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Home , Cholecystitis, Common bile duct stone, Peritonitis

MINISTRY OF HEALTHCARE OF UKRAINE DANYLO HALYTSKY LVIV NATIONAL MEDICAL UNIVERSITY

DEPARTMENT OF # 1

ACUTE

Guidelines for Medical Students

Lviv - 2019 Approved at the meeting of the surgical methodological commission of Danylo Halytsky Lviv National Medical University (Meeting report № 56 on May 16, 2019)

Contributors: GERYCH I. D. - PhD, professor, head of the Department of Surgery №1, Danylo Halytsky Lviv National Medical University VARYVODA E. S. – PhD, associate professor, Department of Surgery №1 KOLOMIYTSEV V. I. – PhD, associate professor, Department of Surgery №1 KHOMYAK V. V. – PhD, assistant professor, Department of Surgery №1 MARINA V. N. - MD, assistant professor, Department of Surgery №1

Referees: ANDRYUSHCHENKO Viktor Petrovych – PhD, professor of Department of at Danylo Halytsky Lviv National Medical University OREL Yuriy Glibovych - PhD, professor of Department of General Surgery at Danylo Halytsky Lviv National Medical University

Responsible for the issue first vice-rector on educational and pedagogical affairs at Danylo Halytsky Lviv National Medical University, corresponding member of National Academy of Medical Sciences of Ukraine, PhD, professor M.R. Gzegotsky

1. Background. Cholelithiasis ( disease), inflammatory diseases of gall-bladder (cholecystitis), ducts considerable place among patients with pathology of organs of alimentary tract. Gallstone disease remains one of the most common medical problems leading to surgical intervention. Cholelithiasis affects approximately 10% of the adult population in the world. It has been well demonstrated that the presence of increases with age. An estimated 20% of adults over 50 years of age and 30% of those over age 70 have biliary calculi. With every year the amount of these patients increase, and a cholecystitis occupies the second place after . In the US, approximately 700,000 are performed every year. In fact, this group of patients represents between 50 and 70 % of surgical admissions for acute cholecystitis. Swift scientific and technical progress in medicine was instrumental in the origin of new perspective directions in treatment of gallstone disease is the use of preparations for dissolution of concrements, wave extracorporal and contact lithotripsy, open and laparoscopic operations. Such operation, as , was first executed by Carl Langenbuch in 1882 and remains basic in surgical treatment of patients with uncomplicated cholecystitis. During many years a method was utilized in whole the world. Low postoperative morbidity and mortality, minimal probability of trauma of bile ducts, especially at the chronic form of disease, convincingly enough testified to it. However, development and perfection of endoscopic technique changed surgery of gall-bladder stone disease high-quality. Inculcated in clinical practice in 80th the method of laparoscopic cholecystectomy under video guidance F. Dubois, P. Mouret becomes the method of choice and on this time all more often successfully used in patients with an acute cholecystitis.

Duration of lesson: 4 hours

Learning Objectives: To know (α = I; α = II):  determination of concept is “gallstone disease”, “acute cholecystitis”;  modern understanding of aetiology and pathogenesis of acute cholecystitis;  classification of acute cholecystitis and complications;  morphologic changes are in a gall-bladder and bile ducts;  features of clinical symptoms depending on the different forms of cholecystitis;  frequency of complications and clinical signs;  diagnostic possibilities of additional methods of investigation (laboratory tests, X-ray, ultrasonography, computed tomography, magnetic resonance imaging, , endoscopic retrograde cholangiopancreatography);  differential diagnostics of acute cholecystitis;  surgical treatment of acute cholecystitis;  principles of surgery;  biliary drainage: indications and methods. Able to (α = II; α = III):  propose a diagnosis;  define the form of cholecystitis;  analyse the laboratory tests and investigations data;  conduct the of acute cholecystitis with acute appendicitis, acute , intestinal obstruction, perforative ulcer;  formulate a final diagnosis;  appoint treatment;  define indications to surgery;  diagnose the of cholecystitis (choledocholithiasis, , cholangitis, biliary pancreatitis, , , , );  appoint postoperative treatment. Practical skills:  capture of anamnesis and its analysis;  examination of patients with , and bile ducts disease;  determination of signs, characteristic for a chronic and acute cholecystitis;  interpretion of laboratory tests data and examination;  formulation of indication and contraindication for surgical treatment;  choose the method of surgery or mini-invasive treatment.

4. Interdisciplinary integration

Subject and proper № To know To be able department Base departments 1 Anatomy, topographical Anatomy and topographical To conduct palpation of anatomy (departments of anatomy of liver, gallbladder and liver and gallbladder. Aanatomy of human, biliary system. Topographical anatomy and operative surgery) 2 Morphology (department of Morphological description of To define morphological Pathoanatomy & acute cholecystitis. changes, inherent the Morphology) different types of acute cholecystitis. 3 Anatomy, topographical Surgical approach, methods of To choose the adequate anatomy (departments of operations method of surgery Anatomy of human, Topographical anatomy and operative surgery) 4 Biological chemistry Test interpretation of surgical To interpretate the (department of Biological diseases tests in patients with an chemistry ) acute cholecystitis. 5 Internal diseases (department Interpretation of examination of To conduct an examination of Internal diseases) organs of abdominal region patient with an acute cholecystitis.

Type clinical departments 1 General surgery (department Basic principles of work of Hospitalize a patient to of General surgery) surgical department and surgical department, to operating block in emergency. prepare to the treatment and diagnostic options and surgery.

2 Department of Internal Methods of diagnostics of acute To find out the complaints diseases cholecystitis and its of patient, collect complications, pathogenesis and anamnesis of disease, clinical variants. conduct an examination of patient, ground a diagnosis, conduct a differential diagnosis, plan of additional examination.

V. Contents of the topic and its structuring

Pay a regard to etiologic factors which result in of gallbladder. Acute cholecystitis more frequent develops on the background of gallstone disease, less than - without it. An acalculous cholecystitis more frequent is early in life. During the reproductive years, the female-to- male ratio is about 4:1, with the sex discrepancy narrowing in the older population to near equality. Chronic inflammation is supported stone; an acalculous cholecystitis more frequent is complication of sphincter of Oddi and dysfunction, invasion of vermin, heterospecific and specific infection. Regardless of inflammation a cholecystitis can be accompanied by a hepatic colic, that characteristically for a calculous cholecystitis, and also periodic attacks. Periodically nascent acute inflammation calms down under the action of medical measures, or destructive changes make progress in the walls of gallbladder. The free outflow of bile recommences in the cases of calming down of process. In a gallbladder the developed fibrotic layer is saved little anymore with education between the muscular pinches of connecting fabric. In a number of cases fibrotic changes support permanent chronic inflammation of gallbladder which is instrumental in the periodic attacks.

