Factors determining the course of the reactive phase of acute pancreatitis and the treatment of patients at this stage

The dissertation is devoted to the study of factors determining the course of the reactive phase of acute destructive pancreatitis and to the improvement of approaches to the treatment of patients at this stage of the disease. Based on a retro- and prospective analysis of clinical material, the state of lipid peroxidation and antioxidant defense in the enzymatic and reactive phases was investigated, along with the role of gastrointestinal paresis, the functional state of the liver, the nature of early surgical interventions, and antibacterial prophylaxis in the development of purulent complications. The practical significance of the work is connected with the substantiation of the expediency of antioxidant therapy in complex conservative treatment and with the clarification of indications for surgical treatment of patients in the reactive phase of acute destructive pancreatitis.

Relevance of the topic.

The incidence of acute pancreatitis has been steadily increasing (Shalimov S.A. et al., 1990; Reshetnikov E.A. et al., 1998; Bagnenko S.F. et al., 2004; Takeda K. et al., 1998). Among patients with acute surgical diseases of the abdominal organs, the proportion of this pathology ranges from 8% to 28% (Ermolov A.S. et al., 2001; Bagnenko S.F. et al., 2004; Lankisch P.G. et al., 1996; Takeda K. et al., 1998). According to world statistical data, the incidence of AP varies from 200 to 800 patients per 1 million population per year (Yudin V.A., 1993; Pavlov V.V., 1996; Krasnorogov V.B. et al., 1998; Borisov A.E. et al., 2000; Watanabe S., 1998). In the hospitals of Saint Petersburg during the period 1993–2002, the absolute number of patients with acute pancreatitis more than doubled, and from 2000 onward AP rose to first place among acute surgical diseases of the abdominal cavity (Borisov A.E. et al., 2000). According to the data of S.F. Bagnenko et al. (2004), this trend has persisted in recent years.

The overall mortality in AP ranges from 3 to 6%, while mortality from its destructive forms has not changed substantially over the past thirty years and averages 25% (Reshetnikov E.A. et al., 1998; Lankisch P.G. et al., 1996; Neoptolemos J.P. et al., 1998).

Despite the active interest in this problem in recent years, there is still no definitive understanding either of the pathogenesis of this disease or of the tactics of its treatment.

For the past century, the concept of enzymatic self-digestion of the pancreas in pancreatic necrosis has been postulated; however, this does not explain all the triggering mechanisms of autolysis of pancreatic cellular structures.

Recently, the role of other possible factors in the genesis of ADP has been actively discussed, in particular the role of oxidative stress and the need to treat this pathology with antioxidants (Shugaev A.I., 1989; Tolstoy A.D., 2000; Nonaka A. et al., 1991; Dabrowski A. et al., 1995; Sweiry J.H., Mann G.E., 1996; Virlos I.T. et al., 2003; Dib M. et al., 2003).

However, there is still no definitive understanding of the role of free-radical forms of oxygen and the state of antioxidant defense in the reactive phase of ADP, and the place of surgical methods of treatment (minimally invasive interventions and traditional laparotomy) in the early therapeutic complex has not been determined (Tolstoy A.D., 1997; Krasnorogov V.B. et al., 1998; Reshetnikov E.A. et al., 1998; Beger H.G. et al., 1992; Neoptolemos J.P. et al., 1998; Takeda K. et al., 1998). The prevention of purulent complications also remains an unsolved problem in pancreatology (Yudin V.A., 1993; Pavlov V.V., 1996; Mamakeev M.M. et al., 1998; Neoptolemos J.P. et al., 1998; Watanabe S., 1998). These circumstances determined the aim and objectives of the study.

Aim of the study: to determine the main factors of the pathogenesis of acute destructive pancreatitis in the enzymatic phase that determine the further course of the disease, and to improve the results of treatment of patients in the reactive phase.

Objectives of the study.

1. To study the state of lipid peroxidation and antioxidant defense in the enzymatic and reactive phases of ADP.

2. To determine the expediency of antibacterial therapy at the early stage for the prevention of purulent complications in the reactive phase of ADP.

3. To evaluate the role of gastrointestinal paresis, the functional state of the liver, and the methods of surgical treatment at the stage of enzymatic toxemia in the development of purulent complications in the reactive phase of ADP.

4. To develop a tactical algorithm for the treatment of patients with ADP in the reactive phase.

Scientific novelty.

It has been established that in the reactive phase of ADP, increased lipid peroxidation processes persist against the background of reduced antioxidant defense, and their normalization occurs only by the end of the second week from the moment of AP onset.

It has been proved that the main factors determining the features of the course of ADP in the reactive phase are: pronounced gastrointestinal paresis, reduced functional state of the liver, and open surgical interventions at the early stage. When these signs are present, the number of purulent complications increases. In their absence, prophylactic antibacterial therapy at the early stage of ADP does not significantly affect the incidence of purulent complications in the reactive phase.

Practical significance of the obtained results.

It has been established that antioxidant therapy is expedient in the complex conservative therapy of ADP in the reactive phase.

It has been proved that indications for surgical treatment of patients with ADP in the reactive phase are infected pancreatic necrosis and purulent-necrotic cellulitis.

It has been established that in hemorrhagic or mixed pancreatic necroses with a predominance of the hemorrhagic component, necro-sequestrectomy can already be performed in the reactive phase.

Main statements put forward for defense.

1. In the reactive phase of ADP, increased lipid peroxidation processes and reduced antioxidant defense persist.

2. The main factors influencing the incidence of purulent complications in the reactive phase of ADP are: pronounced gastrointestinal paresis, reduced functional state of the liver, and open operations in the enzymatic phase. In the absence of these signs, prophylactic antibiotic therapy in the enzymatic phase does not significantly affect the incidence of purulent complications in the reactive phase.

3. Indications for surgical treatment of ADP in the reactive phase are: infected pancreatic necrosis and necrotic cellulitis with endogenous intoxication not amenable to conservative therapy.

Personal participation of the author in the study.

The author carried out an analysis of literature sources, a retro- and prospective analysis of the treatment of patients with acute destructive pancreatitis, and performed the mathematical analysis and processing of the actual material.

Approbation of the work.

The materials of the dissertation were discussed at a meeting of the problem commission "Surgery and Related Specialties" and were reported at the scientific-practical conference "Modern Problems of Surgery" (Saint Petersburg, 2007) and at the conference "Current Issues of Clinical and Experimental Medicine — 2008" (Saint Petersburg, 2008).

Implementation of the results of the study.

The results of the study have been implemented in the practical activities of the Pokrovskaya Hospital and in the educational process of the Department of Emergency Surgery of SEI APE SPb MAPE.

Publications of the results of the study.

Four publications have been issued on the topic of the dissertation, two of them in scientific journals recommended by the Higher Attestation Commission of the Russian Federation for the publication of materials of Candidate's dissertations.

Structure and volume of the dissertation.

The dissertation is presented on 130 pages of computer-typed text. It consists of an introduction, a literature review and four chapters of original observations, a conclusion, conclusions and practical recommendations. The bibliography contains 118 domestic and 146 foreign sources. The work is illustrated with 15 tables and 4 figures.