Method for predicting effectiveness of treatment of acute pancreatitis in early stages

Abstract

FIELD: surgery.SUBSTANCE: used to predict the effectiveness of treatment of acute pancreatitis in the early stages. On the 1st, 4th, 7th and 11th days after hospitalization, venous blood sampling is performed from patients, the level of C-reactive protein, the activity of phospholipase A2 and alpha-amylase in the blood is assessed, and an ultrasound of the abdominal cavity is performed to identify fluid formation in the abdominal cavity. In patients with acute pancreatitis, the probability of developing complications IRO is calculated using the stated formula. With the IRO value less than 3.1 predicts high treatment effectiveness, indicating the absence of the likelihood of complications. With an IRO value from 3.2 to 4.5, average treatment effectiveness is predicted, indicating possible disease progression and development of complications and the need for constant monitoring. If the IRO value is more than 4.5, the treatment is predicted to be ineffective, indicating a high probability of complications and requiring urgent puncture interventions at the site and adjustments to treatment regimens.EFFECT: method provides the possibility of increasing the accuracy of assessing the treatment of acute pancreatitis in the early stages, predicting the course of acute pancreatitis and optimizing treatment by preventing the risk of fluid formations, due to the assessment of the state of the components of the homeostasis system: pancreatogenic, immunoinflammatory, membrane-destabilizing, and visual diagnostics of the abdominal cavity to identify fluid formations in it.1 cl, 4 tbl, 3 ex

Description

[0001] The invention relates to the field of medicine, namely to surgery, and can be used to predict the course of acute pancreatitis (AP) and the development of complications.

[0002] According to world statistics, acute pancreatitis is considered one of the leading diseases of the abdominal organs (AP) in medicine. In this pathology, a steady annual increase in incidence (by 15–30%), the working age of patients, progressive complications, and a high mortality rate (20–45%) are noted (Li T., Qin C., Zhao B., Li Z., Zhao Y., Lin C., Wang W. Global and regional burden of pancreatitis: epidemiological trends, risk factors, and projections to 2050 from the global burden of disease study 2021 / / BMC Gastroenterol 2024. No. 24 (1). P. 398. https: / / doi.org / 10.1186 / s12876-024-03481-8; Protsenko D.N., Tsvetkov D.S., Shifman E.M. Tactics of infusion therapy in patients with acute destructive pancreatitis: a literature review / / Bulletin of Intensive Therapy named after A.I. Saltanova. 2024. No. 2. P. 94-106).

[0003] The pathological process of formation of local complications of AP, such as fluid formations, necrosis, etc., is poorly studied, while in the late phase they determine high (up to 35%) mortality (Rashid MU, Hussain I., Jehanzeb S., Ullah W., Ali S., Jain AG, Khetpal N., Ahmad S. Pancreatic necrosis: Complications and changing trend of treatment / / World J Gastrointest Surg. 2019. No. 11(4). P. 198-217. doi: 10.4240 / wjgs.v11.i4.198). At the same time, there is evidence that the volume and nature of peri- and pancreatic formations are associated with the severity of the disease (Türkvatan A., Erden A., Seçil M., Türkoğlu MA Fluid collections associated with acute pancreatitis: a pictorial essay / / Can Assoc Radiol J. 2014. No. 65(3). P. 260-6. doi: 10.1016 / j.carj.2013.08.003).

[0004] Despite the diversity of opinions among authors, the fundamental issue of this disease remains the choice of treatment method, the basis of which is considered to be conservative therapy. However, it is not always effective in different situations and requires optimization (Vlasov A.P., Trofimov V.A., Vlasova T.I., Myshkina N.A., Muratova T.A., Leshchankina N.Yu., Dukhovnova K.M. Pulmonary distress syndrome in urgent surgery: concept, pathogenesis, principles of correction / / Surgery. Journal named after N.I. Pirogov. 2025. No. 2. P. 77-85; Alsfasser G., Klar E., Feitl J., Schafmayer C. Conservative therapy of severe acute pancreatitis is a safe option - results of a 15-year long-term follow-up cohort study / / Ann Med Surg (Lond). 2023. No. 85(5). P. 1556-1561. doi: 10.1097 / MS9.0000000000000697).

