Diagnostic criteria and severity assessment of acute cholecystitis: Tokyo Guidelines



# Introduction
Early diagnosis of acute cholecystitis allows prompt treatment and reduces both mortality and morbidity.
The accurate diagnosis of typical as well as atypical cases of acute cholecystitis requires specifi c diagnostic criteria. Acute cholecystitis has a better prognosis than acute cholangitis, but may require immediate management, especially in patients with torsion of the gallbladder and emphysematous, gangrenous, or suppurative cholecystitis. The lack of standard criteria for diagnosis and severity assessment is refl ected by the wide range of reported mortality rates in the literature, and this lack makes it impossible to provide standardized optimal treatment guidelines for patients. In these Guidelines we propose specifi c criteria for the diagnosis and severity assessment of acute cholecystitis, based on the best available evidence and the experts' consensus achieved at the International Consensus Meeting for the Management of Acute Cholecystitis and Cholangitis, held on April 1-2, 2006, in Tokyo.

## Diagnostic criteria for acute cholecystitis
Diagnosis is the starting point of the management of acute cholecystitis, and prompt and timely diagnosis should lead to early treatment and lower mortality and morbidity. Specifi c diagnostic criteria are necessary to accurately diagnose typical, as well as atypical cases. The Guidelines propose diagnostic criteria for acute cholecystitis [fig_ref] Table 1: Diagnostic criteria for acute cholecystitis Imaging fi ndings [/fig_ref]. C-reactive protein (CRP) is not commonly measured in many countries. However, because acute cholecystitis is usually associatied with an elevation of CRP level by 3 mg/dl or more, CRP was included. Diagnosis of acute cholecystitis by elevation of CRP level (3 mg/dl or more), with ultrasonographic fi ndings suggesting acute cholecystitis, has a sensitivity of 97%, specifi city of 76%, and positive predictive value of 95% (level 1b). [bib_ref] Diagnostic accuracy of ultrasonography and C-reactive protein concentration in acute cholecystitis: a..., Juvonen [/bib_ref] After the discussion during the Tokyo International Consensus Meeting, almost unanimous agreement was achieved on the criteria [fig_ref] Table 2: Answer pad responses on the diagnostic criteria for acute cholecystitis [/fig_ref]. However, 19% of the panelists from abroad expressed the necessity for minor modifi cations, because, in the provisional version, the diagnostic criteria did not include technetium hepatobiliery iminodiacetic acid (Tc-HIDA) scan as an item.

## Imaging fi ndings of acute cholecystitis
Ultrasonography fi ndings (level 4) 2-5 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 liver disease and/or ascites or right heart failure) Enlarged gallbladder (long axis diameter >8 cm, short axis diameter >4 cm) Incarcerated gallstone, debris echo, pericholecystic fl uid collection Sonolucent layer in the gallbladder wall, striated intramural lucencies, and Doppler signals.
Magnetic resonance imaging (MRI) fi ndings (level 1b-4) [bib_ref] MR imaging in clinically suspected acute cholecystitis. A comparison with ultrasonography, Hakansson [/bib_ref] [bib_ref] The diagnostic utility of HASTE MRI in the evaluation of acute cholecystitis:..., Regan [/bib_ref] [bib_ref] Revised estimates of diagnostic test sensitivity and specifi city in suspected biliary..., Shea [/bib_ref] Pericholecystic high signal Enlarged gallbladder Thickened gallbladder wall.
Computed tomography (CT) fi ndings (level 3b) [bib_ref] Layfi eld L. CT evaluation of acute cholecystitis: fi ndings and usefulness..., Fidler [/bib_ref] Thickened gallbladder wall Pericholecystic fl uid collection Enlarged gallbladder Linear high-density areas in the pericholecystic fat tissue. [bib_ref] Hepatobiliary scanning with 99m Tc-PIPIDA in acute cholecystitis, Mauro [/bib_ref] [bib_ref] The rim sign: association with acute cholecystitis, Bushnell [/bib_ref] Non-visualized gallbladder with normal uptake and excretion of radioactivity Rim sign (augmentation of radioactivity around the gallbladder fossa).

## Severity assessment criteria of acute cholecystitis

## Concept of severity grading of acute cholecystitis
Patients with acute cholecystitis may present with a spectrum of disease stages ranging from a mild, self-limited illness to a fulminant, potentially lifethreatening illness. In these Guidelines we classify the severity of acute cholecystitis into the following three categories: "mild (grade I)", "moderate (grade II)", and "severe (grade III)". A category for the most severe grade of acute cholecystitis is needed because this grade requires intensive care and urgent treatment (operation and/or drainage) to save the patient's life. However, the vast majority of patients present with less severe forms of the disease. In these patients, the major practical question regarding management is whether it is advisable to perform cholecystectomy at the time of presentation in the acute phase or whether other strategies of management should be chosen during the acute phase, followed by an interval cholecystectomy. Therefore, to guide the clinician, the severity grading includes a "moderate" group based on criteria predicting when conditions might be unfavorable for cholecystectomy in the acute phase (level 2b-4). [bib_ref] Laparoscopic cholecystectomy for acute cholecystitis: can the need for conversion and the..., Brodsky [/bib_ref] [bib_ref] Conversion factors in laparoscopic cholecystectomy for acute cholecystitis, Teixeira [/bib_ref] [bib_ref] Laparoscopic cholecystectomy for acute cholecystitis: how do fever and leucocytosis relate to..., Halachmi [/bib_ref] [bib_ref] Laparoscopic versus open cholecystectomy for cholecystitis (200 cases). Comparison of results and..., Araujo-Teixeria [/bib_ref] [bib_ref] Factors associated with successful laparoscopic cholecystectomy for acute cholecystitis, Rattner [/bib_ref] [bib_ref] Gangrenous cholecystitis: analysis of risk factors and experience with laparoscopic cholecystectomy, Merriam [/bib_ref] Patients who fall neither into the severe nor the moderate group form the majority of patients with this disease; their disease is suitable for management by cholecystectomy in the acute phase, if comorbidities are not a factor. Defi nitions of the three grades are given below.

