CC BY
72
UDC 616.37-002-089
MODERN APPROACHES TO SURGICAL TREATMENT OF PANCREATIC NECROSIS
Altai State Medical University, Barnaul
Regional Clinical Hospital of Emergency Medical Care, Barnaul
V.G. Lubiansky, A.N. Zharikov, G.A. Arutyunyan, V.V. Nasonov, V.M. Bykov, D.N. Ustinov, A.R. Aliyev
A retrospective analysis of surgical treatment of 581 patients with pancreatic necrosis with its delimited and widespread forms was conducted. It was found that with abscessed (delimited) forms of purulent process, lethality was 9,1% (10 patients), whereas in generalized, purulent-septic phlegmon of retroperitoneal tissue it reached 50,2% (101 deaths). Experimental studies have shown that in the process of limitation, the leading role is played by the restoration of perfusion blood circulation deficiency in the zone of ischemic pancreatic tissue with the help of local rheological therapy (alprostadil). Along with this, it is established that the processes of restriction in retroperitoneal cellulose are affected by the immaturity of fibrin, which is constantly destroyed by enzymes of the pancreas. In this connection, the possibility of creating a tissue barrier on the path of enzymatic impregnation with the help of a fibrinogen donor (cryoprecipitate) is shown. Achieving early delimitation of the enzymatic-inflammatory process in retropancreatic cellulose allows the formation of cysts or fluid clusters, which can be drained with the help of minimally invasive technologies.
Key words: pancreatic necrosis, pancreatic cysts, rheological therapy, delimitation barrier, minimally invasive technologies.
In recent years, the problem of pancreatic necrosis (PN) has been the leading one in urgent surgery [1]. It is connected with high incidence, which today constitutes from 200 to 800 cases per 100 thousand people [2]. According to professor A.V. Shabunin, in 2015 - 2016 acute pancreatitis took the lead in urgent pathology in Moscow. In other regions it holds stable second or third positions according to incidence. Acute pancreatitis case mortality rate ranges between 18-20%, while by infected forms of pancreatic necrosis it reaches 30% [3,4,5]. If the diagnostics of acute pancreatitis is characterized by a significant progress [6], the surgical tactics involves a variety of methods and approaches far from standard decisions [7,8,9]. In this regard, the problem of delimitation of enzymatic process and inflammatory process, which to a great extent determines progressive course of illness, is of special interest [10]. The elaboration of stimulation methods of delimitation processes and rational surgical approaches is expedien-tial at modern stage, the terms of surgery and choice of method depend exactly on them. The arsenal of surgeons includes both minimally invasive technologies [11, 12, 13, 14] and open methods of treatment, which have their own pathogenetic ground in a number of patients [15].
Objective: to study the possibilities of delimitation of enzymatic-inflammatory process in pancreatic gland and retroperitoneal cellulose in patients with pancreatic necrosis.
Materials and methods
In 2014 in a clinical setting, there were conducted researches devoted to the evaluation of blood circulation in the tissue of pancreatic gland (PG) by pancreatic necrosis [16]. By angiography of celiac
38
artery, circulation there was revealed the blockage of distal blood stream, determined by the disorder of microcirculation and edema of pancreatic gland tissue. The main angiographic feature by the insertion of catheter into gastroduodenal artery (GDA) was the depletion of blood stream of head, body and tail of pancreatic gland (Figure 1).
Exactly the disorders of blood circulation in PG stipulate further necroses, enzymic fistulas with the extension of inflammatory process on retroper-itoneal cellulose. Thus, the intake of drugs improving blood circulation in pancreatic gland at early stages seems appropriate. However, their systemic implementation preconditions the risk of bleedings. At the same time, clinical practice possesses the experience of using topical drugs improving regional blood flow. In this context, there was conducted comparative examination of 125 patients with acute pancreatitis divided into 3 groups. Traditional technologies in patients with open surgeries (1 group) by pancreatic necrosis were compared to patients with local regional therapy in gastrodu-odenal artery and celiac artery (Table 1).