[0005] Data from the International Congress of Emergency Surgery established that early prediction of the course of AP, especially its severe form, is the main task in choosing a treatment method (Sagana RL, Wesorick DH, Byrne BT, Fitzgerald LJ, Georgia TE, Mack M., Wesorick D., Proudlock A. Care of the Hospitalized Patient with Acute Exacerbation of COPD [Internet] / / Ann Arbor (MI): Michigan Medicine University of Michigan. 2022. PMID: 35901227). According to this concept, many different scales have been proposed to assess the severity of AP and the effectiveness of its treatment, based on the results of clinical and laboratory (APACHE II, SOFA, Ranson, etc.), immunological (T-lymphocytes, interleukins, etc.), and biochemical (C-reactive protein (CRP), α3-macroglobulin, etc.) studies (Hu JX, Zhao CF, Wang SL, Tu XY, Huang WB, Chen JN, Xie Y., Chen CRAcute pancreatitis: A review of diagnosis, severity prediction and prognosis assessment from imaging technology, scoring system and artificial intelligence / / World J Gastroenterol. 2023. № 29(37). Р. 5268-5291. doi: 10.3748 / wjg.v29.i37.5268) и др. критериев.

[0006] The data from literary sources show that the use of the above scales is controversial, since no direct relationship was found between the number of their points, the course of the disease and the effect of its treatment (Szatmary P., Grammatikopoulos T., Cai W., Huang W., Mukherjee R., Halloran C., Beyer G., Sutton R. Acute Pancreatitis: Diagnosis and Treatment / / Drugs. 2022. No. 82 (12). P. 1251-1276. doi: 10.1007 / s40265-022-01766-4). The need to predict AP in the first day is interpreted by the extraordinary need of this short period, during which the therapeutic goal is to interrupt or limit its progression. However, many patients are admitted to the clinic late in the onset of the disease, when destructive changes already exist in the pancreas, which will provoke the development of a complex of pathological life-threatening processes, such as renal and hepatic failure, abdominal sepsis, etc.At this stage, it is considered that it is practically impossible to predict the course of the pathological process or manage the outcome; however, determining the course of pathology at an early stage of the destructive process is necessary to assess the group with a high risk of generalized complications, on the one hand, and to optimize further therapy, on the other (Lee DW, Cho CM Predicting Severity of Acute Pancreatitis / / Medicina (Kaunas). 2022. No. 58(6). P. 787. doi: 10.3390 / medicina58060787).

[0007] Based on the results of the clinical examination, a prognostic scheme for the severity of AP was developed, including 16 signs (6 main and 10 additional). According to the conclusions, it was noted that a severe condition is predicted in the presence of 2 main or 1 main and 2 additional signs. The disadvantages of the method are low reliability, specificity and sensitivity in assessing the severity of the disease and determining the effect of its treatment (Tolstoy A.D., Krasnogorov V.B., Goltsov V.R., Dvoynov V.G. The concept of "cliff" of pancreatic necrosis - the key to solving the problem of acute destructive pancreatitis / / Herald of surgery. 2001. Vol. 160. No. 6. pp. 26-30).

[0008] Other authors have proposed a method for determining the severity of patients with AP, predicting its course and the impact of its treatment using discriminant analysis. The disadvantage of this scale is the distribution of the initial results, when a minor change leads to significant changes in the classification. Despite high sensitivity and specificity, the prognostic indicator requires the calculation of 13 laboratory parameters, including specific and expensive ones (Siplivy V.A., Shapovalov E.A., Evtushenkov D.V. Objective assessment of severity and individualized prognosis in acute pancreatitis / / Proceedings of the XIV International Conference of Surgeons-Hepatologists of Russia and the CIS Countries. St. Petersburg. 2007. pp. 227-228).

