Cholecystitis: Clinical Guidelines

List of Abbreviations

BP – blood pressure

ALT – alanine aminotransferase

AST – aspartate aminotransferase

EBD – extrahepatic bile ducts

GD – gallstone disease

GB – gallbladder

CT – computed tomography

LC – laparoscopic cholecystectomy

HC – healthcare organization

MRI – magnetic resonance imaging

MRCP – magnetic resonance cholangiopancreatography

AAC – acute acalculous cholecystitis

CBD – common bile duct

CHD – common hepatic duct

ICU – intensive care unit

AC – acute cholecystitis

ERCP – endoscopic retrograde cholangiopancreatography

US – ultrasound examination

ChE – cholecystectomy

CC – chronic cholecystitis

PTC – percutaneous transhepatic cholangiography

PTCB – ultrasound-guided percutaneous transhepatic cholecystostomy, cholecystocholangiostomy

ALP – alkaline phosphatase

EPST – endoscopic antegrade papillosphincterotomy / endoscopic retrograde papillosphincterotomy / endoscopic atypical papillosphincterotomy

Terms and Definitions

Cholecystitis is an inflammatory lesion of the GB.

Acute cholecystitis is an acute inflammation of the GB accompanied by a local and systemic inflammatory response or the threat of its occurrence.

Chronic cholecystitis is chronic inflammation of the GB.

Acute acalculous (acalculous) cholecystitis is a term used to describe cases of AC where the damaging role is played not by the presence of gallstones, but by other factors.

"Non-functioning" GB is an insufficiently defined term usually used to describe a gallbladder of reduced volume with sclerotic walls and impaired emptying (according to imaging methods).

"Excluded" GB is a term used to describe an enlarged gallbladder with signs of obstruction in the outlet (according to imaging methods) or lack of filling with a contrast agent or radiopharmaceutical.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Cholecystitis is an inflammatory lesion of the GB.

Acute cholecystitis is an acute inflammation of the GB accompanied by a local and systemic inflammatory response or the threat of its occurrence.

Chronic cholecystitis is chronic inflammation of the GB.

Acute acalculous (acalculous) cholecystitis is a term used to describe cases of AC where the damaging role is played not by the presence of gallstones, but by other factors.

"Non-functioning" GB is an insufficiently defined term usually used to describe a gallbladder of reduced volume with sclerotic walls and impaired emptying (according to imaging methods).

"Excluded" GB is a term used to describe an enlarged gallbladder with signs of obstruction in the outlet (according to imaging methods) or lack of filling with a contrast agent or radiopharmaceutical.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Acute acalculous cholecystitis (AAC) develops when damaging factors unrelated to the presence of gallstones act on the GB wall. Microcirculation disorders in the GB wall are considered the main causes; a sharp suppression of GB emptying and an increase in bile lithogenicity contribute to the development of inflammation. Under these conditions, local opportunistic microorganisms are activated or hematogenous infection occurs. As a rule, acute acalculous cholecystitis develops as a complication of [1-8]:

1) a severe underlying disease with circulatory disorders and decreased immune defense (shock, sepsis, severe trauma, burns, systemic connective tissue diseases and vasculitis, sickle cell anemia, cardiovascular diseases, post-reconstructive vascular surgery states, etc.),

2) conditions in which GB emptying is significantly suppressed (administration of opioids, somatostatin analogs, electrolyte disorders, prolonged total parenteral nutrition, autonomic neuropathy),

3) infections and parasitoses affecting the gastrointestinal tract, especially those accompanied by severe dehydration: bacterial (Salmonella, Yersinia, Vibrio cholerae, Campylobacter jejuni, pathogenic Escherichia coli), viral (acute hepatitis A, B), parasite invasions (Clonorchis sinensis, Opisthorchis viverrini, Opisthorchis felineus, Fasciola hepatica, Ascaris lumbricoides),

4) immunodeficient states with the manifestation of Cytomegalovirus, Cryptosporidium infection, Giardia lamblia invasion.

Structural changes in the biliary tract that impede normal bile outflow (choledochal cysts, strictures, enlargement of regional lymph nodes) also predispose to the disease.

Acute calculous cholecystitis is described in the relevant guidelines.

Chronic cholecystitis develops as a result of repeated attacks of acute inflammation or the prolonged action of damaging factors leading to inflammatory changes and atrophy of the mucosa, and fibrosis of the GB wall. The pathogenesis of chronic GB inflammation is insufficiently studied. There are no clear diagnostic criteria for this disease in the literature. With repeated attacks of acute inflammation or during chronic inflammation, the so-called "non-functioning" GB may form – with signs of wall sclerosis, a reduced cavity, impaired contrast enhancement, and a decreased ejection fraction. The majority (90-95%) of chronic GB inflammation cases are represented by chronic calculous cholecystitis [9, 10].

Chronic acalculous cholecystitis (CC) is an insufficiently clearly defined concept. Such a diagnosis is sometimes made based on the presence of nonspecific dyspeptic symptoms and the detection of GB wall thickening according to imaging data. However, in reality, in many cases, the clinical picture may correspond to the criteria of GB functional disorder (synonyms – GB dyskinesia, acalculous cholecystopathy) or GB cholesterosis [11, 12]. Therefore, differential diagnosis is of great importance.

Special forms of cholecystitis are represented by eosinophilic, lymphocytic (synonym – follicular), hyalinizing, and xanthogranulomatous variants [12-17].

Eosinophilic cholecystitis is a rather rare form (from 0.25 to 6.4% of cases) of acute cholecystitis. The clinical picture has no significant differences; blood eosinophilia is not always detected. Histological examination of the GB tissue reveals eosinophilic infiltration of the mucosa (>90% of leukocytes are eosinophils), often spreading to deeper layers and, apparently, into the pericholecystic tissues. The putative causes of eosinophilic GB inflammation are an allergic reaction (to penicillins, cephalosporins), parasitosis, hypereosinophilic syndromes, eosinophilic gastroenteritis; cases of acute calculous obstructive eosinophilic cholecystitis have been described. Many cases are regarded as idiopathic. General patient management principles do not differ from other forms of acute cholecystitis, although they may have their own features depending on the presence of a recognized underlying disease [18].

Lymphocytic, or follicular, cholecystitis is a form of chronic cholecystitis in which a lymphocytic inflammatory response predominates (>30 intraepithelial lymphocytes per 100 biliary epithelial cells are detected), sometimes in the form of follicles protruding into the lumen, which necessitates differential diagnosis with xanthogranulomatosis and GB neoplasms. Lymphocytic cholecystitis accounts for 0.1-1% of chronic cholecystitis cases. Combinations with cholelithiasis, primary sclerosing cholangitis, and isolated cases of combination with periductal liver fibrosis have been described. In general, a higher frequency of biliary tree strictures distal to the GB was noted in such patients. Risk factors have not been clearly established. Characteristic clinical manifestations specifically for this form have not been described. A clear connection with IgG4-related disease has also not been established [19-21].

Xanthogranulomatous cholecystitis is a variant of chronic cholecystitis in which ongoing inflammation leads to extensive thickening and fibrosis extending beyond the gallbladder wall. In this case, complications such as abscess formation and fistula formation are more frequently recorded [9].

Hyalinizing cholecystitis is a form of chronic cholecystitis in which the structures of the gallbladder wall are replaced by dense hyaline sclerosis. Hyalinization is found in 1.6% of GB tissue samples obtained during cholecystectomy; focal or diffuse calcification ("porcelain GB transformation") is also frequently determined. This form of cholecystitis is associated with an increased risk of developing GB carcinoma. Cases of combination of hyalinizing cholecystitis with cholelithiasis and IgG4-related disease have been described, but a causal relationship has not been proven [22].

1.3 Epidemiology of the Disease or Condition

AAC accounts for 5-10% of all cases of acute cholecystitis. The average age of patients is approximately 10 years older than those with acute calculous cholecystitis; a male predominance is noted [10]. Among intensive care unit patients, the probability of this disease is significantly higher. It is recorded in 0.5-0.9% of patients after cardiac surgery and vascular reconstructive interventions, and in 4% of patients after bone marrow transplantation [10, 23]. The prognosis largely depends on the nature of the underlying disease. The frequency of the gangrenous form among all AAC cases reaches 31.2%, mortality is 10-50%, and the frequency of cerebrovascular disorders is 15.9%, which is significantly higher than the rates for acute calculous cholecystitis) [23, 24].

1.4 Features of Coding the Disease or Condition

K81 – Cholecystitis

Excluded: with cholelithiasis (K80.-)

K81.0 – Acute cholecystitis:

• Gallbladder abscess without stones

• Angiocholecystitis without stones

• Cholecystitis:

  - emphysematous (acute) without stones

  - gangrenous without stones

  - purulent without stones

• Gallbladder empyema without stones

• Gallbladder gangrene without stones

K81.1 – Chronic cholecystitis

K81.8 – Other forms of cholecystitis

K81.9 – Unspecified cholecystitis

1.5 Classification of the disease or condition

According to the course of the disease, cholecystitis can be acute and chronic. The concept of "chronic cholecystitis" is not clearly outlined in most modern guidelines due to the lack of strict diagnostic criteria [6, 9, 25, 26].