In the second group of patients there was used alprostadil (vazaprostan) aimed at the liquidation of endothelial dysfunction and opening of peripheral blood stream. The drug is intended for in-tra-arterial injection. Finally, in patients of the third group there was made intra-arterial injection of pentoxifylline with heparin aimed also at anti-aggregatory activity and opening of blood stream. The groups were comparable according to gender, age, duration of disease and also main laboratory parameters (Table 1). The inflammatory process by acute pancreatitis in all groups was characterized by high leukocytosis, stab shift with the increase of enzyme activity.
Note: statistically significant differences of control with parameters of 1,2 and 3 groups: * - p<0,05, ** - p<0,01, *** - p<0,001.
Figure 1.
Angiography in GDA: 1 - GDA; 2 - depletion of blood stream in the zone of head; 3 - catheter in GDA; 4 - deposition of contrast in body and tail of pancreatic gland
Table 1
Initial main laboratory parameters in patients with acute pancreatitis in groups
Parameter Control Group 1 (n=27) Group 2 (n=33) Group 3 (n=65)
X±m X±m X±m
Hemoglobin gm/dl 120,3±1,3 120,6±4,7 127,6±4,7 124,0±4,5
p1-2>0,05 p2-3>0,05 p1-3>0,05
Thrombocytes x109 280,7±15,7 288,9±14,5 303,9±25,9 292,3±17,4
p1-2>0,05 p2-3>0,05 p1-3>0,05
Leucocytes x109 8,3±1,6 14,9±0,7*** 15,2±0,8*** 14,5±0,4***
p1-2>0,05 p2-3>0,05 p1-3>0,05
Stab neutrophiles 2,1±1,7 13,6±1,1*** 16,4±1,6*** 14,4±0,9***
p1-2>0,05 p2-3>0,05 p1-3>0,05
Creatinin mcmol/l 115,8±11,8 126,8± 0,0 123,8±13,0 130,2±10,8
p1-2X ,05 p2-3>0,05 p1-3>0,05
Urea mcmol/l 8,5±0,7 9,6±1 ,1 9,7±0,9 9,6±0,9
p1-2X ,05 p2-3>0,05 p1-3>0,05
Total protein gm/dl 74,5±2,1 60,0±1, 5*** 64,4±1,2*** 60,6±1,1***
p1-2X ,05 p2-3>0,05 p1-3>0,05
Amylase u/l 67,3±9,5 223,1±3( 1 2*** 480,6±87,3*** 256,0±31,9***
p1-2X ,05 p2-3>0,05 p1-3>0,05
Total bilirubin mmol/l 16,5±1,4 23,5±2 ,6* 32,8±5,7** 28,0±2,9***
p1-2>( ,05 p2-3>0,05 p1-3>0,05
As a result, it was determined, that the implementation of local rheological therapy at early stages allows to abort the inflammatory process in pancreatic gland. Patients show the decrease or liquidation of infiltrates, drop in the number of lavages of the abdominal cavity from 3 to 1, shortage of the number of in-patient days from 35,8 to 24,8. The second and third groups of patients show the decrease of mortality (Table 2).
The conducted control angiography of GDA circulation showed, that intra-arterial injection of alprostadil into arterial phase leads to the resto-
ration of arterial stream in the head with decrease into the venous phase of the stasis of contrast agent in the head and tail of the pancreatic gland (Figure 2).
Especially effective was alprostadil (vazapros-tan) by injection into gastroduodenal artery. Intra-arterial drug injection determined the pain management, contributed to the prevention of necrosis site formation in the head of pancreatic gland or decrease of their depth (Fig. 3A, E). This effect is important in the prevention of small passages and the flux of enzymes into cellulose.