[0009] I.P. Parfenov et al. (2011) proposed a prognosis of the development of acute biliary pancreatitis using a mathematical model based on determining the activity of pancreatic enzymes - amylase, lipase in bile and blood. This scale determines only the state of the general inflammatory process, so it is of little information in assessing the status of AP and the effectiveness of its treatment method (Parfenov I.P., Yarosh A.L., Soloshenko A.V., Karpachev A.A., Sergeev O.S. Prognosis of the development of acute biliary pancreatitis / / Surgery. Journal named after N.I. Pirogov. 2011. No. (8). P. 47-50).

[0010] An invasive method for predicting the severity of acute pancreatitis in the first 72 hours from onset is known. It involves laparoscopically determining pathological changes in the pancreas using a score, such as the presence of peritoneal hyperemia, the amount of exudate, etc. (RU 2624165, IPC A61B 1 / 00, published June 30, 2017).

[0011] The disadvantage of this method is its invasiveness, the special skill of the surgeon, the risk of infection and complications.

[0012] A method for predicting the course of acute destructive pancreatitis is known. It can be used on the day of hospitalization and for three days. It is based on determining the proportion of platelets in the blood (RU 2759073, IPC G01N 33 / 49, published November 9, 2021).

[0013] The disadvantage of this method is that this model has greater specificity, but does not reflect the scale of the pathological process.

[0014] A method for determining leukocyte elastase (LE) in blood plasma is adopted to evaluate the processes of neutrophil activation and degranulation, the degree of development of the inflammatory response to predict systemic inflammation, sepsis, and DIC syndrome in acute pancreatitis. The essence of the method lies in determining the amount of LE by immunochemical methods (radioimmunological and enzyme immunoassay) using test systems. [Yarovaya G.A. Properties and clinical diagnostic value of determining elastase from the pancreatic gland and polymorphonuclear leukocytes / / Laboratory Medicine. - 2006. - No. 8. - P. 11-18].

[0015] The disadvantage of this method is its limitations, due to the need for expensive equipment and reagents, as well as the use of radioisotope analysis. Furthermore, it does not allow for the assessment of pancreatic enzyme activity (PEA).

[0016] A method for preventing infectious complications in acute destructive pancreatitis is known, based on measuring the temperature at the point (being studied) above the pancreatogenic infiltrate and comparing it with the exact (control) point, located 2.5-3.5 cm above the middle of the inguinal ligament. The result of aggravation of OP is considered to be an increase in temperature at the point being studied by less than 0.7 °C relative to the control point within 3 days (RU 2672592, IPC A61K 31 / 245, published 11 / 16 / 2018).

[0017] The disadvantages of this method are the technical complexity of the procedure, invasiveness with the risk of complications, and the lack of assessment of the general state of the homeostasis system.

[0018] A known method for predicting the development of generalized complications in acute destructive pancreatitis involves assessing the plasma neutrophil granulocyte count in a modified NBT loading test with opsonized zymosan. A high risk of generalized complications can be suspected if their count exceeds 18% (RU 2393771, IPC A61B 10 / 00, published July 10, 2010).

[0019] The disadvantage of this method is the late assessment of the pathological process, it does not take into account all the important risk factors for complications, it is uninformative and does not reflect the general condition of the patient.

[0020] Thus, various methods have been proposed in surgical practice to predict the course of acute pancreatitis and the risk of complications, on the one hand, and to evaluate the effectiveness of its treatment using clinical, laboratory, and instrumental examinations, on the other. However, each method has its drawbacks: a complex calculation method, which creates difficulties in statistical analysis of the data; specificity – characterizing the consequences of the pathological process but not determining its state; invasiveness with the risk of complications, etc.

