Aim: to present the results of the Expert Panel with a discussion of modern concepts of the pathogenesis of functional gastrointestinal diseases and the possibilities of multitarget therapy with trimebutine.

   Key points. Low-grade inflammation can be considered as a morphological substrate of functional diseases with an increase in activated mastocytes and eosinophils, T-helpers 2 and T-helpers 17 in the gastrointestinal mucosa. In the development in the content of visceral hypersensitivity, the functional connection between mastocytes and TRPV1-positive sensory endings of the vagus nerve is of great importance. Proinflammatory cytokines and matrix metalloproteinases can enter the systemic circulation, provoking the development of systemic manifestations. Increased levels of proinflammatory cytokines are supported by altered intestinal permeability and microbiota. Functional diseases are believed to modify the symptoms and course of concomitant organic diseases of the gastrointestinal tract (for example, functional diseases of the biliary tract may contribute to the development of cholelithiasis, pancreatitis). The peripheral μ-, κ- and δ-receptor agonist trimebutine (Trimedat®) regulates the production of enterohormones, modulates motility throughout the gastrointestinal tract and normalizes visceral sensitivity. The effectiveness of trimebutine in the treatment of functional disorders has been shown in various studies. Trimebutine helps reduce the production of proinflammatory cytokines, including interleukin-6.

   Conclusion. In the treatment of functional diseases of the gastrointestinal tract, trimebutine can be considered as a multitarget agent, since the drug helps to normalize motility, reduces the degree of visceral hypersensitivity, exhibits anti-inflammatory and neuroregenerative effects, and can also increase the effectiveness of treatment of concomitant diseases.

   Aim: to analyse the principles of diagnosis and treatment of intrahepatic cholestasis in chronic liver diseases, to present data on the effectiveness of ademetionine in the treatment of chronic liver diseases with intrahepatic cholestasis and the materials of the Expert Meeting held in 2023.

   Key points. During the Expert Meeting, the problems of diagnostics and treatment of intrahepatic cholestasis in various chronic liver diseases were discussed, the effectiveness of ademetionine was clarified, and optimal regimens for its administration were determined. The relevance of the existing algorithm for diagnosing cholestasis in real clinical practice was assessed. The effectiveness of ademetionine in the treatment of various liver diseases occurring with intrahepatic cholestasis (cholestatic forms of drug-induced liver damage, alcoholic liver disease, non-alcoholic liver disease, primary biliary cholangitis) was demonstrated, manifested by a decrease in clinical and laboratory signs of cholestasis. The anticholestatic mechanisms of ademetionine action were clarified, which consist in normalizing the fluidity of hepatocyte membranes, regulating the activity of Nrf2, a key transcription factor, suppressing lipid peroxidation and the resulting damage to hepatocytes and cholangiocytes. Optimal regimens for prescribing ademetionine for various clinical situations were considered.

   Conclusions. Ademetionine is an effective drug that, due to its pleiotropic action and favourable safety profile, can be used in various chronic liver diseases accompanied by cholestasis, including as a part of the complex therapy.

   Aim: to summarize the literature data of use of laser technologies in the treatment of anorectal diseases.

   Key points. Lazer intervention technologies in the treatment of anorectal diseases such as haemorrhoids, anal fistula, anal fissure and pilonidal disease makes it possible to significantly reduce the intensity of pain syndrome, shorten the time of wound healing and also reduce the duration of the period of disability of the patient without worsening the quality of life. The main advantages of minimally invasive techniques are the absence of extensive wounds, minimal complications and reduction of the disease recurrence rate, minimally invasive methods are almost as effective as traditional ones. Besides, the use of laser allows to perform minimally invasive interventions under local anaesthesia in a day hospital.

   Conclusion. It is necessary to further study and improve the use of laser technologies in the treatment of anorectal diseases, and to actively introduce techniques into practice to improve the results of treatment of patients with these nosologies.

   Aim: to present literature data on the importance of intra-abdominal hypertension in the pathogenesis of peritonitis.

