Aim of review. To summarize modern scientific data on the role of melatonin in healthy people and in digestive diseases. To assess the role of melatonin drugs in gastroenterology and to outline its further application. Summary. Basic physiological functions of melatonin are discussed (biological rhythms, motor and evacuatory, cytoprotective, antioxidant, immunomodulating, anti-stress, antineoplastic etc.). The melatonin role in pathogenesis and prognosis of digestive diseases is covered. Results and perspectives melatonin containing drugs at functional and organic digestive diseases are discussed. Conclusion. The functional diseases and early manifestations of organic gastrointestinal diseases are usu-ally characterized by melatonin producing cell hyperpla-sia related to adaptive body response. At progression of organic disease, development of malignant neoplasms, hypoplasia of melatonin-producing cells was found, melatonin expression is decreased that indicates exhaustion of adaptive mechanisms. Adaptive properties of melatonin allow to recommend its therapeutic application at various disease groups as pathogenic treatment within basic modes of treatment.

Aim of investigation. To specify morphological features of autoimmune gastritis (AIH) and to indicate options for morphological diagnosis of this disease. Material and methods. The gastric biopsy specimens of 8 patients received at routine esophagogastroduodenoscopy (EGDS) were investigated. Biopsy specimens were processed by the standard technique. Serial sections were stained by hematoxyline and eosine, and immunehistochemical standing with anti-chromogranin A antibodies serum. Results. Morphological features of autoimmune gastritis, including cases with primary morphological diagnosis in contrast to the cases with primary serological diagnosis by anti-parietal cells antibodies are presented. The options of polyps or pseudopolyps detection at upper endoscopy are described which at morphological investigation correspond to sites of noninvolved mucosa of the body of stomach or hyperplastic foveolar layer. AIH can be characterized by metaplastic and non-metaplastic atrophy (intestinal and pseudo-pyloric metaplasia), pancreatic metaplasia, inflammatory infiltration with glandular epithelium destruction and T-lymphocyte emperipolesis, as well as by lipomatosis in lymphoid accumulations and neuroendocrine cell hyperplasia. Conclusion. Presented diagnostic features at autoimmune gastritis can be combined that is characteristic for this disease entity. In difficult cases at suspicion for AIH immunehistochemical staining for chromogranin A helps to diagnose neuroendocrine ECL cell hyperplasia, to specify its variant and to confirm the diagnosis.

Aim of investigation. To analyze the role of inflammatory response in determination of the outcome of acute gastroduodenal ulcer bleeding. Material and methods. All patients, enrolled in the study were divided into two groups, according to the bleeding outcome. The 1st group included patients with sustained hemostasis, the 2nd - with recurrent bleeding within 3 days after admission to the hospital. Severity and pattern of neutrophilic and macrophageal infiltration at biopsy specimens was assessed by immunohistochemistry (CD68). Effect of leukocytes on platelet aggregation induced by collagen and adenosinediphosphate was estimated in vitro. Results. Development of ulcer bleeding was followed by acute inflammatory reaction, severe local information and destruction of marginal ulcer zones. Prognostic factors, increasing the risk of recurrent bleeding were established: elevation of peripheral blood fibrinogen level (p=0,049), endoscopic signs of ongoing bleeding (p=0,005), increase in neutrophil (p=0,015) and macrophage count in marginal ulcer zones (p=0,001). Increase in macrophage count had positive correlation to sever ity of edema, neutrophilic infiltration and progressing alteration of the marginal ulcer zones. Inhibiting effect of leukocytes on collagen-induced platelet aggregation (p=0,008) that can limit thrombogenesis adhesion stage was revealed in vitro. Conclusion. Hyperactive response of leukocytes and macrophages can be the cause of recurrent ulcer bleedings.