AETIOLOGY AND PATHOGENESIS Local: 1) Anatomic features of gallbladder and biliary system; 2) Defeat of wall of gallbladder by various mechanical and chemical agents. General: 1) Sensibilisation of organism; 2) Change of imunoresistance and resistance of organism; 3) Violation of the neiro-gumoral adjusting of gallbladder and biliary system. To the causing factors take:  virulent (Table 1) which gets to the wall of gallbladder by a hematogenic, lymphatic ways and from ;  stagnation of bile which arises up as a result of mechanical (obstruction by a stone, narrowing of gallbladder , innate defects) or functional disorders (spasm of sphincters, neuro-humoral dysfunction and other). More frequent all an acute cholecystitis arises up at combination of the following factors:  violation of outflow of bile;  presence of infection;  sensibilisation of organism;  damage of gallbladder wall (mechanical, chemical).

Table 1 Common microorganisms isolated from bile cultures among patients with acute cholecystitis Isolated microorganisms Proportions of isolated from bile cultures organisms (%) Gram-negative organisms 31–44 Klebsiella spp. 9–20 Pseudomonas spp. 0.5–19 Enterobacter spp. 5–9 Gram-positive organisms Enterococcus spp. 3–34 spp. 2–10 spp. 0-5 Anaerobes 4–20

In 90 to 95% of cases, acute cholecystitis is related to gallstones. Obstruction of the cystic duct by a gallstone leads to and is also the first event in acute cholecystitis. If the cystic duct remains obstructed, the gallbladder distends, and the gallbladder wall becomes inflamed and edematous. In the most severe cases (5 to 10%), this process can lead to and of the gallbladder wall. More frequently, the gallstone is dislodged, and the inflammation gradually resolves. Gallstone Pathogenesis. Bile represents the route of excretion for certain organic solids, such as ana cholesterol, the major organic solutes in bile are bilirubin, bile salts, phospholipids, and cholesterol. Bilirubin is the breakdown product of red blood cells and is conjugated with glucuronic acid before being excreted. Bile salts solubilize lipids and facilitate their absorption. Phospholipids (lecithin) are synthesized in the liver in conjunction with bile salt synthesis. The final major solute of bile is cholesterol. The normal volume of bile secreted daily by the liver is 600 to 1200 ml. Cholesterol is highly nonpolar and insoluble in water. The key to maintaining cholesterol in solution is the formation of both micelles, a bile salt-phospholipid-cholesterol complex, and cholesterol- phospholipid vesicles. Present theory suggests that in states of excess cholesterol production, these large vesicles may also exceed their capability to transport cholesterol, and crystal precipitation may occur. Cholesterol solubility depends on the relative concentration of cholesterol, bile salts, and phospholipids. Gallstones represent a failure to maintain certain biliary solutes, primarily cholesterol and calcium salts, in a solubilized state. Gallstones are classified by their cholesterol content as either cholesterol or pigment stones. Pigment stones are further classified as either black or brown. Pure cholesterol gallstones are uncommon (10%), with most cholesterol stones containing calcium salts in their center. In most populations, 70 to 80% of gallstones are cholesterol, and black pigment stones account for most of the remaining 20 to 30%. An important biliary precipitate in gallstone pathogenesis is biliary "sludge," which refers to a mixture of cholesterol crystals, calcium bilirubinate granules, and a mucin gel matrix. has been observed clinically in prolonged fasting states or with the use of long-term total . Both of these conditions are also associated with gallstone formation. The finding of macromolecular complexes of mucin and bilirubin, similar to biliary sludge in the central core of most cholesterol gallstones, suggests that sludge may serve as the nidus for gallstone growth. The risk factors predisposing to gallstone formation include , mellitus, estrogen and , hemolytic diseases, and . The morphological displays of acute cholecystitis carry making progress destructive character often. As a rule, a process is begun with a mucus coat, where a desquamation of epithelium is, was swollen mucus shell and submucous layer, infiltration their leucocytes. Subserosal dilation of blood vessels takes place, bile often with the admixtures of mucus and fibrin. Such changes are characteristic for a catarrhal cholecystitis. At subsequent progress of passionately destructive changes in a mucus shell which loses the protective properties, a process spreads on other layers of wall of gallbladder. There is a considerable oedema of all of layers, their infiltration by different cells, microorganisms. The paretic broaden blood vessels, there are diffuse hemorrhages. Muscular layers loosed a capacity for contraction. In a serosa there is a desquamation of mesotelium, laying of fibrin. Such changes are characterized as a phlegmonous cholecystitis. Accumulation of inside the gallbladder is determined as an empyema of gallbladder. Total destruction of the gallbladder wall is specific for gangrenous cholecystitis. Thus to the gall-bladder large omentum, colon or its mesentery, wall of can be fixed. The conglomerate of tissues which are saturated with an exsudate – paravesical mass (infiltrate) appears in the total. Perforation of the gallbladder occurs in up to 10% of cases of acute cholecystitis. Perforation is a sequela of ischemia and of the gallbladder wall and occurs most commonly in the gallbladder fundus. The perforation is most frequently (50% of cases) contained within the subhepatic space by the omentum, duodenum, liver, and hepatic flexure of the colon, and a localized abscess forms. Less commonly, the gallbladder perforates into an adjacent viscus (duodenum or colon), resulting in a cholecystoent-eric . Rarely, the gallbladder perforates freely into the peritoneal cavity, leading to generalized peritonitis. Emphysematous cholecystitis develops very rarely, more commonly in males and in patients with diabetes mellitus. Severe right upper quadrant pain and generalized are frequently present because of Enterococcus, Klebsiella and Clostridia species.

CLASSIFICATION Classification of gallbladder diseases and biliary system (WHO, ICD – 10): Stone of gallbladder  with an acute cholecystitis к 80.0  with other cholecystitis к 80.1  without a cholecystitis к 80.2 Stone of bile ducts  with a cholecystitis к 80.4  with a cholangitis к 80.3  without a cholecystitis or cholangitis к 80.5  Other forms of cholelithiasis к 80.8  An acute acalculous cholecystitis к 81.0  A chronic acalculous cholecystitis к 81.1  Other forms of cholecystitis к 81.8  Hydrops of gallbladder к 82.1  Fistula of gallbladder к 82.3  Cholangitis к 83.0  The perforation of bile ducts к 83.2  Stricturae of common bile duct к 83.8  Fistula of bile ducts к 83.3  Postcholecistectomy syndrome к 91.5

By morphological changes distinguish: Catarrhal cholecystitis Simple Phlegmonous cholecystitis Gangrenous cholecystitis Destructive Emphysematous cholecystitis

The most often complications of acute cholecystitis: 1. Paravesical mass. 2. Paravesical abscess. 3. Empyema of gallbladder. 4. Perforation of gallbladder. 5. Peritonitis (localized, spread, total). 6. Choledocholitiasis. 7. Obstruction of common bile duct. 8. Obstructive jaundice. 9. Biliary pancreatitis. 10. Cholangitis. 11. of liver. The separate form of pathology is a cholecystpancreatitis, that combination of inflammation of gall-bladder and pancreas.