   Key points. Secondary purulent peritonitis is a severe and fairly common form of abdominal infection with high mortality. According to statistics, hospitalization of patients with signs of local or diffuse peritonitis is more than 15 % among patients with acute surgical pathologies. One of the factors in the development of complications and an unfavorable prognosis for this disease is increased intra-abdominal pressure. To measure this indicator, a Foley catheter inserted into the bladder is used in medical practice. According to reference values, the optimal level of intra-abdominal pressure does not exceed 5 mmHg. A persistent increase in pressure of 12 mmHg and above indicates the development of intra-abdominal hypertension. An increase in the level of intra-abdominal pressure indicates the progression of the inflammatory destructive process in the abdominal cavity and contributes to the development of multiple organ failure with subsequent fatal outcome with untimely treatment. With an indicator exceeding 20 mmHg, there is a risk of developing abdominal compartment syndrome. This condition is characterized by increased pressure in two or more anatomical areas, which leads to decreased blood flow and subsequent tissue hypoxia. Intra-abdominal hypertension also increases the risk of developing postoperative peritonitis in patients who have undergone laparotomy.

   Conclusion. To predict the course of secondary diffuse purulent peritonitis, reduce the risk of complications and mortality, it is necessary to focus on measuring intra-abdominal pressure as a mandatory manipulation in surgical patients. Despite its general availability and ease of implementation, this technique allows assessing the severity of organ dysfunctions.

   Aim: to evaluate the possibility of the MMR-system status, microsatellite instability (MSI) usage in the differential diagnosis of gastric mucosa dysplasia, determination of the gastric adenocarcinoma development risk.

   Material and methods. The study included gastric mucosa specimens of 75 patients: 25 with high-grade dysplasia, 25 with low-grade dysplasia, 25 were indefinite for dysplasia. Gastrobiopsy specimens were examined histologically, immunohistochemically using mouse monoclonal antibodies (Diagnostic BioSystems, USA) to the MMR system proteins: MLH-1 (clone G168-15, dilution 1:50), MSH2 (clone DBM15.82, dilution 1:100), MSH6 (clone 44, dilution 1:50), PMS2 (clone A16-4, ready to use). MSI was studied with multiplex PCR evaluation of DNA microsatellites (NR-21, NR-24, NR-27, BAT-25, BAT-26) from paraffin sections, their analysis with capillary electrophoresis. The obtained data were processed with the Statistica 10.0 (StatSoft, USA), presented using descriptive, analytical statistics. VOSviewer (1.6.20) was used to visualize the bibliometric analysis.

   Results. MMR-deficient cases were found in low (2.8 %) and high-grade (2.8 %) dysplasia with the immunohistochemical evaluation of MMR-system proteins in gastric mucosa specimens. In all indefinite for dysplasia cases MMR-system proteins remained unaffected. Three MSI-positive cases (6.5 %) were detected by PCR with two low-grade dysplasia, one high-grade dysplasia cases. All identified cases were also immunohistochemically MSI-positive.

   Conclusion. Determination of MSI can be used as an auxiliary study within a panel of biomarkers aimed to support the decision-making of a pathologist in the alternative of “indefinite for dysplasia” or “definite dysplasia — obligate precancer”.

   Aim: to study the metabolic activity of the intestinal microbiota depending on the stage of metabolic dysfunction-associated fatty liver disease (MAFLD).

   Materials and methods. The study included 85 patients with MAFLD (27 patients with steatosis without steatohepatitis and fibrosis, 42 patients with steatohepatitis, 16 patients with cirrhosis as an outcome of MAFLD, Child — Pugh class A–B) and 20 healthy people who formed the control group. The level and spectrum of short-chain fatty acids (SCFA) were determined by gas-liquid chromatography.

   Results. It was found that patients with MAFLD at the stage of steatosis and cirrhosis of the liver have unidirectional changes in the metabolic activity of the intestinal microbiota. We established a decrease in the absolute concentrations of SCFA — their total content, the level of acetate, propionate, butyrate, a decrease in the level of isoacids. The SCFA profiles showed an increase in the proportion of acetate and a decrease in propionate and butyrate. Moreover, changes in the named parameters of SCFAs are aggravated with progression to liver cirrhosis. At the stage of steatohepatitis, we identified two subgroups of patients with different levels of metabolic activity of the microbiota. Patients whose microbiota metabolism for SCFA production was high had correspondingly elevated SCFA levels. And, on the contrary, patients in whom the metabolic activity of the microbiota was reduced were characterized by a steady decrease in SCFAs and disease progression to liver cirrhosis. In the study, we showed an inverse correlation between the calculated prognostic indices of NFS and FIB-4, elastography values with the total level of SCFA, the level of acetate, propionate, butyrate. Thus, a decrease in the content of SCFA for patients with MAFLD can be considered as a prognostic marker of an unfavorable course of liver disease.

