in some countries. Gastroenterological complaints account for 4-5% of all cases of patients' visits to general practitioners. At the same time, organic dyspepsia accounts for only 35-40% of all cases of this syndrome, and functional dyspepsia accounts for 50-60% [25, 27].

In accordance with the recommendations of the consensus meeting of the International Working Group for the Improvement of Diagnostic Criteria for Functional Diseases of the Gastrointestinal Tract (Rome III Criteria, 2006), dyspepsia syndrome is defined as a disease characterized by unpleasant sensations (pain, burning, bloating, a feeling of fullness after eating, a feeling of early satiety) localized in the epigastric region, in which it is impossible to identify any organic or metabolic changes capable of causing the indicated symptoms [127; 128].

At the same time, despite the prevalence and relative extent of study of this disease, the lack of effective care for patients with functional dyspepsia leads to a protracted course and recurrence of the disease and increases resistance to therapy, which is often associated with the absence of a combined approach to treatment using all available pharmacological and non-pharmacological (including psychotherapeutic) methods.

Talley et al. (1999) showed that patients with the functional dyspepsia syndrome often present with chronic antral gastritis associated with H. pylori, which, owing to its prevalence and pathogenetic association with peptic ulcer disease and gastric cancer, constitutes an important medico-social problem [16; 24; 209].

The presence of dissociation between the morphological manifestations of gastritis and the clinical picture dictates the need to distinguish chronic gastritis with dyspepsia syndrome. The impossibility of extrapolating any clinical variant of dyspepsia syndrome to a uniform morphological picture of mixed gastritis makes the problem of pathogenetic substantiation of particular symptoms of dyspepsia urgent without frequent endoscopic examinations with biopsy of the antral and fundic parts of the stomach. The presence of signs of recurrent dyspepsia in practically healthy individuals or in patients with chronic gastritis in the phase of stable morphological remission requires a differentiated approach to performing endoscopic and morphological studies [3; 6; 207].

Despite the large number of studies devoted to the problem of dyspepsia, there is no unambiguous opinion on the causes and mechanisms of the onset of clinical symptoms in chronic gastritis, and a number of aspects of this disease remain poorly studied or not studied at all [162]. In particular, the question of the role of H. pylori in the pathogenesis of the functional dyspepsia syndrome remains unresolved [16; 83; 95; 98].

It is known that the data given in the literature on the frequency of particular symptoms of dyspepsia are usually presented without taking into account such a factor as whether patients are admitted to a hospital for examination and treatment or are examined and treated on an outpatient basis; such an important factor as the region in which particular patients reside is also not taken into account: the frequency of dyspepsia symptoms in different regions may vary. Of certain scientific and practical interest is also the determination of the frequency of clinical manifestations of functional dyspepsia in patients hospitalized in the gastroenterological department, as well as the frequency of the combination of chronic gastritis (including Helicobacter-associated gastritis) with functional dyspepsia. Thus, many issues related to the study of functional dyspepsia in the conditions of the Republic of Sakha (Yakutia) remain unresolved, which gives grounds to consider their study relevant.

At present, prokinetics or H2-blockers of histamine receptors are used in the treatment of patients with functional dyspepsia, and only isolated studies are devoted to the use of omeprazole and rabeprazole in the treatment of patients with functional dyspepsia. However, the results of treatment of patients, in the opinion of some researchers, are unpredictable. Apparently, the variant of clinical symptoms of functional dyspepsia is not always taken into account.

The problem of functional dyspepsia in the conditions of the North has been insufficiently studied; there are only isolated scientific studies by V.T. Androsov [1984], A.A. Bezrodnykh et al. [1986], and S.S. Sosina [1992] on chronic gastritis.

Aim of the study: to investigate the features of the clinical and morphological picture of the functional dyspepsia syndrome in indigenous and non-indigenous residents of the Republic of Sakha (Yakutia), as well as to evaluate the effectiveness of treatment depending on gastric acid production and the persistence of H. pylori.

Objectives of the study:

1. To identify distinctive features of the course of clinical variants of the functional dyspepsia syndrome in indigenous and non-indigenous residents of Yakutia.

