RU2617389C1 - Method of diagnosing purulent cholangitis in patients with obstructive jaundice, setting optimal surgical approach - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method of diagnosing purulent cholangitis (PC) in patients with obstructive jaundice (OJ) by examining patient consists in the fact that acetic, propionic, butyric and isovaleric acids are determined in blood by gas chromatography, and if acetic acid concentration is more than 0.33 mmol/l, cholangitis presence is determined, if concentration of any of three acids: propionic is more than 0.012 mol/l, butyric is more than 0.0039 mmol/l, isovaleric is more than 0.00034 mmol/l - presence of purulent cholangitis with active development of anaerobic infection is determined, requiring one of the options of preoperative biliary decompression.

EFFECT: method enables to increase the objectivity and accuracy of purulent cholangitis diagnostics in mechanical jaundice by using quantitative parameters without undesired side effects in patients.

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Description

The invention relates to medicine, namely to surgery.

For a long time, obstructive jaundice (MF) and purulent cholangitis (GC) were considered as sequential pathological processes (Akhaladze G.G. Choledocholithiasis. Cholangitis and biliary sepsis: where is the border? // Annals of surgical hepatology 2013. Volume 18. No. 1 C . 54-58). Nevertheless, obstruction of the bile ducts is often not a determining factor in the development of GC, which does not always occur against the background of the breast. It is known that GC often develops with partial than with complete violation of patency of the bile ducts. Practice shows that with breast cancer and bile infection, often there are initially no manifestations of a systemic inflammatory reaction (SVR) in connection with the protective functions of the liver. Moreover, the number of bacteria and the concentration of endotoxins in the sinusoid for a certain period of time are insufficient to excite Kupffer cells and start SVR (Akhaladze G.G. Pathogenetic aspects of purulent cholangitis, why there is no systemic inflammatory reaction with obstructive jaundice? // Annals of surgical hepatology. 2009 T. 14. No. 2. S. 9-15). In these situations, clinical manifestations, as well as traditionally used biochemical and instrumental techniques for a relatively long period of time do not always reflect the onset of GC development and the real state of the liver cells. At the same time, the rapid development of GC is possible, despite the absence of severe cholestasis and acholy. This is due to the progression of biliary hypertension due to the rapid colonization of bacteria, especially the anaerobic flora (Oderdonk A.V. Discussion in Symposium of Virulente Factor of Anaerobic Bacteria // Rev. Infect. Dis. 1979. V. 1. P. 289-290) .

The positive results of surgical treatment of patients with obstructive jaundice with purulent cholangitis are achieved not only by eliminating the underlying pathology, but also by the possibility of preoperative correction of the impaired functional state of the liver (Addley J., Mitchell RM Advances in the investigation of obstructive jaundice // Curr. Gastroenterol. Rep. - 2012 . - Vol. 14, No. 6. - P. 511-519). Preoperative biliary decompression (DB) and targeted detoxification methods in these patients, eliminating cholemia, create favorable conditions for radical surgery. However, the DB does not always fully ensure adequate decontamination of the bile ducts (Tanaka A., Takada T., Kawarada Y. et al. Antimicrobial therapy for acute cholangitis: Tokyo quidelines // J. Hepatol. Pancreat. Surg. 2007; 14: 59-67 ) Perioperative antibiotic therapy is built taking into account the degree of excretion of antibiotics in bile and the sensitivity of microflora to them. At the same time, the diagnosis of obligate anaerobes, often causing the most severe forms of GC, remains laborious, and the results of bacteriological studies, as a rule, are achieved no earlier than 5-6 days after receiving the material. In addition, indications for preoperative biliary decompression, as well as an assessment of the effectiveness and duration of its implementation, remain an incompletely resolved problem. Therefore, it is relevant to develop and put into practice methods that allow timely diagnosis of GC in patients with breast cancer with the determination of the type of microflora, as well as objectively ascertain the restoration of liver function and regression of liver failure after preoperative biliary decompression.