CLINIC PICTURE The clinical picture of acute cholecystitis depends on morphological changes in a gall-bladder, duration of process, presence of complications, individual features. It follows to notice that direct dependence between clinical information and pathological changes is observed not always. As a rule, a disease is begun with a twinge in right subcostal area, which can be irradiation in a right shoulder-blade, supraclavicular area, suprashoulder and in small of the back. Sometimes pain increases during inspiration. In parts sick there are great crumble pains in the area of heart, right shoulder-blade and left shoulder, which are irradiation from the overhead half of (symptom of Botkin, or cholecyst-cardiac syndrome). Gradual distribution of pain from right subcostal area in other parts of abdomen can be at development of peritonitis. Other important features are and which often arises up on height of pain attack and does not bring a facilitation. On the initial stages of disease vomiting more frequent by content, later in vomit the masses a bile appears often. Characteristic is a loss of appetite, general weakness, decline of capacity. Patients feel bitter taste and dryness, sometimes belch is present. The delay of gases and emptying, inflation of abdomen which more frequent is at a destructive process and during development of peritonitis can disturb part of patients. When a cholecystitis was complicated the obstruction of common bile duct, patients can notice jaundice of skin, brighten excrement masses. At questioning it is possible to find out information about the use in eve the disease of spicy food. At objective patients are inspected on height of pain attack uneasy. Hyperemia of person appears on the early stages, later, especially at progress of destructive processes, a skin becomes pale, covered sweat, acrocyanosis is determined. Appearance of jaundice of skin and mucous shells testifies to violation of arcade of bile on ducts or about the defeat of liver. A tongue is usually covered white or yellow stratifications, at case of destructive cholecystitis - dry. The temperature of body at a simple cholecystitis can not change or be subfebrile. At a destructive cholecystitis a temperature rises till 38-39°С, that characteristically also for development of septic complications. Hart rate gradually increase to the extent of progress of disease and can pass ahead the height of temperature reaction. At the thorax investigation it is possible to define lag in breathing of right half, that it is related to strengthening of pain on inspiration. At palpation between sternoclaidomastoideus muscle peduncles or above a collar-bone arises up pain (phrenicus-sign). In the case of development of proper objective symptoms is marked. At the examination of abdomen for thin people it is possible to see enlarged gallbladder in right subcostal area. The right half of abdomen limitedly takes part in the act of breathing. It is possible to look after displacement of belly-button up to the top and to the right, that arises up in connection with reduction of muscles of right half of abdomen. Supperficial an deep palpation is painful with tenderness at the right epigastrium. It is sometimes possible palpate painful bottom of gallbladder. At formation of perivesicular mass in right subcostal area determined painfully, immobile compression without clear limits. By Palpation it is possible to define the row of characteristic symptoms of acute cholecystitis:  the Kehr’s sign - painful palpation and tenderness are maximal at the point of gallbladder;  the Karavanov’s sign - carefully pressing the area of right subcostal area, there is pain. A hand is detained - pain calms down. Ask a patient to cough - pain increases acutely.  the Murphy’s sign - place a left hand so that four fingers lay on a costal arc, and the first finger pinned the projection of gall-bladder - inspiratory arrest with deep palpation in the right upper quadrant;  the Ortner’s sign - pain arises up at percussion of costal arch on the right. In transition an inflammatory process on a parietal the symptoms of its irritation are determined – rebound tenderness. At auscultation of abdomen at a pain attack it is possible to define weakening or/and absence of intestinal noises. Combination of the last sign with the displays of destructive cholecystitis is an unfavorable criterion which specifies on development of peritonitis. At combination of cholecystitis with a pancreatitis (acute biliary pancreatitis) pain and muscular tenderness take the upper half of abdomen, symptoms, characteristic for a pancreatitis, are determined. ADDITIONAL METHODS OF INVESTIGATION WBC appears at laboratory research, change of shift leucocytes’ formula to the left. As a rule, changes depend on the depth of morphological changes in the gallbladder wall. At the destructive forms of cholecystitis, and also at development of septic complications, the concentration of urea is increased. In the development of jaundice a hyperbilirubinemia is determined, mainly due to direct bilirubin; the colour of changes, a positive reaction is determined on bilious pigments. is the most useful radiologic examination in the patient with suspected cholecystitis. First, in the patient without known gallstones, ultrasound is a sensitive test for establishing the presence or absence of gallstones. Additional findings suggestive of acute cholecystitis include thickening (>4 mm) and layering of the gallbladder wall, and pericholecystic fluid. Focal tenderness directly over the gallbladder (sonographic Murphy sign) is also suggestive of acute cholecystitis. Ultrasound has a sensitivity and a specificity of 85% and 95%, respectively, for diagnosing acute cholecystitis. Informing of method grows till about 100% at application of three- dimensional ultrasound. Specific contra-indications are not to application of this method. Radionuclide scanning is used less frequently for the diagnosis of acute cholecystitis but may provide additional information in the atypical case. Nonfilling of the gallbladder with the radiotracer "99Tc-hepato-iminodiacetic acid (HIDA) indicates an obstructed cystic duct and, in certain clinical settings, is highly sensitive (95%) and specific (95%) for acute cholecystitis. MRCP and drip infusion with CT (DIC-CT) are informative in bile duct investigation. Useful to diagnostics, especially differential, there can be a thermography. Development of destructive forms of cholecystitis is accompanied the acute strengthening of intensity of infrared in the area of gall-bladder which is registered a device.

DIFFERENTIAL DIAGNOSIS Differential diagnosis at an acute cholecystitis is more frequent all conducted with the acute surgical diseases of organs of abdominal region (by a perforative ulcer, acute appendicitis, acute nonbiliary pancreatitis, acute intestinal obstruction), right-side basal pleuropneumonia, heart attack of myocardium (by an cholecysto-cardial syndrome), pathology of the kidney and urino-excretory system. Decision for verification of diagnosis are blood tests, ultrasound of liver and biliary system, intravenous pyelography, chest X-ray, ECG. Diagnostic criteria and severity assessment criteria for acute cholecystitis according the Tokyo Consensus Meeting (2007) and Guideline (2013) are presented at the Table 2 and Table 3.

