Diagnostic and Therapeutic Strategy in Complicated Acute Pancreatitis

The research is dedicated to developing a differentiated diagnostic and therapeutic strategy for complicated acute pancreatitis. The work contains an analysis of modern approaches to the diagnosis and treatment of edematous and destructive pancreatitis, proposes a scientific classification of acute pancreatitis based on etiopathogenetic principles. Prognostic criteria for determining disease severity, progression, and risk of fatal outcome have been developed, along with an early diagnostic algorithm using contrast-enhanced computed tomography. Differentiated surgical strategies have been proposed for patient groups with varying volumes of pancreatic and retroperitoneal necrosis, including splen-preserving resections and closed drainage operations. Factors of high risk for postoperative infectious complications have been identified, and preventive measures have been developed involving antibiotic prophylaxis, extracorporeal therapy, and early immunosuppressive therapy.

Relevance of the Problem

Acute pancreatitis is one of the most common and severe diseases in emergency surgery with an unpredictable outcome [Savelyev B.C. et al., 1983; Filin V.I., Kostyuchenko A.L., 1994; Malfertheiner P., Kemmer T.R., 1991]. The morbidity of acute pancreatitis is steadily increasing, and in recent times it has risen to second or third place among emergency surgical diseases of the abdominal cavity [Mayat B.C. et al., 1983; Kubyshkin V.A., 1985; Nesterko Yu.A. et al., 1994; Malinovsky N.N. et al., 2000; Vashchenko R.V. et al., 2000; Kozlov V.A. et al., 2001; Banks R.A., 1982; Ranson J.H., 1990; Lankisch R.O. et al., 1997]. Acute pancreatitis most commonly occurs in people of working age; however, in 37% of cases, it is encountered in elderly and senile individuals, which is due to age-related involutional changes in the pancreas, pathology of the biliary tract, obesity, and atherosclerosis, which themselves contribute to the development of pancreatitis [Valenkevich L.N., 1984]. Acute pancreatitis occupies first place in the structure of mortality among acute surgical diseases of the abdominal organs [Shimanko I.M., Musselius S.G., 1993; Gulman M.I. et al., 1997]. The proportion of destructive forms reaches 10–20% of the total number of patients with acute pancreatitis [Filin V.I., Kostyuchenko A.L., 1994; Savelyev B.C. et al., 2000; 2001; Heiny N.A. et al., 1985; Banks P.A., 1991; Beger H.G., 1991; Bradley E.L., 1991; Kaufmann P. et al., 1996; Johnson S.H., Imrie C.W., 1992; 1999]. The overall mortality rate in acute pancreatitis currently ranges from 2% to 8.9%, and in destructive forms it reaches 20–45%, and over the past 30 years, both domestically and abroad, the mortality rate has not changed [Tolstoy A.D., 1997; 2001; Reshetnikov E.A. et al., 1998; Vashchenko R.V. et al., 2000; Lankish P. et al., 1996; Buchler P., Reber H., 1999; Johnson S.H., Imrie C.W., 1999; Wyncoll D.L., 1999]. Postoperative mortality in acute pancreatitis in the Russian Federation in 1996–1997 amounted to 22.9–23.6%, and in Moscow in 2000 it was 25.1% [Savelyev B.C. et al., 2003]. The therapeutic strategy in acute pancreatitis over the past decades has fluctuated from one extreme to another, passing through stages of complete refusal of any surgical interventions in sterile pancreatic necrosis to recommendations of subtotal or total pancreatectomy in progressive destructive pancreatitis [Shalimov A.A. et al., 1978; Toskin K.D., Starosek V.A., 1984; Zemskov B.C. et al., 1985; Mohnyuk Yu.V. et al., 1988; Savelyev B.C. et al., 1988, 2000; Kukosh M.V. et al., 1998, 1999]. Some authors recognize the pathogenetic rationale for the use of protease