Diagnostic technique for function-type oddi's sphincter dyssynergia following cholecystectomy

FIELD: medicine.

SUBSTANCE: cholecystokinin level is counted additionally in the patients with post-cholecystectomy syndrome. In case the concentration is below 0.5 ng/ml, and while observing no organic pathology of hepatopancreatoduodenal organs as demonstrated by instrument methods, function-type Oddi's sphincter dyssynergia is diagnosed.

EFFECT: use of the technique allows early diagnosing function-type Oddi's sphincter dyssynergia following cholecystectomy.

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

Applied research methods, such as ultrasonography (USG) agencies typical for hepatic-pancreaticoduodenal area (GPDS), computed tomography, fibroesofagogastroduodenoscopia (peggs), endoscopic retrograde retrograde cholangiopancreatography (ERCP), duodenoscope inspection of the mouth of the large duodenal papilla (LDP) and manometry of the sphincter of Oddi (SO), allow to identify organic changes of the large duodenal papilla [1]. Remains unresolved the question of the establishment of functional disorders of motility of the sphincter of Oddi.

In addition, these diagnostic methods, as ERCP [2, 3], duodenoscope inspection of the mouth of the LDP and manometry WITH [4], require special equipment, availability of highly skilled specialist, traumatic, after these manipulations the high risk of complications (acute pancreatitis, pancreatic necrosis, stricture MDP) and may not be used as a screening.

From non-invasive methods of investigation in the clinic applies dynamic ultrasonography biliary tract and pancreatic duct with the assessment of contractility of the sphincter of Oddi. But this method is not sufficiently informative [5, 6]. When ultrasonography is possible to estimate the diameter of the duct (choledochal Wirsung duct occured), but to assess contractility, especially when there is a spasm, not stenosis of the sphincter of Oddi, is almost impossible. More reliable results may be obtained when assessing contractile function WITH (the functional nature of the violations) with the drug load (neostigmine, sorbitol, atropine, procaine) [7]. But if you are hypersensitive method is not applicable.

There is a method of determining the dyskinesia of the gallbladder and sphincter of Oddi by duodenal intubation by assessing the duration of stage gallbladder bile and voltage biliary excretion [8]. The disadvantages of this method are the invasiveness, duration of the study and the inability to perform a method in a Department emergency surgery.

There is a method of differential diagnosis of dysfunction of the sphincter of Oddi (DSO) organic and functional nature of using ultrasonography to change the diameter of the choledochus when performing relaxation isosorbide dinitrate treatment in combination with food stress [9]. As well as the method of assessing the functional state of the biliary system in patients after cholecystectomy by ultrasonic measurement of the diameter supraduodenal Department of choledochus and diameter intrapancreatic division of the common bile duct and calculation of the index emptying the lobby of the Okha and subsequent pharmacological tests metoclopramide and repeated ultrasound scanning [10].

The disadvantages of these methods is the presence of individual intolerance to the drugs necessary for carrying out the manipulation, and the likelihood of complications after medical and food provocation in the presence of organic obstacles to biliar flow-out.

In the case when in the course of screening and qualifying diagnostic measures establish violations of organic nature, directly or indirectly associated with the DSO (stenosis CD, stricture CD, papilla, residual or recurrent choledocholithiasis and so on), therapeutic management unambiguous and clear. But, when the cause of pain and dyspepsia after the whole set of diagnostic events cannot be established, no detectable organic pathology of hpda organs and comorbidities, capable of simulating the basic pathology, it is necessary to talk about the DSO functional type.

There are several theories of the development of the DSO functional type after cholecystectomy.

According to one of them, after removal of the gall bladder is a decrease in the sensitivity of the receptors of the sphincter of Oddi to cholecystokinin (CCK), increases the tone of the sphincter in response to food stimulation occurs biliary and/or pancreatic hypertension and attack of abdominal pain [11].

According to another theory, after cholecystectomy in a different time,which is determined individually by the compensatory abilities of the body, change the number produced by CCK [12].

The clinic does not apply valuation methods cholecystokinin level before surgery and after cholecystectomy for establishing unclear the cause of pain and dyspepsia.