Table 2. Diagnostic criteria for acute cholecystitis A. Local signs of inflammation (1) Murphy’s sign, (2) RUQ mass/pain/tenderness B. Systemic signs of inflammation (1) , (2) elevated CRP, (3) elevated WBC count C. Imaging findingsa Imaging fi ndings characteristic of acute cholecystitis ------Definite diagnosis (1) One item in A and one item in B are positive (2) C confirms the diagnosis when acute cholecystitis is suspected clinically ------Note: acute hepatitis, other acute abdominal disease, and chronic cholecystitis should be excluded a Imaging findings of acute cholecystitis Ultrasonography • Sonographic Murphy sign (tenderness elicited by pressing the gallbladder with the ultrasound probe) • Thickened gallbladder wall (>4 mm, if the patient does not have chronic and/or or right heart failure) • Enlarged gallbladder (long axis diameter >8 cm, short axis diameter >4 cm) • Incarcerated gallstone, debris echo, pericholecystic fluid collection • Sonolucent layer in the gallbladder wall, striated intramural lucencies, and Doppler signals MRI • Pericholecystic high signal • Enlarged gallbladder • Thickened gallbladder wall CT • Thickened gallbladder wall • Pericholecystic fl uid collection • Enlarged gallbladder • Linear high-density areas in the pericholecystic fat tissue Tc-HIDA scan (technetium hepatobiliary iminodiacetic acid scan) • Non-visualized gallbladder with normal uptake and excretion of radioactivity • Rim sign (augmentation of radioactivity around the gallbladder fossa)

Table 3. Severity assessment criteria for acute cholecystitis .

Mild (grade I) acute cholecystitis “Mild (grade I)” acute cholecystitis does not meet the criteria of “severe (grade III)” or “moderate (grade II)” acute cholecystitis. It can also be defined as acute cholecystitis in a healthy patient with no dysfunction and mild inflammatory changes in the gallbladder, making cholecystectomy a safe and low-risk operative procedure.

Moderate (grade II) acute cholecystitis “Moderate” acute cholecystitis is associated with any one of the following conditions: 1. Elevated WBC count (>18 000/mm3) 2. Palpable tender mass in the right upper abdominal quadrant 3. Duration of complaints >72 ha 4. Marked local inflammation (biliary peritonitis, pericholecystic abscess, hepatic abscess, gangrenous cholecystitis, emphysematous cholecystitis) . a Laparoscopic surgery should be performed within 96 h of the onset of acute cholecystitis

Severe (grade III) acute cholecystitis “Severe” acute cholecystitis is associated with dysfunction of any one of the following organs/systems 1. Cardiovascular dysfunction (hypotension requiring treatment with dopamine ≥5 µg/kg per min, or any dose of dobutamine) 2. Neurological dysfunction (decreased level of consciousness) 3. Respiratory dysfunction (PaO2/FiO2 ratio <300) 4. Renal dysfunction (oliguria, creatinine >2.0 mg/dl) 5. Hepatic dysfunction (PT-INR > 1.5) 6. Hematological dysfunction (platelet count <100 000/mm3).

Fig. 1. Flowcharts for the management of acute cholecystitis. GB, gallbladder; LC, laparoscopic cholecystectomy

MANAGEMENT A choice of rational method of treatment at an acute cholecystitis is important for the increase of efficiency of treatment of such patients. Most widespread is active tactic. It foresees hospitalization of all patients with an acute cholecystitis in surgical permanent establishment, urgent examination and leadthrough at first o'clock all of patient of conservative measures which have also on a purpose preparation to the possible operation. Flowcharts for the management of acute cholecystitis according the Tokyo Consensus Meeting (2007) and Guideline (2013) is presented at the Fig.1. Conservative therapy consists of complex measures which influence on the different links of disease. In the first days of patients limit in the reception of meal, afterwards appoint a diet № 5 by Pevzner,s. For the improvement of outflow of bile spasmolytic preparations are propose: No-Spanum 2,0, Papaverinum 2% - 2,0 (i/v, i/m), Platyphyllinum 0,2% - 1,0, Atropinnum 0,1% - 1,0 subcutaneously. The last two preparations - hyposecretion of glands of mucus shell, pancreas also. In case of pain non-narcotic should be widely used (Diclophenac, Ketorolac, Ketoprofen), and also in combination with spasmolytics (Baralginum, Spasganum, Spasmalgonum, Baralgitax). Introductions of these facilities combine with antihistaminic preparations: 1% Dimedrolum, 2,5% Diprazinum, 1-2% Suprastinum and others like that, which potenciated the action of analgetics and have a certain sedative effect. Narcotic analgetics appointing is not desirable as a result of their the spastic effect on sphincter of Oddi. However, at a necessity introduction, they are combined with spasmolytics. Good anaesthetic an effect the Novocaine blockade of the round ligament of liver has. Antibacterial therapy is recommended (Table 4). It is expedient to use which must ability be concentrated in a bile: Cefoperazone, Ceftazidime, Doxycycline - concentrated in a bile even in the conditions of obstructive jaundice. If it necessary, the аntibacterial preparations of other groups (, , and other) should be used. With the purpose of support of general homoeostasis infusion therapy is applied. At presence of obstructive jaundice the volume of infusion must be increased with diuretic preparations (Furosemid) and hepatoprotectors (Essenciale, Lypoic acid, Thiotriazolin, Lipamid, and other).

Table 4 Antimicrobial recommendations for acute biliary infections (TG-13)

Community-acquired biliary infections Healthcare-associated biliary infectionse Severity Grade I Grade II Grade IIIe

Antimicrobial Cholangitis Cholecystitis Cholangitis and cholecystitis Cholangitis and cholecystitis Healthcare-associated agents cholangitis and cholecystitis

Penicillin-based Ampicillin/sulbactamb is not Ampicillin/sulbactamb is not / Piperacillin/tazobactam Piperacillin/tazobactam therapy recommended without an recommended without an

aminoglycoside aminoglycoside

Cephalosporin- Cefazolina, or cefotiama, or Cefazolina, or cefotiama, or , or cefotaxime, or Cefepime, or ceftazidime, or Cefepime, or ceftazidime, or based therapy cefuroximea, or ceftriaxone, or cefuroximea, or ceftriaxone, or cefepime, or cefozopran, or cefozopran ± metronidazoled cefozopran ± metronidazoled cefotaxime ± metronidazoled cefotaxime ± metronidazoled ceftazidime ± metronidazoled Cefmetazole,a ,a Cefmetazole,a Cefoxitin,a Cefoperazone/sulbactam Flomoxef,a Cefoperazone/ Flomoxef,a Cefoperazone/ sulbactam sulbactam - Ertapenem Ertapenem Imipenem/cilastatin, Imipenem/cilastatin, based therapy meropenem, doripenem, meropenem, doripenem, ertapenem ertapenem Monobactam- - - - ± metronidazolec Aztreonam ± metronidazoled based therapy Fluoroquinolone- Ciprofloxacin, or levofloxacin, or Ciprofloxacin, or levofloxacin, or Ciprofloxacin, or levofloxacin, or - - based therapyc pazufloxacin ± metronidazoled pazufloxacin ± metronidazoled pazufloxacin ± metronidazolec

