Aim of review. To present the modern concept on the mechanisms of pancreatic disease development and role of intestinal and oral microbiome in pancreatitis pathogenesis. Summary. Intestinal barrier dysfunction, bacterial overgrowth syndrome and endotoxinemia are features of acute pancreatitis. Image-recognition systems (toll-like and NOD-like receptors) and microorganism-associated molecular patterns play important role in these processes. Obtained data indicate the presence of oral and gastrointestinal microbial changes at pancreatic diseases. Subsequently,Helicobacterpyloriinfection may play a role in development of autoimmune pancreatitis and pancreatic cancer,PorphyromonasgingivalisandAggregatibacteractinomycetemcomitans- in pancreatic cancer development. Conclusion. Original study results indicate the presence of oral and bowel microbial changes in pancreatic diseases. Taking into account the ability of probiotics to stimulate production of antimicrobial peptides, normalize epithelial barrier function, limit bacterial translocation, their the application may be promising for pancreatic diseases treatment.

Aim of investigation. To study association interleukin-1 (IL-1) gene (rs16944), interleukin-6 (IL-6) gene (rs1800795), interleukin-10 (IL-10) gene (rs1800896) polymorphisms with development of acute pancreatitis (AP) in the Russian population. Material and methods. Whole blood samples were received from 297 AP patients and 238 healthy controls. Genotyping of IL-1 gene (rs16944) polymorphisms, IL-6 gene (rs1800795), IL-10 gene (rs1800896) was carried out by polymerase chain reaction with allele discrimination by TaqMan-probes. Results. The genetic polymorphism combination 511СТ×174GC of IL-1 and IL-6 genes was associated to high risk of AP development (OR=2.25, 95%-CI 1.45-3.49; p=0.0018). According to stratification analysis smoking patients with 511CT genotype had higher AP risk, then the patients with other genotypes (OR=2.22, 95%-CI 1.3-3.79; p=0.003). Paired combination of genotypes to disease risk analysis demonstrated that at 511СT×174GС genotype combination the AP risk is highest at alcohol abuse history for over 10 years (OR=2.88, 95%-CI 1.59-5.23; p=0.0004). Conclusion. Interleukin genetic polymorphism investigation may be useful at assessment of cytokine status in AP patients to predict the outcomes and to develop the personalized approach to treatment and prophylaxis.

Aim of investigation. To study association interleukin-1 (IL-1) gene (rs16944), interleukin-6 (IL-6) gene (rs1800795), interleukin-10 (IL-10) gene (rs1800896) polymorphisms with development of acute pancreatitis (AP) in the Russian population. Material and methods. Whole blood samples were received from 297 AP patients and 238 healthy controls. Genotyping of IL-1 gene (rs16944) polymorphisms, IL-6 gene (rs1800795), IL-10 gene (rs1800896) was carried out by polymerase chain reaction with allele discrimination by TaqMan-probes. Results. The genetic polymorphism combination 511СТ×174GC of IL-1 and IL-6 genes was associated to high risk of AP development (OR=2.25, 95%-CI 1.45-3.49; p=0.0018). According to stratification analysis smoking patients with 511CT genotype had higher AP risk, then the patients with other genotypes (OR=2.22, 95%-CI 1.3-3.79; p=0.003). Paired combination of genotypes to disease risk analysis demonstrated that at 511СT×174GС genotype combination the AP risk is highest at alcohol abuse history for over 10 years (OR=2.88, 95%-CI 1.59-5.23; p=0.0004). Conclusion. Interleukin genetic polymorphism investigation may be useful at assessment of cytokine status in AP patients to predict the outcomes and to develop the personalized approach to treatment and prophylaxis.

Aim of investigation. To estimate the impact of small intestinal bacterial overgrowth (SIBO) to development of hemodynamic disorders at liver cirrhosis (LC). Material and methods. Original study included 50 LC patients and 15 generally healthy controls. Lactulose hydrogen breath test, serum level of C-reactive protein and cardiac ultrasound with simultaneous blood pressure (BP) and heart rate measurement, estimation of basic hemodynamic scores: mean blood pressure (MBP), cardiac output (CO), total peripheral vascular resistance (TPVR) were investigated in all patients. Results. LC patients with SIBO as compared to LC patients without SIBO had lower mean blood pressure (82.7±9.0 mm Hg vs 92.0±14.0 mm Hg) and TPVR (16.4±4.4 mm Hg × min/l vs 21.3±5.3 mm Hg • min/l), higher CO (5.38±1.41 l/min vs 4.52±1.03 l/ min) and serum C-rp (SIBO - 1.2÷10.5÷16.5 mg/l vs 0.6÷2.8÷9.1 mg/l). The presence of SIBO led to similar changes only at decompensated LC. At the same time no significant hemodynamic disorders were revealed at decompensated LC without SIBO and compensated LC irrespective of SIBO. At LC significant correlation of serum C-rp to TPVR (r=-0.367; p=0.009) and CO (r=0.313; p=0.027) was found, but not to mean BP (r=-0.227; p=0.113). Conclusion. SIBO at LC plays important role in vasodilation, arterial hypotension and hyperdynamic circulation. As these hemodynamic disorders aggravate the course of portal hypertension, the treatment of SIBO may reduce severity of the latter.