Table 2
Results of surgical treatment in groups of patients with pancreatic necrosis
Parameters 1 group M±m 2 group M±m 3 group M±m
Number of patients (n) 71 23 12
APACHE - 2 (grades) 12,3±0,7 12,7±1,1 11,8±2,9
Number of abdominal cavity lavages 3,1±0,3 1,0±0,3 1,0±0,5
P1-2 <0,001 P1-3<0,001 P2-3>0,05
Inpatient day 35,8±2,3 24,8±3,6 23,6±2,1
P1-2 <0,05 P1-3<0,05 P2-3>0,05
Mortality (%) 16,9 0 0
Figure 2.
Angiography in GDA after intra-arterial injection of alprostadil: 1 - appearance of vascular pattern in the head of PG; 2 - catheter in the gastroduodenal artery; 3 - appearance of splenic artery; 4 - lack of deposition in the body and tail
of pancreatic gland
The implementation of disaggregant infusion in combination with antibacterial therapy at late stages preconditions a less expressed clinical effect, but improves the results of treatment due to preservation of abacterial environment in the tissues of pancreatic gland not influencing the course of inflammation in the retroperitoneal cellulose.
A considerable number of clinical and experimental researches are devoted to the extension of inflammatory process to the retropancreatic cellulose by pancreatic necrosis. In the work of Fe-dina I.V. [17] it was for the first time shown, that the pancreatic capsule in its back surface is significantly thinner than its front and includes only one layer of connective tissue cells. The retroper-itoneal surface of the capsule has the areas of entry of vessels, through which the enzymic effusion enters cellulose and preconditions the progress of toxemia. According to our previous research
[18], retroperitoneal space produces direct resorption of enzymic effusion into the systemic blood circulation. The matter is that the liver with its reticulo-endothelial system is an effective barrier on the way of toxin influx into the systemic blood stream. The adjunction of their resorption from ret-roperitoneal cellulose boosts toxemia due to influx of toxic product through lumbar veins into lower hollow vein and further into lungs forming lung injury - lung distress syndrome.
This serve the basis for the analysis of treatment results of 581 patients with pancreatic necrosis with its delimited and common forms. Delimited forms included abscesses of pancreatic gland and retro-peritoneal cellulose having capsule in 118 patients. Common forms classified as phlegmons of retro-peritoneal cellulose or, according to the current classification, sterile or infected retroperitoneal necrosis, were registered in 200 patients. The others
had sterile pancreatic necrosis. The consisted of 406 men (69,8%), 175 women (30,2%). The average age was 47±68 years. The analysis of surgical treatment showed, that the mortality in patients with PN constituted 19,8% (114 cases). Mortality by sterile type was low - 3 patients (0,8%), which is connected with the lack of purulo-necrotic inflammation. By the infected forms of PN (abscess, phlegmon) the frequency of lethal outcomes grew and reached 32,7% (111 patients). It is characteristic that the rate of mortality in this group turned out to be signifi-
cantly differentiated. Thus, by abscess (delimited) forms of purulent process it constituted 9,1% (10 patients), while by generalized purulent-septic phlegmons of retroperitoneal cellulose it grew up to 50,2% 9 (101 case). Consequently, even by infected PN in case of formation of good tissue delimitation (demarcation zone) there is the possibility to localize the infection in the necrosis areas (ab-scessation or cyst formation). This aspect is a relatively favorable outcome and significantly improves the chances of recovery.