Aim of investigation. To estimate the clinical and prognostic value of carriage of various blood coagulation and platelet receptors gene allelic variants in development of cryoglobulinemic vasculitis at chronic hepatitis C (CHC). Material and methods. Original study included overall 200 patients with CHCs and liver cirrhosis in its outcome, who were divided into 3 groups: patients without cryoglobulinemia (CG, n=123), those with asymptomatic cryoglobulinemia (ACG, n=40) and with cryoglobulinemic vasculitis (CGV, n=37). Assessment of polymorphism of the studied genes was carried out by real-time polymerase chain reaction with melting curve analysis. Results. CGV patients in comparison to those with ACG had 4G mutant allele are significantly more frequent (odds ratio (OR): 4G=2,008) as well as genotypes 5G4G+4G4G (OR: 5G4G+4G4G=4,950) of the gene PAI-675 5G/4G, and in comparison to patients without CG - CC mutant genotype of the gene ITGB3 1565 T/C (р =0,047). The multifactor analysis at comparison of patients with CGV and without it revealed the quantity of mutant alleles of PAI-675 5G/4G and ITGB3 1565 T/C genes and infection duration as independent factors for vasculitis development, while at comparison of patients with CGV and ACG - only quantity of mutant alleles of these genes. Patients with CGV allele C and CC homozygosity of the gene ITGB3 1565 T/C is associated to presence of renal diseases, while allele C genotypes (TC+CC) of ITGB3 1565 T/C gene is associated with involvement of muscular and nervous system. Conclusion. Carriage of mutant genotypes of PAI-675 5G/4G and ITGB3 1565 T/C genes is a factor which allows to predict CGV development in CHC patients, and can determine clinical manifestations of the latter.

Aim of investigation. To estimate clinical efficacy and safety of ursodeoxycholic acid («Livodexa®») in a dose of 15 mg/kg/day for 3 months in the treatment of primary biliary cirrhosis (PBC) of the I to III stage. Material and methods. Open single center clinical trial included 30 patients with PBC of the I-III stage. All patients received «Livodexa®» in the daily dose of 15 mg/kg taken two times per day for 3 months. Efficacy and safety investigation of the drug was carried out at the day 30 (visit 2) and at the day 90 (visit 3) according to the laboratory tests results, quality of life assessment by SF-36 questionnaire, registration of frequency and severity of the adverse events (AE). Results. The median age (interquartile range) of PBC patients enrolled in the original study was 53 (48-61) years, the women prevailed: 29 (96,6%). The majority (43,2%) of patients had PBC of the histological grade II according to the Ludwig system. Treatment with «Livodexa®» in a dose of 15 mg/kg/day resulted in a statistically significant decrease of biochemical marker levels: alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total and conjugated bilirubin at the 30th day of treatment (visit 2; p<0,001 for each parameter, except for aspartate aminotransferase: p=0,001) and at the 90th day (visit 3; p<0,001 for each parameter). According to quality of life estimation by SF-36 questionnaire, frequency and severity of AE, «Livodexa®» is characterized by high safety and tolerance profile. Conclusion. Treatment of patients with I to III stage of PBC with «Livodexa®» in a dose of 15 mg/kg/day is characterized by improvement of laboratory scores and quality of life parameters. Good tolerance and safety of the drug allows to recommend it for treatment of these patients.