The objective of the invention is to increase the objectivity of early diagnosis of dysfunction of the sphincter of Oddi function type after cholecystectomy.

The task to solve due to the fact that in patients with postcholecystectomy syndrome additionally determine the level of cholecystokinin and at concentrations below 0.5 ng/ml, and in the absence of organic pathology of hpda organs on the results of instrumental methods of examination - diagnose dysfunction of the sphincter of Oddi function type.

The concentration of CCK<0.5 ng/ml indirectly indicates the presence of hypertonic sphincter apparatus biliary system, including the sphincter of Oddi. And when combining this indicator with characteristic clinical manifestations, changes of biochemical parameters of blood during the attack, the absence of organic pathology (by ultrasound (US) and fibroesofagogastroduodenoscopia (peggs)) indicates the presence of DSO functional nature.

The method is as follows: all patients diagnosed with post-cholecystectomy syndrome in on what tuplenie conduct complex clinical (complaints, medical history, personal history, physical examination), laboratory (full blood count, urinalysis, blood chemistry, blood glucose level) and instrumental (ultrasonography of the abdominal cavity and retroperitoneal space, fibroesofagogastroduodenoscopia, electrocardiography, chest x-ray) examination to exclude comorbidities, according to testimony - consultation of specialized professionals. Additionally assess the level of cholecystokinin plasma by ELISA for determination of cholecystokinin with stage inactivated (an enzyme Immunoassay for the determination of the peptide with the stage inactivated (Peninsula Laboratories Inc, USA). In the samples (blood plasma) determine the concentration of cholecystokinin (ng/ml). The normal level of cholecystokin ranges from 0.5 to 1 ng/ml [11]. The time of denition of the level of CCK - 5.5 hours. When the level of CCK below 0.5 ng/ml, and in the absence of organic pathology of hpda organs on the results of instrumental methods of examination - diagnose dysfunction of the sphincter of Oddi function type.

The sample of 89 patients of both sexes with postcholecystectomy syndrome (PAS) aged 25 to 80 years.

The average age was - 52,5±1 year.

The study included 69 (77.5%of women and 20 (22.5 percent)men with pain and dyspeptic phenomena - with PHAS functional types at different times after cholecystectomy (HAE), made of an open, minilaparotomy and video-assisted laparascopic accesses.

Runtime HAE varied within wide limits. In the period up to 1 month were delivered 14 (16%) patients, from 1 to 3 months - 9 (10%), from 3 to 6 months - 16 (18%), from 6 months to 1 year - 11 (12%), from 1 year to 5 years - 17 (19%) and in terms of more than 5 years - 22 (25%) of the patients.

For complex examination of patients not detected organic pathology from GPDS. Upon receipt they complained of abdominal pain in biliary or pancreatic type, nausea, dry mouth, some marked by vomiting of bile, bringing relief, diarrhea or constipation.

Blood sampling of patients was performed once at admission before treatment.

Blood was taken in the amount of 9 ml and placed in a polypropylene tube containing ethylenediaminetetraacetic acid (EDTA) (1 mg/ml blood) and Aprotinin (500 Ked/ml of blood), centrifuged at 1600 rpm for 15 minutes. The plasma was transferred to a new polypropylene tube. For maximum stability was stored at -70°C. the Study of the level of CCK was performed using an immunoassay kit for determining peptide with extraction separation columns C18 Sep (Peninsula Laboratories Inc, USA). The calculation result is s carried out automatically on the device Universal Microplate Reader ELx 800 (BIO-TEK INSTRUMENTS INC) by placing in the apparatus of the tablet and calculate the optical density at a wavelength of 450 nm. Automatically calculates the concentration of a calibration curve. The result was represented in digital form. Unit - ng/ml.

The control group was 15 healthy donors without pathology of hpda organs. The average concentration of CCK in the control group was 0.57±0,023 ng/ml.

