You are in: eMedicine Specialties > Radiology > GASTROINTESTINAL Cholecystitis, AcuteArticle Last Updated: Jul 27, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia Ali Nawaz Khan is a member of the following medical societies: American Institute of Ultrasound in Medicine, Radiological Society of North America, Royal College of Physicians, Royal College of Physicians and Surgeons of the United States, Royal College of Radiologists, and Royal College of Surgeons of England Coauthor(s): Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; Tufail Ahmed Patankar, MBBS, FRCR, PhD, DMRD, DMRE, DNBE, Consulting Neuroradiologist and Interventional Neuroradiologist, Department of Neuroradiology, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust; Lalam Radhesh Krishna, MBBS, MRCS, Specialist Registrar, Department of Radiology, North Manchester General Hospital; Hemalatha Chandramohan, MBBS, Staff Physician, Department of Geriatric Medicine, Stepping Hill Hospital, United Kingdom; David Sherlock, MBBS, FRCS, Consulting Staff, Department of Surgery, North Manchester General Hospital, Christie Hospital; Ravi D Kadasne, MBBS, MD, Specialist in Radiology, Emirates International Hospital Editors: John L Haddad, MD, Clinical Associate Professor, Department of Radiology, Weill Medical College of Cornell University; Director of Body MRI, Department of Radiology, Methodist Hospital in Houston; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Arnold C Friedman, MD, FACR, Associate Chairman, Department of Radiology, University of Florida Health Science Center; Chief, Department of Radiology, Shands-Jacksonville Hospital; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; John Karani, MBBS, FRCR, Consulting Staff, Department of Radiology, King's College Hospital, London Author and Editor Disclosure Synonyms and related keywords: AC, AAC, acute acalculous cholecystitis, acalculous cholecystitis, necrotizing cholecystitis, emphysematous cholecystitis INTRODUCTIONSection 2 of 12
  BackgroundAcute cholecystitis (AC) occurs as a result of inflammation of the gallbladder (GB) wall usually secondary to cystic duct obstruction. In 90% of patients, AC is initiated by impaction of a calculus in the neck of the GB or in the cystic duct.22 Acute acalculous cholecystitis (AAC) represents inflammation of the GB in the absence of GB calculi. AAC occurs more commonly in children and adults who are critically ill or in those who have recently undergone stress in the form of severe trauma, burns, or major surgery. Acute emphysematous cholecystitis is characterized by the presence of gas within the wall and/or lumen of the GB. It occurs more commonly in diabetic men and less frequently in association with cholelithiasis. Emphysematous cholecystitis is considered either a complication of AC or a separate entity. For excellent patient education resources, see eMedicine's Liver, Gallbladder, and Pancreas Center. Also, visit eMedicine's patient education article Gallstones. PathophysiologyAC represents an acute inflammation of the GB caused in most instances by obstruction of the cystic duct, usually by a gallstone and resulting in acute inflammation of the GB wall. AC is one of the major complications of cholelithiasis. The inflammatory process begins with a calculous obstruction of the cystic duct or GB neck. The exact mechanism by which GB inflammation is initiated is unknown. Microorganisms can be identified in 80% of cases early in the disease onset; such organisms include primarily Escherichia coli, other gram-negative aerobic rods, enterococci, and a number of anaerobes. The bacterial invasion is not considered to be a primary event, because in 20% of patients, no bacterial growth occurs in surgical specimens.1 The general consensus is that bacterial infection is a secondary event, not an initiating one. Other factors that may initiate the inflammatory process include formation of inflammatory mediators (eg, lysolecithin and prostaglandins), as well as increased intraluminal pressure along with compromise of the blood supply and chemical irritation by bile acids. Spontaneous resolution of AC may occur within 5-7 days after onset of symptoms, because of reestablishment of cystic duct patency. In the majority of such cases, fibrotic wall thickening of the GB occurs, which is characteristic of chronic cholecystitis. In more than 90% of cholecystectomy specimens, the histologic pattern is AC superimposed on chronic cholecystitis. If the cystic duct patency is not reestablished, inflammatory cell infiltration of the GB wall follows, with the occurrence of mural and mucosal hemorrhagic necrosis. Gangrenous cholecystitis may be seen in as many as 21% of AC patients.2 Acalculous cholecystitis occurs in a different clinical setting, occurring more often in males, usually children and in those older than 65 years. The pathophysiology of acalculous cholecystitis is not well understood but is probably multifactorial. Systemic mediators of inflammation, localized or generalized tissue ischemia, and bile stasis probably work together. The population at risk for acalculous