2. To study the clinical, endoscopic, and morphological features of the course of various variants of the functional dyspepsia syndrome depending on the persistence of H. pylori.

3. To study the features of acid production by means of intragastric pH-metry in patients with the functional dyspepsia syndrome.

4. To evaluate the effectiveness of the use of medicinal preparations of various pharmacological groups in the treatment of the functional dyspepsia syndrome.

Scientific novelty. For the first time in the Republic of Sakha (Yakutia), a comprehensive examination of patients with various clinical variants of the functional dyspepsia syndrome was carried out, including a detailed description of the forms of the disease and a study of gastric secretion by means of 24-hour intragastric pH-metry. A morphological study of the gastric mucosa was performed with an assessment of the degree of its infection with H. pylori. It was established that indigenous residents with functional dyspepsia exhibited signs of chronic gastritis with intestinal metaplasia of the gastric mucosa.

Practical significance. The indications for the use of anti-Helicobacter and antisecretory drugs have been refined for the purpose of adequate treatment of patients with functional dyspepsia, and the high effectiveness of their use has been demonstrated. It has been established that eradication of H. pylori in most cases contributes to the relief of symptoms in various clinical variants of functional dyspepsia.

The results of the work confirmed the validity of distinguishing two main clinical variants of the functional dyspepsia syndrome depending on the predominance of the leading clinical symptom. The necessity of evaluating the morphological examination of the gastric mucosa for the prevention of precancerous conditions and of the individual characteristics of 24-hour gastric acid production when prescribing anti-Helicobacter and antisecretory drugs in the combined treatment of functional dyspepsia has been demonstrated.

Main propositions submitted for defense:

1. For the purpose of verifying the diagnosis of functional dyspepsia, patients require an in-depth examination to exclude precancerous conditions of the gastrointestinal tract.

2. The clinical picture of chronic gastritis with the functional dyspepsia syndrome is associated with the microbial expansion of Helicobacter pylori, which promotes the development of atrophy and intestinal metaplasia of the gastric mucosa in indigenous residents.

3. Individualization of treatment and the use of modern anti-Helicobacter and antisecretory drugs leads to a more rapid relief of the symptoms of functional dyspepsia and is able to arrest the further progression of atrophy and intestinal metaplasia of the gastric mucosa, which reduces the risk of gastric cancer in residents of Yakutia.

Implementation. The results of the study and the developed practical recommendations have been implemented in the diagnostic and therapeutic work of the gastroenterological department of the Municipal Institution "Yakutsk City Clinical Hospital" (GE of YaGKB), and are also used in the teaching materials of lectures and practical classes at the therapeutic departments of the Medical Institute of M.K. Ammosov Yakutsk State University.

Approbation of the work. The main propositions of the dissertation were reported and discussed at a joint meeting of the Department of Propaedeutics of Internal Diseases, Faculty and Hospital Therapy of the MI of YaSU and specialists of Yakutsk City Clinical Hospital No. 1; the interregional scientific and practical conference "Molecular and Cellular Aspects of Human Pathology in the North" (Yakutsk, 2007); the scientific and practical conference dedicated to the 165th anniversary of Yakutsk City Clinical Hospital No. 1 (Yakutsk, 2008); the All-Russian scientific and practical conference with international participation "International Polar Year: Achievements and Prospects for the Development of Circumpolar Medicine" (Arkhangelsk, 2009); the jubilee gastroenterological scientific and practical conference of Yakutsk City Clinical Hospital No. 1 (Yakutsk, 2009); and the Fifteenth Russian Gastroenterology Week (Moscow, 2009).

Publications. Ten papers have been published on the topic of the dissertation, of which 3 are in journals included in the list of the Higher Attestation Commission.

Scope and structure of the dissertation. The dissertation is set out on 114 pages of typewritten text; it is illustrated with 20 tables and 5 figures and consists of an introduction, four chapters, a conclusion, conclusions, practical recommendations, and a bibliographic reference list comprising 223 sources, including 103 works by domestic and 120 by foreign authors.