Figure 3. Computer tomography A - Pancreatic necrosis. 3rd day of the disease before intra-arterial injection of alprostadil: 1 - enlargement of gall bladder; 2 - tissue necrosis in the zone of PG tail, 3 - edema and infiltration in the parapancreatic cellulose in the zone of body and tail of PG, 4 - edema and infiltration of retropancreatic cellulose, 5 - edema and infiltration of the front folium of the left pararenal fascia. E - Pancreatic necrosis after the treatment on the 5th day (the same patient): 1 - decrease of gall bladder size; 2 - necrosis in the zone of PG tail; 3 - decrease of edema and infiltrative changes in the parapancreatic cellulose in the zone of body and tail of PG, 4 - decrease of edema and infiltration of retropancreatic cellulose and
the front folium of the left pararenal fascia
In confirmation of that, we had conducted a series of experiment modelling the correlation of plasm fibrinogen/fibrin with proteolytic enzymes (chymopsin) really occurring by pancreatic necrosis in parapancreatic infiltrate. For this purpose were used: native stabilized human plasm and officinal diagnostic and treatment agent - 5% solution of aminocaproic acid (OAO "Krasfarma", Krasnoyarsk, RF), thrombin (OOO "Technology-Standard", Barnaul, RF), 1 % solution of calcium gluconate (OAO "Farmak", Kiev, Ukraine), solution of chymopsin (OOO "Samson", Saint-Petersburg, Russia). The conducted tube tests showed, that the enzymes of pancreatic gland (fresh native juice, Chymopsin drug) possess the expressed properties for the suppression (rapid slowdown) of fibrin clot formation in human plasm. However, the most interest was attracted by a series of experiments aimed at the study of dynamics of unstable fibrin clot lysis under the influence of both native juice of pancreatic gland and the standardized drug Chymopsin (chymotrypsin + trypsin). To make the process maximum objective there was evaluat-
ed the dynamics of the weight change of the newly formed fibrin clots in the context of 60 second (1 group) and 900 second (2 group) maturity.
As it is shown in Table 3, the addition of chymopsin into the tubes with fresh fibrin clots in the first series of experiment lead a significant and statistically valid lysis of freshly obtained fibrin clots, mainly up to 2/3 of the initial weight. It is typical, that proteolytic enzymes did not influence the weight of more mature clots (900 second maturity), in other words, did not lead to their lysis (Table 3).
Consequently, the intensive process of fibrin formation in the retroperitoneal cellulose by acute pancreatitis can be simultaneously and continuously accompanied by proteolytic lysis of newly formed unstable (immature) fibrin (fibrinolysis) by the enzymes of pancreatic gland actively entering the retroperitoneal cellulose.
Thus, the lack of biologically consistent delimiting tissue barrier by infected pancreatic necrosis is extremely unfavorable for the course of illness with uncontrolled extension of septic phlegmon in
The natural donator of fibrinogen was the blood product - cryoprecipitate, made out of fresh-frozen donor cryoplasm. The original experimental method of creation of fibrin "tissue barrier" included injected infiltration of parapancreatic cellulose by cryoprecipitate solution in combination with solutions of aminocaproic acid and calcium gluconate. To obtain the medical parapancreatic infiltrate the retroperitoneal parapancreatic cellulose was injected with 50-75 ml of such mixture on the model of experimental pancreatic necrosis. The analysis of histologic specimen revealed, that parapancreatic fatty tissue, already on the 1st day after the experiment, contained a network of numerous small centers (deposits) of fibrin. Especially well observed were numerous insular deposits of "fresh" fibrin on the background of leukocytic infiltration in the retroperitoneal cellulose.
Table 3
The dynamics of dissolution of freshly formed fibrin clots by their reaction with chymopsin drug (5 mg) and 5%
aminocaproic acid (daily exposure dose)
Laboratory experiment conditions Fibrin weight (dry) (mg)
Fibrin clot (60 second maturity) - daily exposure dose with physiological solution (control) 80,1±2,5
Fibrin clot (60 second maturity) daily exposure dose with chymopsin (5 mg) 30,2±2,6 p<0,001
Fibrin clot (60 second maturity) daily exposure dose with chymopsin (5 mg) by aminocaproic acid 41,3±8,8 p!<0,01 p2<0,05
Fibrin clot (900 second maturity) daily exposure dose with chymopsin (5 mg) 76,8±1,7 p>0,1
Note: p1 - statistical significance of the variation from control parameter (physiological solution), p2 - statistical significance of the variation from the parameter in the experiment with isolated chymopsin activity.
