Pathogenetic Justification of the Efficacy of Extracorporeal Treatment Methods in Complex Therapy of Peritonitis in Oncological Patients

The dissertation is devoted to the pathogenetic justification of the efficacy of the application of extracorporeal treatment methods — hemosorption and intravascular laser irradiation of blood — in the complex therapy of peritonitis in oncological patients. The research is aimed at studying clinico-biochemical and immunological indicators reflecting the severity of the systemic inflammatory response syndrome and the state of immunoreactivity in the early postoperative period in patients with disseminated suppurative peritonitis. The relevance of the work is due to the high postoperative mortality in this category of patients, which is largely determined by the severity of systemic inflammation and secondary immunodeficiency, as well as the insufficient frequency of application of effective methods of detoxification therapy in oncological patients.

Relevance of the Research. To date, postoperative mortality among oncological patients with disseminated suppurative peritonitis ranges from 6.2% to 60% [54, 64, 140]. Unsatisfactory treatment outcomes are largely determined by the severity of the systemic inflammatory response syndrome, pronounced immunosuppression, and the development of multiple organ dysfunction syndrome [26, 57, 113, 115]. The totality of these pathological processes serves as the basis for the inclusion in the complex of postoperative intensive therapy of such patients of extracorporeal therapy methods, which exert detoxifying, reocorrigating, and immunomodulating effects [20, 37, 56, 62]. At the present time, extracorporeal therapy methods occupy a worthy place in the complex treatment of patients with peritonitis. The use of hemosorption, intravascular laser irradiation of blood (IVL) in the terminal and toxic phases of disseminated peritonitis positively affects the course of the disease, treatment outcomes, and the dynamics of markers of endogenous intoxication, cellular, and humoral immunity [47, 49-52, 54]. However, at present, effective methods of detoxification therapy for peritonitis in oncological patients are applied relatively rarely. In this regard, it appears relevant to provide a pathogenetic justification for the efficacy of the use in complex therapy of oncological patients with peritonitis of hemosorption and intravascular laser irradiation of blood, as well as to develop optimal methods for the prevention of pyoseptic complications in them in the early postoperative period.

Objective of the Research. Based on the study of clinico-biochemical and immunological indicators, to provide a pathogenetic justification for the efficacy of the use of laser irradiation of blood and hemosorption in the treatment of oncological patients with peritonitis.

Tasks:

1. To study the dynamics of clinico-laboratory indicators reflecting the severity of systemic inflammation, metabolic disturbances, and the degree of immunodeficiency in the development of peritonitis in oncological patients in the early postoperative period.

2. To evaluate the influence of hemosorption on the change in clinical and laboratory (biochemical, hematological, and immunological) indicators in oncological patients with peritonitis.

3. To study the influence of intravascular laser irradiation of blood on parameters of the systemic inflammatory response and immunoreactivity in oncological patients with peritonitis in the early postoperative period.

4. To identify the efficacy of combined application of laser irradiation of blood and hemosorption on parameters of systemic inflammation and immunoreactivity in oncological patients.

5. To assess the diagnostic and informational significance of the studied parameters of systemic inflammation and immunoreactivity.

Novelty of the Research.

1. It has been established that in the early postoperative period in oncological patients with disseminated suppurative peritonitis, the leading pathogenetic factors determining the severity of the general condition are the systemic inflammatory response syndrome and secondary immunodeficiency.

2. A positive influence of the combined application of extracorporeal therapy methods (hemosorption, intravascular laser irradiation of blood) on parameters of immunoreactivity in oncological patients with disseminated suppurative peritonitis in the postoperative period has been identified.

3. For the first time in oncological patients with disseminated suppurative peritonitis, high sensitivity, specificity, and prognostic significance of the studied parameters of the systemic inflammatory response syndrome (leukocytosis, LII), the immune system (CD4, CD8), and cytokines (TNF-α, IL-6) have been demonstrated.

4. Correlational relationships between markers of the systemic inflammatory response syndrome and indicators of cellular and humoral immunity in oncological patients with disseminated suppurative peritonitis have been identified against the background of basic treatment and combined therapy in the early postoperative period.

Practical Significance. The results obtained indicate that the assessment of the severity of the systemic inflammatory response syndrome in oncological patients with disseminated suppurative peritonitis should be carried out using markers of this syndrome and parameters of the body's immune system, which possess high diagnostic, informational, and prognostic value. Optimal combinations of extracorporeal therapy methods, including hemosorption and intravascular laser irradiation of blood, against the background of basic therapy in oncological patients with disseminated suppurative peritonitis made it possible to shorten the duration of patients' stay in the intensive care and resuscitation department and to improve the quality of life of patients. The applied combinations of extracorporeal therapy methods have been introduced into the practice of the intensive care and resuscitation departments.

Implementation of the Research Results. The results of the research have been introduced into the practice of the Department of Anesthesiology and Resuscitation of the Omsk Regional Clinical Oncological Dispensary, the Omsk Regional Clinical Hospital, and are also used in the educational process at the Department of Anesthesiology, Resuscitation and Emergency Medicine, as well as at the Department of Pathophysiology with a course in clinical pathophysiology of the Omsk State Medical Academy.

Defense of the Work. The materials of the dissertation were reported at the conference "Actual Questions of Pathophysiology" (Saint Petersburg, 2003), the III Russian Congress on Pathophysiology "Dysregulatory Pathology of Organs and Systems" (Moscow, 2004), the II All-Russian Scientific and Practical Conference "Intensive Care Medicine: Problems and Solutions" (Leninsk-Kuznetsky, 2004), the Scientific and Practical Conference "Clinical and Fundamental Aspects of Critical States" (Omsk, 2007), the Interregional Scientific and Practical Conference "Days of Immunology in Siberia" (Omsk, 2007), at the meeting of the Society of Pathophysiologists and Anesthesiologists-Resuscitologists of the City of Omsk (Omsk, 2006).

Publications. Six scientific works have been published on the topic of the dissertation, including one article in a journal recommended by the Higher Attestation Commission.

Propositions to be Defended.

1. The performed standard therapy in oncological patients with peritonitis does not allow for a reduction in the severity of the systemic inflammatory response syndrome and disturbances of immunoreactivity, which contributes to the development and maintenance of organ dysfunctions.

2. The application of extracorporeal therapy methods in oncological patients with peritonitis allows for a decrease in the severity of the systemic inflammatory response syndrome and disturbances of immunoreactivity, which contributes to a reduction in the severity of the clinical manifestation of multiple organ dysfunction syndrome.

3. The complex of laboratory and functional indicators used by us in the diagnosis of the systemic inflammatory response syndrome is highly specific and sensitive, and the evaluated research results possess high prognostic positivity and low prognostic negativity, as well as a low frequency of false-positive results.

Volume and Structure of the Dissertation. The work consists of an introduction, a literature review, a description of the material and methods of research, two chapters containing the results of original research, a discussion of the obtained results, conclusions, and practical recommendations. The volume of the dissertation is 122 pages of typed text, with actual data illustrated by 9 figures, 31 tables, and 6 schemes. The bibliography includes 211 sources, of which 67 are foreign.