Moxifloxacin Moxifloxacin Moxifloxacin

a Local antimicrobial susceptibility patterns (antibiogram) should be considered for use b Ampicillin/sulbactam has little activity left against Escherichia coli. It is removed from the North American guidelines c Fluoroquinolone use is recommended if the susceptibility of cultured isolates is known or for patients with β-lactam allergies. Many extended-spectrum β-lactamase (ESBL)- producing Gram-negative isolates are fluoroquinolone-resistant d Anti-anaerobic therapy, including use of metronidazole, tinidazole, or , is warranted if a biliary-enteric is present. The , piperacillin/tazobactam, ampicillin/sulbactam, cefmetazole, cefoxitin, flomoxef, and cefoperazone/sulbactam have sufficient anti-anerobic activity for this situation e Vancomycin is recommended to cover Enterococcus spp. for grade III community-acquired acute cholangitis and cholecystitis, and healthcare-associated acute biliary infections. Linezolid or daptomycin is recommended if vancomycin-resistant Enterococcus (VRE) is known to be colonizing the patient, if previous treatment included vancomycin, and/or if the organism is common in the community

Surgical management of acute cholecystitis Operations at times of performance may be divided on: 1. Urgent operation - performs during the first 6-12 hours since admission of patient to the department by vital indications, when an acute cholecystitis was complicated widespread peritonitis. 2. Early operation - performs during the first 24-72 hours since admission of patient to the department, when conducted therapy for such patients is unsuccessful. 3. Delayed early operation – performs in 3-7 days, after calming down of the acute signs of cholecystitis and complications. 4. Elective operation - performs in different terms after discharge of patient from the department.

The optimal surgical treatment for acute cholecystitis was recommended by Tokyo Guidelines (2013) according to the grade of severity: Grade I (Mild) acute cholecystitis: Early laparoscopic cholecystectomy is the preferred procedure. Grade II (Moderate) acute cholecystitis: Early cholecystectomy is recommended in experienced centers. However, if patients have severe local inflammation, early gallbladder drainage (percutaneous or surgical) is indicated. Because early cholecystectomy may be difficult, medical treatment and delayed cholecystectomy are necessary. Grade III (Severe) acute cholecystitis: Urgent management of organ dysfunction and management of severe local inflammation by gallbladder drainage should be carried out. Delayed elective cholecystectomy should be performed when cholecystectomy is indicated.