At the same time, the zone of formation of a "delimiting barrier" was characterized by the appearance of numerous fibroblasts, separate capillary vessels. Such histological picture is typical for the formation of local center of granulation tissue and is one of the conditions for further development of cicatrical encapsulation - tissue limitation of necrotic tissues and cyst formation.
In a clinical setting the terms of barrier formation and delimitation are significantly varied. First and foremost, they depend on the immunobiologi-cal state of the organism and presence of multi-organ failure. The matter is that enzyme toxemia has an expressed immunodepressive effect. The disorder of protein synthesis predetermines prolongation of barrier formation terms, while the depression of lymphoid element synthesis by sepsis does not favor their migration to the center of inflammation. Thus, modern adequate treatment contributes to the delimitation with cyst formation and fluid assembly in the retroperitoneal cellulose. There ex-
the retroperitoneal cellulose and influences badly the prognosis of pancreatic necrosis course.
The analysis of immediate clinical outcomes of the surgical treatment of patients with pancreatic necrosis and experiments showed the necessity of conduction of treatment measures aimed at the localization of purulent-destructive process and constraint of the spread infection in the form of local center - cyst or abscess. This condition could be reached by means of formation of an effective natural or artificial tissue delimitation barrier, while the process is localized in the borders of parapancreatic cellulose and its course is aseptic. According to this assumption, there were conducted experiments on 8 animals (outbred dogs weighing from 20 to 28 kg) with modelling of acute pancreatitis and further creation of an artificial fibrin barrier in the retroperitoneal cellulose.
Figure 4. Microphoto Experimental reproduction of "fibrin" barrier
in the retroperitoneal cellulose by injection of cryoprecipitate (5th day): 1 - fibrin of various maturity; 2 - fatty tissue. Van Gieson's staining, x 80 zoom
ists a group of patients with retroperitoneal necrosis which further develops into phlegmon of retroperitoneal cellulose, though by adequate therapy the number of such patients does not exceed 10 % of the total cohort. Consequently, the main trend in treatment of pancreatic necrosis is the delimitation of inflammation and cyst formation. Usually, according to the endoscopic ultrasonic examination, depending on the state of patient these terms range from 4 to 6 weeks.
The drainage of formed delimitation elements (false cysts and fluid assembly) is in the focus of the researches conducted in clinical setting by assistant Nasonov B.B. Types of drainage vary from trans-intestinal to paracentetic endermic or drainage through minimal access. Firstly, there was made the analysis of the results of transabdominal drainage of postnecrotic cysts in 26 patients with medium and severe forms of acute pancreatitis in the age from 28 to 64. These patients were operated after the formation of delimitation barrier and appearance of postnecrotic cyst in 3-4 weeks after the disease onset (sequestration phase of acute pancreatitis). After the formation of postnecrotic cysts there were made puncturing under US control with further insertion of 10 mm drainages for lavage and sequestrotomy. According to the results of dynamic US and fistulogra-phy, it was stated, that the cyst cavity collapsed after drainage gains irregular form. This can lead to not always total emptying with further abscess formation and requires extension of wound. Thus, 12 (46%) patients were exposed to reintervention with the extension of existing drainage wound up to 4-5 sm and resection of sequestra by open method through minimal access with substitution of drainages for the bigger ones. Respectively, the duration of hospital treatment of such patients was prolonged (averagely from 25,4±1,5 to 38,1±2,1 days). In 3 (11,5%) of them the conduction of repeated transcutaneous drainage under US control turned out to be sufficient. 11 (42,3%) patients out of 26 did not require reintervention. The clinical picture of the course of acute pancreatitis in all cases had positive dynamics. The duration of hospital treatment after the conducted minimal invasion constituted averagely 22,5±1,7 days. Positive dynamics after transcutaneous paracentetic drainage of postnecrotic cysts and through minimal access was registered by dynamic US and CT of the abdominal cavity made during postsurgical period. The analysis of the treatment outcomes showed, that among the patients three died, which constituted (11,5%). They had developed the clinical picture of abdominal sepsis on the background of long-term treatment.