There are morphological variants of chronic cholecystitis – eosinophilic, lymphocytic (follicular), xanthogranulomatous, and hyalinizing.

Classification principles of AC:

I. By etiology: calculous; acalculous; parasitic.

II. Pathogenetic classification: obturation; enzymatic; vascular.

III. Clinical and morphological forms:

- catarrhal form;

- destructive forms: phlegmonous; gangrenous; perforated.

IV. By severity (Tokyo guidelines 2013): Mild (Grade I); Moderate (Grade II); Severe (Grade III).

Complications of acute cholecystitis include perivesical infiltrate, perivesical abscess, gallbladder perforation, peritonitis, internal or external biliary fistula, and Mirizzi syndrome [24, 25, 27-29].

1.6 Clinical presentation of the disease or condition

Clinical manifestations of acute cholecystitis depend on the pathomorphological changes of the gallbladder, as well as the presence and extent of complications. Due to the variety of symptoms, diagnostic difficulties and errors are possible.

In acute acalculous cholecystitis, symptoms are similar to those of acute calculous cholecystitis. However, given that it often develops against the background of a severe underlying disease, confusion and significant hemodynamic changes may be observed simultaneously; the development of paralytic ileus is more characteristic. Due to the variety of symptoms, diagnostic difficulties and errors are possible [24, 25, 27, 28, 29].

Acute acalculous cholecystitis in most cases develops against the background of a severe underlying disease with impaired vital functions, making patient history taking often difficult or impossible. The physician must be particularly vigilant to recognize this condition in a timely manner [10]. The development of acute cholecystitis is accompanied by progressive pain involving the right upper quadrant and epigastric region, which may radiate to the interscapular region, right scapula, clavicle, or shoulder, as well as the sternum area [9, 10]. The pain is constant, dull, and sometimes agonizing. Nausea and vomiting are characteristic. Signs of peritoneal irritation join in—a more distinct localization of tenderness upon palpation, increased pain upon compression or percussion of the abdominal wall at the height of inspiration. Of major diagnostic importance is the detection of signs of paralytic ileus, which is more characteristic of acute acalculous cholecystitis than of calculous cholecystitis due to frequent hemodynamic disorders and electrolyte imbalances associated with the underlying disease. Clinical manifestations of ileus include anorexia, nausea, recurrent vomiting that brings no relief, abdominal distension, and weakened bowel sounds. Shortness of breath may occur due to forced limitation of inspiration depth. Palpation and percussion of the abdomen reveal characteristic symptoms (Appendix G, tables 1 and 2), with Murphy's sign recognized as the most informative [10, 30]. Depending on the body's reactivity and the nature of the underlying disease, fever may be subfebrile, febrile, or absent. Jaundice may develop due to the involvement of adjacent liver tissue, bile ducts, and lymph nodes in the inflammation. In the absence of gallbladder perforation, signs of diffuse peritonitis are absent. A complete blood count in most cases reveals moderate neutrophilic leukocytosis with a left shift. A biochemical blood test may show moderate hyperbilirubinemia, a moderate increase in transaminase activity, and elevated C-reactive protein levels. In HIV infection, the course of acute acalculous cholecystitis with cholestatic syndrome has been described [10].

Against the background of treatment for the underlying disease, the symptoms of acute acalculous cholecystitis may be variable and masked. Acute acalculous cholecystitis should always be suspected in severely/critically ill patients or those with serious chronic diseases who present with abdominal pain and signs of systemic inflammatory response/sepsis in the absence of jaundice [10]. One must also rely on the appearance of signs of paralytic ileus.

Early recognition of acute acalculous cholecystitis is of paramount importance, as the disease in most cases progresses with the development of life-threatening complications, including biliary peritonitis, sepsis, and infectious-toxic shock [10, 24, 25].

Chronic acalculous cholecystitis may manifest with recurrent exacerbations featuring pain in the right upper quadrant and epigastric region radiating to the interscapular region, right scapula, or shoulder. However, unlike acute cholecystitis, there are no signs of peritoneal irritation, Murphy's, Vasilenko's, or Ortner's signs, nor are there signs of ileus or acute inflammatory response on laboratory tests. Presumably, chronic cholecystitis can be paucisymptomatic or asymptomatic and is detected by imaging methods or, in rare cases, upon the development of complications—acute cholecystitis, emphysematous cholecystitis, abscesses, fistulas, biliary strictures, or gallstone ileus. Chronic cholecystitis is thought to increase the risk of gallbladder neoplasms; this has been most convincingly demonstrated in the hyalinizing form, a long history of large gallstone carriage, fluke infestations, and sclerosing cholangitis, where gallbladder involvement is also possible [10, 30].

Chronic cholecystitis is often accompanied by dyspeptic symptoms caused by motility disorders of the upper gastrointestinal tract and comorbid diseases—heartburn, bitter taste in the mouth, nausea, heaviness and fullness in the epigastric region after eating, and bowel habit disturbances. These symptoms cannot be considered strictly specific to cholecystitis.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis of "Acute acalculous cholecystitis"

The diagnosis of acute acalculous cholecystitis is established based on the following data:

- clinical (pain in the right upper quadrant);

- laboratory (blood leukocyte count greater than 10×10⁹/L with an increased count of neutrophil and band forms);

- instrumental (characteristic ultrasound signs of acute acalculous cholecystitis: enlargement of the gallbladder; wall thickening greater than 3 mm with signs of edema and disturbed echostructure; in the absence of calculi in the gallbladder lumen, particularly a blocking calculus in the gallbladder neck in the case of acute calculous cholecystitis; presence of perivesical fluid accumulation).

Differential diagnosis in suspected acute acalculous cholecystitis includes a number of extra- and intra-abdominal diseases:

- right-sided lower lobe pneumonia;

- myocardial infarction;

- herpes zoster;

- peptic ulcer disease in exacerbation phase;

- perforated ulcer;

- acute pancreatitis;

- hepatitis;

- acute intestinal obstruction;

- acute appendicitis.

• Clinical symptoms of acute cholecystitis are recommended to be examined in all patients with acute upper abdominal pain syndrome prior to instrumental and laboratory examination [27, 28, 33-36, 47].

GCR BLEL 1Grade of Recommendation – B (Level of Evidence – 1)

Comment. The diagnosis of acute calculous or acalculous cholecystitis cannot be reliably established or ruled out based on physical examination alone [33-36].

• The diagnosis of acute and chronic cholecystitis in all cases is recommended to be established taking into account the entire complex of clinical, laboratory, and instrumental data [23, 26, 28].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment. While criteria for establishing the diagnosis of acute acalculous cholecystitis are defined, specific diagnostic criteria for chronic acalculous cholecystitis have not been developed. In the presence of clinical symptoms, the purpose of additional examination is to rule out other gallbladder diseases (e.g., cholelithiasis, cholesterosis, tumors), as well as to rule out acute cholecystitis.

• In patients with acute cholecystitis, it is recommended to use the classification and diagnostic criteria of the Tokyo guidelines (2007, 2013) when formulating the final diagnosis [33, 35].

強B (level of recommendation — B)УДД 3Level of Recommendation — B (Level of Evidence — 3)

Comment. The scoring scale for assessing the probability of acute cholecystitis and its severity classification were proposed by the Tokyo Guidelines of the international expert meeting of surgeons in 2013 (TG13) and are based on the presence of certain forms (grades) of varying severity of acute cholecystitis in patients (Appendix G4, G5).

2.1 Complaints and Anamnesis

Complaints and anamnestic data characteristic of patients with acute and chronic cholecystitis are specified in section 1.6.

2.2 Physical Examination

Physical examination data characteristic of patients with acute cholecystitis are given in Appendices G1 and G2.

2.3 Laboratory Diagnostics

• Patients with clinical manifestations of acute cholecystitis are recommended to undergo a complete (clinical) blood count to determine the severity of inflammatory changes [27, 28, 33, 36, 55].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment. Patients with clinical manifestations of acute cholecystitis are recommended to undergo laboratory testing as an ancillary method to determine the severity of the condition [31, 36, 42, 43]. However, neither a single laboratory test nor any combination thereof allows for a definitive diagnosis or exclusion of acute cholecystitis. There are no specific blood test changes in acute cholecystitis, though a leukocyte count greater than 10 × 10⁹/L with an increased number of neutrophil and band forms is useful for confirming an ongoing inflammatory process in the gallbladder. At the same time, leukocytosis is an unreliable indicator—a number of studies have shown that only 60% of patients with acute cholecystitis had a count above 11 × 10⁹/L. A leukocyte count greater than 15 × 10⁹/L may indicate gallbladder perforation or gangrene.

• Patients with suspected acute cholecystitis are recommended to have serum C-reactive protein levels measured to improve diagnostic accuracy [44, 45].