Aim of publication. To present with clinical guidelines of the Russian gastroenterological association on Clostridium difficile-associated disease management to practical doctors. Summary. Clostridium difficile-associated disease develops at disorders of intestinal microbiome with excessive colonization of C. difficile which toxins cause colonic inflammation and damage. C. difficile toxins A and B are major virulence factors causing damage of intestinal wall and inflammation due to damage of intestinal epithelial barrier, induction of proinflammatory cytokines, apoptosis and a necrosis of epithelial cells. Current epidemiologic trends of C. difficile-associated disease are characterized by growth of both inpatient and community-acquired morbidity, expansion of risk groups, increase in number of more severe cases including those, caused by more virulent BI/NAP1/027strain, tendency to relapsing, increase in lethal outcomes. C. difficile infection is the most common cause of intrahospital diarrhea leading to significant mortality. Risk factors of C. difficile-associated include antibacterial therapy, hospital admission, elderly age, comorbidity and immunosuppressive treatment. At the present time several laboratory methods for diagnosis of Clostridial infection exist: fecal ELISA test for toxins A and B, PCR, test for C. difficile glutamate dehydrogenase. Detection of densely adhered to underlying mucosa greenish or creamy deposits (pseudomembranes) is the endoscopical marker of severe C. difficile-associated disease i.e. pseudomembranous colitis. C. difficile-associated disease treatment includes vancomycin and metronidazole, the choice of drug and dose depends on disease severity. Significance of sorbents and probiotics in patient management is under discussion. Prophylaxis requires rational application of antibiotics, decrease, whenever possible, of terms of hospital stay, timely diagnosis and observance of sanitary and epidemiologic rules in medical institutions. Conclusion. Epidemiologic growth, risk of significant morbidity made C. difficile-associated disease a socially important disease. The present guidelines direct the doctor to correct diagnosis and adequate treatment of C. difficile infection.

Aim of review. To present literature data on diagnosis and treatment of incomplete internal rectal fistulas. Summary. Incomplete internal rectal fistulas is an insufficiently studied «niche» in proctology. First of all, the definition itself is a terminological void which does not permit definition of these fistulas as a separate nosological entity. Second, as difficult diagnostic procedures are required (due to the absence of external orifice) preoperative assessment of the structure of fistulous tract is complicated. In regards to this the standard treatment of these fistulous does not exist. According to literature data, the frequency of recurrence of incomplete internal fistulous ranges from 8 to 22%. Conclusion. The literature analysis demonstrated that there is a small number of publications in which this problem is considered. Because of lack of classification of this pathology there is no uniform treatment approach which would allow to decrease the risk of relapses, and maintain retention function as well.

Aim of investigation. To determine the content of growth factors (G-CSF, GM-CSF) and chemokines (MCP-1, MIP-1β) in resected colon specimens of patients with severe ulcerative colitis (UC). Material and methods. Overall 48 biopsy specimens of the colonic mucosa resected at 7 patients with total UC were investigated. All patients underwent colectomy due to severe disease, resistant to conservative treatment. Inflammation activity was determined according to severity of erosive and ulcerative lesions of the colon. Growth factor and chemokine levels in supernatant fluid after centrifugal separation of homogenate of 10 mg biopsy specimen were investigated by the protein analyzer «Bio-Plex» («Bio-Rad», USA). Biopsy specimens of uninvolved colonic mucosa resected in 10 cancer patients were used as a control. Results. Growth factor and chemokine levels were significantly elevated in colonic biopsy specimens of UC patients in comparison to that of controls: G-CSF 52,5±17,0 and 0,4±0,1 pg/10 mg (p<0,01), GM-CSF6,8±1,0 and 2,7±0,26 pg/10 mg (p <0,001), MCP-1 26,0 ±11,4 and 1,5±0,15 pg/10 mg (p <0,05), MIP-1β 12,5±2,8 and 3,2±0,4 pg/10 mg (p <0,01) respectively. The content of G-CSF, MCP-1 and MIP-1β in colonic biopsy specimens was increased in comparison to their level in non-involved terminal ileum biopsy specimens. Levels in the left part of the colon and transverse colon were higher, than in the cecum and ascending colon. Growth factor and chemokine concentrations were significantly higher at severe inflammation in comparison to moderate inflammatory activity: G-CSF - 25 fold, MCP-1 - 6,4 fold, MIP-1β -3 fold and GM-CSF - 2,6 fold. Profiles GM-CSF > G-CSF and MIP-1β> MCP-1 were observed in 22 (95,7%) and 19 (82,6%) of 23 colonic biopsy specimens of the control group respectively, profiles G-CSF > GM-CSF and MCP-1> MIP-1β - in 17 (89,4%) and 12 (63,1%) of 19 colonic biopsies of UC patients with severe inflammatory activity. Conclusions. Significant increase in neutrophil growth factor level G-CSF and monocyte chemokine MCP-1 was observed in colonic biopsy specimens of UC patients at widespread destructive and inflammatory ulcerative process.