In the study of the concentration of CCK in patients with PAS showed a trend of lower levels of CCK. In the period up to 1 month after surgery, the average level of CCK remains at the lower limit of normal (0,58±0.05 ng/ml), in terms of 1 to 3 months - 0,22±0.02 ng/ml, from 3 to 6 months to 0.14±0,009 ng/ml, in terms from 6 months to 1 year from 1 year to 5 years varies in the range of 0.16±0,005 - 0,1±0,002 ng/ml, more than 5 years - 0,08±0,008 ng/ml Thus, the level of CCK after gallbladder removal bubble has a progressive tendency to decrease. The drawing shows the concentration of CCK in plasma of patients with clinical manifestations of the DSO functional types at different times after cholecystectomy (n=89), where the vertical is indicated concentrations of CCK (ng/ml), across - the period of time after surgery, which was performed blood sampling:

1 - up to 1 month;

2 - from 1 to 3 months;

3 - from 3 to 6 months;

4 - 6 months to 1 year;

5 - from 1 year to 5 years;

6 - more than 5 years.

Thus, already in the first month after HE neuropeptide link reacts to new conditions b is larnage tract by reducing the level of CCK in the absence of the main target of action of CCK - bile pusara.

Example 1.

Patient K., 51, was taken to the XO-I GKB №7 07.02.2009 by ambulance with a presumptive diagnosis: post-cholecystectomy syndrome, acute pancreatitis.

At admission the patient complained of pain in the epigastrium and left hypochondrium, nausea, single vomiting bile, dry mouth. Pain in acute about 24 hours ago after errors in diet (intake of fatty foods).

From the anamnesis of life: hepatitis, tuberculosis, diabetes, cancer, sexually transmitted diseases denies. Injury, blood transfusion was not. Underwent a laparoscopic cholecystectomy 3 months ago. Allergic anamnesis is not burdened.

Objectively: the patient's state of moderate severity. Clear consciousness. The active position. The body temperature to 36.8°C. the Skin and visible mucous usual coloration and humidity. Visible pathology of bone and joint system. The vesicular breathing, is all lung fields, no wheezing. The NPV of 16 per minute. Cor tones clear, rhythmic. HR=Ps=76 per minute. HELL 140/90 mm Hg Language moist, moderately white furred. Abdomen normal configuration, symmetrical, evenly participates in the act of breathing, palpation painful, moderately intense in the epigastrium and left hypochondrium. Symptoms carte, Cochrance positive. But the ohms of peritoneal irritation no. Symptom XII ribs negative on both sides. The chair was in the morning, decorated. Dysuria is not.

Data on laboratory studies: hemoglobin 128 g/l, erythrocytes of 3.9×10⁹/l, leukocyte count of 8.2×10⁹/l, band 1, segmented 69, lymphocytes 18, monocytes 12; glucose 4.3 mmol/l; bilirubin total of 12.0 mmol/l, direct-4.5 mmol/l, indirect 7.5 µmol/l, amylase 8.2 mg/s×l, urea of 4.9 mmol/l, total protein and 70.5 g/l, Alt of 0.65 mmol/h×l, AST 0.27 mmol/h×L.

The level of CCK plasma - 0.15 ng/ml.

Data instrumental methods: ultrasonography of the abdominal cavity and retroperitoneal space - after cholecystectomy. Diffuse changes in the pancreas. Choledoch - 7 mm Biliary hypertension no. Kidney - without a pathology. Fibroesofagogastroduodenoscopia - atrophic gastritis. Electrocardiography - alone without pathology. Chest x-ray from the side of the lungs and heart age-related changes.

Confirmed diagnosis of postcholecystectomy syndrome. Dysfunction of the sphincter of Oddi functional type (level of CCK - 0.15 ng/ml).

Prescribed conservative treatment: intravenous infusion of glucose-procaine mixture, antispasmodic drugs (according to the standard scheme) and mebeverine hydrochloride 1 capsule (200 mg) 4 times a day orally for 9 days.

Amid conservativegreen the patient's condition has improved - pain syndrome and dyspepsia cropped. Jaundice no. Body temperature is normal.

