Medicine and physiology

DOI: https://doi.org/10.62204/2336-498X-2023-3-12

THE MAIN ASPECTS OF THE CLINICAL COURSE

OF ACUTE PANCREATITIS IN OBESE PATIENTS

Olha Tkachuk,

postgraduate student,

Shupyk National Healthcare University of Ukraine,

tkachukolga19@gmail.com; ORCID: 0000-0001-5048-1795  

Olexandr Pogorelov,

Ph.D. in Medezine,

Shupyk National Healthcare University of Ukraine,

avpogorelov60@’gmail.com; ORCID: 0009-0006-4560-0335

Varsik Dadayan,

Ph.D. in Medezine,

Medical Clinic “Grace”, Ukraine,

dr.varsik@gmail.com; ORCID: 0000-0002-6543-9159

Annotation. Obesity is a problem of the third millennium. It is known that obesity is the main factor in the development of various diseases, including acute pancreatitis.

The aim is to study the clinical course of acute pancreatitis in obese patients.

Patients with acute pancreatitis and obesity have a statistically higher percentage of the severe course of the disease (р=0.01; α=0.05), a positive relationship between the body mass index and the level of leukocytes (r=0.128; p=0.038) was found, and also with the level of C-reactive protein (r=0.18; p=0.003). It should also be noted that in obese patients, the level of interleukin-1 increases by 2.3 times (p=0.01; α=0.05), and the level of interleukin-6 by 2.4 times (p=0.01; α=0.05). A statistically significant difference in increased cytokine levels in obese patients suggests an enhanced protease response and a “cytokine storm” that is the starting point of a non-reversible chain reaction. In patients with third-degree obesity, a strong correlation with the severity of acute pancreatitis was established (r=0.85, p=0.001; α=0.05).

Keywords: pancreatitis, obesity, cytokine.

Obesity is a problem of the third millennium. It is known that obesity is the main factor in the development of various diseases, including acute pancreatitis. Obesity itself is a pro-inflammatory state with an increased level of such pro-inflammatory cytokines: tumor necrosis factor (TNF-a), interleukins (IL) IL-10, IL-6, IL-1b. Acute pancreatitis is also a disease whose pathogenesis is based on cytokine reaction and autolysis. Thus, against the background of an already formed inflammatory response, the inflammatory reaction is even more intensified and increased, and the level of pro-inflammatory cytokines reaches critical indicators.

The aim is to study the clinical course of acute pancreatitis in obese patients. 

Materials and methods. For the purpose of the study, among patients with severe acute pancreatitis and obesity (average BMI was 37.48±2.19 kg/m2), there were 482 cases of acute pancreatitis retrospectively. Patients were divided into 2 groups. The first group (n = 260) included patients with acute pancreatitis and obesity (experimental group), the second (control) – patients with acute pancreatitis and normal body weight (n = 222). General analysis of peripheral blood with determination of hemoglobin level, number of erythrocytes, leukocytes and platelets was performed using an automatic analyzer ABX Micros 60 (ABX Diagnostic, France). Blood was collected for biochemical research from the cubital vein after a 12-hour fast. When studying lipid metabolism, it was recommended to refrain from eating excessive food with an excessive fat content for three days before the study. Biochemical parameters and electrolytes of blood serum (bilirubin, aminotransferases, α-amylase, alkaline phosphatase, protein, glucose, creatinine, urea, calcium, sodium, potassium, phosphorus) were studied with Cobas devices Emira (“Roche”, Germany), and Humastar 300 (“Human”, Germany) using reagents from the company “Roche Diagnostics” (Germany). Determination of the level of procalcitonin in blood serum was carried out using a quantitative enzyme-linked immunosorbent assay (ELISA) RayBio Human Procalcitonin ELISA (RayBiotech Inc, USA) on the analyzer “Stat Fax 303 Plus”. In a healthy person, a procalcitonin level of up to 0.05 pg/ml is considered normal.