CGR CLOE 2Clinical Practice Guideline Recommendation Grade – C (Level of Evidence – 2)

Comment. In acute cholecystitis, an elevated C-reactive protein level is detected in the majority of cases, and to a greater extent in elderly patients, which may be explained by the higher frequency of severe clinical courses. CRP has a better discriminatory ability than blood leukocyte count in most forms of acute cholecystitis and serves as a useful diagnostic marker for acute cholecystitis. However, in patients with severe underlying diseases and in immunocompromised individuals, C-reactive protein production may be impaired, rendering its determination uninformative.

• Patients with clinical manifestations of acute cholecystitis are recommended to undergo a general general-medical biochemical blood test including total bilirubin, alkaline phosphatase, ALT, and AST to diagnose cholestatic syndrome [27, 28, 30, 46, 55].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment. In acute cholecystitis, blood ALT activity is typically elevated in half of patients, AST is above normal in 60%, alkaline phosphatase increases in 70–80% of cases, and bilirubin in 60%. In fact, enzyme levels are affected by gallbladder inflammation, which may be complicated by acute hepatocellular injury. In addition, other trends (statistically non-significant) in biochemical blood parameters are noted. Thus, hyperenzymemia in acute cholecystitis tends to be more pronounced in patients with developing intrahepatic purulent-septic complications, while hyperglycemia may occur in patients with pericholecystic abscesses [31, 42, 43, 46–48].

• Patients with clinical manifestations of acute cholecystitis are recommended to have blood amylase activity and blood glucose levels determined to rule out biliary pancreatitis and concomitant diabetes mellitus [27, 28, 33, 55].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment. Biochemical blood test parameters are of great importance in diagnosing concurrent acute pancreatitis and diabetes mellitus. An increase in serum amylase activity may indicate the development of biliary pancreatitis.

• To assess hemostasis and blood rheological properties, patients with clinical manifestations of acute cholecystitis are recommended to undergo a coagulogram (screening test of the hemostatic system) [27, 28, 33, 55].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

• All patients with suspected acute acalculous cholecystitis sre recommended to undergo a microbiological (culture) blood test for sterility [41].

Level of Recommendations – CLevel of Evidence – 4Level of Recommendations – C (Level of Evidence – 4)

Comment. The parameters of microbiological (culture) blood testing for sterility are of great importance in choosing the optimal antibiotic therapy tactics and assessing prognosis.

• All patients with suspected chronic acalculous cholecystitis in the exacerbation phase are recommended to undergo microscopic stool examination for helminth eggs and larvae [49, 50].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment. Microscopic stool examination for helminth eggs and larvae makes it possible to exclude infection with parasites affecting the biliary tract with a relatively high degree of probability.

2.4 Instrumental Diagnostics

• All patients with suspected acute and chronic cholecystitis are recommended to undergo an ultrasound examination of the liver, gallbladder, and ducts to confirm the diagnosis [27, 28, 37, 39, 59, 60].

GCR ALEL 1Grade of Recommendation — A (Level of Evidence — 1)

Comment. Ultrasound examination (US) of the liver, gallbladder, and ducts is an accessible, non-invasive, inexpensive instrumental diagnostic method not associated with ionizing radiation. Ultrasound of the liver, gallbladder, and ducts makes it possible to detect the presence or absence of gallstones or biliary sludge, the size, number, and location of stones, the presence of inflammatory changes in the gallbladder wall, and dilatation of the bile ducts.

Main US signs of acute acalculous cholecystitis:

- increase in longitudinal (>8 cm) or transverse (>4 cm) dimensions;

- wall thickening greater than 3 mm with signs of edema and impaired echostructure (layering and heterogeneity, the so-called "double-rim" sign);

- presence of perivesicular fluid accumulation.

- Positive ultrasound Murphy's sign, consisting of the intensification or appearance of pain when pressure is applied with the transducer to the anterior abdominal wall in the projection of the visualized gallbladder fundus during a deep breath by the patient [61, 62].

- In acute calculous cholecystitis, a fixed (blocking) calculus may be detected in the neck of the gallbladder.

The diagnosis of acute acalculous cholecystitis in all cases requires the exclusion of calculi in the gallbladder.

It should be noted that none of these signs has sufficient diagnostic value on its own, so when performing an ultrasound, their presence must be considered in combination. Gallbladder wall thickening can occur not only in acute cholecystitis but also in liver diseases, cardiac and renal failure, as well as in hypoproteinemia and a number of other diseases and conditions not requiring emergency surgical intervention. Ultrasound allows differentiation between acute obstructive catarrhal and acute destructive cholecystitis and highlights gangrenous cholecystitis based on the presence of thin hyperechoic linear structures in the gallbladder lumen, foci of echogenic shadowing corresponding to gas within the wall or lumen of the gallbladder, and overt disruptions in the integrity of the gallbladder wall and pericholecystic abscess. The combination of signs significantly increases diagnostic accuracy. Thus, the presence of calculi in the lumen combined with wall thickening and a positive US Murphy's sign has a predictive value of 94% [63].

According to meta-analysis, ultrasound in the diagnosis of acute cholecystitis has a sensitivity of 81% and a specificity of 83% [64].

Clear diagnostic criteria for chronic cholecystitis based on ultrasound data have not been established. The main significance lies in excluding the signs of acute cholecystitis described above (in patients with right upper quadrant pain). Indirect signs of chronic cholecystitis include fibrous changes in the gallbladder wall (compaction, structural irregularity, thickening up to 4 mm or more), wrinkling or enlargement of the gallbladder, and impaired emptying ("non-functioning", "excluded" gallbladder) [9, 22, 26].

Ultrasound is important for differentiating calculous from acalculous cholecystitis, differential diagnosis with other gallbladder diseases (cholesterolosis, tumors), and screening for gallbladder tumors in cholecystitis within the framework of autoimmune biliary tract disorders.

• Patients with an atypical clinical presentation of acute cholecystitis, insufficient informativeness of ultrasound of the liver, gallbladder, and ducts, as well as for the differential diagnosis of the disease and its complications, are recommended to undergo CT of the abdominal organs with intravenous bolus contrast enhancement (if technically feasible) [65–71].

GCR BLEL 2Grade of Recommendation – B (Level of Evidence – 2)

Comment. CT of the abdominal organs with intravenous bolus contrast enhancement makes it possible to detect enlargement of the gallbladder, thickening of its walls, subserosal edema, mucosal thickening with extension of the process to the gallbladder bed tissue, increased density of pericholecystic adipose tissue (as a sign of acute inflammation), the presence of fluid in the pericholecystic space, pericholecystic abscess, and the presence of gas within the gallbladder. The sensitivity of CT for detecting complications of acute cholecystitis is significantly higher than that of ultrasound (85% vs. 68%). CT and ultrasound are complementary methods for assessing the state of the gallbladder [67–70].

The disadvantages of CT examination include: difficulties in detecting gallstones, difficulties in interpreting gallbladder wall thickening and adjacent fatty tissue, which may not be related to gallbladder disease. One must also take into account that this research method is associated with patient exposure to ionizing radiation and incurs additional financial costs.

• For patients with clinical signs of acute cholecystitis when ultrasound of the liver, gallbladder and bile ducts, and abdominal CT with intravenous bolus contrast enhancement are insufficiently informative, abdominal MRI (if technically feasible) is recommended for differential diagnosis and detection of disease complications [59, 71, 72].

GCR ALEL 1Grade of Recommendation — A (Level of Evidence — 1)

Comment. The method plays a significant role in detecting gallbladder perforation, pericholecystic abscess, and cholecystoenteric fistulas; it has a major advantage over ultrasound and CT as it provides specific information on the causes, degree of inflammation, presence or absence of gallbladder wall necrosis or abscess, and other complications of acute cholecystitis. The MRI signs of acute uncomplicated cholecystitis include 6 criteria: (a) presence of stones in the gallbladder, often localized in its neck or cystic duct; (b) thickening of the gallbladder wall (>3 mm); (c) gallbladder wall edema; (d) enlargement of the gallbladder (diameter >40 mm); (e) presence of pericholecystic fluid; (f) presence of fluid around the liver (the so-called "C" sign – a small amount of fluid between the liver and the right dome of the diaphragm or abdominal wall, distinct from pericholecystic fluid). Detection of one or more of these MRI criteria indicates acute cholecystitis with a sensitivity of 88% and a specificity of 89%.

• For patients with clinical manifestations of acute cholecystitis when ultrasound of the liver, gallbladder and bile ducts, and abdominal CT with intravenous bolus contrast enhancement are insufficiently informative, hepatobiliary scintigraphy with iminodiacetic acid (HIDA scan) (if technically feasible) is recommended for differential diagnosis and detection of disease complications [59, 73].

GCR BLEL 2Grading of Recommendations Assessment, Development and Evaluation – B (Level of Evidence – 21)

Comment. Hepatobiliary scintigraphy in acute cholecystitis can reveal delayed and inadequate filling of the gallbladder (delayed visualization of the gallbladder up to 1 hour from the start of the study or more is characteristic). Signs of gallbladder perforation can also be detected. Hepatobiliary scintigraphy is generally not performed in critically ill patients due to the risk of delaying management decisions because the study takes a significant amount of time. The sensitivity and specificity of the method are 67–100% and 58–88%, respectively [27, 66]. False-positive results may be observed in hepatocyte dysfunction, fasting and total parenteral nutrition, prior biliary papillosphincterotomy, history of cholecystectomy, and hyperbilirubinemia.