In recent years, we have implied trans-intestinal drainage in treatment of postnecrotic PG cysts. The method was introduces due to wide implementation of bolus MSCT and endoscopic ultra-
sonography (EUS) [19], which allow to evaluate the topographic anatomic distribution of postne-crotic cysts, their correlation with stomach wall, the degree of capsule maturity and its thickness (Figure 5).
Figure 5.
Sterile pancreatic necrosis. MSCT of abdominal cavity (contrast per os): postnecrotic cyst (4), zone of attachment to the stomach wall (3)
We have examined the treatment of 26 patients. According to trans-abdominal US the formed capsule was revealed in 10 (45%) patients, according to MSCT - in 1 (4,5%) patient, by EUS - in 22 (90%) out of 24 patients. In 2 patients there were registered fluid assemblies, which differed from cysts by the lack of the wall on the background of inflammatory infiltration of surrounding tissues (Fig. 6a). EUS allows to determine not only the degree of delimitation of the forming cyst in the optimum way, but also the presence of sequestra in its cavity (Figure 6b).
Finally, by using Doppler mapping regime it is possible to choose a nonvascular section suitable for transgastral cyst emptying [20]. During the examination it is also possible to evaluate the diameter of Wirsung's duct and its correlation with the cyst. The procedure of transgastral drainage begins with the puncturing of stomach wall through nonvascular "route". Then in the point of content extraction, which is found in the area of cyst prolapse into the stomach, the stomach wall was burned through in the targeted point by cys-totome and the cyst lumen was cannulated, there was made the PG enzyme sampling of content, cytological examination, bacterial flora inculation. Through the cystotome canal the guidewire was inserted into the cyst lumen, through it there was installed a 16-18 mm balloon after the removal of tube with further dilation of the whole in the posterior stomach wall. Then there was made the exploration and sanation of cyst cavity, and if necessary -sequestrotomy. It should be mentioned, that there
is a risk of bleeding, that is why the whole should not exceed 1-2 sm. In cases, when it has a tendency to stricture formation, it is possible to be extended by a repeated balloon dilation or subsidiary incision (Fig. 7a) with the removal of sequestra
by means of a special trap-basket (Fig. 76). The san-ation of cyst cavity and removal of free lying sequestra are reasonable to be done not earlier then in 2-3 days after drainage.
Figure 6. EUS
Sterile pancreatic necrosis. A - fluid assembly from infiltrate in parapancreatic cellulose without capsule. E - postnecrotic cyst of peritoneal omental sac with formed walls (capsule) and sequestra (1)
Figure 7. EUS
A - Balloon dilation of the whole in the stomach for cyst-gastroanastomosis formation by pancreatic necrosis. E - Necrotic sequestrotomy through the formed cyst-gastroanastomosis
During postsurgical period there was performed dynamic observation with the evaluation of the state of anastomosis and cyst cavity on the 3rd, 7th and 14th day. By examination on the 3rd day there was registered the reduction of cyst-gastroanasto-mosis size, though the gastroscop easily enters the cyst lumen. By the observation in the cyst cavity there were seen the remnants of necrotic masses on the walls, the cavity lumen reduced considerably. On the 5th day, as a rule, there can be observed the diminution of cyst lumen and the reduction
of the cyst-gastroanastomosis diameter. To prevent early closure of anastomosis there is carried its balloon dilation leaving stents of "pigtail" type (Figure 8 a,b).