inhibitors [Savelyev B.C. et al., 1983; Vashchenko R.V. et al., 2000], while others completely deny their efficacy [Gagushin V.A., 1988; Kostyuchenko A.L., Filin V.I., 2000]. With the appearance of cytostatics (5-fluorouracil) [Laptev V.V., 1981; Dalgat D.M., 1985], great hopes were placed on the suppression of pancreatic secretion; however, their systemic use revealed immunosuppressive properties, thereby increasing the risk of developing infectious complications [Belyi I.S., 1983; Laptev V.V., Pivazyan G.A., 1988; Martov Yu.B. et al., 2001; Nesterko Yu.A., Laptev V.V., Mikhailusov S.V., 2004]. At present, sandostatin (octreotide) has gained wide use in the conservative treatment of acute pancreatitis [Gelfand B.R. et al., 1998; Zatevakhin I.I. et al., 2000; Tolstoy A.D., 2001; Buchler M., 1993; Steinberg W., Tenner S., 1994], inhibiting pancreatic and gastric secretion. However, its efficacy in mild and severe acute pancreatitis has not yet been proven [Ivanov Yu.V., 1999; McKay S. et al., 1997], although it reduced mortality in severe forms [Andriulli A. et al., 1998; Paran H. et al., 2000]. In connection with the development of severe endogenous intoxication in complicated acute pancreatitis, over the past decades, extracorporeal methods of therapy have been widely used: hemosorption, plasmapheresis, hemofiltration [Savelyev B.C. et al., 1983; Vladimirov V.G., Sergeenko V.I., 1986; Bondarev V.I. et al., 1989; Kozlov K.K., 1996; Tolstoy A.D. et al., 2001]. However, it turned out that they also do not stop the destructive process in the pancreas, especially in the case of disseminated pancreatic necrosis [Vladimirov V.G., Sergeenko V.I., 1986]. In recent years, a promising method of preemptive conservative treatment at the early stage of the disease, with the aim of "interrupting" it, has been developed [Krasnogorov V.B. et al., 1998; Tolstoy A.D. et al., 2001; Bagnenko S.F. et al., 2002]. Nevertheless, there will always be a group of patients for whom surgical treatment is indicated [Kukosh M.V. et al., 1998]. The timing of surgical interventions is determined by the timing of hospitalization, the time of initiation of therapy, the volume and efficacy of treatment, and depends on the etiology, form, and severity of the disease [Nesterko Yu.A., Laptev V.V., 1988; Beger H.G., 1989, 1991; D'Egilio A., Schein M., 1991; Buchler M. et al., 1992]. Recently, most authors have indicated that surgical intervention in the zone of sterile necroses is fraught with the development of purulent complications [Mayat B.C. et al., 1980; Laptev V.V. et al., 1993; Ferguson S.M., Bradley E.L., 1990], whereas in most patients with complicated acute pancreatitis, adequate and potent conservative therapy leads to resorption of foci of destruction without causing infection [Savelyev B.C. et al., 1999; Beger G.G., Eisenman R., 2002; Ranson J.H.C., 1979, 1981; Schaffner J., 1992]. In the opinion of some authors, one should altogether refuse surgical interventions in the early phases of the disease and operate on patients only upon the development of purulent complications [Tsatsanidi K.N. et al., 1988; Savelyev B.C. et al., 1999; Bagnenko S.F. et al., 2002; Filimonov M.I. et al., 1999, 2003; Beger G.G., Eisenman R., 2002; Ranson J.H.C., 1981, 1984; Smadja S., Bismuth H., 1986; Bradley E.I., 1996]. At the same time, ischemic pancreatic tissue, necrotized retroperitoneal fat, and enzymatic peritoneal exudate serve as a source of endotoxemia, polyorgan insufficiency, and infection. The development of systemic inflammatory response syndrome before surgery leads to high mortality: with insufficiency of one organ it reached 40%, of two organs – 60%, and of three or more organs (for at least 3 days) – 