The concentration of  C-reactive protein (CRP) in blood serum was determined by turbidimetric analysis with a Cobas device Mira (“Roche”, Germany) using “Roche” reagents “Diagnostics” (Germany). The reference value of CRP in blood serum is from 0 to 5 mg/l. The concentration of interleukin-6 (IL-6) in blood serum was carried out using a quantitative ELISA with a Cobas 6000 device (“Roche”, Switzerland) using Roche reagents “Diagnostics” (Switzerland). Reference values of IL-6 in blood serum are 1.5-7.0 pg /ml. The concentration of interleukin-1 (IL-1) in blood serum was carried out using a quantitative immunochemical and immunochemiluminescent method with an IMMULITE 1000 device ( Siemens , Germany). Reference values of IL-1 in blood serum are up to 5 pg/ml. The statistical calculation of the obtained results was carried out using Excel 8.0 spreadsheets (Microsoft, USA) and the statistical program Statistica 10 (Microsoft, USA). To compare two independent parametric indicators, Student’s t-test was performed, if several independent parametric indicators were compared, simple variance analysis was used, taking into account the number of degrees of freedom (df). Relative indicators were compared using the χ² test. The relationship between the values was studied by Pearson’s correlation analysis (in the case of a normal distribution of the variation series) or Spearman’s rank correlations (if the values were not subject to a normal distribution) with the determination of the correlation coefficient (r).

The results. According to the results of laboratory data, a moderate increase in the level of leukocytes was noted in both obese and normal weight patients (Table 1). The level of leukocytes in obese patients was 1.31 times higher than in the control group (p=0.03; α=0.05). The creatinine level of both obese patients and the control group was higher than normal (151.26±7.56 compared to 116.56±8.08; p=0.03, α=0.05). The urea index, despite the statistically significant difference (p=0.04, α=0.05), was increased only in obese patients. A decrease in the level of albumin less than 32g/l was registered in the two compared groups (25.79±2.47 compared to 28.81±2.21; p=0.001, α=0.05). In obese patients, we note a 1.5 times higher glucose level compared to the control group (p=0.001, α=0.05). The level of interleukin-1 in obese patients was 2.3 times higher compared to the control group (p=0.01, α=0.05); interleukin-6 was 2.4 times higher, respectively (p=0.01, α=0.05). In the study group, a 1.7-fold increase in the level of procalcitonin was registered compared to the control group (p=0.01, α=0.05).

                                                                                                                Table 1

Basic laboratory indicators of people with acute pancreatitis

With the help of multiple regression, a positive relationship between body mass index and

• leukocyte level (r=0.128; p=0.038);
• the level of C-reactive protein (r=0.18; p=0.003);
• interleukin-1 level (r=0.14; p=0.034);
• interleukin-6 level (r=0.27; p=0.004);

The results of the analysis of the actual material regarding the dependence of the severity of the course of acute pancreatitis on the presence or absence of obesity are presented in Figure 2 . It was found that 171 (35.48%) patients had a mild course of acute pancreatitis, while 210 (43.57%) had a moderate course, and 101 (20.95%) had a severe course. Obese patients had a statistically higher percentage of cases of severe acute pancreatitis (85 (32.69%) compared to 16 (7.21%); p=0.01 ) . The frequency of moderate course of acute pancreatitis did not have a statistically significant difference in the two compared groups (102 (39.23%) compared to 108 (48.65%); p>0.05). As for the mild course of acute pancreatitis, it occurs more often in patients with normal body weight than in obese patients (98 (44.14%) compared to 73 (28.08%); p=0.01).

Fig. 2. The course of acute pancreatitis.

Using Spearman’s correlation analysis , a positive relationship was established between the degree of obesity and the severity of acute pancreatitis in (r=0.48; p=0.001; α=0.05). At the 1st degree of obesity, an inverse relationship was registered (r= -0.76; p=0.001; α=0.05). This indicates that patients with first-degree obesity are more likely to have a mild degree of severity. At the II degree of obesity, a weak correlation between the two variables was established (r=0.33; p=0.004; α=0.05). In patients with third-degree obesity, a strong correlation with the severity of acute pancreatitis was established (r=0.85, p=0.001; α=0.05). Based on the correlation-regression analysis of the dependence of the variable severity of acute pancreatitis on BMI > 40 kg/m2 and taking into account the correction, the coefficient of determination was determined – R2 =0.72; p=0.001. This indicates that, with a 95% CI, about 72% of patients with a BMI > 40 kg/m2 have a severe course of acute pancreatitis.

Correlations between the severity of the course of acute pancreatitis and

• gender (r=0.03; p=0.62);
• age (r=0.14; p=0.03);
• metabolic syndrome (r=0.13; p=0.03);
• concentration of glucose in blood plasma (r=0.01; p=0.86);
• calcium concentration in blood plasma (r=0.02; p=0.96);
• leukocyte level (r=0.15; p=0.013);
• level of C-reactive protein (r=0.14; p=0.02).