Material and methods. The original study included overall 120 patients with ALD, who were randomized in two identical groups. The patients of the main group (group A) received 2 courses of therapy: the first - Phosphogliv 5 mg/day as intravenous bolus injection for 2 wks, followed by the oral intake of 2 capsules t.i.d. for 10 wks (the total treatment duration was 24 wks). Patients of the control group (group B) received placebo in the same regimen. The dynamics of serum alanine transaminase (ALT), aspartate transaminase (AST), liver scores by noninvasive FibroMax test was applied to assess the treatment efficacy and safety, along with change in quality of life of patients. Results. In 24 wks in group A in comparison to the group B significantly lower mean ALT level was found: 35,2±29,4 U/l vs 48,4±36,1 U/l (р =0,044), AST level became normal in higher rate of patients: 69,4% vs 47,7% (р =0,034), that had more prominent decrease in gamma-glutamyltranspeptidase (GGT) level - 47,4±36,5% vs 25,1±63,9% (р =0,039), the rate of patients with Aktitest A2-A3 range decreased - 8,5% vs 21,4% (p<0,05) with no patients remained in FibroTest F3-F4 range; significantly more pronounced improvement by the vitality and social functioning scales of «SF-36» questionnaire was registered. The safety profile was comparable in both groups. Conclusions. Expected effects of the drug include reduction of inflammatory activity in the liver, improvement of cholestasis at longer follow-up period, decrease in fibrosis severity, improvement of quality of life at favorable safety profile.

National college of gastroenterologists, hepatologists

Aim of publication. To present the modern concept on etiology and pathogenesis of constipation, its classification, basic diagnostic and treatment methods to general practitioners. Summary. The prevalence of constipation in general population is quite high and averages 12 to 19%. Two types of constipation are usually distinguished: primary (functional) and secondary that is related to mechanical obstruction of the intestinal passage of bowel content, neurologic and endocrine diseases, systemic diseases of connective tissue, intake of drugs etc. At diagnosing of functional constipation early detection of «alarm symptoms» which require thorough patient investigation is important. Moreover, insufficient treatment response require step-by-step instrumental diagnostics. Constipation treatment has to be comprehensive and include general recommendations (intensification of physical activity, increase in dietary fiber in daily ration etc.), intake of psyllium, laxatives, including first of all of polyethyleneglycol, at insufficient response enterokinetic agents. Conclusion. Successful treatment of constipation requires correct detection of its cause, following essential dietary recommendations and stepwise application of pharmaceutical agents.

The aim of review. To present the analysis of available data on approach to pharmacological antineoplastic therapy at rectal cancer (RC) after chemoradiotherapy followed by surgical treatment, as well as within the «watch & wait» concept. Summary. The present time adjuvant chemotherapy is the standard of treatment for III stage rectal cancer after preoperative chemoradiotherapy and surgery. However according to detailed analysis, in this group of patients adjuvant chemotherapy has inconsistent results and no clear-cut advantage can be found at absence of lymph node involvement according to histological study or complete tumor regression due to preoperative chemoradiotherapy. The meta-analysis (2015) of 4 randomized third-phase clinical trials (EORTC 22921, I-CNR-RT, PROCTORSCRIPT, CHRONICLE) demonstrated the lack of significant of 5-fluorouracil-based adjuvant chemotherapy. Efficacy of 5-fluorouracil monotherapy was directly compared to 5-fluorouracil with oxaliplatin combination in several randomized trials. Results of the studies indicate that patients with stage ypI or complete morphological response obtain no significant advantage from adjuvant chemotherapy. The same conclusion can be drawn concerning patients with postponed or cancelled surgery who received treatment within «watch & wait» program. At meta-analysis of 12 studies implementing «watch & wait» protocol with subsequent chemotherapy no definite advantages of adjuvant chemotherapy were demonstrated as well. On the other hand, 5-fluorouracil and oxaliplatin-based chemotherapy should be recommended to patients with ypIII stage of the disease and II stage patients having risk factors. Conclusion. The decision to prescribe adjuvant chemotherapy seems to be correct in relation to pathologic study results and degree of preoperative chemoradiotherapy response.

Aim of clinical case presentation. To discuss the consequences of erroneous management approach at suspicion for appendicular infiltrate, as well as options and difficulties of complicated Crohn’s disease treatment. Summary. Surgical treatment of fistulizing Crohn's disease with interorgan and external fistulas with development of pathological cavity having anterior abdominal wall opening is described. Past history of disease was five years. The patient underwent appendectomy in the presence of infiltrate with subsequent development of external intestinal fistula. Repeated surgery for fistula elimination was unsuccessful, however allowed to establish Crohn's disease diagnosis. Patient refused from surgical treatment, therefore despite the lack of permanent remission at infliximab treatment, therapy was maintained until patient developed anaphylactic reaction. As a result, ileocecal resection along with resection of ileum fragment and distal third of sigmoid colon, restoration of intestinal continuity, and resection of anterior abdominal wall with fistulous tract block and subsequent reconstruction were executed. The collagen allo-graft is applied to restore anterior abdominal wall defect. At continuation of biological therapy by adalimumab no data on disease relapse were received. Conclusion. The presence of infiltration in the right iliac area requires ruling out of the Crohn's disease diagnosis. At fistulizing form treatment should be provided at the specialized institutions. It is important to note that treatment efficacy at exclusively conservative management, including biological therapy is quite low. Biological therapy allows to suppress disease manifestations and facilitate conditions for subsequent surgical intervention.