RU2629396C1 - Method for diagnostics of type iii oddi's sphincter dysfunction in patients operated due to cholelithiasis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention is intended for the early diagnosis of type III Oddi's sphincter dysfunction in patients operated due to cholelithiasis. The level of digestive tract neuropeptides and nitric oxide is additionally determined when entering the surgical department and at concentrations of neuropeptide-dilators below 0.5 ng/ml, neuropeptide constrictors above 1.0 ng/ml, nitric oxide below 9.75 μmol/l, type III Oddi's sphincter dysfunction is diagnosed.

EFFECT: method allows to increase the efficiency of early diagnosis and timely conduct preventive and curative measures and dispensary observation of this category of patients.

3 dwg, 1 tbl, 1 ex

Description

The invention relates to medicine, can be used in surgery and gastroenterology.

Applied research methods, such as ultrasound examination (ultrasound) of the organs of the hepatopancreatoduodenal zone (GPDZ), multispiral computed tomography with cholangiography (MSCT with CG), magnetic resonance imaging with cholangiography (MRI with CG), fibroesophagogastroscopy (FEGGR), , duodenoscopy with an examination of the mouth of the large duodenal nipple (BDS) and manometry of the sphincter of Oddi (CO), allow to identify organic changes in the terminal section of the common bile and (CBD) and the major duodenal papilla. But the question of establishing a diagnosis of dysfunction of the sphincter of Oddi (DSS) type III (functional nature) remains unresolved.

Diagnostic methods such as ERCP, duodenoscopy with examination of the BDS mouth and CO manometry require special equipment, an experienced highly qualified specialist, are traumatic, after these manipulations there is a high risk of complications (acute pancreatitis, pancreatic necrosis, BDS strictures) and cannot be used as screening.

Of the non-invasive research methods in clinical practice, dynamic ultrasonography of the biliary tract and pancreatic duct is used with an assessment of the contractility of CO [1]. But this method is not informative enough. With ultrasonography, it is possible to assess the diameter of the ducts (OP and Wirsung duct), but to assess contractility, especially when there is a spasm of CO, and not stenosis of the BDS, is almost impossible. More reliable results can be obtained by evaluating the contractile function of CO (with spasm) with a drug load (proserin, sorbitol, atropine, novocaine). But in the presence of individual intolerance, the method is not applicable.

A known method for determining dyskinesia of the gallbladder and WITH by duodenal sounding by evaluating the duration of the stage of production of cystic bile and tension of bile secretion [3]. The disadvantages of this method are invasiveness, the duration of the study and the inability to perform the method in emergency surgery.

There is a method for differential diagnosis of organic and functional DLS with the help of ultrasonography to change the diameter of the OSP during relaxation with isosorbide dinitrate in combination with food load, as well as a method for assessing the functional state of the biliary system in patients after cholecystectomy by ultrasound measurement of the diameter of the supraduodenal part of the body and the diameter of the intrapancreatic OSH and calculation of the index of emptying OSH and the subsequent pharmacological Both metoclopramide and repeated ultrasound scanning [1].

The disadvantages of these methods include the presence of individual intolerance to the drugs necessary for the manipulation, as well as the likelihood of complications after drug and food provocation in the presence of an organic obstruction to the bile duct.

In the case when, during screening and clarifying diagnostic measures, violations of the organic nature associated with DLS and pathology of AFL (stenosis of the BDS, stricture of the BDS, stricture of the pancreatic stricture, papillitis, residual or recurrent choledocholithiasis) are established, the treatment tactics are clear and clear.

But when it is not possible to establish the cause of pain and dyspepsia after the entire complex of diagnostic measures, the organic pathology of the GPDZ organs and associated diseases that can simulate the main pathology are not detected, it is necessary to assume type III sphincter Oddi dysfunction.

Known methods for diagnosing dysfunction of the sphincter of Oddi type III after cholecystectomy by cholecystokinin level (CCK). The methods consist in determining the level of SSC in blood plasma and the diagnosis of functional disorders of the biliary tract by changing its level [2, 4, 5].

However, the level of other markers-dilators and markers-constrictors is not taken into account, which reduces the diagnostic value of this method.

In addition, the data obtained in the works of E.V. Bystrovskaya [2] and L. M. Nemtsov [4] are controversial. So in the works of L.M. Nemtsov described a progressive decrease in SSC in patients after cholecystectomy, which explains one of the etiopathogenetic aspects of dysfunction of the sphincter of Oddi inorganic etiology. In the works of E.V. Bystrovskaya et al. Reflected an increase in the level of SSC in patients after cholecystectomy, and this fact explains both the development of the organic and functional pathology of the sphincter apparatus of the organs of the hepatopancreatoduodenal zone.