[0021] The closest analogues of the claimed solution are a method for assessing the course of the early postoperative period in patients with urgent abdominal diseases, based on the values ​​​​of catabolic processes in the blood plasma, including the level of leukocytes, medium-weight molecules (an indicator of endotoxicosis), malondialdehyde and lysoforms of phospholipids (lipid peroxidation parameters) (RU 2729730, IPC G01N 33 / 48, published 11.08.2020).

[0022] This method has several drawbacks, including that it does not determine the functional state of detoxifying organs such as the kidneys and liver, which play a significant role in the pathogenesis of AP. It also does not assess the activity of pancreatic enzymes, which are considered a key factor in disease progression.

[0023] The technical result achieved through the use of the claimed invention is an increase in the accuracy of assessing the treatment of acute pancreatitis in the early stages.

[0024] The proposed method for predicting the treatment of acute pancreatitis in the early stages aims to expand the range of specific indicators capable of predicting the course of acute pancreatitis and optimizing treatment effectiveness by preventing the risk of fluid formation. It assesses the state of several components of the homeostasis system, including the pancreatogenic, immune-inflammatory, and membrane-destabilizing components. This method also includes visual diagnostics of the pancreas and the presence of fluid formations.

[0025] The essence of the invention is that the method for predicting the effectiveness of treatment of acute pancreatitis in the early stages, including taking venous blood from patients on the 1st, 4th, 7th and 11th days after hospitalization, assessing the level of C-reactive protein, the activity of phospholipase A2 and alpha-amylase in the blood, and conducting an ultrasound of the abdominal cavity, identifying fluid formation in the abdominal cavity, characterized by the fact that in patients with acute pancreatitis, the probability indicator of the development of complications IRO is calculated according to the formula:

[0026]

[0027] where IRO is the indicator of the probability of developing complications;

[0028] CRB1 – current C-reactive protein level;

[0029] CRB2 – the level of C-reactive protein at the previous moment;

[0030] D1 – current alpha-amylase activity in the blood;

[0031] D2 – alpha-amylase activity in the blood at the previous moment;

[0032] F1 – current phospholipase A2 activity;

[0033] F2 – activity of phospholipase A2 at the previous moment;

[0034] V – indicator of fluid formation in the abdominal cavity: 0 – absence; 1 – presence and moderate growth - by 20-30%; 2 – rapid growth - by 40-100%; 3 – increase by more than 100%,

[0035] and with an IRO value of less than 3.1, high treatment effectiveness is predicted, indicating the absence of the probability of complications; with an IRO value from 3.2 to 4.5, average treatment effectiveness is predicted, indicating possible disease progression and development of complications and the need for constant monitoring; with an IRO value of more than 4.5, ineffective treatment is predicted, indicating a high probability of complications and requiring urgent puncture interventions in the lesion and adjustment of treatment regimens.

[0036] Table 1 shows the IRO, Table 2 shows the dynamic values ​​of the probability indicator of developing complications for patient A. with acute pancreatitis, Table 3 shows the dynamic values ​​of the probability indicator of developing complications for patient B. with acute pancreatitis, and Table 4 shows the dynamic values ​​of the probability indicator of developing complications for patient C. with acute pancreatitis.

[0037] Novelty of the technique:

[0038] 1. The serum alpha-amylase activity level can be used to determine the functional status of the pancreas and the progression of the disease; the plasma CRB level can be used to determine the intensification of the immune-inflammatory process; the level of cellular membrane destruction can be determined by the phospholipase A2 level; and the dynamics of this complication of the disease can be determined by the fluid formation level.

[0039] 2. The parameters under study are determined by calculating their changes during the control observation period (1, 4, 7 and 11 days), which allows for a systematic quantitative assessment of the course of AP.

[0040] 3. When calculating the probability of complications developing in acute care settings, it is necessary to pay attention to absolute and relative circumstances to exclude the possibility of an erroneous prognosis.

[0041] The method is carried out as follows.

[0042] In patients with AP, on the 1st, 4th, 7th and 11th days after hospitalization in the clinic, a number of homeostasis system parameters (CRB level, phospholipase A2 and alpha-amylase activity) and the presence / absence of fluid formation are determined.