By the observation on the 14th day the cyst walls cleared totally, were covered with single fibrin strands, the cyst lumen reduced significantly. The endoscopic drainage of postnecrotic cysts was performed in 26 patients. 23 (87,5%) of them were with cyst, 3 (12,5%) patients had fluid assemblies on the background of PN. The average
period of postnecrotic cysts formation constituted 4,5 months. According to the visualization methods, cysts were localized: in 19 (73,07%) patients in the projection of the left sections of PG (body-tail), in 6 (23,07%) in the projection of right sections of PG. In 1 (3,86%) case the cyst of large and PG was not clearly visible. The sizes of fluid assemblies varied from 5.5 sm to 30.0 sm. Cystogastros-
tomy under EUS control was performed in 12 patients, in 3 cases - transgastral cyst stenting, in 9 patients - transgastral puncturing of cysts and fluid assemblies. The thickness of cyst capsule constituted 2,2±1,2 mm. For all patients there had passed 6 weeks after the disease onset. Complications during postsurgical period were not registered. Cyst recurrence in long dates did not occur.
Figure 8. Sterile PN
Formed false postnecrotic cyst: A - EUS. Cyst-gastroanastomosis with inserted stents of "pigtail" type, E - MSCT of abdominal cavity (3D reconstruction). Location of stents draining the cyst (arrow)
Transgastral drainage under EUS control possesses a number of obvious advantages, the most important of which is the lack of laparotomy, sufficient emptying of cyst into the stomach lumen, additional lysis of sequestra by hydrochloric acid entering the cyst cavity from the stomach. Considering quick reduction of cyst size, it is also significant, that by the mentioned treatment method the length of patient's stay in the hospital and treatment expenditures are reduced.
With respect to the obtained data, there arises the question of presence of open operations in pancreatic necrosis surgery. In our opinion, they can and should be implemented by septic phlegmons being the consequence of common retroperitoneal necrosis. However, open surgery is always accompanied by introduction of infection and is connected with the risk of abdominal bleedings in consequence of protracted bandaging, there is always a risk of spleen injure, vessel arro-sion and formation of immature intestinal fistula. Finally, long-term treatmen and contamination lead to abdominal sepsis with further disorders of blood coagulation system, risk of PATE, heart attacks and brain attacks.
Conclusion
1. Local rheological therapy allows to improve blood circulation in the vascular circulation of pancreatic gland and reduce the risk of necrosis progression.
2. The influx of enzymes from necrosis centers of pancreatic gland preconditions enzymic lysis of fibrin and hinders the process of delimitation in pancreatic gland and parapancreatic cellulose.
3. Formation of delimitation barriers in the form of fibrous capsule of cyst happens upon the expiration of 4 - S weeks of illness and can be stimulated by local implementation of fibrinogen donators.
4.Local transdermal and transgastral cyst and fluid assembly drainage leads to the reduction of mortality in comparison with open drainage methods.
References
1. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Working Group IAP/APA (International Association of Pancreatology /American Pancreatic Association) Acute Pancreatitis Guidelines. Pancreatology. 2(13; 13: 1-15.
2. Dibirov M.D., Bagnenko S.F., Blagovest-nov D.A., Galperin E.I., Dyuzheva T.G., Prudkov M.I., Filimonov M.I., Chzhao A.V.
Russian clinical recommendations: Diagnostics and treatment of acute pancreatitis. Saint-Petersburg; 2014.
3. Yermolov A.S., Ivanov P.A., Turko A.P. Main causes of mortality by acute pancreatitis in Moscow hospitals. "Analysis of mortality by acute pancreatitis according to the materials of Moscow hospitals". Moscow: N.V. Sklifosovsky Research Institute for Emergency Medicine of Moscow Healthcare Department. 2001;
4. Grigoryev Ye.G., Sadakh M.V., Boiko T.N., et al. Necrotic meso- and paracolitis at terminal stage of infected pancreatic necrosis. Infections in surgery. 2008; 6(4): 38-43.
5. Dibirov M.D., Rybakov G.S., Ashimova A.A., et al. Causes of mortality by pancreatic necrosis and ways of its reduction. Infections in surgery. 2012; 10(2): 21-25.