   Aim: to substantiate the expediency of using a segment of the jejunum on a vascular pedicle in esophagoplasty.

   Materials and methods. At the National Medical Research Center of Surgery named after A.V. Vishnevsky, 12 patients underwent esophagoplasty with a combined visceral transplant, of which 9 (75.0 %) received a gastrointestinal graft and 3 (25.0 %) — a colon-jejunum one. Esophagectomy with simultaneous esophageal plastic surgery was performed in 10 (83.3 %) patients, in 4 (40 %) of them — in combination with distal gastric resection. The indication for surgery in 3 patients was cicatricial stricture of the esophagus and stenosis of the pylorus, in 2 — achalasia of the cardia of the terminal stage (in one patient — with ulcerative stenosis of the pylorus). Three more patients underwent esophagectomy due to peptic strictures: esophagogastroanastomosis (n = 1), esophagoenteroanastomosis (n = 1) and esophagus after Nissen surgery (n = 1). Cancer recurrence after proximal gastric resection and gastrectomy in 2 patients was an indication for esophagectomy. Also, 2 (16.7 %) patients were hospitalized in the National Medical Research Center of Surgery named after A.V. Vishnevsky with incomplete esophagoplasty: one person — after Dobromyslov — Torek surgery for spontaneous rupture of the esophagus, and one patient — after the unsuccessful Lewis surgery for esophageal cancer performed in other hospitals.

   Results. The average duration of post-operative stay was 12.7 ± 6.3 days. The postoperative period was smooth in 10 (83.3 %) patients. The failure of the cervical anastomosis was revealed in 1 (8.3 %) patient on day 5 after esophageal plastic surgery with colon-jejunum graft, which was resolved conservatively without repeated surgery. Relaparotomy was required in one patient on day 7 after surgery for bile peritonitis, the cause of which was destructive acalculous cholecystitis with perforation. All 12 patients were discharged from the clinic with full nutrition through the mouth. In the long-term period, 11 (91.7 %) patients remained under observation, 1 (9.1 %) developed an esophagogastroanastomosis stricture 1.5 months after esophageal plastic surgery, which was resolved by 4 courses of bougation during the first 9 months after surgery. No other complications were noted.

   Conclusion. The segment of the jejunum on the vascular pedicle, used for esophagoplasty, in the condition of a shortage of plastic material, allows not only to complete the reconstruction at once, but also to restore the natural passage of food and prevent bile reflux.

Aim: to present data on the involvement of macrophages in the pathogenesis of celiac disease and the development of possible treatment methods for this disease aimed at changing the function of macrophages.

Key points. Celiac disease is an autoimmune disease with a characteristic serological (antibodies to tissue transglutaminase, endomysium, deamidated gliadin peptides) and histological profile (inflammatory infiltration of the villous epithelium by lymphocytes and their atrophy, crypt hyperplasia) caused by gluten consumption in genetically predisposed individuals. Macrophages, as key cells that provide a link between innate and adaptive immunity, are of significant importance in the pathogenesis of celiac disease. Gliadin peptides stimulate the activation of macrophages according to the proinflammatory phenotype with the production of cytokines, which causes the immune response of T-helpers 1 and T-helpers 17. The result of these processes is the development of an inflammatory reaction and damage to the intestinal mucosa due to the production of matrix metalloproteinases and reactive oxygen species by macrophages. Therapeutic tactics for celiac disease today include a gluten-free diet, which is not so easy to follow. Of interest is the study of the possibility of using polyphenols in celiac disease, which are capable of precipitating gliadins and inhibiting the polarization of macrophages towards a proinflammatory phenotype, while simultaneously stimulating an increase in the population of macrophages of an anti-inflammatory phenotype associated with a decrease in tissue damage.