98% [Knaus W.A. et al., 1985]. The question of indications for surgery in sterile pancreatic necrosis is not finally resolved [Kubyshkin V.A., 1985; Gostishchev V.K., Glukhko V.A., 1996; Burnevich S.Z. et al., 2000; Fugger R. et al., 1991; Bradley E.L., 1993; Bosscha K. et al., 1998]. One of the indications for emergency surgery is the progression of complicated acute pancreatitis and enzymatic peritonitis [Emelyanov S.I. et al., 1986; Shevchuk M.G. et al., 1988; Pederzoli P. et al., 1990]. At the same time, the results of surgical treatment of destructive pancreatitis remain far from reassuring, and mortality reaches 32–66% [Ivanov Yu.V., Mozgalin A.G., 1999]. The causes of such high mortality include: late hospitalization, errors in diagnosis and determination of disease severity, untimely and incomplete conservative basic therapy, and very often late surgical treatment, often disproportionate to the extent of necrosis in the pancreas and peripancreatic fat [Kukosh M.V., Gomozov G.I., 1995]. Surgeons still quite often perform laparotomy for diagnostic purposes without preoperative verification of pancreatic necrosis, and in the case of infected pancreatic necrosis, the operation often ends only with drainage and tamponade of the abdominal cavity, without performing radical necrosectomy interventions [Kukosh V.I. et al., 2000; Makarov N.A. et al., 2001]. In choosing the diagnostic and therapeutic strategy in destructive pancreatitis, an important place is occupied not only by reliable, objective, and timely assessment of foci of necrosis and their extent in the pancreas and peripancreatic fat, the character of peritoneal exudate in the abdominal cavity, but also by the assessment of the severity of the patient's condition before surgery. At present, the most commonly used prognostic scales are: Savelyev B.C. (1993), Ranson (1974), Glasgow (1984), APACHE-II (1985), Tolstoy A.D. (1997), Vashchenko R.V. et al. (2000). The Ranson prognostic criteria are effective in only 77% of patients [Puolakkainen P. et al., 1986; Teerenhovi O. et al., 1988; Demmy T. et al., 1988]. Therefore, in recent times, instrumental diagnostic methods have been introduced: ultrasonography (US), laparoscopy (LC), and computed tomography (CT) [Danilov M.V., Fedorov V.D., 1995; Fedorov V.D. et al., 1999; Rozin D., 1998]. At present, certain aspects of early diagnosis and comprehensive treatment of destructive pancreatitis remain debatable. Above all, these include dynamic assessment of disease severity, diagnosis of the depth and extent of destruction in the pancreas and retroperitoneal fat in sterile pancreatic necrosis, and thus the choice of indications for conservative or surgical treatment at optimal times. The most optimal timing of pancreatic resection in disseminated pancreatic necrosis has not been fully addressed [Gagushin V.A., 1988], nor has retroperitonealostomy in massive necrotic parapancreatitis [Eramishantsev A.K., 1996; Galperin E.I., 2000]. To date, there is no single classification of acute pancreatitis recognized by all surgeons [Bagnenko S.F. et al., 2002]. Moreover, the indications for a reasonable combination of laparotomic and minimally invasive interventions aimed not only at drainage but also at eliminating foci of destruction both in the pancreas and retroperitoneal fat have not been fully determined [Galperin E.I., 2000]. Thus, the relevance of the problem of developing early diagnosis in complicated acute pancreatitis and prognostic criteria, which would allow timely selection of the most optimal therapeutic strategy, including the performance of adequate-volume surgical interventions and ensuring the prevention of postoperative infectious complications, becomes obvious.