• For patients with acute acalculous cholecystitis who have common bile duct dilation on ultrasound and abnormal laboratory parameters (elevated alkaline phosphatase, total bilirubin ≤4 mg/dl [68 µmol/l]), but without clear visualization of a stone in the duct, MRCP or endoscopic ultrasonography of the pancreatobiliary zone (if technically feasible) is recommended to confirm or rule out choledocholithiasis [58, 71, 72, 74].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. Endoscopic ultrasonography of the pancreatobiliary zone and MRCP are diagnostic methods that allow high-accuracy detection of extrahepatic bile duct stones >5 mm in size. These studies are indicated for intermediate probability of choledocholithiasis (Appendix G, Table 3). A systematic review showed that the sensitivity and specificity of endoscopic ultrasonography of the pancreatobiliary zone are 95% and 97%, respectively; these values for MRCP are 93% and 96%, respectively. MRCP allows visualization of the biliary tract anatomy without contrast agents and is an extremely useful diagnostic method for detecting calculi in the extrahepatic bile ducts; it helps differentiate pancreatic and biliary tract pathology; and it can be useful in determining the cause of right upper quadrant pain in pregnant women [72].

• In diagnostically complex cases, after exhausting all non-invasive diagnostic methods, patients with suspected acute cholecystitis are recommended to undergo diagnostic laparoscopy, or diagnostic laparotomy if laparoscopy is unfeasible or uninformative [10, 25, 48].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

• When acute cholecystitis or an exacerbation of chronic cholecystitis is suspected, patients with risk factors for coronary artery disease and/or other symptoms suggestive of potential coronary artery disease are recommended to undergo electrocardiography to rule out acute coronary syndrome [9, 56, 57].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. In ischemia of the inferior wall of the left or right ventricle, clinical symptoms may include epigastric pain, nausea, and vomiting. The presence of other symptoms indicating cardiovascular disease (dizziness, shortness of breath, severe weakness, cardiac arrhythmias) or risk factors for coronary artery disease should prompt the exclusion of acute coronary syndrome. The development of acute biliary obstruction may cause ST-segment abnormalities (depression or elevation) on the electrocardiogram, the origin of which remains insufficiently clear, as well as heart rate changes. Cholelithiasis is often combined with coronary artery disease. The interpretation of electrocardiographic changes must be very careful and take into account other clinical and laboratory parameters indicating myocardial injury (hemodynamics, blood troponin levels, etc.) to avoid unnecessary therapeutic interventions (in particular, thrombolysis).

2.5 Other Procedures

• To establish the diagnosis of acute or chronic acalculous cholecystitis, oral cholecystography and cholangiography, as well as intravenous cholecystography and cholangiography, are not recommended [10, 23, 26].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

• For patients with signs of acute or chronic acalculous cholecystitis and concomitant history indicating possible protozoan and parasitic invasion, as well as a history of staying in endemic areas, an initial consultation (examination) by an infectious disease specialist is recommended to resolve the issue of further examination and treatment, in the absence of complications requiring emergency surgery [9, 10].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. In such cases, the development of acute or chronic parasitic cholecystitis is possible [9, 10]. However, waiting for an infectious disease consultation when a parasitic cause of acute cholecystitis is suspected, and indications for emergency surgery are present, is impractical. At the same time, the parasitic cause of acute cholecystitis, like the infectious one, can be determined after cholecystectomy, in which case consultation will be required postoperatively [52].

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

In acute acalculous cholecystitis, hospitalization of the patient in a surgical inpatient department for treatment is indicated.

In chronic acalculous cholecystitis, treatment can be performed in an outpatient setting.

3.1. Conservative management

• For patients with an exacerbation of chronic acalculous cholecystitis, the administration of antispasmodics (drugs for functional gastrointestinal disorders) is recommended until symptoms resolve to relieve pain [75–80].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. Antispasmodics (drugs for the treatment of functional gastrointestinal disorders) have demonstrated efficacy in relieving biliary pain and dyspeptic symptoms caused by smooth muscle spasm. Spasm of the biliary sphincters impairs gallbladder emptying and normal bile outflow into the duodenum, contributing to inflammation and biliary sludge. It is preferable to use drugs with spasmolytic action (ATC A03) that have the highest selectivity for biliary smooth muscle and minimally pronounced systemic effects [75–80].

• For patients in whom acute acalculous cholecystitis or an exacerbation of chronic acalculous cholecystitis develops as part of an intestinal infection, parasitosis, or systemic collagenosis, monitoring and treatment in accordance with established care standards for these conditions are recommended [7–10].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment. Treatment of cholecystitis that has developed as part of an intestinal infection or parasitosis requires etiotropic therapy. Acute acalculous cholecystitis can act as one of the first signs of an exacerbation of a systemic connective tissue disease. There is experience of successfully relieving inflammation through the use of systemic corticosteroids (H02A) at a dose of about 1 mg/kg (in the absence of signs of an infectious process and under careful monitoring of the disease course). However, according to most publications, patients successfully underwent early cholecystectomy [81, 82].

• For patients with acute acalculous cholecystitis, infusion therapy is recommended to correct hemodynamic and metabolic disorders [85, 86].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. Initial management of acute acalculous cholecystitis (AAC) involves infusion therapy and antibiotic administration, with monitoring of blood pressure, heart rate, and urine output. It should be kept in mind that during conservative treatment of AAC, clinical manifestations of the disease may either subside or progress. Conservative treatment of AAC, especially in elderly and senile patients, often masks clinical symptoms without preventing the progression of destructive changes in the gallbladder and inflammatory phenomena in the abdominal cavity. In this regard, it is advisable to perform a follow-up blood leukocyte count and control ultrasound of the gallbladder and bile ducts.

Prolonged conservative treatment with a dubious effect can significantly complicate subsequent surgical treatment and increase the risk of complications. Of particular danger is the administration of prolonged conservative treatment for AAC in patients with diabetes mellitus.

The entire package of therapy for severe forms of AAC is best carried out in an intensive care unit (ICU) with monitoring of basic hemodynamic parameters: cardiac output, urine output, arterial and central venous pressure, body temperature, and other parameters. Blood substitutes and perfusion solutions (B05) can be used for infusion therapy.

Control parameters for the effectiveness of treatment carried out in the ICU are: central venous pressure (CVP) at 8 to 12 mm Hg, mean arterial pressure (MAP) > 65 mm Hg, venous oxygen saturation > 70%, urine output > 0.5 mL/kg/h. Adrenergic and dopaminergic agents (C01CA) are indicated for persistent hypotension despite adequate infusion therapy.

Treatment is carried out against the background of correction of comorbid diseases, for which relevant specialists are involved [84, 88-92].

The duration of attempted conservative relief of AAC and the timeframe for assessing its effectiveness should be planned taking into account the circumstance that 3 days after the onset of the disease, the severity of its course changes from Grade I to Grade II, which may entail a limitation in the feasibility of laparoscopic cholecystectomy [94].

Antibacterial therapy in patients with AC

• Patients with acute acalculous cholecystitis, in order to prevent the progression of inflammation and the development of complications, are recommended to be prescribed systemic antibacterial drugs [10, 84, 91-93, 95, 102].

GCR ALEL 2Grade of Recommendation – A (Level of Evidence – 2)

Comment. When prescribing systemic antibacterial drugs to patients with AAC, it is recommended to give preference to drugs with good penetration into the biliary tract [95, 96].

It is advisable to prescribe therapy based on a combination of penicillins, including combinations with beta-lactamase inhibitors (piperacillin+tazobactam), third- or fourth-generation cephalosporins (cefepime**, ceftazidime** (possibly in combination with #metronidazole**); carbapenems (imipenem+cilastatin**, meropenem**, doripenem); monobactams (aztreonam, possibly in combination with #metronidazole**) fluoroquinolones (ciprofloxacin**, #levofloxacin**, moxifloxacin** (possibly in combination with #metronidazole**).

In Grade I and II severity of AAC, antibiotic therapy can be completed within 24 hours after cholecystectomy. In complicated cases, the duration of antibiotic therapy is extended to 4-7 days after the elimination of the infection focus and resolution of biliary drainage disorders [97-98].

If microbiological blood culture reveals gram-positive microorganisms (Enterococcus spp., Streptococcus spp.), the duration of antibiotic therapy after the elimination of the infection focus should be at least 14 days.

Antibiotic therapy is not a means of radical treatment, but it can significantly improve the prognosis. General principles for selecting antibiotics in AAC correspond to those for treating intra-abdominal infections (Appendix B4).

4.2. Surgical treatment

When determining surgical tactics for acute acalculous cholecystitis, it is advisable to use the recommendations of the Tokyo Guidelines 2013 (Appendix G5), according to which the disease is classified into Grade I, II, and III [53, 98].

