Diagnosis and Treatment of Acute Pancreatitis in the Enzymatic Phase of the Disease

This dissertation is devoted to the development and justification of diagnostic and treatment algorithms for patients with acute pancreatitis during the enzymatic phase of the disease — the first five days from the onset of the pathological process. The research encompasses questions of etiology, pathogenesis, classification, and severity assessment of acute pancreatitis, as well as a comparative analysis of various treatment approaches — conservative, minimally invasive, and surgical. Special attention is given to the prevention of purulent complications and multi-organ insufficiency, which remain the principal cause of high mortality in necrotizing forms of the disease. The author proposes differentiated diagnostic and treatment algorithms for mild, moderate, and severe forms of acute pancreatitis, including indications for antienzymatic, antisecretory, and antibiotic therapy, methods of extracorporeal therapy such as plasmapheresis, and minimally invasive surgical interventions. The results of the investigation have been implemented in clinical practice and approved by the Association of Surgeons of Saint Petersburg in the form of protocols for the diagnosis and treatment of acute pancreatitis.

Relevance of the Problem. At present, the overall mortality rate in acute pancreatitis (AP) ranges from 3% to 6%, whereas mortality from necrotizing pancreatitis has not changed substantially over the past three decades and averages 25% (Tolstoy A.D., 1997; Reshetnikov E.A. et al., 1998; Lankisch P.Q. et al., 1996; Neoptolemos J.P. et al., 1998; Takeda K. et al., 1998).

In the enzymatic phase of acute pancreatitis (the first five days of the disease), pancreatic necrosis of varying extent develops, endotoxemia occurs, and in some patients multi-organ insufficiency and endotoxic shock ensue (Atanov Yu.P., 1991; Bondarev V.I. et al., 1991; Rybakov G.S., 1994; Reshetnikov E.A. et al., 1998; Tolstoy A.D. et al., 2004; Bradley E.L., 3rd, Steenhaus E.R., 1991; Kawarada Y. et al., 1991; Schroder T. et al., 1991; Chelase F. et al., 1997; Matsuno S., 1997). The period required for the formation of pancreatic necrosis is approximately three days, after which demarcation occurs (Filin V.I., 1982; Vashetko R.V., 1993; Tolstoy A.D., 1997), followed by the development of purulent complications, which constitute the principal cause of fatal outcomes in AP (Kawarada Y. et al., 1991; Jukemura J. et al., 1995; Farkas G. et al., 1996; Uhl W. et al., 1998).

The prevention of purulent and other complications leading to high mortality in acute pancreatitis remains an unresolved problem in pancreatology today (Yudin V.A., 1993; Pavlov V.V., 1996; Krasnogorov V.B. et al., 1998; Mamakeev M.M. et al., 1998; Neoptolemos J.P. et al., 1998; Watanabe S., 1998). The literature still contains no unified opinion on the strategy for comprehensive treatment of AP at the early stage of the disease: indications for antisecretory, antienzymatic, and antibiotic therapy have not been established in relation to the duration, severity, and etiology of the disease; there is no consensus on the efficacy of various methods of extracorporeal therapy; and the role of surgical treatment methods (minimally invasive interventions and traditional laparotomy) in the early treatment complex has not been determined (Filin V.I., 1982; Kurygin A.A. et al., 1988; Tolstoy A.D., 1997; Krasnogorov V.B. et al., 1998; Reshetnikov E.A. et al., 1998; Amurawaiye E.O., Brown R.A., 1991; Beger H.G. et al., 1992; Neoptolemos J.P. et al., 1998; Takeda K. et al., 1998).

The incidence of acute pancreatitis in major megacities is steadily increasing (Lashcheker V.M., 1982; Saveliev B.C. et al., 1983; Shalimov S.A. et al., 1990; Reshetnikov E.A. et al., 1998; Huang Z.Q., 1992; Lankisch P.G. et al., 1996; Takeda K. et al., 1998). This is attributable to various and ambiguous causes, one of which is the absence of an optimal algorithm for the diagnosis of acute pancreatitis in the early stages, as well as objective criteria for early prognosis of disease severity and methods for its monitoring.

Therefore, scientific investigations concerning the diagnosis and treatment strategy for AP in the enzymatic phase of the disease are currently relevant.

The objective of the study was to develop and provide scientific justification for the application of cost-effective and clinically effective diagnostic and treatment algorithms for acute pancreatitis of varying severity in the enzymatic phase of the disease.

Research Tasks:

1. To develop a diagnostic model capable of identifying acute pancreatitis within the first day of the disease, verifying its severity, and forecasting complications.

2. To develop a treatment strategy for mild acute pancreatitis and to evaluate the efficacy of antienzymatic and antisecretory therapy.

