Correction of Morphofunctional Disorders of the Stomach and Duodenum in Chronic Biliary-Dependent Pancreatitis

The dissertation is devoted to the study of morphofunctional disorders of the stomach and duodenum in patients with chronic biliary-dependent pancreatitis and to the development of approaches for their correction. The work examines the issues of combined pathology of the organs of the gastroduodenal zone in chronic pancreatitis associated with diseases of the biliary tract. The study analyzes the clinical and morphological manifestations of lesions of the stomach and duodenum, the state of local immunity, and the features of the microbiocenosis of the small intestine using the hydrogen breath test and the gas-liquid chromatography method for short-chain fatty acids. Algorithms for diagnosis and therapy schemes are proposed, including antibacterial agents and local use of the immunomodulator tactivin, aimed at normalizing the immune response and eliminating secondary immune deficiency in this category of patients.

Relevance:

Chronic pancreatitis (CP) is one of the pressing problems of modern gastroenterology. The close attention of researchers to the problem of CP is due to its high prevalence. In the United States, the detection rate of chronic pancreatitis is 10 per 100,000 population. The prevalence of CP in Europe is 25 cases per 100,000 population (Khazanov A.I., 1997).

In Russia, over the past 30–40 years, a twofold increase in the number of patients with CP has been recorded (Khazanov A.I., 1999; Vasil'ev A.Yu., Maev I.V., Dibirov M.D., 2005, et al.). Annually, 8–9 new cases per 100,000 population are detected. According to Postnikova T.N. (1989) and Kashkina E.I. (2000), CP accounts for 5.1% to 9% of patients with gastroenterological pathology, and the prevalence of CP is 26–50 cases per 100,000 population.

All types of CP are characterized by an unfavorable, progressive course, as evidenced by high mortality, reaching 20% within 10 years from the onset of the disease. Among patients with CP, early complications develop in 30% of cases (purulent-septic complications, bleeding from ulcerations of the gastroduodenal zone mucosa, thrombosis in the portal vein system, stenosis of the common bile duct, etc.). With the further progression of CP, especially with ineffective treatment, functional insufficiency of the pancreas (P) develops (Protsenko S.I., 2001). A twenty-year history of the disease increases the risk of pancreatic cancer by 5 times.

The listed pessimistic trends are associated with the growth of alcoholism, diseases of the biliary tract, and pathology of the gastroduodenal zone (GDZ). The development of CP is facilitated by nutritional disorders, the use of pancreatotoxic medications, hyperlipidemia, and other endo- and exogenous factors (Lopatkina T.N., 1997; Balashov V.I., 2001).

Despite a fairly large number of studies devoted to the analysis of the causes of CP formation, it has not yet been determined to what extent the presence of one factor or another, or their combination, influences the timing of development, the character, and the duration of the course of CP. The least studied issues in the problem of CP are those of combined pathology of the digestive organs. The close anatomical and physiological interrelation and joint participation in the digestive process of the pancreas, stomach, and duodenum indicates the involvement of the latter in the pathological process in patients with CP.

In this regard, the study of the state and clinical course of pathological processes in the GDZ, as well as the assessment of local immunity and microbiocenosis in patients with chronic biliary-dependent pancreatitis (CBP), is currently relevant.

Objective of the study: To improve the results of treatment of patients with chronic biliary-dependent pancreatitis and concomitant pathology of the gastroduodenal zone by correcting morphofunctional disorders of the stomach and duodenum.

Tasks of the study:

1. To determine morphological changes in the gastric mucosa, as well as the intensity of the local immune response in patients with chronic biliary-dependent pancreatitis.

2. To identify the degree of bacterial colonization of the small intestine in patients with chronic biliary-dependent pancreatitis using the hydrogen breath test.

3. To study the state of microbiocenosis by determining the concentration of short-chain fatty acids in the duodenal contents in patients with chronic biliary-dependent pancreatitis.