• Patients with acute acalculous cholecystitis in the absence of signs of resolution of the inflammatory process (clinical, laboratory, instrumental), with the aim of preventing complications, are recommended surgical intervention (cholecystectomy or ultrasound-guided percutaneous transhepatic cholecystostomy (A16.14.006.002 Ultrasound-guided percutaneous transhepatic cholecystostomy, cholecystocholangiostomy), the choice of which is determined by anesthetic risk, presence of complications, and general condition of the patient (Appendix B2) [3, 10, 53, 54].

GCR CLEL 3Grade of Recommendation — C (Level of Evidence — 3)

Comment. AAC is characterized by rapid progression and a high risk of gangrene (up to 50%), gallbladder perforation, and high mortality (about 30% among patients who received timely care and 75% among those who did not receive adequate treatment) [10, 54]. In the vast majority of cases, surgical treatment is the only method capable of radically influencing the prognosis of the disease; conservative treatment only leads to delayed surgery and the development of complications; under conditions of high intraluminal pressure, drugs do not penetrate into the gallbladder wall.

• Surgical treatment for patients with acute acalculous cholecystitis with the aim of preventing potential complications is recommended to be performed early (within 72 hours) from the onset of the disease [3, 94, 100-105].

GCR BLEL 1Grade of Recommendation – B (Level of Evidence – 1)

Comment. Currently, active surgical tactics are most preferred, in which the question of the need for surgery is decided immediately upon establishing the diagnosis of Grade II AAC. Patients of young and mature age with AAC, without severe comorbid diseases, with a disease duration of not more than 3 days, and with the absence of gross cicatricial-infiltrative changes in the area of the gallbladder neck and pathology of extrahepatic bile ducts according to ultrasound of the liver, gallbladder, and ducts, are recommended to undergo laparoscopic cholecystectomy [53, 94, 100-104].

In the absence of cholecystectomy, approximately one-third of patients develop complications [54, 94, 100-104].

With unjustified delays in surgical intervention in the first 5-7 days or during the second week, the development of an infiltrate in the subhepatic space is often observed, including the altered gallbladder (with phenomena of phlegmonous or gangrenous inflammation), greater omentum, loops of the small and large intestine, and elements of the hepatoduodenal ligament, which complicates cholecystectomy and increases the risk of intraoperative complications [25, 53, 54, 94].

Performing operations in the first 3 days from the onset of the disease is accompanied by fewer technical difficulties, a lower risk of intra- and postoperative complications, lower mortality, and shortens the total time of treatment and rehabilitation [102-107].

• To prevent the development of complications, patients with acute acalculous cholecystitis are recommended to undergo early cholecystectomy, preferably via a laparoscopic approach, as soon as appropriate conditions for surgical intervention are prepared [3, 51, 53, 94, 100-104].

GOM ALOE 1Level of Evidence – A (Level of Data Reliability – 1)

Comment. Laparoscopic cholecystectomy (LCE) is the standard intervention. Numerous studies have shown that LCE carries a low risk of adverse outcomes and has clear advantages over open laparotomy or mini-laparotomy approaches (cholecystectomy or minimally invasive cholecystectomy) in many respects: lesser degree of tissue damage and postoperative pain intensity, lower mortality, shorter hospital stay, earlier recovery of working capacity, and a less noticeable cosmetic defect [24, 48, 53, 94, 101-108].

Early LCE is defined differently in various studies. For some authors, early LCE is an operation performed in patients with symptoms of less than 72 hours, for others — with symptoms of less than 7 days, but within 4-6 days after diagnosis, which roughly corresponds to 10 days from the onset of symptoms. Most experts believe that early cholecystectomy should be performed as soon as appropriate conditions for surgical intervention are prepared [25, 94, 100-104].

According to the Tokyo Guidelines (2018), when planning early laparoscopic cholecystectomy, risk factors must be taken into account, in particular a high Charlson Comorbidity Index (CCI) [53].

• Patients with acute acalculous cholecystitis complicated by gallbladder perforation, diffuse or generalized peritonitis, are recommended to undergo emergency surgery [24, 25, 83].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment. Emergency surgery is performed within the next 2–3 hours from diagnosis and is indicated for all forms of destructive cholecystitis complicated by localized or diffuse peritonitis. Preoperative preparation is carried out during this time. The surgical access is chosen by the surgeon, taking into account a number of factors: the patient's condition, the nature of the disease's complications, and the technical feasibility of performing laparoscopic cholecystectomy.

• To prevent potential complications, laparoscopic cholecystectomy is recommended to be performed in all patients in compliance with the principles of the Critical View of Safety [112, 113].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. A key safety element of any type of cholecystectomy is the dissection of the neck and 1/3 of the body of the gallbladder with verification of the orifices of the cystic duct and cystic artery. Only after ensuring that exclusively 2 tubular structures—the cystic duct and the cystic artery—approach the gallbladder part dissected on all sides and separated from the liver bed, can one proceed to their transection. During laparoscopic cholecystectomy, this moment must be clearly visible on the monitor screen as the critical view of safety. To clarify anatomical relationships, intraoperative cholangiography (A06.14.003 Operative and postoperative cholangiography) through the cystic duct or the neck of the gallbladder, intraoperative ultrasound, or ICG visualization (if technically feasible) can be used. If difficulties arise during surgery in patients with acute cholecystitis, it is recommended to re-examine the anatomical landmarks, invite a more experienced surgeon, proceed to cholecystectomy "from the fundus", or convert to open surgery.

• If a bile duct injury is identified during a laparoscopic surgery and indications for an open procedure are established, conversion by a surgeon experienced in hepatobiliary surgery is recommended in order to perform reconstructive surgery [112,113].

GCR CLEL 3Grade of Recommendation — C (Level of Evidence — 3)

• If the surgical team lacks experience in reconstructive hepatobiliary surgery, conversion (transition from laparoscopic to laparotomic access) in a patient with a bile duct injury is not recommended. It is advisable to leave a subhepatic drain (laparoscopic drainage of the peritoneal cavity) and refer the patient to a medical facility with experience in treating such injuries [112,113].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

• In patients with acute acalculous cholecystitis with anomalies of the biliary tract structure or a high risk of performing cholecystectomy in complex intraoperative situations, to safely complete the operation, it is recommended to perform cholecystostomy (A16.14.006 Cholecystostomy, A16.14.006.001 Laparoscopic cholecystostomy) or subtotal cholecystectomy, either laparoscopic or open (A16.14.009 Cholecystectomy, A16.14.009.001 Minimally invasive cholecystectomy, A16.14.009.002 Laparoscopic cholecystectomy) [112,113].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. If Mirizzi syndrome is suspected, separation of the gallbladder neck from the common hepatic duct and common bile duct should be avoided. It is recommended to transect the gallbladder neck transversely and explore its lumen from the inside. In this case, the duct wall defect can be sutured using viable remnants of the cystic neck over a T-tube in the common hepatic and common bile ducts. If the duct wall is completely destroyed, it is better to complete the operation by external drainage of the proximal and distal stumps of the bile duct [115, 116].

• For patients with acute acalculous cholecystitis who have a high operative and anesthesiological risk due to decompensation of concomitant diseases (ASA ≥3) and a severe course of the disease (Grade III), percutaneous transhepatic gallbladder drainage under ultrasound guidance (A16.14.006.002) is recommended [35, 117-122].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. Performing a cholecystectomy under these conditions is associated with an unjustifiably high risk of intra- and postoperative complications. Conservative treatment only leads to a delayed operation time and the formation of pericholecystic complications. In case of a high operative and anesthesiological risk, percutaneous transhepatic gallbladder drainage is advisable. Complications of puncture drainage of the gallbladder account for up to 10.8%, and its ineffectiveness, which necessitated surgery, was recorded in 32.4% of cases. This procedure is recognized as effective therapy for patients with exceptionally high perioperative risk, but it is also accompanied by a high rate of complications [25,110].

• In patients with acute acalculous cholecystitis who have undergone percutaneous transhepatic gallbladder drainage, it is recommended to perform a repeat ultrasound of the liver, gallbladder, and ducts to determine the effectiveness of gallbladder decompression, rule out potential complications, and determine further management tactics [25, 110].

GCR BLEL 2Grade of Recommendation – B (Level of Evidence – 2)

Comment. There may be either no signs of resolution of inflammation, or migration of the drain from the gallbladder (biliary drain), or the appearance of signs of gallbladder wall perforation, which will require emergency surgery [10, 25, 110].

• In patients with acute acalculous cholecystitis who do not show improvement 12–24 hours after percutaneous transhepatic gallbladder drainage placement, cholecystectomy is recommended to prevent complications [10, 25, 110].

GCR BLEL 2Grade of Recommendation – B (Level of Evidence – 2)

• In patients with acute acalculous cholecystitis who have undergone percutaneous transhepatic gallbladder drainage and in whom the inflammatory process resolves clinically, laboratory-wise, and according to follow-up ultrasound, subsequent cholecystectomy is not recommended [10, 35, 93].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment. In the absence of sludge and gallstones according to follow-up ultrasound of the liver, gallbladder, and ducts, with contraction of the gallbladder and no fluid collections pericholecystically or in the subhepatic space, provided there is a minimal amount of output through the drain, the cholecystostomy tube (biliary drain) can be removed. As a rule, removal of the biliary drain is performed 4–6 weeks after percutaneous transhepatic gallbladder drainage placement. The risk of cholecystitis recurrence in such cases is low (about 7% over a mean follow-up period of 32 months) [10, 93].