[0043] The method (Dawson R. et al., 1991) for assessing the activity of alpha-amylase in blood plasma was carried out by a photometric reaction of starch with a hydrolysis enzyme. 0.5 ml of the obtained starch was placed in 2 test tubes with 0.1 ml of 3% sodium chloride solution and 0.2 ml of 0.1 M phosphate buffer. The tubes were heated for 10 minutes at 37 ° C. Then 0.1 ml of blood serum was added, incubated for 30 min, and 0.1 ml of 1 N hydrochloric acid solution was added. 0.2 ml of the contents of each test tube was added to the flask, then 40 ml of water, 0.5 ml of hydrochloric acid, 0.1 ml of iodine solution, and distilled water to the mark. 1 N was added to the controls. hydrochloric acid solution before incubation. Samples were measured using a photoelectrocolorimeter.

[0044] Phospholipase (PL) intensification was determined by mixing 10 mmol CaCl2, 150 mmol Triton X-100, and 1.2 mmol egg yolk phosphatidylcholines. Enzyme activity was determined in a medium containing 150 mmol Triton X-100, 10 mmol Tris-HCL buffer, and 1.2 mmol substrate. Egg yolk phosphatidylcholines were used as a substrate. Enzyme activity was assessed using a setup consisting of an ultra-thermostat, an EV-74 ionomer, a microburette, and a microburette. The result was recorded titrimetrically and expressed as μmol / s / g protein (Trofimov V. A., 1999).

[0045] IRO is calculated based on laboratory values.

[0046] An IRO value of less than 3.1 indicates the absence of a risk of complications and the adequacy of the treatment.

[0047] An IRO value of up to 3.3-4.5 indicates possible worsening of the OP and the likelihood of complications, the need for constant monitoring for prompt adjustment of treatment and the possible use of minimally invasive interventions.

[0048] An IRO value of 4.5 or more indicates the progression of AP, a high probability of complications, an urgent revision of the treatment method and the inclusion of efferent methods of conservative therapy or surgical interventions (Table 1).

[0049] Thus, early detection of IRO in patients with AP allows us to predict the course of the disease and the risk of various complications, assess the effectiveness of the treatment regimens used and the need for their adjustment.

[0050] The IRO indicator was determined during clinical and biochemical examination of 55 OP patients.

[0051] Example 1. Patient A., 41 years old, was admitted to the surgical department on February 2, 2025, with a diagnosis of acute pancreatitis. Complaints of girdle pain of moderate intensity, nausea, bloating, and repeated vomiting. Anamnesis: the cause of AP was a nutritional error. The patient was ill for two days. He did not seek medical attention. Clinical examination revealed that the general condition is satisfactory, consciousness is clear, and the position is active. Body temperature is 36.7°C. The tongue is moist, the abdomen is symmetrical, not distended, evenly participates in the act of respiration, and is painful in the projection of the pancreas. The diagnosis of AP was biochemically and instrumentally confirmed. Drug treatment was prescribed in accordance with clinical recommendations.

[0052] Over the course of 11 days of conservative therapy, the studied parameters (C-reactive protein, alpha-amylase, FL, fluid formation index) were monitored dynamically. It was found that during the first days of hospitalization, the IRO value was 2.7, on the 4th day – 3.0, on the 7th day – 2.4, and on the 11th day – 2.1. This indicated the absence of a risk of complications, on the one hand, and the productive effect of standard therapy, on the other. The patient was discharged from the clinic with recovery on February 11, 2025 (Table 2).

[0053] Table 2 presents the IRO values ​​calculated based on the level of C-reactive protein, alpha-amylase and FL activity and the fluid formation index in the dynamics of the patient's treatment.

[0054] Example 2. Patient B., 45, was admitted to the surgical department on February 5, 2025, with a diagnosis of acute pancreatitis. Complaints include girdle pain, general weakness, nausea, and repeated vomiting. Anamnesis indicates that the cause of the pathology was a gastronomic error. The patient had been ill for 20 hours. The diagnosis of acute pancreatitis was based on clinical, laboratory, and instrumental examinations. Drug therapy was administered according to clinical guidelines.