Aim of investigation. To evaluate morphological characteristics of the resected specimen after open and laparoscopic surgery with D3-lymphadenectomy for left-sided colon cancer. Material and methods. The investigation was designed as retrospective-prospective comparative case-match study. From archival cases and prospectively collected database cases with left-sided colon cancer stage I-III treated by complete mesocolic excision (CME) with D3-lymphadenectomy were selected. Patients who underwent open surgery formed the first group. The second group included patients after laparoscopic surgery. Results. Each group consisted of 54 patients. There were no significant differences in terms of age, gender, body mass index, tumor location, and tumor stage between the two groups. No statistically significant difference in specimen morphological characteristics after open and laparoscopic surgery with D3-lymphadenectomy for left-sided colon cancer was observed. Conclusion. The feasibility and safety of laparoscopic technique in treatment of left-sided colon cancer is reasonable regarding to the specimen quality. Similar clinical and pathological results suggest that there is no oncological difference between open and laparoscopic techniques with D3-lymphadenectomy for left-sided colon cancer. However, further studies are required to estimate long-term oncological results.

Aim of investigation. To develop standardized technique of sacrectomy at locally advanced rectal cancer. To describe the surgical maneuvers allowing to decrease the degree of blood loss, duration of procedure and degree of surgical injury. To develop method for sacrectomy border location for the correct intraoperative navigation. Results. The distal sacrectomy technique at rectal cancer is presented in details. Abdominal-transsacral approach that includes turning patient to the prone posture for perineal stage is optimal. Small pelvis preoperative magnetic-resonance tomography with special marking may be applied for intraoperative navigation. Lateral spread of the rectal tumor requires ligation of the internal iliac arteries from abdominal approach, dissection and underrunning of the fastened veins both from abdominal and crotch access after removal of neoplastic speciemen. Conclusion. Achievement of radical degree of treatment for locally advanced rectal cancer with sacral involvement is possible only at combined operation with distal sacrectomy. Such surgical intervention is technically complex and requires special skills of pelvic operations. Technique standardization of operations, that include distal sacrectomy, could make them feasible and safe in the conditions of specialized hospital.

Aim of the lecture. To analyze the changes in the Rome IV criteria of the irritable bowel syndrome (IBS) in comparison to their previous version. Summary. The term «discomfort» was withdrawn from the definition of IBS, and the phrase «pain decreases after defecation» was replaced by «pain related to defecation»; number of days when patient experience abdominal pain, required for diagnostics of this disease is changed. As in the previous version, it is recommended to estimate compliance of the patient’s symptoms to Rome criteria, though it is noted that IBS-like clinical symptoms may be attributed to other diseases (celiac sprue, chronic inflammatory bowel diseases etc.). It causes the need of the limited laboratory and instrumental investigation of the patients. The new drugs (rifaximin, lubiprostone, linaclotide etc.) are included in the treatment modes. Conclusion. Rome-IV criteria of IBS represent a certain step forward, especially regarding diagnosis and treatment of the discussed disease.

Aim of the clinical case presentation. To discuss the principles of the correct and healthy nutrition, which are the universal and applicable for the most of overweight and obese patients and obesity-related disorders, exemplified by clinical case. Summary. Obesity has multifactorial adverse effect on human body i.e.: predisposition to diabetes mellitus, cardiovascular diseases, excessive musculoskeletal load, cosmetic defect, etc. It represents serious problem for the majority of economically developed European countries, USA and Russia. Presented principles will help healthy people to maintain active longevity by prevention of cardio-vascular diseases, Alzheimer's disease and some other disorders. The data is presented in the form of a clinical discussion in which on the example of the young patient with morbid obesity all aspects of effective medical communication are analyzed in detail. Specific recommendations which the patient has to receive from the doctor are discussed: motivations for lifestyle modification, optimum daily caloric food load, amount of physical activity, optimum nutritional pattern.