• All patients with chronic cholecystitis occurring in the form of hyalinizing cholecystitis or with signs of a "non-functioning gallbladder" are recommended elective cholecystectomy to prevent the development of gallbladder adenocarcinoma, provided there is a low operative and anesthesiological risk [22, 99].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. Besides the fact that significant changes in the gallbladder wall in chronic cholecystitis are associated with chronic infection and the risk of acute cholecystitis, pronounced fibrosis of the gallbladder is associated with an increased risk of gallbladder adenocarcinoma.

Postoperative treatment

• In the postoperative period, patients who have undergone surgical treatment for acute acalculous cholecystitis are recommended serial monitoring of basic laboratory parameters (complete blood count, general clinical blood biochemistry including total blood bilirubin level) for early detection of potential complications [82,114].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment. In the postoperative period, in patients who underwent intervention for acute acalculous cholecystitis, in addition to control blood tests, monitoring of the abdominal drain is recommended, which includes assessing its functional capacity, the nature (blood, bile) and volume of discharge, and removal in the absence of exudate.

• In the postoperative period, in patients who underwent intervention for acute acalculous cholecystitis, if complications are suspected, a comprehensive abdominal ultrasound, or an ultrasound of the liver and ducts, or a CT scan of the abdominal organs is recommended to detect intra-abdominal fluid collections and dilatation of the ductal system [10, 82, 113].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. If bile-tinged contents are found in the drain or a fluid collection is detected in the abdominal cavity during instrumental examination, endoscopic retrograde cholangiopancreatography (ERCP) should be performed as an urgent procedure to evaluate the bile ducts. Therapeutic intervention such as bile duct stenting or endoscopic bougienage and balloon dilation of the Sphincter of Oddi (A16.14.043) may be performed, which can be the definitive treatment in a number of cases. Endoscopic retrograde sphincterotomy should not be performed. The proximal part of the bile ducts can be visualized by performing MRCP or percutaneous transhepatic cholangiography (PTC) followed by percutaneous transhepatic cholangiostomy, if necessary performed on non-dilated bile ducts. Aside from confirmed bile leakage from the cystic duct or the gallbladder bed, which can be managed endoscopically, patients with all other injuries should be referred to specialized centers or experts with experience in reconstructive hepatobiliary surgery should be invited [25, 112, 113].

4.3. Diet therapy

• For patients with acute cholecystitis in the preoperative period and on the day of surgery, fasting is recommended to prevent complications due to emergency surgical indications and concomitant intestinal paresis. In the postoperative period, early enteral nutrition is recommended with a gradual increase in the frequency and volume of fluid and food intake [123].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

• During the first 1–2 days from the onset of acute acalculous cholecystitis (AAC), the patient is recommended to completely refrain from food to prevent gallbladder contractions and worsening vomiting under conditions of peristaltic disorders; intake is restricted to small portions of warm liquids (weak tea, diluted fruit and berry juice, low-mineralized water) [124].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

• For all patients with acute and chronic acalculous cholecystitis, therapeutic nutrition is recommended to prevent the development of complications [124].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. After cholecystectomy, starting from the 2nd–3rd day, pureed food is introduced in small, frequent portions (5–6 times a day): mucosal and pureed soups (rice, semolina, oatmeal), porridge (rice, oatmeal, semolina), kissel, jelly, mousses from non-acidic fruits and berries. Then, low-fat cottage cheese, steam-cooked pureed lean meat, boiled lean fish, and dried white bread are added. If cholecystectomy was not performed, after the inflammation subsides within 5–10 days, Diet No. 5a is prescribed, and after 3–4 weeks, Diet No. 5.

In chronic cholecystitis, foods with an irritating effect on the mucous membrane must be excluded from the diet: canned foods and marinades, alcohol, carbonated beverages, spicy, salty, and smoked foods, and vegetables rich in essential oils (radish, black radish, turnip, onion, garlic); the consumption of chocolate and pastries is restricted. Regarding the intake of fats and egg yolks, an individual approach is followed based on tolerability and the presence of gallstones. Among animal fats, butter is preferred as the most easily digestible.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• For patients with chronic acalculous cholecystitis in remission, in the absence of contraindications, sanatorium-resort treatment is recommended for the purpose of restoring or compensating for bodily functions impaired as a result of the infectious-inflammatory process and surgical intervention [125].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. To reduce the tendency to spasm, it helps to take low- and medium-mineralization water in a warm or hot form ("Essentuki-Novaya", "Borjomi", "Smirnovskaya") 3–4 times a day 30–40 minutes before meals for 3–4 weeks. If well tolerated, high-mineralization waters can be used in a chilled form ("Essentuki No. 17"). Natural factors also have a positive effect on the state of the nervous system.

Medical rehabilitation is carried out for all patients with AAC; the choice of the optimal rehabilitation method depends on each specific case [126–129]. It should be borne in mind that physical rehabilitation after minimally invasive cholecystectomy options proceeds significantly faster than after open cholecystectomy, while the functional adaptation of the digestive system, due to the absence of the gallbladder, does not have significant differences following different methods of its removal.

Constant bile secretion into the gastrointestinal lumen after cholecystectomy can lead to altered alkalinization rhythm, erosive duodenitis, reflux gastritis, reflux esophagitis, and irritable bowel syndrome. These changes generally lack a prominent clinical picture and persistent consequences, and resolve with adherence to diet and a fractional meal schedule.

• Medical rehabilitation for all patients after cholecystectomy is recommended to be started as early as possible and conducted simultaneously with treatment in order to restore the psychoemotional state and facilitate the transition to daily activities [126–128].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. Rehabilitation is carried out in specialized care departments (stage I), in inpatient medical rehabilitation departments (stage II), and in the outpatient rehabilitation department, day hospital rehabilitation department, or sanatorium rehabilitation department (stage III).

Upon the development of functional insufficiency after the completion of surgical treatment or conservative therapy (at the end of the first stage of rehabilitation), the patient may be referred for rehabilitation to the second or third stage of rehabilitation in accordance with the assessment of their self-care ability and rehabilitation potential.

Rehabilitation is organized by a multidisciplinary rehabilitation team comprising: a surgeon, a physical therapy physician, and a medical psychologist. A set of measures for social and domestic rehabilitation and the restoration of motor activity is carried out. At the first stage, the attending physician is a surgeon, and all rehabilitation measures are coordinated with them and with the anesthesiologist-reanimatologist (if the patient is in the ICU). Other specialists may be involved if necessary.

The most serious rehabilitation problems for patients with severe forms of acute cholecystitis and a complicated postoperative course include:

• Post-intensive care syndrome;

• Immobilization syndrome, motor deprivation, and sensory deprivation;

• Nutritional deficiency;

• Cognitive dysfunction;

• Pain;

• Stress.

A prolonged stay in the ICU or medical organization for severe acute cholecystitis can lead to motor deficit (loss of the ability to walk), muscle atrophy, pressure ulcers, emaciation, and other problems that can lead not only to functional insufficiency but also to disability. The actions of the rehabilitation team should be aimed at preventing the negative impact of the hospital environment on the patient's functioning.

There is no data on the superiority of certain physical therapy methods in acute cholecystitis; physical therapy can be considered as an alternative and complementary technique in addition to basic care. Verticalization of the patient should be carried out in accordance with profile guidelines and taking into account surgical contraindications,

Patients with pain syndrome should be provided with analgesic measures. In the absence of contraindications, a multimodal analgesic regimen is recommended (organized jointly with a medical psychologist and an occupational therapist), including opioids (N02A), non-steroidal anti-inflammatory and antirheumatic drugs (M01A), and paracetamol**.

• After cholecystectomy, sanatorium-resort treatment is recommended for all patients in the absence of contraindications [125].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment. After cholecystectomy, rehabilitation can be carried out after 2–3 weeks in local sanatoriums specializing in the treatment of gastrointestinal diseases, recovery centers, health resorts, as well as at resorts with low- and medium-mineralized waters (sodium bicarbonate, sodium-calcium bicarbonate, sodium chloride bicarbonate, sulfate-calcium-magnesium-sodium, and others in a form warmed to 42–44°C, 30–60 min before meals).

5. Prevention and Dispensary Observation

Preventing the development of acute acalculous cholecystitis is problematic, unlike the prevention of acute calculous cholecystitis, since its causes are diverse and far from always established even during surgical treatment.

Following cholecystectomy and discharge from the hospital, patient monitoring during the first month is carried out jointly by a general practitioner (primary general practitioner's consultation (examination), follow-up general practitioner's consultation (examination)) and a surgeon (primary surgeon's consultation (examination), follow-up surgeon's consultation (examination)). Subsequently, consultations and additional examinations are carried out according to indications, depending on the specifics of the postoperative course and the appearance of clinical symptoms. Patients who have undergone cholecystectomy belong to the dispensary observation group II [129].