Operative Risk Factors. A careful evaluation of the overall general medical condition of the patient is necessary before selection of the appropriate management for the patient with acute cholecystitis, especially complicated with obstructive jaundice. The preoperative assessment should include the usual evaluation of cardiac risk factors, respiratory status, and renal function, as well as overall performance status measured by one of several performance scales (APACH II, ASA, SOFA). In addition, patients have several further physiologic abnormalities, which require careful evaluation. These abnormalities include alterations in hepatic and pancreatic function, the gastrointestinal barrier, immune function, hemostatic mechanisms, and wound healing. Hepatic protein synthesis, hepatic reticuloen-dothelial function, and other aspects of hepatic metabolism may be significantly altered in patients with obstructive jaundice. In addition, endotoxemia may contribute to renal, cardiac, and pulmonary insufficiency observed in patients with acute cholecystitis. The optimal treatment for acute cholecystitis is essentially early cholecystectomy, and the use of an established optimal surgical treatment for each grade of severity of acute cholecystitis is necessary. Early laparoscopic cholecystectomy is indicated for patients with Grade I (Mild) acute cholecystitis, because laparoscopic cholecystectomy can be performed in most of these patients. Early laparoscopic or open cholecystectomy (within 72 h after the onset of acute cholecystitis) is required in patients with Grade II (Moderate) acute cholecystitis in experienced centers, but for some patients with Grade II (Moderate) acute cholecystitis, it is difficult to remove the gallbladder surgically because of severe inflammation limited to the gallbladder. This severe local inflammation of the gallbladder is defined by factors such as >72 h from the onset, a white blood cell count >18,000, and a palpable tender mass in the right upper abdominal quadrant. Continued medical treatment or drainage of the contents of the swollen gallbladder by percutaneous transhepatic gallbladder drainage or surgical is preferable, and a delayed cholecystectomy after the improvement of inflammation of the gallbladder is indicated. Among patients with Grade II (Moderate), for those with serious local complications including biliary peritonitis, pericholecystic abscess, or for those with gallbladder torsion, emphysematous cholecystitis, gangrenous cholecystitis, and purulent cholecystitis, emergency surgery is conducted (open or laparoscopic depending on experience) along with the general supportive care of the patient. The urgent management of Grade III (Severe) acute cholecystitis is always necessary because the patients have organ dysfunction, and the simultaneous drainage of the gallbladder contents is required to treat the severe inflammation of the gallbladder. Delayed (elective) cholecystectomy is required 2 to 3 months later, after the improvement of the patients’ general condition when cholecystectomy is indicated. The timing of the surgical management of patients with acute cholecystitis undergoing percutaneous transhepatic gallbladder drainage (PTGBD) is another. PTGBD is known to be an effective option in critically ill patients, especially in elderly patients and patients with complications. Cholecystectomy is often performed following PTGBD after an interval of several days. However, performing a cholecystectomy 2 weeks later is also common. Overall, early cholecystectomy following PTGBD is preferable when the patient’s condition improves, and if the patient has no complications. Complications of PTGBD sometimes occur, such as intrahepatic hematoma, pericholecystic abscess, biliary pleural effusion, and biliary peritonitis, which may be caused by puncture of the liver and the migration of the . However, such migration should be prevented. On the other hand, PTGBA (percutaneous transhepatic gallbladder aspiration) is often used by many facilities, and produces good treatment outcomes. Choice of method of cholecystectomy. Until the first half of the 1990s, there were opinions that laparoscopic surgery was not indicated in patients with acute cholecystitis. Open cholecystectomy was the standard technique. However, more recently, laparoscopic surgery has also been introduced for acute cholecystitis, and is now generally considered to be the first option for surgery, similar to open cholecystectomy. Several reports, including randomized controlled trials (RCTs) comparing laparoscopic cholecystectomy and open cholecystectomy, have indicated that laparoscopic cholecystectomy is associated with a significantly shorter postoperative hospital stay and a lower incidence of complications. A meta-analysis has also shown that laparoscopic cholecystectomy not only resulted in treatment effects similar to those produced by open cholecystectomy, but that it is also a useful surgical procedure in terms of its low mortality and morbidity. However, the above reports have failed to examine its use for acute cholecystitis according to the grade of severity. Laparoscopic cholecystectomy is not recommended for all cases of acute cholecystitis due to the possibility of patients in whom cholecystectomy is difficult because of severe inflammation. Uncontrolled coagulopathy is one of the few current contraindications to laparoscopic cholecystectomy. In addition, patients with severe chronic obstructive pulmonary disease or congestive heart failure may not tolerate the required for performing laparoscopic surgery. Currently, the major contraindication to completing a laparoscopic cholecystectomy is an inability to clearly identify all of the anatomic structures. A liberal policy of converting to an open operation when important anatomic structures cannot be clearly defined represents good surgical judgment rather than a complication. The conversion rate for elective laparoscopic cholecystectomy is about 5%, whereas the conversion rate in the emergency setting for acute cholecystitis may be as high as 30%. The technical difficulty of laparoscopic cholecystectomy is increased in several clinical settings. Laparoscopic cholecystectomy can be performed safely in acute cholecystitis, albeit with a higher conversion rate and operative time than in the elective setting. Morbid obesity, once believed to be a relative contraindication to the laparoscopic approach, is not associated with a higher conversion rate. Longer trocars and instruments and increased intra-abdominal pressure may be helpful in these patients. Prior upper may increase the difficulty of, or preclude the use of, laparoscopic cholecystectomy. However, placement of a Hasson cannula often reveals few adhesions or adhesions that can be dissected laparoscopically permitting completion of a laparoscopic cholecystectomy. Laparoscopic cholecystectomy has also been completed safely in patients with cirrhosis, although difficulty retracting the firm liver and increased bleeding from collaterals have been noted. On the other hand, there has been a change in the perioperative management of open cholecystectomy patients in the last few years, and the current management aims to reduce postoperative pain and encourage early ambulation and early discharge. These changes show that, in terms of the postoperative course, open cholecystectomy with mini-incision is able to produce as good results as those obtained by laparoscopic cholecystectomy, although the superiority of laparoscopic cholecystectomy as a surgical technique for acute cholecystolithiasis can be recognized. In fact, a RCT was carried out to reappraise the use of laparoscopic cholecystectomy and open cholecystectomy by a subcostal muscle transection mini-incision. This study indicated that no significant differences were observed between the two types of cholecystectomies with regard to the rate of postoperative complications, the degree of pain at discharge, the duration of sick leave, and the direct medical cost. At the moment, laparoscopic cholecystectomy is comprehensively preferred as the surgical treatment for acute cholecystitis. However, the first priority is the safety of the patients. With this in mind, open minimally invasive surgery can be considered to be as effective as laparoscopic surgery. Laparoscopic Cholecystectomy Laparoscopic surgery requires a space for visualization and instrument manipulation, and this space is usually created by establishing a pneumoperitoneum with carbon dioxide. Special hollow insufflation needle (Veress) with a retractable cutting sheath is inserted into the peritoneal cavity through a supraumbilical incision and used for insufflation. Once an adequate pneumoperitoneum has been established, a 10-mm trocar is inserted through the supraumbilical incision. The laparoscope is then inserted through the umbilical port, and an examination of the peritoneal cavity is performed. Additional trocars are inserted under direct vision. Most surgeons use a second 10-mm trocar placed subxiphoid and two additional 5-mm trocars positioned subcostally in the right upper quadrant in the midclavicular and anterior axillary lines. Five-millimeter cameras and 3-mm instruments are also available. The two smaller ports are used for grasping the gallbladder and placing it in the ideal position for an antegrade cholecystectomy. The lateral port is used to retract the gallbladder cephalad, elevating the inferior edge of the liver and exposing the gallbladder and the cystic duct. The medial 5-mm cannula is used to grasp the gallbladder infundibulum and to retract it laterally to further expose the triangle of Calot. This maneuver may require bluntly taking down any adhesions between the omentum or duodenum and the gallbladder. The junction of the gallbladder and cystic duct is identified by stripping the peritoneum off the gallbladder neck and removing any tissue surrounding the gallbladder neck and the proximal cystic duct. Once the cystic duct is identified, an intraoperative cholangiogram may be performed by passing a cholangiogram catheter into the cystic duct. Once the cholangiogram is completed, two clips are placed distally on the cystic duct, and it is divided. A large cystic duct may require placement of a pretied loop ligature to provide a secure closure. The next step is the identification and division of the cystic artery. The artery is usually encountered running parallel to and behind the cystic duct. Once the artery is identified and isolated, clips are placed proximally and distally on the artery, and it is divided. Once the artery and any branches are controlled, the gallbladder is dissected out of the gallbladder fossa by use of either a hook or spatula cautery. The peritoneum overlying the gallbladder is placed on tension by use of the two grasping forceps, and the peritoneum and adventitia between the gallbladder and liver are divided with the cautery. Just before the gallbladder is removed from the liver, the operative field is carefully searched for hemostasis, and adequate placement of the cystic duct and artery clips is confirmed. The gallbladder is then dissected off the liver and is usually removed through the umbilical port. The fascial defect and skin incision may need to be enlarged to remove the gallbladder and contained gallstones. If the gallbladder has been entered during the dissection or if it is acutely inflamed or gangrenous, the gallbladder may be placed in a plastic specimen retrieval bag before it is removed from the peritoneal cavity. Complications of laparoscopic cholecystectomy were reported soon after its introduction, and include bile duct , intraperitoneal hemorrhage needing , bowel injury, and hepatic injury, as well as the commonly observed complications associated with conventional open cholecystectomy, such as wound infection, , atelectasis, deep vein thrombosis, and urinary tract infection. Laparoscopic cholecystectomy is not always associated with a higher incidence rate compared with open cholecystectomy, but any serious complication that requires re-operation and/or prolonged hospitalization may become a serious problem for patients, even those who firmly believe that laparoscopic cholecystectomy is less invasive. In spite of many improvements in the technique and equipment, as well as the surgeon’s learning curve, the BDI rate remains high compared to open cholecystectomy. Open Cholecystectomy Open cholecystectomy can be performed through either an upper midline or a right subcostal (Kocher) incision (small incision can be used for minilaparotomy). Identification and division of the cystic duct and artery initially limit bleeding from the gallbladder for the remainder of the dissection. With lateral traction on the gallbladder neck, the peritoneum overlying the triangle of Calot is incised, and the cystic duct is identified and ligated. Cholangiography is performed at this time if indicated. The cystic duct is then ligated both proximally and distally and divided. Similarly, the cystic artery is ligated and divided after it is carefully traced onto the gallbladder. If the anatomy cannot be clearly identified, the gallbladder should be dissected from the fundus downward toward the gallbladder neck (antegrade cholecystectomy), making the ductal and vascular anatomy easier to identify. The gallbladder is dissected out of the gallbladder bed by incising the overlying peritoneum with cautery. At this point, cystic duct cholangiography is performed. Rarely, a small duct entering the gallbladder from the liver is encountered and should be ligated. A closed suction drain is placed if there is concern about the security of the cystic duct closure (e.g., as in gangrenous cholecystitis). Indications and significance of gallbladder drainage Although early cholecystectomy, a one-shot definitive treatment for acute cholecystitis, remains the reference standard, perioperative mortality rates in elderly or critically ill patients are reported to be high (up to 19 %). Therefore, PTGBD is considered a safe alternative, especially in surgically high- risk populations. There is no doubt that PTGBD with administration of antibiotics can convert a septic cholecystitis into a non-septic condition. From a technical point of view, it is a rather uncomplicated procedure with a low complication rate reported (range from 0 to13%). A systematic reviews report that 30-day or in-hospital mortality after PTGBD is high (15.4 %), but that procedure-related mortality is low (0.36 %). Of note, mortality is predominantly related to the severity of the underlying disease rather than the ongoing gallbladder sepsis. For patients with moderate (grade II) disease, gallbladder drainage should be used only when a patient does not respond to conservative treatment. For patients with severe (grade III) disease, gallbladder drainage is recommended with intensive care. Predictors for failure of conservative treatment are: age above 70 years old, diabetes, tachycardia and a distended gallbladder at admission. Likewise, WBC >15000 cell/μl, an elevated temperature and age above 70 years old were found to be predictors for the failure of conservative treatment at 24-h and 48-h follow-up. PTGBD is the most common gallbladder drainage method for elderly and critically ill patients. There are several alternatives to PTGBD. Percutaneous transhepatic gallbladder aspiration (PTGBA) is an alternative in which the gallbladder contents are puncture-aspirated without placing a drainage catheter. Endoscopic naso-biliary gallbladder drainage (ENGBD) and endoscopic gallbladder stenting (EGBS) are also alternatives via the transpapillary route. With the recent improvement in endoscopic ultrasound (EUS), EUS-guided gallbladder drainage is performed via the antrum of the stomach and the bulbus of the duodenum. However, these alternatives are not fully examined; PTGBD is still recognized as a standard drainage method.