[0055] This patient underwent IRO monitoring for 11 days. On the first and fourth days, the value was 5.1 and 5.8, respectively, indicating a risk of complications. An abdominal ultrasound was performed, which revealed the presence of fluid in the abdomen. A decision was made to perform abdominal debridement and drainage under ultrasound guidance. Abdominal exudate continued to separate for 7 days. Clinical examination revealed an improvement in the patient's general condition. Laboratory tests revealed normalization of homeostasis parameters, including CRB levels, alpha-amylase activity, and FL. At the same time, the IRO value significantly decreased, reaching 3.7. On the 11th day, the IRO level was 2.7, indicating no risk of complications. The patient was discharged from the clinic in satisfactory condition on February 19, 2025.

[0056] Table 3 shows the results of the scale taking into account the values ​​of C-reactive protein, alpha-amylase and phospholipase activity and the presence of fluid formation during the patient's treatment.

[0057] Example 3. Patient B, 65 years old, was admitted to the clinic on February 20, 2025, with a diagnosis of AP. The cause of the disease was alcohol abuse. Clinical signs of AP were revealed during the examination. Characteristic signs of the disease were determined using laboratory and instrumental methods. Standard therapy was administered in accordance with clinical guidelines.

[0058] During hospitalization and during the first 4 days of treatment, the patient's condition did not improve. When monitoring the studied parameters, it was established that the IRO value was 5.9 on the first day and 6.4 on the 4th day. These data indicated a high risk of complications. Ultrasound revealed the presence of a fluid formation in the omental bursa. Ultrasound monitoring revealed a dynamic increase in the size of the formation. Drainage of the omental bursa under ultrasound guidance is indicated. The patient's condition continued to deteriorate. On the 7th day, an increase in the IRO value was noted, reaching 7.1. The patient underwent an ultrasound of the AP, which revealed a decrease in the size of the omental formation, but the presence of a fluid formation in the paracolic tissue on the left. Drainage of this area was performed. On the final (11th) day, the patient's condition did not improve, the IRO value was 8.2, pronounced destructive changes in the pancreas and the presence of sequesters were detected.The patient underwent a number of other surgical procedures, including a necrosequestrectomy. His condition improved. He was discharged in satisfactory condition on April 19, 2025.

[0059] Table 4 presents the IRO data taking into account the values ​​of CRP, alpha-amylase and FL activity and the presence of fluid formation in the abdomen in the dynamics of the patient's treatment.

[0060] Thus, the proposed method, unlike existing scales and methods, allows for a reliable early determination of the risk of complications in acute pancreatitis and the optimal selection of a treatment regimen. This is based on the fact that it evaluates several components of the homeostasis system, including the activity of the inflammatory process, the functional state of the pancreas, the degree of membrane-destabilizing reactions, as well as a sonographic visual assessment of the abdominal organs and retroperitoneal space for the presence of fluid formations. Together, the studied parameters assess virtually the entire spectrum of possible structural and functional changes in acute pancreatitis, which underlies the method's high information content.

[0061] Table 1

[0062] The likelihood of developing complications in acute pancreatitis in the early stages Lack of probability There is a possibility High probability Complication development index below 3.1 3,2-4,5 4.6 and above

[0063] Table 2

[0064] Indicator Observation period, days 1 4 7 11 Complication development index 2.7 (absence) 3.0 (absence) 2.4 (absence) 2.1 (absence)

[0065] Table 3

[0066] Indicator Observation period, days 1 4 7 11 Complication development index 5.1 (high) 5.8 (high) 3.7 (average) 2.7 (absence)

[0067] Table 4

[0068] Indicator Observation period, days 1 4 7 11 Complication development index 5.9 (high) 6.4 (high) 7.1 (high) 8.2 (high)

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