Peculiarities of the course of reflux esophagitis in patients with chronic pancreatitis

The dissertation is devoted to the study of the clinical and pathogenetic features of reflux esophagitis in patients with chronic pancreatitis. It addresses the prevalence of gastroesophageal reflux in chronic pancreatitis, disorders of esophageal motility and reduced tone of the lower esophageal sphincter in connection with duodenostasis and increased intragastric pressure, as well as the atypical and oligosymptomatic presentation of reflux esophagitis in combined pathology. The morphofunctional state of the esophagogastric and pancreatoduodenal complex, Helicobacter pylori contamination, the state of metabolic processes and lipid free-radical oxidation, and features of blood serum structuring are examined. On the basis of a comprehensive investigation, predictors of the development of reflux esophagitis in patients with chronic pancreatitis are proposed, which are of importance for early diagnosis, prognosis, and the choice of treatment tactics.

Relevance of the topic. The increasing prevalence of reflux esophagitis (RE), the recurrent course of the disease, and the elevated risk of esophageal cancer in RE constitute a pressing medical and social problem (Greenberger N.N., 2000; Roshchina T.V., Shulpekova Yu.O., Ivashkin V.T., 2000; Starostin B.D., 2000). During fibrogastroduodenoscopy (FGDS), RE is detected in 6–15% of individuals (Ivashkin V.T., Trukhmanov A.S., 2003).

At the same time, according to pH-metry data, gastroesophageal reflux is identified in every third patient with chronic pancreatitis (CP) (Kazakevich V.V., Petrenko V.F., 1987). Impaired esophageal motility and reduced tone of the lower esophageal sphincter (LES) in CP patients are associated with suppression of the motor function of the duodenum, duodenostasis, and increased intragastric pressure (Geller L.I., 1976; Karaman N.V., Zimovskiy V.L., 1982; Kazakevich V.V., 1996; Matveev N.L., Protasov A.V., 2000). Meanwhile, the features of the course of RE in CP patients have not been sufficiently studied (Avidan B., Sonnenberg A., 2002), although it has previously been established that in peptic ulcer disease, diabetes mellitus, and pathology of the biliary tract, heart, and vessels, RE presents with few symptoms and atypical manifestations (Geller L.I., 1989; Komarov F.I., Grebenev A.L., 1995; Zaitseva E.I., 1997; Lluch I. et al., 1999). Moreover, a number of studies have demonstrated a discrepancy between the clinical picture and instrumental findings when RE is combined with other diseases, which in turn leads to delayed diagnosis and the development of complications (Firsova L.D., 1986; Il'inich V.K., Reshetnikov E.A., 1989; Gonchar N.V., 2003).

Taking into account the available data, it may be assumed that systemic metabolic disturbances and intensification of SROL during CP exacerbation contribute to the formation of erosive lesions of the esophagus in CP patients (Gubergrits N.B., Khristich T.N., 2000; Zhukova E.N., 2000; Korot'ko G.G., 2002; Uspenskiy Yu.P., Grinevich V.B., 2002; Ponomareva A.I., Lipatova T.E., 2003; White R.J., Morris G.P., 2002). In this regard, studying the features of the course of RE in CP patients in order to develop adequate methods of treatment and prevention is of current relevance.

Aim: to identify predictors of the development of RE in CP patients based on a study of the morphofunctional characteristics of the esophagogastric and pancreatoduodenal complex (EGPDC) and the state of metabolic processes.

Research objectives: 1. To study the clinical manifestations of RE in CP patients.

2. To characterize the morphofunctional state of the esophagogastric and pancreatoduodenal complex in patients with RE and CP.

3. To identify the pattern of Helicobacter pylori contamination in patients with RE and CP.

4. To investigate the state of metabolic processes in patients with RE and CP.

5. To assess the state of lipid free-radical oxidation processes.

6. To identify the features of blood serum structuring in patients with RE and CP.

7. Based on the data obtained, to propose predictors of the development of RE in CP patients for the purposes of prognosis and early diagnosis.

Novelty of the research results. For the first time, on the basis of a comprehensive study of the secretory and motor function of the EGPDC, H. pylori contamination, exocrine function of the pancreas, metabolic processes, and the state of lipid free-radical oxidation, predictors of the development of RE in CP have been determined.

For the first time, micromorphotypes of blood serum structuring characteristic of patients with RE in CP have been identified, and a method for the express diagnosis of hyperfermentemia in CP patients has been proposed (a patent for invention No. 2216734, dated 20.11.2003, has been obtained).

Scientific and practical significance of the results obtained. The identified predictors of the development of RE in CP patients may be used as criteria for early diagnosis and prognosis of the disease. The proposed criteria for predicting the development of RE in CP patients make it possible to choose preventive measures and treatment tactics.

Practical implementation of the results obtained

Based on the materials of the dissertation, 15 publications have been issued, including an RF patent for invention (see Appendix 3). The results of the study were discussed at the 29th–32nd Conferences of Gastroenterologists (Smolensk–Moscow, 2001, 2002, 2003, and 2004), the 18th and 19th All-Russian Conferences with international participation "Physiology and Pathology of Digestion" (Gelendzhik, 2002; Sochi, 2004), the 7th All-Russian Gastroenterological Week (Moscow, 2001), and the XXXth and XXXIInd Scientific Sessions of the Central Research Institute of Gastroenterology (Moscow, 2002, 2005).

The procedure for predicting and early diagnosing RE in CP patients has been introduced at the Russian Center for Functional Surgical Gastroenterology and at the Gastroenterological Therapeutic Department of the State Healthcare Institution Krasnodar Regional Clinical Hospital No. 1 named after Professor S.V. Ochapovsky.

Main propositions of the dissertation submitted for defense

1. The morphofunctional state of the EGPDC in patients with reflux esophagitis in chronic pancreatitis is characterized by histological signs of pronounced inflammatory infiltration of the esophagus, stomach, and duodenum, with a high correlation between H. pylori contamination of the gastric antrum and the severity of infiltrative changes in the mucosa of the distal esophagus.

2. In patients with RE in CP, an imbalance between promoters and inhibitors of lipid free-radical oxidation is detected, along with a decrease in trypsin-inhibitory activity of blood serum, an increase in the level of medium-mass molecules, dyslipidemia, dysproteinemia, and hyperfermentemia.