Endolymphatic antibiotic and immune-corrective therapy in the prevention of postoperative complications in non-specific diseases of the colon

The dissertation is devoted to the development and clinical substantiation of the method of endolymphatic antibiotic and immune-corrective therapy, as well as local endoscopic immunotherapy with tactivin for the prevention and treatment of postoperative purulent complications in patients with non-specific inflammatory diseases of the colon (Crohn's disease and non-specific ulcerative colitis). The work summarizes data on risk factors for purulent complications in the surgical treatment of such patients, carries out a retrospective assessment of their frequency and structure, and examines disorders of systemic and local immunity in purulent-inflammatory processes of the abdominal cavity and non-specific colitis. Based on the data obtained, indications and schemes for the endolymphatic administration of antibiotics in combination with immunomodulators are proposed, and a technique for the endoscopic local use of tactivin is developed. The author describes the technique of catheterization of the peripheral collector lymphatic vessel and clinical-immunological monitoring, which makes it possible to assess the activity of the inflammatory process and the effectiveness of the therapy. The practical significance of the work is associated with the introduction of the proposed method in the surgical departments of a number of city clinical hospitals in Moscow.

The presented work lies at the intersection of abdominal surgery, clinical lymphology and immunology and is aimed at improving the prevention of postoperative purulent complications in patients with chronic inflammatory diseases of the colon.

Relevance of the study

The relevance of treating patients with Crohn's disease (CD) and non-specific ulcerative colitis (NUC) at the beginning of the 21st century is determined by the increasing incidence of this disease, especially among young people. According to WHO data, the incidence of CD increased from 1975 from 0.2-1.9 to 4.7-5.9 cases per 100,000 population. According to large-scale epidemiological studies conducted in Europe and the United States, the prevalence of CD ranges from 34 to 146 observations per 100,000 people. At the same time, the prevalence of UC ranges from 28 to 117 patients per 100,000 people. The incidence of CD is highest in the age group from 20 to 29 years. This trend has persisted over the past 40 years. The peak incidence of UC falls in the age period from 20 to 40 years. In general, UC is more common in men than in women. In ulcerative proctitis, respectively, the male-to-female ratio is 1.39:1. The risk of developing UC in men after 40 years exceeds that in women by almost 2 times. At the same time, in CD, women are ill slightly more often than men (1:1.12) (Adler G. 2001; Ekbom A., Helmick C., Zack M., Adami H.O. 1991; Greenwald B.D., James S.P., 1995).

The use of complex conservative treatment (glucocorticoids, sulfonamides, parenteral nutrition) allows achieving remission in almost 90% of patients with NUC and reducing mortality to 5%. However, given the unpredictable course of the disease, especially with total colonic lesions and the presence of life-threatening complications, fifteen-year survival does not exceed 50%, and disease relapses are observed in at least 75% of patients. The prognosis of the disease in CD is somewhat worse than in NUC. More than 2/3 of patients develop complications, the presence of which is an indication for emergency and urgent surgical interventions. Postoperative mortality in CD exceeds 10-15% (Adler G., 2001; Belousova E.A., 2002.).

Most surgeons believe that almost all patients (sooner or later) with chronic non-specific diseases of the colon undergo surgical interventions (more often on an emergency basis) (Adler G. 2001). Thus, some authors have established that 5 years after the onset of the disease the probability of performing surgery is 40%, after 10 years - 70%, and after 20 years - almost 90% of patients (Golovenko O.V., Kapuller L.L., Mikhailova T.L., Veselov V.V., Khalif I.L. 2005; Ekbom A., et al. 1997). The frequency of surgical interventions depends not only on the duration of the disease, but also on the localization of the process. With combined lesions of the small and large intestine, the probability of surgery is highest. It remains quite high with isolated lesions of the small intestine and is lowest with isolated lesions of the colon (Vorobyov G.I., Mikhailova T.L., Kostenko N.V. 2004; Ekbom A., et al. 1997).

Postoperative complications in patients operated on for chronic non-specific diseases of the small and large intestine are associated with such important factors as: a) the timing of the operation (planned or emergency), b) the presence or absence of risk factors (malabsorption syndrome, abscesses, fistulas, long-term corticosteroid therapy, etc.) (Vorobyov G.I., 2001; Andrews H.A., Keighlei M.R.B., Alexander-Williams J., et al., 1991). Summary data from the literature have shown that currently the frequency of early postoperative complications in planned operations does not exceed 10%, while in interventions performed on an emergency basis it reaches 70% of observations (Gaiduk S.S., Zubarev P.N., 2006, Belousova E.A., 2002). Analysis of the immediate results of surgical treatment of patients with NUC and CD showed that the majority of early postoperative complications are purulent-septic conditions (Fedorov V.D., Levitan M.Kh., Kapuller L.L., 1980).