Goal of the Investigation

To develop a differentiated diagnostic and therapeutic strategy based on early diagnosis of complicated acute pancreatitis and its assessment using prognostic criteria, with the selection of patient groups requiring conservative or selective surgical treatment.

Tasks of the Investigation

1. To create an algorithm for early diagnosis of acute destructive pancreatitis.

2. To develop a system of prognostic criteria for the severity, progression, and risk of fatal outcome of complicated acute pancreatitis.

3. To evaluate the existing classification and develop a convenient, comprehensive classification of acute pancreatitis, including destructive forms.

4. To identify the main causes of fatal outcomes in destructive pancreatitis.

5. To develop a differentiated surgical strategy in complicated destructive pancreatitis depending on the extent of destruction of the pancreas and retroperitoneal fat, as well as the prevention of destruction in the pancreas in biliary ductal acute pancreatitis.

6. To study the efficacy of splen-preserving resections of the pancreas and operations with splenectomy, depending on the volume of removed necrotic pancreatic tissue and the age of patients, in complicated disseminated pancreatic necrosis.

7. To determine the frequency of diabetes mellitus after pancreatic resections and drainage operations, and to study the role of decompensated diabetes mellitus in the development of postoperative purulent-septic complications and mortality.

8. To determine the factors of high risk for the development of postoperative infectious complications in complicated destructive pancreatitis.

9. To identify immune disturbances in complicated acute pancreatitis and to study the possibilities of antibiotic prophylaxis and early immunocorrection in reducing the frequency of postoperative infectious complications and mortality.

Scientific Novelty of the Investigation

A diagnostic and therapeutic algorithm has been developed for progressive biliary (ductal) acute pancreatitis and parenchymatous complicated acute pancreatitis.

For diagnosing the extent of sterile and infected pancreatic necrosis (parapancreatitis), computed tomography with double contrast and assessment of the volume of destruction of the pancreas and retroperitoneal tissue have been proposed. Prognostic criteria for determining the severity, progression, and risk of fatal outcome in patients with sterile complicated acute pancreatitis have been proposed, with the allocation of 2 groups: those requiring conservative and selective surgical treatment.

A scientific classification of acute pancreatitis has been developed, based on etiopathogenetic principles, with the allocation of disease phases, the extent of necrosis in the pancreas (retroperitoneal tissue) depending on the volume of destruction, as well as local and systemic complications. The efficacy of early closed drainage operations on the abdominal cavity and retroperitoneal fat in complicated acute pancreatitis (less than 50% of the pancreas) has been proven, compared with open drainage interventions. In progressive complicated disseminated sterile pancreatic necrosis involving more than 50% of the pancreas (without diffuse enzymatic parapancreatitis), early extended splen-preserving resections of the pancreas have been proposed (with the aim of preventing systemic inflammatory response syndrome).

With the aim of preventing pancreatic destruction, in patients with biliary (ductal) edematous pancreatitis, early (within the first 48 hours) radical operations on the common bile duct (choledochoduodenostomy) and bile duct stenting (endoscopic papillosphincterotomy) have been proposed. For the reduction of the frequency of infectious complications in severe complicated acute pancreatitis, a combination of antibiotic prophylaxis (intravenous and endolymphatic) with immunosuppressive therapy (T-activin) is recommended.

Practical Significance of the Work

1. A three-stage method for early diagnosis of complicated acute pancreatitis has been proposed, including an emergency stage, a dynamic stage, and a concluding (preoperative and intraoperative) stage, aimed at identifying the etiology and pathogenesis of acute pancreatitis, the degree of destruction in the pancreas and retroperitoneal tissue, and local and systemic complications.

2. The refined scientific classification of acute pancreatitis allows for a more targeted approach to solving the problems of early diagnosis and effective treatment of destructive forms and their complications.

3. In accordance with the etiology and pathogenesis of acute pancreatitis, the following forms have been identified: ductal, parenchymatous, and mixed, which allow for optimal treatment aimed at interrupting the pathological process at an early stage of the disease.

4. Contrast CT diagnosis of complicated acute pancreatitis has been introduced, with the allocation, depending on the magnitude of pancreatic destruction, of local complicated acute pancreatitis (up to 30% of the pancreas), diffuse complicated acute pancreatitis (less than 50% of the pancreas), disseminated complicated acute pancreatitis (more than 50% of the pancreas), as well as, depending on the degree of infiltration of the retroperitoneal tissue, of local parapancreatitis (one fat compartment) and diffuse (two or more fat compartments).

5. Prognostic criteria for assessing the severity, progression, and risk of fatal outcome in complicated acute pancreatitis have been developed, with the allocation of two groups of patients: those requiring conservative and those requiring selective surgical treatment.

6. A differentiated surgical strategy in complicated acute pancreatitis (less than 50% or more than 50% of the pancreas) has been proposed, using both closed drainage operations and radical interventions (pancreatic resections, necrosectomies).