6. Organization of Medical Care

1. All patients with suspected acute acalculous cholecystitis must be examined by a surgeon.

2. The detection of signs of acute acalculous cholecystitis serves as an indication for urgent hospitalization of patients to the surgical department of the nearest medical organization of any level.

3. If conservative treatment is ineffective within 24–48 hours, the patient is indicated for transfer from a level I medical organization to a level II medical organization or to an interdistrict surgical department, or where there is the opportunity to perform laparoscopic cholecystectomy and endoscopic intervention on the bile ducts, if necessary.

4. Patients with moderate or severe acute acalculous cholecystitis must be immediately referred to surgical departments of level II or III medical organizations.

Indications for hospitalization in a medical organization

Indications for patient hospitalization are clinical, laboratory, and instrumental signs of acute acalculous cholecystitis.

Criteria for patient discharge from a medical organization

Satisfactory general condition and well-being of the patient, normalization of body temperature, normalization of laboratory parameters and follow-up ultrasound data of the surgical area, liver, and ducts (A04.16.001). The duration of inpatient treatment for patients with acute calculous cholecystitis is determined by the possibility of relieving the acute attack, performing cholecystectomy according to indications, and the presence of complications in the postoperative period.

7. Additional Information

The outcome of the disease or condition may be influenced by:

• Purulent-necrotic and other complications of acute cholecystitis (cholangitis, obstructive jaundice, peritonitis, sepsis, gastrointestinal bleeding, etc.);

• Polyvalent allergy;

• History of leukemia, oncological diseases, tuberculosis, or positive test results for HIV infection, hepatitis B and C, syphilis;

• Pronounced congenital defects confirmed by history and/or physical examination, leading to impaired normal functioning and requiring correction (congenital heart defects, gastrointestinal tract, urogenital system, skeleton; Marfan syndrome, Klinefelter syndrome, Edwards syndrome, Opitz syndrome, Goldenhar syndrome, and others);

• Cardiovascular diseases: post-infarction cardiosclerosis, silent myocardial ischemia, pericarditis, aortic aneurysm, grade III hypertension, effort angina, unstable angina, Prinzmetal's angina;

• Clinically significant rhythm and conduction disorders (atrial fibrillation/flutter, frequent ventricular extrasystole of bigeminy/trigeminy type, ventricular tachycardia, complete left bundle branch block, trifascicular block, ventricular fibrillation, sinoatrial block greater than grade I, atrioventricular block grade II–III, Wenckebach-Mobitz / Frederick syndrome);

• Chronic heart failure grade III-IV according to NYHA;

• Chronic cor pulmonale in the decompensation stage;

• Bronchial asthma;

• Pulmonary embolism;

• Acute myocardial infarction;

• Acute cerebrovascular accident;

• Transient ischemic attack;

• Acute pneumonia, pleurisy;

• Systemic connective tissue diseases according to medical history — systemic sclerosis, systemic lupus erythematosus, systemic vasculitis, antiphospholipid syndrome, dermatomyositis, sarcoidosis, rheumatic fever, and others;

• Type I and type II diabetes mellitus;

• Obesity with a body mass index of 40 or more (grade III);

• Acute renal failure;

• Chronic kidney disease with a glomerular filtration rate of less than 30 mL/min;

• Gastric and duodenal ulcer in the acute stage, liver cirrhosis;

• Multiple sclerosis and other demyelinating diseases;

• Any psychiatric disorders according to medical history;

• Hematological diseases according to medical history;

• Drug addiction or chronic alcoholism according to medical history;

• Pregnancy, lactation period.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Working Group Chairs:

Revishvili A.Sh. – Academician of the RAS, Doctor of Medical Sciences, Professor, Vice-President of the Russian Society of Surgeons (Moscow)

Ivashkin V.T. – Academician of the RAS, Doctor of Medical Sciences, Professor, President of the Russian Gastroenterological Association (RGA), Russian Society for the Study of the Liver (RSSL) (Moscow)

Working Group Members:

Gulyaev A.A. – Doctor of Medical Sciences, Professor (Moscow) – Member of the RSS

Zharkova M.S. – Candidate of Medical Sciences (Moscow) – Member of the RGA, Member of the RSSL

Korolev M.P. – Doctor of Medical Sciences, Professor (Saint Petersburg) – Honorary Chairman of RENDO

Lapina T.L. – Candidate of Medical Sciences, Associate Professor (Moscow) – Member of the RGA

Maev I.V. – Academician of the RAS, Doctor of Medical Sciences, Professor (Moscow) – Member of the Presidium of the RGA

Okhlobystin A.V. – Candidate of Medical Sciences, Associate Professor (Moscow) – Member of the RGA

Trukhmanov A.S. – Doctor of Medical Sciences, Professor (Moscow) – Chief Scientific Secretary of the RGA

Sheptulin A.A. – Doctor of Medical Sciences, Professor (Moscow) – Member of the RGA

Shirokova E.N. – Doctor of Medical Sciences, Professor (Moscow) – Member of the RGA and RSSL

Shulpekova Yu.O. – Candidate of Medical Sciences (Moscow) – Member of the RGA and RSSL

Fedorov E.D. – Doctor of Medical Sciences, Professor, Chairman of the Board of RENDO (Moscow)

Emelyanov S.I. – Corresponding Member of the RAS, Professor (Moscow) – Member of the RSS

Bronshtein G.P. – Surgeon (Moscow)

Vetshev P.S. – Doctor of Medical Sciences, Professor (Moscow) – Member of the RSS

Kaminsky M.N. – Candidate of Medical Sciences (Khabarovsk) – Member of the RSS

Kriger A.G. – Doctor of Medical Sciences, Professor (Moscow) – Member of the RSS

Mamoshin A.V. – Doctor of Medical Sciences (Moscow) – Member of the RSS

Natroshvili A.G. – Doctor of Medical Sciences (Moscow) – Member of the RSS

Natroshvili I.G. – Doctor of Medical Sciences (Kislovodsk) – Member of the RSS

Olovyanny V.E. – Doctor of Medical Sciences (Moscow) – Member of the RSS

Prudkov M.I. – Doctor of Medical Sciences, Professor (Yekaterinburg) – Member of the RSS

Sazhin A.V. – Corresponding Member of the RAS, Professor (Moscow) – Member of the RSS

Shulutko A.M. – Doctor of Medical Sciences, Professor (Moscow) – Member of the RSS

No conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

These proposed guidelines aim to provide practitioners with up-to-date concepts of the etiology and pathogenesis of cholecystitis, and to familiarize them with modern diagnostic and treatment algorithms for the main clinical courses of this disease; however, they are not a universal and comprehensive care protocol.

In situations not described in these guidelines, as well as in critical situations and/or under resource-constrained conditions, it is advisable to rely on provisions from other consensus documents, decisions of local ethics committees and medical boards, personal experience, and common sense.

Target audience of these clinical guidelines:

Surgeons, gastroenterologists, endoscopists, anesthesiologists-resuscitologists, radiologists, clinical laboratory diagnosticians, ultrasound diagnosticians, internists, general practitioners (family physicians), surgical and gastroenterological clinical residents.

Table 1. Scale for assessing levels of reliable evidence (LRE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for methods of prevention, treatment, and medical rehabilitation, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)

Table 3. Scale for assessing the grades of recommendation (GR) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines have been developed taking into account the following regulatory and legal documents:

• Order of the Ministry of Health of the Russian Federation No. 906n dated November 12, 2012, "On Approval of the Procedure for Providing Medical Care to the Population in the Profile 'Gastroenterology'";

• Order of the Russian Ministry of Health No. 203n dated May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care";

• Decree of the Government of the Russian Federation No. 1968 dated November 17, 2021, "On Approval of the Rules for the Phased Transition of Medical Organizations to the Provision of Medical Care Based on Clinical Guidelines Developed and Approved in Accordance with Parts 3, 4, 6–9, and 11 of Article 37 of the Federal Law 'On the Fundamentals of Protecting the Health of Citizens in the Russian Federation'";

• Order of the Ministry of Health of the Russian Federation No. 922n dated November 15, 2012, "On Approval of the Procedure for Providing Medical Care to the Adult Population in the Profile 'Surgery'";

• Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019, "On Approval of the Procedure and Timelines for the Development of Clinical Guidelines, Their Revision, the Standard Template of Clinical Guidelines and Requirements for Their Structure, Composition, and Scientific Validity of Information Included in Clinical Guidelines";

• Order of the Ministry of Health of the Russian Federation No. 617n dated June 23, 2020, "On Amendments to Appendices No. 1, 2, and 3 to the Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019, 'On Approval of the Procedure and Timelines for the Development of Clinical Guidelines, Their Revision, the Standard Template of Clinical Guidelines and Requirements for Their Structure, Composition, and Scientific Validity of Information Included in Clinical Guidelines'";

• Order of the Ministry of Health of the Russian Federation No. 321 dated May 19, 2022, "On the Working Group of the Ministry of Health of the Russian Federation on Updating Methodological Approaches to the Payment for Medical Care at the Expense of Compulsory Medical Insurance Funds within the Framework of the State Guarantee Program for Free Medical Care to Citizens";

• Order of the Ministry of Health of the Russian Federation No. 530n dated August 5, 2022, "On Approval of Unified Forms of Medical Documentation Used in Medical Organizations Providing Inpatient Care, Day Care, and Procedures for Maintaining Them";

• Letter of the Federal Compulsory Medical Insurance Fund No. 6545/30-5 dated December 30, 2014, "On Targeted Audits of Medical Care Quality";

• Order of the Federal Compulsory Medical Insurance Fund No. 38n dated April 12, 2021, "On Declaring Void the Order of the Federal Compulsory Medical Insurance Fund No. 36 dated February 28, 2019, 'On Approval of the Procedure for Organizing and Conducting Quality Control, Timeliness, Quality, and Conditions of Medical Care Provision under Compulsory Medical Insurance'" (Registered with the Ministry of Justice of Russia on May 13, 2021, No. 63409).