No methods were found in the sources for assessing the level of neuropeptides (NPs), including SSK before surgery and after cholecystectomy, to establish an unclear cause of pain and dyspepsia.

The objective of the proposed method is the early diagnosis of dysfunction of the sphincter of Oddi type III in patients operated on for gallstone disease.

The problem is solved due to the fact that in patients operated on for cholelithiasis, the level of neuropeptides of the digestive tract and nitric oxide is additionally determined upon admission to the surgical department and when the concentration of neuropeptides-dilators is lower than 0.5 ng / ml, and neuropeptides are higher 1.0 ng / ml, nitric oxide below 9.75 μmol / L diagnose type III sphincter of Oddi dysfunction.

The method is as follows. Upon admission, all patients diagnosed with postcholecystectomy syndrome (PCES) undergo comprehensive clinical (collection of complaints, medical history, life history, physical examination), laboratory (detailed blood count, general urine analysis, biochemical blood test, blood glucose level) and instrumental (ultrasonography organs of the abdominal cavity and retroperitoneal space, fibroesophagogastroduodenoscopy, electrocardiography, chest x-ray) examination to exclude concomitant pathology, according to Azaniyam - consultations of specialized specialists.

Additionally assess the level (PCES) of NP and nitric oxide of the blood plasma by enzyme immunoassay for the determination of neuropeptides (cholecystokinin (CCK), vasoactive intestinal peptide (VIP), somatostatin-14 (SST-14), neuropeptide Y (NPY), peptide YY (PYY) , substance P (SP), bradykinin (VK) and neurotensin (NT) with or without preincubation, and nitric oxide (enzyme-linked immunosorbent assay for determining peptides with or without pre-incubation (Peninsula Laboratories Inc, USA). (blood plasma) determine the concentration of neuropeptides (ng / ml) and oxide nitrogen (μmol / l).

Normally, the NP level ranges from 0.5 to 1.0 ng / ml, nitric oxide - from 9.75 to 19.5 μmol / L. At the level of NP dilatators below 0.5 ng / ml, NP constrictors above 1.0 ng / ml, nitric oxide below 9.75 μmol / L, as well as in the absence of organic pathology of the GPDZ organs, sphincter dysfunction is diagnosed by the results of instrumental examination Oddi III type.

A total of 40 patients of both sexes with postcholecystectomy syndrome (PCES) and 30 healthy people aged 20 to 80 years were examined. The average age was (49.3 ± 11) years.

The study included patients with PCES of inorganic etiology (type III DLS), confirmed by ultrasonography (no organic pathology of the GPDZ organs was found, the condition after cholecystectomy), who were urgently admitted to the surgical department with different periods from the time the disease started; which conservative therapy was carried out.

Blood sampling to determine the level of NP and nitric oxide was performed once upon admission. Blood was collected in an amount of 9 ml and placed in a polypropylene tube containing ethylenediaminetetraacetic acid (EDTA) (1 mg / ml of blood) and aprotinin (500 KED / ml of blood), centrifuged at 1600 rpm for 15 minutes. Plasma was transferred to a new polypropylene tube. To achieve maximum stability, it was stored at -70 ° C. The study of the level of NP and nitric oxide was carried out using an enzyme immunoassay for determining the peptide with or without extraction on separation columns (Peninsula Laboratories Inc, USA). The results were calculated automatically on a Universal Microplate Reader ELx 800 device (BIO-TEK INSTRUMENTS INC) by placing a tablet in the device and calculating the optical density at a wavelength of 450 nm. Automatically calculated the concentration according to the calibration graph. The result was digitally presented. The unit of measurement is ng / ml and μmol / l, respectively.

In patients with a diagnosis of PCES, type III DLS, when studying the concentration of NP dilators, a tendency to a decrease in their concentration was revealed. Moreover, the dynamics of indicators is fundamentally different from the dynamics of indicators of patients with PCES of organic etiology.

Within a period of up to one month after cholecisectomy, normal values of NP-dilators were obtained with a further progressive decrease to 0.16 ± 0.04 ng / ml in a period of three to six months, in a period of six months to one year, a slight increase in concentration to 0 , 29 ± 0.09 ng / ml, and then a decrease to 0.092 ± 0.04 ng / ml over a period of more than five years (table 1, figure 1, 2).

Table 1 shows the concentration of NP and nitric oxide in the blood plasma of patients with PCES, type III DSO. Symbols of statistical significance: * - p <0.05 compared with indicators up to one month (at U emp. <U cr.). ** - p≤0.01 compared with indicators in a period of up to one month (with U emp. <U cr.).