Postcholecystectomy Pain or other symptoms originally attributed to the gallbladder may persist or recur months or years after cholecystectomy Recurrence of pain or other symptoms after cholecystectomy has been reported in as many as 20% of patients. However, with improvements in biliary imaging over the past decade, the incidence of "postcholecystectomy syndrome" has certainly decreased. Several common causes of postcholecystectomy pain are listed in Table 5. Episodic right upper quadrant pain associated with jaundice and chills occurring shortly after cholecystectomy is most commonly associated with a retained or bile duct injury or leak. Acute epigastric pain not associated with jaundice may be due to unrecognized pancreatitis, , or even . Formerly, a long cystic duct stump was believed to be a potential source of symptoms after cholecystectomy. However, with the laparoscopic technique, the cystic duct is left long by design to minimize the risk of bile duct , and no increased risk of biliary symptoms has been observed. Finally, a small group of patients have persistent biliary-type pain after cholecystectomy as a result of abnormalities in the sphincter of Oddi. Table 5. Causes of postcholecystectomy pain. Biliary Nonbiliary Choledocholithiasis Pancreatitis Bile duct stricture/injury Irritable bowel syndrome Sphincter of Oddi dysfunction Peptic ulcer disease Stenosing papillitis Gastroesophageal reflux disease Liver disease Wound neuroma

Questions (α =І, α =ІІ): 1. Anatomy and physiology of gallbladder and extrahepatic bile ducts. 2. Aetiology and pathogenesis of acute cholecystitis. 3. Classification of acute cholecystitis. 4. Methods of examination of the patients with an acute cholecystitis. 5. Clinical picture of acute cholecystitis in young and elderly patients. 6. Differential diagnostics of acute cholecystitis. 7. Medical program of acute cholecystitis. 8. Complication of acute cholecystitis. 9. Features of clinical picture of acute cholecystitis are at presence of concomitant pathology. 10. Clinical picture of complications of acute cholecystitis and their differential diagnostics. 11. An indication to the urgent operations at an acute cholecystitis. 12. An indication to the early operations (24-72 hours) at an acute cholecystitis. 13. Operative interferences at acute cholecystitis. 14. Operative interferences at complications of acute cholecystitis. 15. An indication to mini-invasive operative interferences (endoscopic, laparoscopic, under CT and ultrasound guidance) at acute cholecystitis.. 16. Intraoperative complications at cholecystectomy and their treatments. 17. Complications after cholecystectomy, their prophylaxis and treatment. 18. Preoperative preparation of patients with an acute cholecystitis. 19. Postoperative conduct of patients, operated concerning an acute cholecystitis.

Practical task (α =І, α =ІIІ): 1) To collect anamnesis, conduct palpation, percussion, auscultation of patient with an acute cholecystitis; 2) To choose the most often signs of acute cholecystitis from information of anamnesis; 3) To discover and estimate protective tenderness of muscles in the right subcostal area, an acute gallbladder or mass, presence of fluid collections in ; 4) To demonstrate the presence of symptoms and their degree; 5) To conduct differential diagnostics of acute cholecystitis; 6) To determine a indications for operations in acute cholecystitis; 7) To ground and formulate the previous diagnosis of basic disease, complications and concomitant pathology; 8) To use deontology principles;

Typical tasks (α =ІІ): 1. Female, 45 y.o., after of spicy food complains with acute pain in a right subcostal area with an irradiation in a right shoulder-blade, nausea, dryness and bitter taste in a mouth. HR - 92 b/min., rhythmic. BP - 135/85 mm Hg. A tongue is dry, covered with yellow stratification. Abdomen tense and acutely painful in the right subcostal area. The signs of peritoneum irritation absent. Ortner,s sign is positive. Preliminary diagnosis? A. Acute cholecystitis B. C. D. Hepatitis E. Acute appendicitis

2. Male 47 y.o., complains with pain at the right subcostal area irradiated to the back, fever till 38.70C. He is ill during 3th days. Skin is of normal colour; HR - 88 b/min., BP - 120/80 mm Hg. A tongue is dry. An abdomen is symmetric, muscular defence in the right subcostal area is present, where the enlarged painful gallbladder is palpable. Ortner,s sign is positive. Leucocytes – 14.2 х 109/l. What diagnosis das patient have? A. Empyema of gallbladder B. Hydrops of gallbladder C. Cholangitis D. Acute biliary pancreatitis E. Choledocholithiasis.