In recent years, a method for determining the quantitative and qualitative composition of volatile fatty acids (VFAs), which are the main metabolites of anaerobic and aerobic microorganisms, has been used in patients with various pathologies to diagnose infection and verify the species composition of microflora. Studies have shown that the determination of VFA by gas-liquid chromatography (GLC) is highly accurate, sensitive, affordable and quick to obtain the result (Beloborodova N.V., Beloborodov S.M. Metabolites of anaerobic bacteria (volatile fatty acids) and macroorganism reactivity // Antibiotics and chemotherapy. 2000. No. 2. S. 28-36).

Moreover, a comprehensive determination of the values of individual indicators of volatile fatty acids in patients with breast cancer with GC to select the optimal surgical tactics has not yet been carried out.

The technical result is achieved by the fact that, including clinical and additional examination methods, a method for the diagnosis of GC in patients with breast cancer with the choice of surgical tactics involves determining the values of acetic, propionic, butyric and isovalerianic acids. At a concentration of acetic acid greater than 0.33 mmol / L, the presence of cholangitis is established, and at a concentration of any of the three acids: propionic more than 0.012 mol / L, butyric greater than 0.0039 mmol / L, isovalerianic more than 0.00034 mmol / L establish the presence of purulent cholangitis with the active development of anaerobic infection, requiring one of the options for preoperative biliary decompression and the appointment of appropriate antibacterial drugs.

We determined the concentration of acetic, propionic, butyric, and isovalerianic acids in the blood of patients with breast by gas chromatography. We found a statistically significant significant increase in the average concentrations of these acids in the blood in patients with MF and purulent cholangitis compared with a group of MF patients without cholangitis. The most informative were the M-m indicators of the difference in the average concentration values and standard errors in determining the average values of acid concentrations in the blood in patients with purulent cholangitis. These indicators were selected as the most informative diagnostic criteria for purulent cholangitis.

Radical surgical interventions against the background of MF and GC are accompanied by severe complications and high mortality. At conciliation conferences held in Japan in 2007 and 2013, as well as expert meetings, international standards for the diagnosis and treatment of GC were developed. The basis for the use of preoperative DB are signs of organ dysfunction, as well as a response to elementary antibacterial and infusion therapy (Wada K., Takada T., Kawarada Y. et al. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo quidelines // J. Hepatobil Pancreat. Surg. 2007; 14: P. 52-58; Takada T. et al. Update Tokyo Guidelines for the management of acute cholangitis and cholecystitis / T. Takada et al. // J. Hepatobiliary Pancreat. Sci. 2013. Vol. 20, N 1. P. 1-105). However, a timely, objective assessment of the body's response to the therapy remains an unresolved problem, and the diagnosis of anaerobic flora takes a long time. Therefore, research is ongoing aimed at developing new objective criteria for the diagnosis of GC in patients with MF and the type of microflora, as well as the effectiveness and duration of preoperative biliary decompression.

Volatile fatty acids (VFAs) are the main waste products of bacteria. Therefore, they are used as markers of infection. The leading role in the infection of bile with mammary gland is played by the aerobic-anaerobic association of microorganisms, coming in various ways from the gastrointestinal tract, including translocation. Acetic acid is produced by aerobic and anaerobic flora, and propionic, butyric, and isovalerianic acids are mainly metabolic products of anaerobic bacteria only. The formation of isovalerianic acid is associated with the destruction of polypeptides by anaerobic bacteria with proteolytic activity (Minushkin O.N., Ardatskaya M.D. Possibilities and prospects for studying short-chain fatty acids in the pathology of the gastrointestinal tract using diseases of the intestine and organs of the hepatobiliary system as an example. Wedge lab. Diagn. 2004; 2: 19-20, 31-36).

Thus, determining the level of VFA is a timely criterion for the diagnosis of cholangitis and the type of microflora in breast cancer, requiring biliary decompression and the appointment of existing antibacterial drugs.

The method is as follows: after a detailed examination and diagnosis of the breast, a conventional blood sampling is performed and VFA parameters are determined by gas-liquid chromatography. Then, against the background of the ongoing treatment, a repeat blood sampling is carried out in dynamics according to the indications for the study. The preparation of blood samples for chromatography is carried out by the conventional method of liquid extraction. Gas-liquid chromatography for the quantitative determination of acetic, propionic, butyric, and isovalerianic acids was performed on a Kristallux-4000 gas chromatograph with an HP-FFAP quartz capillary column of 50 m length, 0.3 mm inner diameter, and with a flame ionization detector in isothermal mode at temperature 200 ° C. The carrier gas is helium (Beloborodova N.V., Kurchavov V.A., Boyko N.B. et al. Diagnosis of anaerobic infections in children by chromatography. Guidelines. - Reg. No. 96/130. - State register of new medical technologies. - Issue 3). The identification and quantification of acetic, propionic, butyric and isovaleric acids was carried out using analytical standards.