Figure 1 shows the concentration of NP dilators and NP constrictors in the blood plasma of patients with PCES, type III DSO. The x axis indicates neuropeptides-dilators and neuropeptides constrictors. On the Y axis is the concentration of neuropeptides, ng / ml. The first column for each of the indicators of neuropeptides indicates a period after cholecystectomy of less than one month, the second from one to three months, the third from three to six months, the fourth from six months to one year, the fifth from one to two years, the sixth from two to five years, the seventh - more than five years. Symbols of statistical significance: * - p≤0.05 compared with indicators in terms of up to one month (with U emp. <U cr.). ** - p <0.01 compared with indicators in the period up to one month (with U emp. <U cr.).

Figure 2 shows the concentration of groups of neuropeptides (dilatators and constrictors) in the blood plasma of patients with PCES, type III DSO. The X-axis indicates the time after cholecystectomy, the Y-axis indicates the concentration of neuropeptides, ng / ml. The upper curve reflects the dynamics of neuropeptides-contraceptors, the lower curve shows the dynamics of neuropeptides-dilators.

It was noted that the indicators of the concentration of nitric oxide in blood plasma after cholecystectomy with functional pathology of GPDZ organs vary within normal limits (Figure 3). The X-axis indicates the time after cholecystectomy, the Y-axis indicates the concentration of nitric oxide, µmol / L.

Figure 3 shows the concentration of nitric oxide in the blood plasma of patients with PCES, type III DSO. Symbols of statistical significance: * - p≤0.05 compared with indicators in terms of up to one month (with U emp. <U cr.). ** - p≤0.01 compared with indicators in a period of up to one month (with U emp. <U cr.). In the period up to one month after cholecisectomy, an increase in NP-constrictors was obtained by a factor of 1.9, with a further gradual increase to 2.32 ± 0.4 ng / ml in a period of one to three months, then a gradual decrease in time from three up to six months, from six months to one year and from one year to two years - up to 1.41 ± 0.46 ng / ml, 1.67 ± 0.29 ng / ml and 1.64 ± 0.35 ng / ml, respectively. In terms of two to five years, the average concentration of NP constrictors was 2.06 ± 0.22 ng / ml, and in terms of more than five years - 1.56 ± 0.26 ng / ml.

At the same time, it is noteworthy that the average concentrations of NP dilatators remain at a relatively stable low level, the average concentration of nitric oxide corresponds to the normal range, and the concentrations of NP constrictors are at a consistently high level exceeding the upper limit of the norm of 1.8 times, which was not observed in any of the previous groups. This allows us to conclude that functional disorders after cholecystectomy are characterized by low or normal rates of dilator markers and increased rates of constriction markers.

The concentration of NP dilators <0.5 ng / ml and nitric oxide <9.75 μmol / L indicates the presence of hypertonicity of the sphincter apparatus of the biliary system, including the sphincter of Oddi. A combination of this indicator with characteristic clinical manifestations, changes in blood biochemical parameters during an attack, and the absence of organic pathology (according to ultrasound, PEG, duodenoscopy with examination of the BDS mouth) indicates type III DLS.

Thus, already in the first month after cholecystectomy, the neuropeptide link responds to new conditions of the functioning of the biliary tract by lowering the level of NP dilatators and increasing the level of NP constrictors at a normal level of nitric oxide due to the absence of the main target of action - the gall bladder and, as a result, discoordination of motility, which is not always in the early stages after cholecystectomy, manifests itself clinically due to the activation of compensatory capabilities.

Example No. 1.

Patient A., 50 years old, was taken to the surgical department of KMKB No. 4 on 09/20/2015 by an ambulance team with a presumptive diagnosis: postcholecystectomy syndrome, acute pancreatitis (?).

Upon admission, the patient complained of pain in the epigastric region and the left hypochondrium, nausea, double vomiting with an admixture of bile, which did not bring relief, dryness, bitterness in the mouth. According to the patient, she fell ill acutely about 24 hours ago after an error in the diet (intake of fatty foods).

From the anamnesis of life: hepatitis, tuberculosis, diabetes, cancer, sexually transmitted diseases denies. There were no injuries, blood transfusions. She underwent laparoscopic cholecystectomy 6 months ago. An allergic history is not burdened.

Objectively: the patient's condition is moderate. Consciousness is clear. The position is active. Body temperature 36.8 ° C. The skin and visible mucous membranes of normal color and moisture. There is no visible pathology of the osteoarticular system. The vesicular breathing is carried out in all pulmonary fields, no wheezing. BH 16 per minute. Heart tones are clear, rhythmic. Heart rate = Ps = 79 per minute. HELL 130/80 mm RT. Art. The tongue is moist, moderately coated with a white coating. The abdomen of the usual configuration, symmetrical, evenly participates in the act of breathing, painful on palpation, moderately strained in the epigastric region and left hypochondrium. Symptoms of Kerte, Chukhrienko are positive. There are no symptoms of peritoneal irritation. Symptom XII rib negative on both sides. The chair was in the morning, decorated. There is no dysuria.