4. To evaluate the effectiveness of local use of the immunomodulator tactivin in patients with chronic biliary-dependent pancreatitis combined with pathology of the stomach and duodenum. Scientific novelty:

In this work, for the first time, the features of clinical and morphological manifestations of pathology of the stomach and duodenum in patients with chronic biliary-dependent pancreatitis have been studied in detail. Qualitative and quantitative changes in the gastric mucosa in chronic biliary-dependent pancreatitis are shown.

For the first time, with the help of the hydrogen breath test, an assessment was made of the degree of bacterial colonization of the small intestine in patients with chronic biliary-dependent pancreatitis.

For the first time, with the help of the gas-liquid chromatography method, the state of microbiocenosis was studied by determining the concentration of short-chain fatty acids in the duodenal contents of patients with chronic biliary-dependent pancreatitis combined with pathology of the stomach and duodenum.

In our work, an assessment was made of the local immune status in patients with chronic biliary-dependent pancreatitis, and the effect of the immunomodulator tactivin on the gastric mucosa was evaluated. Practical significance:

A comprehensive assessment of the state of the stomach and duodenum in patients with chronic biliary-dependent pancreatitis will improve the early diagnosis of combined pathology for the implementation of timely and adequate therapeutic and preventive measures.

The developed morphological and endoscopic criteria for the diagnosis of CP combined with changes in the gastroduodenal zone will allow a differentiated approach to the treatment of this category of patients.

The developed algorithm of diagnostic measures will make it possible to predict the development of chronic biliary-dependent pancreatitis combined with changes in the gastroduodenal zone. The practical application of the algorithm will allow, depending on the clinical situation, determining an individual organizational, diagnostic, and therapeutic tactic in the management of this category of patients.

The results of the use of various medications in the treatment of biliary-dependent CP combined with changes in the stomach and duodenum will make it possible to develop rational therapy regimens depending on the clinical, microbiological, and immune status of the patient.

Propositions for defense

1. The course of chronic biliary-dependent pancreatitis is accompanied by a complex set of microbiological, immunological, and morphological changes on the part of the gastroduodenal zone.

2. Morphological changes in the gastric mucosa in the combination of CBP and various pathological conditions of the GDZ are characterized by the development of atrophic and metaplastic processes, as well as changes in lymphoid tissue, indicating the formation of an intense local immune reaction.

3. Microbiological homeostasis in patients with CBP is characterized by the presence of excessive bacterial contamination of the small intestine, an effective method for detecting which is the hydrogen breath test.

4. The combination of CBP with various pathologies of the GDZ is accompanied by significant disturbances of the intestinal microbiocenosis, which are expressed in changes in the concentration of short-chain fatty acids in the duodenal contents; an increased growth of mixed anaerobic flora with proteolytic and hemolytic activity is noted, as well as an imbalance of aerobic/anaerobic populations of microorganisms. 5. In the treatment of chronic pancreatitis and bacterial contamination of the small intestine, for the correction of morphofunctional disorders of the stomach and duodenum, the timely use of antibacterial therapy with simultaneous prevention of dysbiosis is advisable. Local immunomodulating therapy using tactivin is promising, the use of which normalizes the immune response and eliminates secondary immune deficiency in CBP.

Implementation of the results into practice

The scientific propositions and recommendations contained in the dissertation have been included in the educational process at the Department of Gastroenterology of the Russian Medical Academy of Postgraduate Education. The proposed scheme of diagnostic measures has found application in the practice of the Department of Gastroenterology of City Clinical Hospital No. 33 named after Professor A.A. Ostroumov in Moscow.

The results of the research on the topic of the dissertation were reported at medical conferences, at the 11th Russian Gastroenterological Week (Moscow, 2005); abstracts were published in the materials of the 6th Congress of Gastroenterologists of Russia (Moscow, 2006) and in the materials of the 12th Russian Gastroenterological Week (Moscow, 2006). Six works have been published on the topic of the dissertation.