TREATMENT OF ACUTE PERITONITIS: CHANGE FROM EVIDENCE TO PERSONALIZED MEDICINE BASED ON GENETIC ASSESSMENT

The treatment results of 254 patients with peritonitis are presented in the article. The leading mechanisms of inflammatory reaction in peritonitis were studied. It is shown, that the severity of inflammatory-destructive changes in the peritoneum and the spread of inflammatory process in the peritoneal cavity are directly proportional to the concentration of interleukin 1β, which has genetic determination. Aim: To improve the treatment results of patients with acute peritonitis by assessing the individual peculiarities of the inflammation mechanisms and selecting personalized treatment methods. Materials and Methods. All patients were examined with the use of general clinical, biochemical, immunoenzymatic, genetic methods. The age of the examined patients ranged from 18 to 84 years and averaged 55.3 ± 4.72 years old. The level of serum cytokines and serotonin was determined by the immuno-assay. The alleles of polymorphic regions of the IL1β (511C/T) and the SLC6A4 genes were studied by genomic DNA isolation from peripheral blood leukocytes with following polymorphic site amplification by polymerase chain reaction. The fragments were visualized using the UV light emitter and the DNA Molecular Weight Marker of 100-1000 bp. Results. The activity of interleukin 1β in different var-iants of gene IL1β (511C/T) is determined. It was found that the lowest concentration of interleukin 1β was observed in the CC variant of gene, probably higher in the CT variant and the highest in the case of the TT variant. The structure of gene variants in local (non-encapsulated), general diffuse, subtotal and total peritonitis is determined based on which the prediction method of peritonitis course is developed. In the study of peritonitis pathogenesis, the manifestations of the redox system unbalance were identified with activity changes of the peroxidation pro-cesses, which were increased directly proportional to inflamma-tion spread in the peritoneal cavity. The same pattern is charac-teristic for proteolytic activity – the increase of proteolysis by means of azoalbumin (to low molecular weight structures) and azocasein (to median-molecular structures). The fibrinolytic activity is activated mainly due to nonenzymatic fibrinolysis. The analysis of the causes and mechanisms of peritonitis complicated by dynamic intestinal obstruction shows its dependence on serotonin concentration in the blood. Serotonin low activity causes the development of this complication. The relationship between the severity of intestinal paresis in peritonitis and variants of SLC6A4 gene, which regulates the serotoninergic mechanisms of the intestinal contractility, is shown. It is effective to create conditions for prolonged local supply of anticytokine drugs by developed techniques in patients with genetically determined disorders of cytokine imbalance. It is advisable for such patients to expand the indications for Open packing of abdomen (laparapertio) as preplanned following sanitation of the peritoneal cavity. It is expedient to expand the indications for intestinal intubation and use local delivery of serotonergic drugs to the intestinal wall according to the devel-oped techniques in the case of predicted serotonin deficiency on the base of genetic determination. Conclusions. Taking into account the individual fea-tures of inflammatory process mechanisms the stages of surgical interventions, the treatment schemes and the prevention methods of different complications have been improved. Such personalized approach to diagnosis, prognosis of acute peritonitis and choice of therapeutic tactics with surgical intervention improve and well-grounded selection of medical therapy allowed reducing the mortality down to 7.48%.