The applied method used in patients with MF and GC determines the algorithm of surgical tactics: preoperative biliary decompression with an assessment of its effectiveness and duration, establishing the type of microflora with the choice of an antibacterial drug, the optimal timing of a radical operation. The use of a concentration of volatile fatty acids increases the accuracy of the diagnosis of GC due to quantitative parameters. In this case, the diagnosis is carried out without complications.

To prove the accuracy of the diagnosis of GC in patients with MF, a comparison of the results was carried out using the proposed method and generally accepted methods. Diagnosis of MF and GC syndrome, as well as the underlying disease, was established in accordance with modern domestic and foreign guidelines (Halperin E.I., Vetshev P.S. Guidelines for biliary tract surgery. 2nd ed .: Vidar-M., 2009. 568 p .; Zatevakhin I.I., Kirienko A.I., Kubyshkin V. A. Abdominal surgery. National management. Moscow. “GEOTAR-Media.” 2016. 903 p .; WadaK., Takada T., Kawarada Y . et al. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo quidelines // J. Hepatobil. Pancreat. Surg. 2007; 14: P. 52-58).

We examined 29 patients with a confirmed diagnosis of breast and GC, who underwent two-stage surgical treatment. The age of the examined patients ranged from 19 to 82 years. The control group consisted of 18 patients with breast and the absence of cholangitis.

The proposed method made it possible to establish GC, to determine the species composition of microflora in 27 of 29 patients with MF (coincidence with the final diagnosis - 93.1%).

Consequently, the concentration of acetic, propionic, butyric and isovaleric acids in the blood can be used to diagnose the objective criterion of GC, the type of microflora in patients with breast cancer.

Examples of the use of the method in patients with breast and GC

Example 1: Patient K., 59 years old, was hospitalized in our clinic with a diagnosis of obstructive jaundice. About three weeks ago, relatives noted the appearance of sclera in the patient with jaundice. However, she did not notice a significant deterioration in her condition and continued to work in her specialty. A few days later, there was some yellowing of the skin, and then jaundice became pronounced, and against its background, an increase in body temperature to subfebrile digits began, accompanied by periodic chills. During an outpatient examination during an ultrasound, a tumor of the proximal hepatic ducts (Klatskin tumor) is suspected and the patient is referred to our clinic. Upon admission, the patient's condition is moderate. Total bilirubin is 227 μmol / L. A significant decrease in total protein, as well as coagulation factors, was noted. Clinical manifestations and laboratory values of white blood testified to a pronounced inflammatory process. Ultrasound revealed the following: the gallbladder in a collapsed state; in the upper part of the common bile duct, a large calculus is located, which completely covers the lumen; an increase in the diameter of the proximal OPP and intrahepatic bile ducts. Diagnosed with Mirrisi syndrome complicated by breast and cholangitis. When studying the history, it was found that over the past 5 years she periodically had pains in the upper abdomen, sometimes accompanied by a rise in body temperature. I took medications on my own, after which the condition returned to normal. The determination of acetic, propionic, butyric and isovaleric acids in the blood was carried out. The following results were obtained: acetic acid - 0.4260 mmol / L, propionic - 0.0086 mmol / L, butyric - 0.0021 mmol / L, isovalerianic - 0.00028 mmol / L. This indicated the presence of a pronounced infectious process with the presence of mixed microflora. During percutaneous transhepatic puncture of the intrahepatic bile ducts, infected bile with fibrin flakes was obtained. Therefore, percutaneous transhepatic cholangiostomy was performed and preoperative preparation was prescribed. Against the background of complex therapy, the patient's condition gradually improved, and the value of bilirubin on the 10th day began to be 44 μmol / L. At the same time, a significant decrease in the analyzed parameters was found: acetic acid - 0.236 mmol / L, propionic - 0.0060 mmol / L, butyric - 0.0016 mmol / L, isovalerianic - 0.00014 mmol / L. It was decided to perform surgery. During the operation, the diagnosis of Mirizzy's syndrome (type 3 according to the classification of A. Csendes) was confirmed. A cholecystectomy was performed according to the Pribram technique, leaving a portion of the posterior wall of the gallbladder in the neck. After the calculus was removed, a defect 1.8 cm in diameter, corresponding to the size of the calculus, appeared at the site of the cystic-choledochal fistula. Plastic surgery of the defect of the pancreas with a de-epithelialized fragment of the gallbladder wall was performed, choledochotomy (outside the fistula zone), drainage of the pancreas by Keru. Discharged with recovery. According to clinical, instrumental, laboratory, chromatographic data, the patient was diagnosed with obstructive jaundice with purulent cholangitis with the presence of mixed microflora, which confirms the result of the application of the claimed diagnostic method.