3. To determine the optimal composition and timing of the therapeutic complex for moderately severe acute pancreatitis and to conduct a critical analysis of the outcomes of operative and conservative treatment.

4. To investigate the efficacy of various modern methods of comprehensive treatment for severe acute pancreatitis and the optimal timing of their initiation, to develop indications for various types of surgical interventions, and to define the components of specialized conservative comprehensive treatment.

5. To determine the cost-effectiveness of the developed diagnostic and treatment algorithms for acute pancreatitis of varying severity in the enzymatic phase of the disease.

Scientific Novelty

Based on clinical-laboratory, instrumental, and morphological investigations, the following results were obtained:

1. An adequate method for prognosis and diagnosis of the severity of acute pancreatitis has been developed, enabling verification of various severity forms of AP — mild, moderate, and severe — with 95% probability within the first three to five days of the disease.

2. Indications for targeted antisecretory, antienzymatic, and antibiotic therapy have been established, along with regulations and forms of their administration in the enzymatic phase of acute pancreatitis depending on disease severity.

3. The efficacy of plasmapheresis (membrane and exsanguination types) has been evaluated, and indications, timing, and regimens for the application of serial plasmapheresis in various forms of acute destructive pancreatitis have been developed.

4. Indications for minimally invasive surgical treatment methods (sanative laparoscopy, laparocentesis) have been developed, and a method of laparoscopic decompressive drainage of the retroperitoneal fat tissue has been proposed and tested in clinical conditions for diffuse enzymatic parapancreatitis.

5. Diagnostic and treatment algorithms have been developed for various forms of acute pancreatitis in the enzymatic phase of the disease.

6. An economic justification has been conducted for the application of diagnostic and treatment algorithms in the clinical management of acute pancreatitis.

Implementation. The results of the investigation have been implemented in the practical activities and educational process of surgical clinics at the GU SPb NII Emergency Medicine named after I.I. Janelidze, the 2nd Department (Advanced Surgical Training for Physicians), and the Department of Military-Naval Hospital Surgery at the S.M. Kirov Military-Medical Academy, and are also used in the presentation of lecture material on acute pancreatitis and in practical sessions. Based on the dissertation research, "Protocols for the Diagnosis and Treatment of Acute Pancreatitis" were developed, approved by the Association of Surgeons of Saint Petersburg on March 12, 2004, and recommended for practical application in hospitals of Saint Petersburg.

Presentation of the Work. The research findings were reported at the scientific-practical conference "Current Issues of Clinical Diagnosis and Treatment" dedicated to the 200th anniversary of the Military-Medical Academy (Saint Petersburg, 1999), the scientific conference of listeners of the Faculty of Advanced Medical Personnel of the Military-Medical Academy (Saint Petersburg, 1999), the All-Russian Scientific-Practical Conference of Surgeons "Current Issues of Surgery of the Pancreas and Abdominal Aorta" (Pyatigorsk, 1999), the All-Russian Scientific-Practical Conference of Surgeons "December Readings on Acute Pancreatitis" (Minsk, 1999), the 1st Scientific-Practical Conference of the Northwestern Region of Russia "Artificial Nutrition and Infusion Therapy of Patients in Critical Conditions" (Saint Petersburg, 2001), the I Congress of Anesthesiologists and Reanimatologists of the Northwest (Saint Petersburg, 2001), the IX Conference of Surgeons-Hepatologists of Russia and the CIS Countries (Saint Petersburg, 2002), the 1st Scientific-Practical Conference of the Northwestern Region of the Russian Federation with international participation "High Surgical, Laser, and Information Technologies in Medicine of Saint Petersburg and the Northwestern Region of the Russian Federation: Prospects for Further Development" (Saint Petersburg, 2003), the Scientific-Practical Conference of Physicians of Russia "Uspensky Readings" (Tver, 2003), meetings of the Association of Surgeons of Saint Petersburg (2003, 2004), the "Round Table on the Problem: Acute Pancreatitis" at the SPb NII Emergency Medicine named after I.I. Janelidze (2004), the Scientific-Practical Conference of Physicians of the Novgorod Region (Novgorod, 2004); the 6th International Slavic-Baltic Scientific-Practical Forum "Saint Petersburg — Gastro-2004" (Saint Petersburg, 2004), and the 1st Congress of Moscow Surgeons "Emergency and Specialized Surgical Assistance" (Moscow, 2005).

Publications. Twenty-eight printed works on the dissertation topic have been published, including 1 monograph (co-authored), and 4 inventions have been registered.

Structure of the Dissertation. The work consists of an introduction, seven chapters, a conclusion, conclusions, practical recommendations, and a bibliography; it is presented across 398 pages, illustrated with 8 figures and 168 tables. The bibliography comprises 345 sources, of which 197 are by foreign authors.