3. Patient 67 y.o. was admitted to hospital with complains on pain in right epygastrium, temperature up to 38.4°С. He is ill for three days. During palpation the abdomen is tender; gallbladder is enlarged and painful. Leukocytes – 18х109/l, bending neutrophiles – 19 %. Ultrasonography: large (13.0х7.0 cm) gallbladder with thick layered wall is obstructed in the neck with 15 mm stone. What diagnosis das patient have? A. Acute hepatitis B. Hydrops of gallbladder C. Cholelithiasis, acute cholecystitis D. Acute biliary pancreatitis E. Choledocholithiasis.

Atypical tasks (α =ІIІ): 1. In a 42-year-old women, after consumption of fatty food, developed an acute pain in the right upper quadrant, sclera icterus. Body temperature – 37.2°C. On examination: slight muscle rigidity in the right upper quadrant, signs of peritoneum irritation are negative. Biochemical test: bilirubin – 51 µmol/l (mostly due to indirect), amylase – 25 g/h/l. US: enlarged gallbladder with stones from 3 to 9 mm in diameter, CBD – 7 mm. Formulate the diagnosis. A. Chronic calculous cholecystitis, choledocholithiasis, obstructive jaundice. B. Acute biliary pancreatitis, choledocholithiasis, obstructive jaundice. C. Cancer of head of pancreas. D. Acute calculous cholecystitis, choledocholithiasis, obstructive jaundice. E. Cholelithiasis, calculous cholecystitis, toxic hepatitis.

2. A 45-year-old women complains of colic pain in the upper right quadrant, nausea, vomiting. Onset of the disease 48 hours ago after fatty food consumption. CBC: Hb – 127 g/l, erythrocytes – 3.7 x 1012/l, leucocytes – 14.0 x 109/l, banding – 10% segmented neutrophils – 77%, ESR – 24 mm/h. Biochemical test: bilirubin – 19.6 µmol/l, protein – 72 g/l, glucose – 5.0 mmol/l, amylase – 22 g/h/l, AsAT – 0,4 mmol/l, AlAT – 0.6 mmol/l, Ca2+ - 2.3 mmol/l. US: gallbladder wall is thicken to 9 mm, inside the gallbladder group of large stones to 20 mm in the diameter, CBD – 6 mm. Formulate the diagnosis. A. Chronic calculous cholecystitis, choledocholithiasis, obstructive jaundice. B. Acute biliary pancreatitis. C. Chronic calculous cholecystitis, choledocholithiasis, biliary colic. D. Acute calculous cholecystitis, acute biliary pancreatitis, obstructive jaundice. E. Acute calculous cholecystitis.

3. In a 42-year-old women, after consumption of fatty food, developed an acute pain in the right upper quadrant, sclera icterus. Body temperature – 37.2°C. On examination: slight muscle rigidity in the right upper quadrant, signs of peritoneum irritation are negative. Biochemical test: bilirubin – 51 µmol/l (mostly due to indirect), amylase – 25 g/h/l. US: enlarged gallbladder with stones from 3 to 9 mm in diameter, CBD – 7 mm. What the tactics of treatment? A. Open cholecystectomy, choledocholithotomy, external biliary drainage. B. Laparoscopic cholecystectomy, choledocholithotomy, external biliary drainage. C. Open cholecystectomy. D. Therapeutic ERCP, laparoscopic cholecystectomy. E. Laparoscopic cholecystectomy.

MCQs (α =І, α =ІІ) 1. Operative treatment at an acute calculous cholecystitis is indicated: A. All of patient in a urgent order B. In default of effect from conservative therapy during 48-72 hours C. At appearance of vomiting D. At increase of temperature till 37,7°С E. At exposure positive Ortner,s sign

2. The most informing methods of examination in acute cholecystitis are: A. Computer tomography (CT) B. Plain X-ray abdomen C. Ultrasound examination (US) D. Oral cholecystography E. GI X-ray with Ba passage

3. Morphological forms of acute cholecystitis are: A. Fibrinous B. Phlegmonous C. Haemorrhagic D. Pancreatic E. Biliary

4. For an acute “destructive” cholecystitis are characteristically: A. B. Leukopenia C. Eosinophilia D. Shift of the leukocyte formula “to the left” E. Shift of the leukocyte formula “to the right”

5. Conservative treatment of acute cholecystitis includes: A. Antibiotics B. Coagulants C. Spasmolytics D. Infusion therapy E. Diet N 15

6. What operation is favourable at presence of small stones in the gallbladder? A. Cholecystectomy “from a neck” B. Cholecystectomy “from a fundus” C. Choledocholithotomy D. Drainage of CBD E. Cholecystectomy does not indicated

7. The signs of an acute cholecystitis is: A. The Meerson,s sign B. The Ortner,s sign C. The Halsted’s sign D. The Oppengeym,s sign E. The Obrazcov,s sign

8. The Myussi-Georgievskiy,s sign: A. Sharp pain at pattering on a right costal arc B. Pain at pressing on between the peduncles of right m. sternoclеidomastoideus C. Pain at palpation in the projection of the gall-bladder D. Pain at pressing on between the peduncles of left m. sternoclеidomastoideus E. Pain at pressure round a belly-button

9. What does it mean - laparoscopic cholecystectomy? A. Cholecystectomy by laparoscopic manipulators through a front abdominal wall under video guidance B. Remove of gallbladder through the stomach wall by gastroscope usage C. Percutaneous transhepatic sclerosing of gallbladder cavity under laparoscopic guidance D. Remove of gallbladder is during laparotomy by laparoscopic instruments E. Cholecystectomy by minilaparotomy approach with laparoscopic instruments

10. Urgent operation is indicated at: A. Perforation of gallbladder, peritonitis B. Biliary pancreatitis C. Biliary colic D. Obstruction of the cystic duct E. Stricture of CBD

11. In acute cholecystitis is contra-indicated the injection of: A. No-spanum B. Spazmalgon, Baralgin and Spazgan C. Morphine hydrochloride D. Omnoponum E. Atropine sulphate

12. Base conservative therapy of an acute cholecystitis includes: A. Spasmolytics, Analgetics, infusions, antibacterial therapy B. Anticoagulants, spasmolytics, analgetics C. Spasmolytics, analgetics, laxatives, infusions D. Anaesthetic, infusions, bile-expelling preparations

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