Example 2. Patient U., 53 years old, was transferred to our clinic from the city hospital. About a year ago, during an emergency cholecystectomy for acute gangrenous cholecystitis, the common hepatic duct was crossed. A hepaticohepatic anastomosis was formed on a T-shaped drainage. On the 5th day, anastomosis failure and the development of biliary peritonitis arose. Relaparotomy was performed and external hepaticostomy was formed. After 6 months, a reconstructive operation was performed in the form of a hepaticojejunoanastomosis on the Ru loop turned off. In the postoperative period, the condition improved significantly, but periodically there were rises in body temperature, accompanied by chills. Two weeks ago, the patient was hospitalized in the city hospital due to jaundice and high body temperature with chills. After the treatment and examination, she was transferred to our clinic with a diagnosis of cicatricial stricture of hepaticojejunoanastomosis, cholangitis, liver abscess, and obstructive jaundice. Upon admission, the patient is in serious condition. Total bilirubin 263 μmol / L. Marked violations of cellular and humoral immunity are noted. The parameters of VFA in the blood are determined. The following results were obtained: acetic acid - 0.5836 mmol / L, propionic - 0.0421 mmol / L, butyric - 0.0043 mmol / L, isovalerianic - 0.00039 mmol / L. This indicated a pronounced infectious process with the presence of anaerobic flora. According to the established percutaneous transhepatic cholangiostomy, purulent bile began to stand out. Percutaneous transhepatic puncture and debridement of the abscess located in the 5th segment of the liver were also performed. A comprehensive preoperative preparation was carried out in the intensive care unit taking into account the revealed anaerobic microflora and impaired immune status. The condition has improved somewhat. A study of VFA parameters after 10 days showed a slight decrease. Therefore, preoperative preparation was continued. After another 8 days, against the background of an improvement in the general condition, as well as a bilirubin level of 39 μmol / L, a significant decrease in the studied parameters of VFA was noted. The patient was operated on. Marked infiltration in the area of the liver gate was noted. After isolation, a stricture of the previously performed anastomosis is established. Resection of anastomosed tissues and the formation of hepaticojejunoanastomosis were performed. Despite the extremely difficult course of the postoperative period, recovery gradually came. According to clinical, instrumental, laboratory, chromatographic data, the patient was diagnosed with obstructive jaundice with purulent cholangitis with the active development of anaerobic infection, which confirms the result of the application of the claimed diagnostic method.

Therefore, the claimed method is objective and informative. Using the clinical signs of the disease and the concentration of acetic, propionic, butyric and isovalerianic acids in the blood, it is possible to diagnose the presence of purulent cholangitis, as well as the type of microflora in patients with breast cancer. This method allows to increase the objectivity and accuracy of the diagnosis of GC, as well as the type of microflora in breast due to the use of quantitative parameters without undesirable side effects in patients.

Claims (1)

A method for diagnosing purulent cholangitis in patients with obstructive jaundice by examining a patient, characterized in that the gas chromatographic method determines acetic, propionic, butyric and isovaleric acid in the blood and determines the presence of cholangitis at a concentration of acetic acid greater than 0.33 mmol / l, and at a concentration of any three acids: propionic more than 0.012 mol / l, butyric more than 0.0039 mmol / l, isovalerianic more than 0.00034 mmol / l - establish the presence of purulent cholangitis with the active development of anaerobic infection, tr super- one embodiment of preoperative biliary decompression.