The data of laboratory research methods: hemoglobin 135 g / l, red blood cells 3.5 × 10 ¹² / l, white blood cells 8.9 × 10 ⁹ / l, stab neutrophils 5, segmented neutrophils 57, lymphocytes 15, monocytes 23; glucose 4.9 mmol / l; total bilirubin 10.0 μmol / L, direct 4.0 μmol / L, indirect 6.0 μmol / L, blood amylase 98 IU / L, urine amylase 504.0 U / L, urea 4.0 mmol / L, total protein 75.3 g / l, Alt 30 IU / L, AcT 34.5 IU / L.

Blood plasma cholecystokinin level - 0.12 ng / ml, vasoactive intestinal peptide - 0.23 ng / ml, somatostatin-14 - 0.45 ng / ml, neuropeptide Y - 0.33 ng / ml, peptide YY - 0.39 ng / ml, substances R - 2.4 ng / ml, neurotensin - 3.0 ng / ml, bradykinin - 1.89 ng / ml, nitric oxide - 15.8 μmol / L.

Data instrumental methods of research: ultrasonography of the abdominal cavity and retroperitoneal space - a condition after cholecystectomy. Diffuse changes in the pancreas. Choledoch - 7 mm. There is no biliary hypertension. Kidneys - without pathology. Fibroesophagogastroduodenoscopy - diffuse atrophic gastritis. Electrocardiography - alone without pathology. Chest x-ray - age-related changes in the lungs and heart.

The diagnosis is confirmed: postcholecystectomy syndrome. Functional type sphincter Oddi dysfunction (plasma cholecystokinin level - 0.12 ng / ml, vasoactive intestinal peptide - 0.23 ng / ml, somatostatin-14 - 0.45 ng / ml, neuropeptide Y - 0.33 ng / ml, peptide YY - 0.39 ng / ml, substance P - 2.4 ng / ml, neurotensin - 3.0 ng / ml, bradykinin - 1.89 ng / ml, nitric oxide - 15.8 μmol / l.).

Conservative treatment was prescribed: intravenous infusion of antispasmodic drugs, saline solutions (according to the standard scheme) and mebeverine hydrochloride, 1 capsule (200 mg) 3 times a day orally.

Against the background of conservative treatment, the patient's condition improved - pain and dyspepsia were stopped. There is no jaundice. The body temperature is normal.

The patient was discharged on the 5th day in satisfactory condition in the absence of complaints with recommendations for dieting and taking selective antispasmodic drugs: mebeverine hydrochloride, 1 capsule (200 mg) 3 times a day orally for one month after discharge from the hospital and in the event of such pain .

The advantages of the proposed method is its novelty and information content, which allows it to be used to diagnose type III sphincter of Oddi sphincter dysfunction in patients operated on for cholelithiasis, and to carry out preventive and therapeutic measures (prescribing selective antispasmodic drugs) and clinical observation of this category of patients.

LIST OF SOURCES

1. Vakhrushev Ya.M. Evaluation of the functional state of the hepatobiliary system in patients with biliary dyskinesia / Ya.M. Vakhrushev, I.A. Penkina // Therapist. archive. - 2007. - T. 79, No. 2. - S. 41-44.

2. Change in the concentration of cholecystokinin-pancreosimine in patients with cholelithiasis before and after cholecystectomy / E.V. Bystrovskaya, A.A. Ilchenko, V.N. Drozdov [et al.] // Experiment. and clinic. gastroenterology. - 2010. - No. 4. - S. 28-32.

3. Maksimov, V.A. Duodenal sounding - a modern view (on the 100th anniversary of duodenal sounding) / V.A. Maximov // Therapist. archive. - 2010. - T. 82, No. 1. - S. 63-64.

4. Nemtsov L.M. Serum cholecystokinin and clinical and functional variation of biliary pathology / L.M. Nemtsov // Experiment. and clinic. gastroenterology. - 2014. - T. 112, No. 12. - S. 24-29.

5. RF patent No. 2416802, G01N 33/78, bull. No.11, 04/20/2011

Claims (1)

A method for the diagnosis of type III sphincter of Oddi dysfunction in patients operated on for cholelithiasis, including a laboratory study of blood plasma, characterized in that it further determines the level of neuropeptides of the digestive tract and nitric oxide upon admission to the surgical department and when the concentration of dilated neuropeptides is less than 0, 5 ng / ml, constrictor neuropeptides above 1.0 ng / ml, nitric oxide below 9.75 μmol / L diagnose type III sphincter Oddi dysfunction.

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