The patient was discharged on the 9th day in a satisfactory condition with no complaints with the recommendations of diet and receiving selective spasmolytic drugs: mebeverine hydrochloride 1 capsule (200 mg) 4 times a day orally for 14 days after discharge from hospital and in the event of such pain.

Example 2.

Patient K., aged 65, was delivered in XO-I GKB №7 28.12.2008 by ambulance with a presumptive diagnosis: post-cholecystectomy syndrome, acute pancreatitis.

At admission the patient complained of pain in the epigastrium and left hypochondrium, nausea, double vomiting food mixed with bile, neprinosâŝego relief, dryness in the mouth. Ill acutely about 12 hours ago, after errors in diet (alcohol and fatty foods).

From the anamnesis of life: hepatitis, tuberculosis, diabetes, cancer, sexually transmitted diseases denies. Injury, blood transfusion was not. Suffering from hypertension. Underwent cholecystectomy from mini-access 5 months ago. Allergic anamnesis is not burdened.

Objectively: the patient's state of moderate severity. Clear consciousness. The active position. The body temperature of 36.2°C. the Skin and visible mucous regular color and is laineste. Visible pathology of bone and joint system. The vesicular breathing, is all lung fields, no wheezing. The NPV of 20 per minute. Cor tones clear, rhythmic. HR=Ps=87 per minute. HELL 150/100 mm Hg Tongue moist, coated with white bloom. Abdomen normal configuration, symmetrical, evenly participates in the act of breathing, palpation painful, moderately intense in the epigastrium and left hypochondrium. Symptoms carte, Cochrance positive. Symptoms of peritoneal irritation no. Symptom XII ribs negative on both sides. The chair was last night, decorated. Dysuria is not.

Data on laboratory studies: hemoglobin 162 g/l, erythrocytes of 4.9×10⁹/l, leukocyte count of 7.8×10⁹/l, stab 3, segmented 71, lymphocytes 22, monocytes 4; glucose 4.0 mmol/l; total bilirubin 19.0 µmol/l, direct-5.0 mmol/l, indirect 14.0 µmol/l, amylase 7,0 mg/×l, urea of 6.9 mmol/l, total protein of 67.5 g/l, Alt 0.84 mmol/h×l, AST of 0.56 mmol/h×L.

The level of CCK plasma - 0.22 ng/ml.

Data instrumental methods: ultrasonography of the abdominal cavity and retroperitoneal space - after cholecystectomy. Diffuse changes in the pancreas. Choledoch - 6 mm Biliary hypertension no. Kidney - without a pathology.

Fibroesofagogastroduodenoscopia - atrophic gastritis, duodenitis. Electracard ografia - signs of left ventricular hypertrophy. Chest x-ray from the side of the lungs and heart age-related changes.

Confirmed diagnosis of postcholecystectomy syndrome. Dysfunction of the sphincter of Oddi functional type (level of CCK plasma - 0.22 ng/ml).

Prescribed conservative treatment: intravenous infusion of glucose-procaine mixture, antispasmodic drugs (according to the standard scheme) and mebeverine hydrochloride 1 capsule (200 mg) 4 times a day orally for 9 days.

On the background of conservative treatment the patient's condition improved, the pain and dyspepsia cropped. Jaundice no. Body temperature is normal.

The patient was discharged on the 9th day in a satisfactory condition with no complaints with the recommendations of diet and receiving selective spasmolytic drugs: mebeverine hydrochloride 1 capsule (200 mg) 4 times a day orally for 14 days after discharge from hospital and in the event of such pain.

The advantages of the proposed diagnostic method is its novelty, the rapidity of results (reaction time of 5.5 hours and informative, so you can use it for a comprehensive diagnosis of the dysfunction of the sphincter of Oddi after cholecystectomy in the early stages.

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Method for the diagnosis of dysfunction of the sphincter of Oddi function type after cholecystectomy, including laboratory testing of blood plasma, characterized in that it further determine the level of cholecystokinin and when the values of its concentration below 0.5 ng/ml, and in the absence of organic pathology of organs typical for hepatic-pancreaticoduodenal area according to the results of instrumental methods of examination diagnose dysfunction of the sphincter of Oddi functional type.