Surgical treatment of patients with non-specific colitis is accompanied by a high frequency of postoperative purulent complications; according to various authors they range from 20% to 78% and largely depend on the timing and nature of the performed operation. Thus, in emergency and urgent operations purulent complications amounted to 64%, in planned ones - 10% (Fedorov V.D., Dultsev Yu.V., 1984, Jarneroff G., Lennard-Jones J., 1992, Phillips S.F., Pemberton J.H., Shorter R.G., 1992, Vorobyov G.I. 2001). To date, postoperative complications are diagnosed in 50-90% of patients, and mortality ranges from 12.5 to 60% (Mustyats A.P., Grintsov A.G., Miminoshvili O.I., 1991; Hurst R.D., Finco C., Rubin M., 1995; Hurst R.D., Finco C., Rubin M., 1995).

An indisputable fact in the prevention and treatment of purulent complications after operations on the gastrointestinal tract is the use of various antibacterial drugs. Thus, in recent years significant results have been achieved with the prophylactic use of antibacterial agents. However, in non-specific colitis the question of the advisability of using antibiotic prophylaxis of purulent postoperative infection has not found wide application. This is due to the fact that a single use of antibiotics is an inadequate measure in such patients, and long-term use leads to pronounced side effects.

Despite the proven and well-known significance of the lymphatic system in the course and outcome of acute and chronic inflammatory diseases of the abdominal organs, the possibility and advisability of using endolymphatic methods of treating patients with non-specific diseases of the colon remains poorly studied. It is this that determines the need to study the lymphological aspects of antibiotic pharmacokinetics to determine the feasibility of blocking the spread of infection from the primary focus through the lymphatic system.

In recent years, an increasing number of clinicians have used the method of endolymphatic administration of antibiotics developed by I.V. Yarema, R.T. Panchenkov, Yu.E. Vyrenkov, E.G. Shcherbakova. The method proved to be highly effective in the complex treatment of patients with purulent-inflammatory diseases of the chest and abdominal cavities, pelvis, surgical sepsis, osteomyelitis (Panchenkov R.T., Yarema M.V., 1980; Buyanov V.M., 1998; Akhundov I.T., 1998; Dzhumabaev S.U., 1998; Briskin B.S., 1998; Vyrenkov Yu.E., 1998).

The widespread, and often unjustified, use of antibiotics and hormones currently changes the functional activity of the immune system, suppressing cellular and humoral immunity, which ultimately leads to a pronounced response of the immune system directly to the microbial factor (Belotsky S.M., 1994).

In assessing the immunological reactivity of patients with purulent-inflammatory processes of the abdominal cavity, the relative and absolute content of T- and B-lymphocytes and their functional activity are of great importance. A pronounced decrease in the total level of T- and B-lymphocytes in peripheral blood is regularly observed in peritonitis and sepsis. It was found that the total population of T- and B-lymphocytes in patients with local purulent processes and in healthy individuals differs little, whereas an increase in the number of activated subpopulations of T- and B-lymphocytes is an adequate response to the action of an infectious agent and precedes the generalization of the process (Beburishvili A.G., Pugacheva L.L., Golbraikh V.A., Kozlov M.P., Kochneva E.V., 1992; Volozhin A.I., Sashkina T.N., Savchenko Z.I., 1995).

Surgical intervention and anesthesia cause an even greater decrease in indicators of cellular and humoral immunity. Operative risk is accompanied by the release into the bloodstream of adrenocorticotropic hormone, corticosteroids, catecholamines, insulin, which suppress the division of immunocytes, their migratory ability, and the formation of antibodies. Corticosteroids cause lymphopenia mainly due to a decrease in the proportion of T-helpers and the exit of lymphocytes from recirculation. Immunosuppression caused by operative stress-injury persists for 3 days after the operation, with subsequent restoration to the initial level on days 7-8 (Belotsky S.M., 1985; Volodin N.N. 2002).

Thus, all of the above determined the relevance of this study. Aim of the study.

The aim of this study is: to improve the results of treatment of patients with non-specific inflammatory diseases of the colon using endolymphatic antibiotic and immune-corrective therapy in combination with endoscopic local immunotherapy.

Objectives.

1. To conduct a retrospective analysis of risk factors contributing to the occurrence of postoperative purulent complications in the surgical treatment of non-specific diseases of the colon.

2. To study the effectiveness of endolymphatic use of antibiotics for the prevention and treatment of purulent postoperative complications in non-specific diseases of the colon.

3. To identify features of general immunity disorders in patients with non-specific colitis depending on the nature and prevalence of the purulent-inflammatory process, as well as to develop a scheme of immune correction with tactivin during endolymphatic administration of the drug.

4. To study changes in local immunity in patients with non-specific colitis and to develop methods of local immunotherapy based on the local use of immunomodulators.

Scientific novelty.