Appendix B. Physician Action Algorithms

Appendix B1. Diagnostic algorithm for acute acalculous cholecystitis

Appendix B2. Surgical treatment algorithm for acute acalculous cholecystitis

Appendix C. Patient Information

General information

The primary cause of gallbladder inflammation (cholecystitis) is cholelithiasis; however, in some cases it develops in the absence of stones, referred to as "acalculous cholecystitis." Cholecystitis can have a chronic or acute course. Chronic acalculous cholecystitis may be caused by alterations in bile composition, impaired normal bile outflow from the gallbladder, or lipid deposition in the gallbladder wall. Signs of chronic cholecystitis exacerbation include pain in the right upper quadrant and epigastric region radiating to the right scapula, and nausea. Chronic cholecystitis may develop as a consequence of incomplete resolution of inflammation following an episode of acute cholecystitis.

Acute acalculous cholecystitis typically develops against the background of severe conditions such as stroke, trauma and burns, vascular surgery, and intestinal infections. This is a more severe condition requiring mandatory hospitalization, conservative or surgical treatment. In this case, gallbladder inflammation develops due to a sharp impairment of its wall blood supply and reduced resistance to common intestinal microflora, or pathogenic intestinal bacteria (e.g., Shigella or Salmonella pathogens) cause its infection. Signs of acute cholecystitis include progressive, agonizing pain in the right upper quadrant and epigastric region radiating to the right scapula, at the level of the lower thoracic vertebrae, into the right side of the neck, and fever; nausea and vomiting are frequently observed.

Every patient diagnosed with chronic acalculous cholecystitis must adhere to dietary rules limiting fatty foods to prevent exacerbation, avoid long intervals between meals, and be aware of their main clinical symptoms. If signs suggesting acute cholecystitis appear, a physician must be called. To confirm the diagnosis of acute cholecystitis, in addition to physical examination, blood tests (complete blood count, general clinical biochemical blood test), and ultrasound of the liver, gallbladder, and ducts are indicated. In a number of cases, more complex examinations become necessary, such as magnetic resonance cholangiopancreatography, abdominal computed tomography with intravenous contrast administration, or pancreatobiliary endosonography, which reliably rule out cholelithiasis and assess the extent of the inflammatory process.

If confirmed, the patient must remain under the observation of a surgeon in a surgical inpatient unit. In the acute phase of the process (the first 1–2 days), a strict sparing diet is recommended. Systemic antibacterial drugs are used to treat acute cholecystitis. If no improvement occurs, surgical treatment (typically cholecystectomy) is required.

Chronic cholecystitis in most cases develops due to gallstones in the gallbladder (as part of cholelithiasis). The main symptoms are a dull, aching pain in the right hypochondrium (mild attacks), a tendency to nausea after eating fatty foods, often accompanied by bloating. As a rule, the diagnosis is established based on the presence of characteristic symptoms and ultrasound data (some thickening and compaction of the gallbladder wall, moderate tenderness at the gallbladder point). Treatment mainly involves a sparing diet and antispasmodics.

Postoperative period recommendations

After surgery, the patient should adhere to relatively simple and feasible restrictions for 1–2 months. They are quite simple to follow, especially considering that ignoring them is fraught with rather unpleasant and undesirable consequences.

Diet

After surgery for cholecystitis, food at home should be pureed and porridge-like. Milk and milk kissels, liquid porridges (preferably on water), chicken and vegetable broth, and vegetable purees are allowed. Dietary nutrition is prescribed to the patient for the first 2–3 months after surgery. The diet affects the composition of the intestinal microflora and the activity of its functions. It is necessary to follow these principles:

• frequent and fractional meals; simultaneous consumption of large portions of food is contraindicated;

• food should not be hot or cold, but only slightly warmed;

• adequate nutrition providing the body with a full range of nutrients, vitamins, and minerals, since stimulation and strengthening of the immunity are required during the recovery period;

• exclusion of foods that promote fermentation and gas formation in the digestive tract; the diet should not contain legumes, heavy animal fats, any varieties of cabbage, smoked meats, marinades and pickles; alcoholic and carbonated beverages are not recommended.

During the first two weeks, the following are excluded from the diet:

• smoked, salted, fatty, fried, and spicy dishes;

• sausages;

• spices, mayonnaise, ketchup;

• bakery products;

• alcohol (until complete recovery).

The patient is strongly advised to monitor their weight. Since physical activity in the postoperative period is significantly minimized, it is easy to gain excess weight, which is highly undesirable. To restore normal microflora, dairy and fermented milk products, as well as ample fluid intake, are beneficial for the body. Meat and fish should not be consumed in the first weeks after surgery, but broths and pureed meat/fish minced dishes are acceptable. It is better to give up bread and bakery products; a great alternative to them can be crispbreads with a minimum of fiber and carbohydrates.

Vegetables (carrots, beets) and bananas are well tolerated by the body, while citrus fruits are best avoided. At the same time, for immunization, the body needs vitamin C, which can be obtained from other foods or taken in tablet form, along with other vitamins and multivitamin complexes. Ending the diet should not be abrupt. It is recommended to gradually expand the diet. Under no circumstances should one abruptly return to foods previously excluded from the diet. In general, the postoperative diet is not strict, and therefore it will be useful to follow the rules already habitual over several months thereafter. This will only benefit the body.

Physical activity after surgery for cholecystitis

Over the following 6 weeks, muscle fusion occurs, against which the risk of adhesions and hernias remains. Lifting heavy objects and vigorous physical exertion are strictly prohibited. At the same time, it is noted that daily slow-paced walking of 2–3 kilometers in the afternoon helps prevent adhesions. Therapeutic exercises are prescribed. Notably, the best recovery of muscle tissue occurs in those individuals who previously led an active lifestyle and kept their bodies toned. After a few months, one can return to moderate loads, gradually supplementing therapeutic exercises with general exercises.

• take short walks on foot;

• after the formation of the postoperative scar, visit the swimming pool and perform simple physical exercises;

• for those who lead an active lifestyle, as well as overweight patients, wear a special abdominal binder.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1.

Russian title: Physical examination data of the abdomen in acute cholecystitis

Source: Ivashkin V.T. Ed. by Okhlobystin A.V. Propaedeutics of Internal Diseases. GEOTAR-Media, Moscow, 2020, 784 p.

Type: reference material on symptom elicitation technique

Content:

Key: not required

Appendix G2.

Russian title: Diagnostic accuracy of individual physical signs in acute cholecystitis

Source: Trowbridge R.L., Rutkowski N.K., Shojania K.G. Does this patient have acute cholecystitis? JAMA 2003;289(1):80–86.

Type: reference material on diagnostic accuracy of symptoms

Content:

Key: not required

Appendix G3.

Russian title: Risk stratification for choledocholithiasis

Source: Ansaloni L, Pisano M, Coccolini F, et al. 2016 WSES guidelines on acute calculous cholecystitis. World J Emerg Surg 2016; 11:25, DOI 10.1186/s13017-016-0082-5.

Type: rating scale

Purpose: determination of the risk class of choledocholithiasis

Content:

Key:

Appendix G4.

Russian title: TG18/TG13 diagnostic criteria for acute cholecystitis

Source: Okamoto K., Suzuki K., Takada T. Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis J Hepatobiliary Pancreat Sci (2018) 25:55-72 https://doi.org/10.1002/jhbp.516

Type: rating scale

Purpose: diagnosis of acute cholecystitis

Content:

*, e.g., pericholecystic fluid, gallbladder enlargement, wall thickening, double-rim sign, gallstones/debris in the lumen

Key (interpretation): Probable diagnosis of acute cholecystitis: ≥1 item in Section A + ≥1 item in Section B or C. Definite diagnosis of acute cholecystitis: ≥1 item in Sections A, B, and C.

Appendix G5.

Russian title: TG18/TG13 severity grading for acute cholecystitis

Source: Okamoto K., Suzuki K., Takada T. Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis J Hepatobiliary Pancreat Sci (2018) 25:55-72 https://doi.org/10.1002/jhbp.516

Type: rating scale

Purpose: severity grading of acute cholecystitis

Content:

Key:

Grade 1: Grade II and III criteria and signs of organ dysfunction are absent. Mild inflammatory changes of the gallbladder are noted.

Grade 2: presence of ≥1 Grade II sign.

Grade 3: presence of ≥1 Grade III sign.