Discussion. It is known that obese patients have an increased risk of acute pancreatitis [1-11]. Multifactorial local and systemic changes were included in the pathogenesis of acute pancreatitis and prediction of adverse course in obesity . Scientists have investigated that there is a correlation between an increase in parapancreatic adipose tissue and body mass index [17,26]. It has also been proven that parapancreatic adipose tissue has a direct toxic effect on the pancreatic parenchyma [22]. Recent research data indicate that adipose tissue in obesity is shallowly dispersed and unsaturated , and lipolysis only worsens local and systemic disorders of the body’s functions. An increase in cytokines in severe acute pancreatitis is considered a secondary factor compared to lipotoxicity [14-20]. It was also investigated that the deposition and deposition of intra-abdominal fat in the parapancreatic tissue of the retroperitoneal space contributes to a worse prognosis in acute pancreatitis and the development of infected necrotic pancreatitis [21-26].

In obese patients, according to recent studies, lipolysis of peripancreatic tissue led to aseptic necrotic pancreatitis with systemic complications . Obesity itself is a proinflammatory state with an increased level of such pro-inflammatory cytokines: tumor necrosis factor (TNF-a), interleukins (IL) IL-10, IL-6, IL-1b. [11,14,18]. Thus, against the background of an already formed inflammatory response, the inflammatory reaction is even more intensified and increased, and the level of pro-inflammatory cytokines reaches critical indicators.

In addition to the hypotheses about the development of pancreonerosis of the gland and parapancreatic fatty tissue and inflammatory factors, there is a hypothesis about the limitation of the movements of the diaphragm and chest. This hypothesis states that restrictions of respiratory movements lead to a decrease in inspiratory capacity and an increase in physiological arteriovenous shunting , which, as a result, causes hypoxemia . In acute pancreatitis, hypoxemia causes a lack of oxygen in the tissues and exacerbates the destruction of cells from the inflammatory reaction, which later quickly turns into the stage of multiple organ failure, which can cause death [16].

Conclusions. Patients with acute pancreatitis and obesity have a statistically higher percentage of the severe course of the disease (р=0.01; α=0.05), a positive relationship between the body mass index and the level of leukocytes (r=0.128; p=0.038) was found, and also with the level of C-reactive protein (r=0.18; p=0.003). It should also be noted that in obese patients, the level of interleukin-1 increases by 2.3 times (p=0.01; α=0.05), and the level of interleukin-6 by 2.4 times (p=0.01 ; α=0.05). A statistically significant difference in increased cytokine levels in obese patients suggests an enhanced protease response and a “cytokine storm” that is the starting point of a non-reversible chain reaction. In patients with third-degree obesity, a strong correlation with the severity of acute pancreatitis was established (r=0.85, p=0.001; α=0.05).

References:

1. APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology, 13(4(2013 Aug 31), p.15
2. Dumnicka, D. Maduzia, P. Ceranowicz, R. Olszanecki, R. Drożdż, B. Kuśnierz Cabala The interplay between inflammation, coagulation and endothelial injury in the early phase of acute pancreatitis: clinical implications. Int J Mol Sci, 18 (2) (2017 Feb 8), p. 354
3. Kebkalo, O. Tkachuk, A. Reiti.: Peculiarities of Clinical Indices, Duration and Complication of Acute Pancreatitis in Patients with Comorbid Obesity; ISSN 23064269. Lviv Clinical Bulletin. 2019, 2(26)–3(27):16-23.
4. Afghani , J. Pandol , T. Shimosegawa , R. Sutton etc. . Acute pancreatitis progress and challenges: a report on an international symposium. Pancreas, 44 (8) (2015 Nov), p. 1195
5. H. Janisch, TB Gardner Advances in management of acute pancreatitis Gastroenterol Clin North Am, 45 (1) (2016 Mar 31), pp. 1-8
6. A. Bendersky, M.K. Mallipeddi, A. Perez, T.N. Pappas. Necrotizing pancreatitis: challenges and solutions. Clin Exp Gastroenterol, 9 (2016), p. 345
7. Kebkalo A., Tkachuk O., Reyti A.: Features of the course of acute pancreatitis in patients with obesity; Pol Przegl Chir 2019:91(6):28–34
8. Erhart, C. Schafmayer, H.C. Held, J. Hampe. Antibiosis of necrotizing pancreatitis. Visceral Medicine, 30 (5) (2014 Oct 7), pp. 318-324
9. A. Banks, T.L. Bollen, C. Dervenis, H.G. Gooszen, C.D. Johnson, M.G. Sarr, etc. Classification of acute pancreatitis 2012: revision of the Atlanta classification and definitions by international consensus Gut, 62 (1) (2013 Jan 1), pp. 102-111
10. Greenberg, J. Hsu, M. Bawazeer, J. Marshall, J. Friedrich, A. Nathens. Clinical practice guideline: management of acute pancreatitis. Can J. Surg, 59 (2) (2016 Apr), p. 128
11. Meher, T. Mishra, P. Sasmal, S. Rath, R. Sharma, B. Rout, et al. Role of biomarkers in diagnosis and prognostic evaluation of acute Pancreatitis . J. Biomarkers, 2015 (2015 Aug 5)
12. Bruno, Dutch Pancreatitis Study Group. Improving the outcome of acute Pancreatitis. Dig Dis, 34 (5) (2016 Jun 23), pp. 540-545
13. Srinivasan, L. Venkatakrishnan, S. Sambandam, G. Singh, M. Kaur, K. Janarthan, et al. Current concepts in the management of acute pancreatitis. Family Med Prim Care, 5 (4) (2016 Oct), p. 752
14. Huan, D. Kim, P. Ou, A. Alfonso, A. Stanek. Mechanisms of interleukin 22’s beneficial effects in acute pancreatitis. World J Gastrointest Pathophysiol , 7 (1) (2016 Feb 15), p. 108
15. Kitagawa, T. Hayakawa. Antiproteases in the treatment of acute pancreatitis. JOP, 8 (4 Suppl ) (2007 Jul 9), pp. 518-525
16. Dellinger, M. Levy, A. Rhodes, D. Annane, H. Gerlach, S. Opal, et al.