7. A splen-preserving pancreatic resection with preservation of the short gastric vessels has been developed for complicated disseminated pancreatic necrosis (more than 50% of the pancreas) in patients under 60 years of age.

8. The surgical strategy has been determined for progressive biliary acute pancreatitis (with mechanical jaundice and destructive cholecystitis).

9. Factors of high risk for the development of postoperative infectious complications and fatal outcome in severe complicated acute pancreatitis have been identified, and proposals have been developed for their reduction using: radical operations on the pancreas and retroperitoneal tissue, extracorporeal therapy, antibiotic prophylaxis, and early immunosuppressive therapy with correction of hyperglycemia.

Publications

Based on the materials of the dissertation, 50 scientific works have been published, 9 of them in publications recommended by the Higher Attestation Commission, 1 monograph, 1 textbook, and 1 methodological recommendations. 15 certificates for rationalization proposals have been obtained.

Public Presentation of the Work

The main provisions of the investigation were presented in reports at the XI International Conference of Surgeons-Hepatologists of Russia and the CIS "Actual Problems of Surgical Hepatology" (Smolensk, 1999), the All-Russian Conference of Surgeons "Actual Questions of Surgery of the Pancreas and Abdominal Aorta" (Pyatigorsk, 1999), the International Congress of Surgeons (Petrozavodsk, 2002), the IV Russian Scientific Forum with International Participation "Saint Petersburg – Gastro-2002" (Saint Petersburg, 2002), the Russian Scientific-Practical Conference with International Participation "Clinical and Theoretical Aspects of Acute and Chronic Pain" (Nizhny Novgorod, 2003), the 1st Congress of Physicians of Russian Railways (Moscow, 2004), the IV International Conference "Actual Aspects of Extracorporeal Blood Cleansing in Intensive Care" (Moscow, 2004). The results of the work were reported and discussed at an expanded meeting of the Department of Hospital and Military Field Surgery with a course of Disaster Medicine and Civil Defense of the Military Medical Institute of the FSB of Russia and the Scientific Society of Surgeons of Nizhny Novgorod and the Oblast (2005).

Main Propositions to be Defended

1. Prognostic criteria for severity, progression, and risk of fatal outcome, together with contrast CT, allow the allocation of groups of patients with complicated acute pancreatitis who are candidates for conservative or selective surgical treatment.

2. The improved scientific classification of acute pancreatitis makes it possible to select an optimally justified diagnostic and therapeutic strategy in complicated acute pancreatitis.

3. The identification, in severe complicated acute pancreatitis, of two groups of patients with disseminated complicated acute pancreatitis (more than 50% of the pancreas) and diffuse-local complicated acute pancreatitis (less than 50% of the pancreas), makes it possible to use two types of surgical interventions: radical – splen-preserving pancreatic resections and necrosectomies, or closed drainage operations on the abdominal cavity and retroperitoneal tissue.

4. Prognostically unfavorable signs of fatal outcome in complicated acute pancreatitis and factors of high risk for the development of postoperative infectious complications make it possible to develop pathways for their prevention, including: radical operations on the pancreas and retroperitoneal tissue, extracorporeal therapy, antibiotic prophylaxis with early immunosuppressive therapy, and correction of hyperglycemia with insulin.

Implementation in Practice

The results of the investigations are used in the Municipal Healthcare Institution of the City Hospital No. 13 of Nizhny Novgorod, the Nizhny Novgorod Road Clinical Hospital, the Municipal Healthcare Institution of Clinical Hospital No. 40, and the Municipal Healthcare Institution of Clinical Hospital No. 33 of Nizhny Novgorod. The materials of the dissertation are used in the training of listeners and clinical residents at the Department of Hospital and Military Field Surgery with a course of Disaster Medicine and Civil Defense of the Military Medical Institute of the FSB of Russia.

Structure and Volume of the Dissertation

The dissertation is presented on 355 pages and consists of an introduction, a literature review, 6 chapters of original research, a conclusion, conclusions, and practical recommendations. The bibliography contains 277 works by domestic and 313 works by foreign authors. The work is illustrated with 46 tables and 56 figures.