The most significant risk factors contributing to the development of purulent complications in the surgical treatment of patients with non-specific diseases of the colon have been determined.

For the first time, the advantages of the endolymphatic method of administering antibiotics and immunomodulators over traditional ones have been revealed: the method allows creating effective concentrations of the antibiotic in the affected tissues of the colon exceeding the minimum inhibitory concentration (MIC) against the majority of potential causative agents of inflammatory processes in operations on the colon, and promotes the prolongation of drug circulation in the blood serum.

A dynamic study of T- and B-systems of immunity in blood and lymph in purulent-inflammatory complications of non-specific diseases of the colon has been carried out.

For the first time, indications and schemes for the endolymphatic use of antibiotics in combination with immunomodulators in the complex treatment of surgical patients with non-specific diseases of the colon have been developed.

Objective criteria for the effectiveness of endolymphatic use of antibiotics and immunomodulators in the treatment and prevention of purulent postoperative complications in patients with non-specific diseases of the colon have been determined.

A study of local immunity indicators in patients with non-specific colitis has been carried out. The conducted immunopathomorphological studies have shown that the local application of immunomodulators improves the initially reduced indicators of the local immune response, normalizes the quantitative ratio of T-lymphocytes, plasma cells and dendritic macrophages, increases their functional activity, and increases the synthesis of immunoglobulins in tissues. Practical value.

The main risk factors for the development of purulent complications in non-specific diseases of the colon have been identified.

It has been determined that endolymphatic antibiotic therapy is a highly effective method of treating purulent complications in CD and NUC due to the creation of a high and long-lasting concentration of antibiotics in the blood serum and inflammatory tissues.

The method of dynamic clinical and immunological control (monitoring) is a highly informative criterion reflecting the degree of activity and nature of the inflammatory process in purulent complications in patients with non-specific diseases of the colon.

A technique for administering the immunomodulator tactivin for the complex therapy and prevention of postoperative complications in non-specific diseases of the colon has been proposed.

Based on the analysis of the effectiveness of various routes of administration of antibiotics and the immunomodulator tactivin, the doses of drugs necessary to obtain a sufficient immune response and reduce the frequency of infectious complications have been determined. Statements for defense.

1. The developed program for the prevention and treatment of purulent complications in non-specific diseases of the colon with the help of endolymphatic administration of medicinal agents allows improving the immediate results of surgical treatment of such patients.

2. In patients with purulent complications in non-specific diseases of the colon, pronounced changes develop in the systemic general immunity, the degree of which depends on the severity of intoxication. Traditional methods of tactivin administration in purulent complications, although increasing the effectiveness of treatment by normalizing the indicators of systemic immunity, do not ultimately eliminate the depression of the immune response in the lymphatic system.

3. Endolymphatic administration of tactivin restores the parameters of systemic immunity, increases the local immune resistance of lymph nodes and has a higher clinical effectiveness.

4. Local administration of tactivin improves the initially reduced indicators of cellular immunity, normalizes the ratio of T-lymphocytes, plasma cells and dendritic macrophages, increases the functional activity of lymphocytes, increases the level of lymphocytes in tissues, increases the effectiveness of complex treatment of patients with non-specific colitis, and promotes a more pronounced positive clinical, laboratory and immunological dynamics.

Implementation of the results of the work into practice

The developed method of endolymphatic antibiotic and immune-corrective therapy and local endoscopic injection immunotherapy in CD and NUC has been introduced into the practice of surgical departments and departments of anesthesiology and intensive care of City Clinical Hospital No. 33 and No. 40 and the Clinical Hospital of the Central Union of Russia.

Approval of the work

The main provisions of the dissertation were reported and discussed at:

1. Joint scientific-practical conference of the departments: operative surgery and topographic anatomy, hospital surgery of the faculty of general medicine, anesthesiology and intensive care, disaster medicine, pathological anatomy of the Moscow State University of Medicine and Dentistry; laboratory of operative surgery and clinical lymphology of the Russian Medical Academy of Postgraduate Education, employees of surgical departments of City Clinical Hospital No. 33 named after Prof. A.A. Ostroumov, City Clinical Hospital No. 40 and the Clinical Hospital of the Central Union of Russia of the Moscow Department of Health (Moscow 2007).

2. Jubilee scientific-practical conference dedicated to the 175th anniversary of the founding of the hospital of the Central Union of Russia (Moscow 2006).

3. Scientific-practical conference "Topical issues of surgery" (Moscow 2006).

Publications

The main provisions of the dissertation are reflected in 6 published scientific works.

Structure and scope of the work

The dissertation consists of an introduction, three chapters, a conclusion, conclusions, practical recommendations and a list of references. The work is set out on 157 pages, illustrated with 15 figures and 28 tables. The list of references includes 248 titles, including 146 works of domestic and 102 foreign authors.