Conclusion. Impaired macrophage function/differentiation results in either inadequate, excessive immune activation or failure to mount effective protective immune responses against pathogens, which may result in the development of gastrointestinal diseases. Studying the involvement of macrophages at different stages of celiac disease progression is important for the development of new treatments for this disease.

   Aim: Diagnostic criteria for functional disorders of the biliary tract are presented in the materials of the Rome IV consensus, as well as expert councils of Russian and foreign specialists. Episodes of functional biliary pain are caused by a violation of bile outflow through the cystic duct and sphincter of Oddi. It has been suggested that there is a “biliary continuum” in which in some patients’ biliary dysfunction is transformed into cholelithiasis.

   Key points. Lithogenic bile is considered as the pathophysiological basis for the development of biliary dyskinesia and cholelithiasis. Lithogenic bile provokes inflammation of low grades in the mucous membrane of the biliary tract, decreased contractility of the gallbladder and impaired relaxation of the biliary sphincters, impaired physiological response to cholecystokinin. Changes in motility of the biliary tract may be associated with the influence of hydrophobic bile salts and impaired eicosanoid metabolism. Hyperplasia of the epithelium and muscle layer, hypersecretion of mucin and cholesterol precipitation further impair the outflow of bile. Experimental data and some clinical observations indicate the possibility of transformation of biliary dysfunction into cholelithiasis. Dysfunction of the sphincter of Oddi is one of the possible consequences of cholecystectomy and, in fact, acts as a variant of postcholecystectomy syndrome. The basis for the treatment of biliary dysfunctions are antispasmodics of different classes, which can be combined with ursodeoxycholic acid. The biliary tract-selective antispasmodic hymecromone has shown high effectiveness in relieving biliary pain, which also has a moderate choleretic effect and the ability to prevent the crystallization of cholesterol in bile and can be used both for functional diseases and for cholelithiasis. The domestic drug hymecromone “Odecromone” entered the pharmaceutical market.

   Conclusion. There is no doubt that the relevance of further study of the patterns of development of biliary dysfunctions and GI is obvious. The study of this problem will contribute to the development of effective preventive approaches, including in the field of nutraceuticals.

   Aim: to demonstrate the need for a detailed differential diagnosis and selection of therapy in a patient with decompensated liver cirrhosis of combined etiology (HCV infection and primary sclerosing cholangitis).

   Key points. The patient came to the clinic with complaints of shortness of breath with minimal physical activity, abdominal enlargement, swelling of the legs, yellowness of the skin, and severe weakness. The complaints arose two months after suffering from left-sided focal pneumonia. Laboratory tests revealed signs of systemic inflammation, liver failure, and acute kidney injury. According to the results of instrumental studies, massive hydrothorax was noted in the right pleural cavity. The patient underwent a series of thoracentesis, and a total of about four liters of non-inflammatory pleural fluid was evacuated. Differential diagnosis was based on the presence of dyspnea and respiratory failure. The patient received effective antiviral therapy with drugs using an interferon-free regimen. Subsequently, conservative therapy was carried out, against the background of which the symptoms regressed and the patient’s condition improved.

   Conclusions. Hepatopleural syndrome is a serious complication in patients with decompensated liver cirrhosis, although it does not always appear secondary to massive ascites. To resolve hepatic hydrothorax, it is necessary to carry out diuretic therapy, replacement transfusion therapy with albumin preparations, and if there is a large amount of fluid in the pleural cavities, therapeutic and diagnostic thoracentesis is recommended.

   Aim: to optimize outcomes of the treatment and prevention of gastrointestinal diseases in adults and children.

   Key points. The Methodological Guidelines contain sections on the terminology, classification, mechanisms of action, requirements for sale in the Russian Federation, requirements for proving the efficacy and safety of probiotics, prebiotics, synbiotics and metabiotics, as well as functional foods enriched with them. An overview of relevant data allowing to include these drugs and products in the treatment an d prevention of gastrointestinal diseases in adults and children is presented.

   Conclusion. The clinical efficacy of probiotics, prebiotics, synbiotics and metabiotics depends on the specificity and quantity of their components, the dosage form, the regimen and duration of treatment. Products and functional foods with proven efficacy and safety are recommended for the treatment and prevention of gastrointestinal diseases in adults and children.