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med, 39 (2) (2013 Feb 1), pp. 165-228

17. Surati, K. Suthar, J. Shah, B. Parekh. A study of recent trends in acute pancreatitis. Int J Med Sci Public Health, 3 (2014), pp. 63-68
18. Yang, X. Meng, P. Xu. Central role of neutrophil in the pathogenesis of severe acute pancreatitis. J Cell Mol Med, 19 (11) (2015 Nov 1), pp. 2513-2520
19. Schouten, W. Wiersinga, M. Levi, T. Van. Der Poll Inflammation, endothelium, and coagulation in sepsis. J Leukoc Biol , 83 (3) (2008 Mar 1), pp. 536-545
20. Chen, S. Wang, F. Lee. Action of antiproteases on the inflammatory response in acute pancreatitis. JOP, 8 (4 Suppl ) (2007 Jul 9), pp. 488-494
21. Santvoort H., Besselink M., Bakker O., Hofker H., Boermeester M., Dejong C., et al. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010;362:1491–502
22. Bakker O., Santvoort H., Brunschot S., Geskus R., Besselink M., Bollen T., et al. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial. JAMA. 2012 ;307:1053–61
23. Brunschot S., Grinsven J., Santvoort H., Bakker O., Besselink M., Boermeester M., et al. Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomized trial. Lancet. 2018 ;391:51 –8
24. Gurusamy K., Belgaumkar A., Haswell A., Pereira S., Davidson B.. Interventions for necrotising pancreatitis. Cochrane upper GI and pancreatic diseases group. Cochrane Database Syst Rev. 2016; 137: 201–53
25. Driedger M., Zyromski N., Visser B., et al. Surgical transgastric necrosectomy for necrotizing pancreatitis – a single-stage procedure for walled-off pancreatic necrosis. Ann Surg. 2018; https://doi.org/10.1097/ SLA00000000000003048
26. Jaipuria J., Bhandari V., Chawla A., Singh M. Intra-abdominal pressure: time ripe to revise management guidelines of acute pancreatitis? World J Gastrointest Pathophysiol . 2016 ;7:186–98
27. De Waele J., Hesse U., Pattyn P., Decruyenaere J., de Hemptinne B. Postoperative lavage and on-demand surgical intervention in the treatment of acute necrotizing pancreatitis. Acta Chir Belg. 2000 ;100:16–20
28. Harris J., Jury R., Catto J., Glover J. Closed drainage versus open packing of infected pancreatic necrosis. Am Surg. 1995; 61:612– ; discussion 7-8

Pliakos I., Papavramidis T., Mihalopoulos N., Koulouris H., Kesisoglou I., Sapalidis K., et al. Vacuum-assisted closure in severe abdominal sepsis with or without retention sutured sequential fascial closure: a clinical trial. Surgery . 2010;148:947–53