6. Dyuzheva T.G., Dzhus Ye.V., Ramishvili V.Sh., Shefer A.V., Platonova L.V., Galperin E.I. Earlier CT-symptoms of predicting various forms of parapancreatic necrosis. Annals of surgical hepatology. 2009; 14(4): 54-63.
7. Shabunin A.V., Lukin A.Yu., Shikov D.V. Optimum treatment of acute pancreatitis depending on the "model" of pancreatic necrosis. Annals of surgical hepatology. 2013; 18(3): 70-78.
8. Stoyko Yu.M., Zamyatin M.N., Levchuk A.L. et al. Modern trends in treatment of destructive pancreatitis at early stages. Doctor. 2007; 12: 18-21.
9. Korymasov Ye.A., Machekhin P.V., Bog-danov V.Ye., Gorbunov Yu.V. et al. Clinical protocol of diagnostics and treatment of acute pancreatitis in Samara oblast. Samara: SSMU; 2010.
10. Timerbulatov V.M., Mustafin T.I., Tim-erbulatov M.V. Variants of dissemination of purulent-necrotic process by acute pancreatitis. Surgery. N.I. Pirogov journal. 2008; 4: 31-35.
11. Bagnenko S.F., Tolstoy A.D., Rukhlya-da I.V. Minimaly invasive technologies in treatment of severe forms of acute pancreatitis at different stages of disease. I.I. Gre-kov bulletin of surgery. 2002; 161(6): 30 - 34.
12. Achkasov Ye.Ye., Kharin A.L., Kanner D,Yu. Paracentetic treatment of false cysts of pancreatic gland. Surgery. 2007; 7: 65-67.
13. Morton J.M., Brown A., Galanko J.A., et al. A national comparison of surgical versus percutaneous drainage of pancreatic pseudocysts: 1997 - 2001. J Gastrointest Surg. 2005; 9: 15-204.
14. Bello B., Matthews J.B. Minimally invasive treatment of pancreatic necrosis. World J. Gastroenterol. 2012; 18(46): 6829-6835.
15. Prudkov M.I., Galimzyanov F.V. Evolution of infected pancreatic necrosis, topical diagnostics and treatment of complications. Annals of surgical hepatology. 2012; 17(2): 42-49.
16. Lubyansky V.G., Arutyunyan G.A., Aliyev A.R., Zharikov A.N. Correction of regional blood circulation in complex treatment of patients with acute pancreatitis. Annals of surgical hepatology. 2014; 3: 86-92.
17. Fedina I.Yu. Peculiarities of connective-tissue formations of human pancreatic gland and their role in the development of complications by pancreatic necrosis. 2011.
18. Lubyansky V.G., Chernenko V.F., Aliyev A.R., Zharikov A.N. et al. Role of organ-tissue barriers in the formation of systemic inflammatory reaction and neutralization of toxins by pancreatic necrosis, choice of rational tactics of complex surgical treatment. Bulletin of experimental and clinical surgery. 2011; 4(1): 51-56.
19. Zhandarov K.I., Savitsky S.Ye., Oslavsky A.I. Endoscopic drainage of pancreatic gland cysts. 12 Moscow international congress on endoscopic surgery, Russian scientific center of surgery named after member of Academy of Sciences B.V. Petrovsky of RASM. Moscow, 2008.
20. Vidyarthi G., Steinberg S. Endoscopic management of pancreatic. SurgClin North Am. 2001; 81: 405-410.
Contacts:
Corresponding author - Lubyansky Vladimir Grigoryevich, Doctor of Medical Sciences, Professor of the Department of hospital surgery with the course of further vocational education named after Professor I.I. Neimark of the FSBEI HE Altai State Medical University of the Ministry of Health of the Russian Federation, Barnaul. 656024, Barnaul, Lyapidevskogo Ulitsa, 1. Tel.: (3852) 689674. Email: [email protected]