## Mild (grade i) acute cholecystitis
Mild acute cholecystitis occurs in a patient in whom there are no fi ndings of organ dysfunction, and there is mild disease in the gallbladder, allowing for cholecystectomy to be performed as a safe and low-risk procedure. These patients do not have a severity index that meets the criteria for "moderate (grade II)" or "severe (grade III)" acute cholecystitis.

## Moderate (grade ii) acute cholecystitis
In moderate acute cholecystitis, the degree of acute infl ammation is likely to be associated with increased operative diffi culty to perform a cholecystectomy (level 2b-4). [bib_ref] Laparoscopic cholecystectomy for acute cholecystitis: can the need for conversion and the..., Brodsky [/bib_ref] [bib_ref] Conversion factors in laparoscopic cholecystectomy for acute cholecystitis, Teixeira [/bib_ref] [bib_ref] Laparoscopic cholecystectomy for acute cholecystitis: how do fever and leucocytosis relate to..., Halachmi [/bib_ref] [bib_ref] Laparoscopic versus open cholecystectomy for cholecystitis (200 cases). Comparison of results and..., Araujo-Teixeria [/bib_ref] [bib_ref] Factors associated with successful laparoscopic cholecystectomy for acute cholecystitis, Rattner [/bib_ref] [bib_ref] Gangrenous cholecystitis: analysis of risk factors and experience with laparoscopic cholecystectomy, Merriam [/bib_ref] Severe (grade III) acute cholecystitis Severe acute cholecystitis is associated with organ dysfunction.

## Criteria for the severity assessment of acute cholecystitis
Acute cholecystitis has a better outcome/prognosis than acute cholangitis but requires prompt treatment if gangrenous cholecystitis, emphysematous cholecystitis, or torsion of the gallbladder are present. The progression of acute cholecystitis from the mild/moderate to the severe form means the development of the multiple organ dysfunction syndrome (MODS). Organ dysfunction scores, such as Marshall's multiple organ dysfunction (MOD) score, and the sequential organ failure assessment (SOFA) score, are sometimes used to evaluate organ dysfunction in critically ill patients. The Guidelines classify the severity of acute cholecystitis into three grades [fig_ref] Table 5: Criteria for severe [/fig_ref] : "severe (grade III)": acute cholecystitis associated with organ dysfunction, "moderate (grade II)": acute cholecystitis associated with diffi culty to perform cholecystectomy due to local infl ammation, and "mild (grade I)": acute cholecystitis which does not meet the criteria of "severe" or "moderate" acute cholecystitis (these patients have acute cholecystitis but no . Criteria for 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. Grade I can also be defi ned as acute cholecystitis in a healthy patient with no organ dysfunction and only mild infl ammatory changes in the gallbladder, making cholecystectomy a safe and low-risk operative procedure. organ dysfunction, and there are mild infl ammatory changes in the gallbladder, so that a cholecystectomy can be performed with a low operative risk). Almost unanimous agreement on the criteria was achieved [fig_ref] Table 6: Answer pad responses on the criteria for severe [/fig_ref]. When acute cholecystitis is accompanied by acute cholangitis, the criteria for the severity assessment of acute cholangitis should also be taken into account. Being "elderly" per se is not a criterion for severity itself, but indicates a propensity to progress to the severe form, and thus is not included in the criteria for severity assessment. Panelists from abroad (n = 21) 95% 5% 0% Japanese panelists (n = 21) 81% 19% 0% Audience (n = 68) 91% 9% 0%
[table] Table 1: Diagnostic criteria for acute cholecystitis Imaging fi ndings: imaging fi ndings characteristic of acute cholecystitis [/table]
[table] Table 2: Answer pad responses on the diagnostic criteria for acute cholecystitis [/table]
[table] Table 4: Criteria [/table]
[table] Table 5: Criteria for severe (grade III) acute cholecystitis "Severe" acute cholecystitis is accompanied by dysfunctions in any one of the following organs/systems 1. Cardiovascular dysfunction (hypotension requiring treatment with dopamine 5 g/kg per min, or any dose of dobutamine) 2. Neurological dysfunction (decreased level of consciousness) 3. Respiratory dysfunction (PaO 2 /FiO 2 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 ) [/table]
[table] Table 6: Answer pad responses on the criteria for severe (grade III) acute cholecystitis [/table]
[table] Table 7: Answer pad responses on the criteria for moderate (grade II) acute cholecystitis [/table]