AC often has predisposing factors for bile stasis; such populations include patients with starvation, on parenteral nutrition, using narcotic analgesics, and lacking mobility in postoperative states. Hypovolemia and shock also predispose such patients to tissue ischemia, although ischemia may be a primary event causing acalculous AC, such as small-vessel vasculitis, or may be a complication of hepatic chemoembolization. Often, functional cystic duct obstruction is present and is related to inflammation and viscous bile. Extrinsic compression may also play a role in the development of bile stasis. The majority of patients with acalculous AC disease have secondary infection with gram-negative enteric flora3; however, in patients with typhoid fever, infection as a primary event has been identified with Salmonella organisms. AIDS-related cholecystitis and cholangiopathy may be secondary to cytomegalovirus (CMV) infection and infections with Cryptosporidium organisms. In patients who have emphysematous cholecystitis, ischemia of the GB wall is followed by infection with gas-forming organisms that produce gas in the GB lumen, in the GB wall, or both. In 30-50% of patients, preexisting diabetes mellitus is present, and the male-to-female ratio is 5:1.22 Gas may be confined to the GB; however, in 20% of cases, gas is also seen in the rest of biliary tree. Gallstones are not present in 30-50% of cases, and the mortality rate is 15%.22 There is a predisposition for gangrene formation and perforation, but clinical symptoms are mild, which can be deceptive. Emphysematous cholecystitis may occur after chemoembolization as palliation for hepatocellular carcinoma, following atheromatous embolism during aortography, and after GB hypoperfusion during cardiorespiratory resuscitation. The following factors have been associated with acalculous cholecystitis4:
Empyema of the GB may develop as a complication of AC. In AC, the GB is usually distended as a result of inflammatory cells mixed with bile and calculi. The bile becomes infected as the disease progresses. In 85% of patients, the cystic duct disimpacts, and the inflammation in the GB settles. If the cystic duct remains obstructed, the inflammatory process may progress to a GB empyema and eventually result in perforation. FrequencyUnited StatesBecause of the close relationship between gallstones and AC, the distribution and the incidence of AC follow that of cholelithiasis. Gallstones may be present in more than 20 million persons in the United States, resulting in 500,000 cholecystectomies annually. In 10-20% of patients, AC complicates the course of symptomatic gallstones.22 AAC accounts for 5-15% of cases of AC,22 with the incidence being higher in ICU patients, particularly those with burns and trauma. Most cases of AC in the ICU are acalculous, but in this setting, the overall incidence of acalculous AC is only 0.2%. In the majority of postoperative cases (90%), AC is acalculous.5 InternationalThe incidence rates of AC are approximately the same in Western Europe and the United States. Worldwide, the exact incidence is not known. Mortality/MorbidityThe AC mortality of 5-10% is mostly confined to patients older than 60 years. AC may be complicated by empyema, gangrenous cholecystitis, GB perforation, pericholecystic abscess, and bilioenteric fistula. Gangrenous cholecystitis is a frequent cause of GB perforation. Suppurative complications are more frequent in the elderly. Most localized perforations can be satisfactorily treated by means of surgery. Although free intraperitoneal perforation is rare, it is associated with a mortality of 25%. Necrosis of the GB wall occurs in about 60% of cases of acalculous cholecystitis because gangrene and perforation are frequent. Mortality can be as high as 9-66%.6 The higher mortality in AAC has been attributed to delayed diagnosis and comorbidities. The morbidity associated with emphysematous cholecystitis is also higher, because GB wall gangrene and perforation. Recurrent symptoms are common in patients with AC who are treated expectantly, and most patients need elective cholecystectomy. RaceBecause of the close relationship between gallstones and AC, the incidence of AC is expected to be higher in races with a higher incidence of gallstones. Such populations include Native Americans and persons of Chinese or Japanese descent. SexThe male-to-female ratio of AC is 1:3. AAC is more common in men than in women; the male-to-female ratio in AAC is 2-3:1. Acute emphysematous cholecystitis is also more common in men than in women. AgeAC affects all age groups, but the peak incidence is in persons aged 40-60 years. Approximately 50% of cases of AC in children are acalculous. AnatomyThe GB stores and concentrates bile, and the ducts function as a bile drainage system. The flow of bile through the bile ducts is affected by several factors, including hepatic secretory pressure, tone in the sphincter of Oddi, the rate of GB fluid absorption, and GB contraction. Anatomically, the GB is a pear-shaped musculomembranous reservoir lying in the GB fossa on the inferior aspect of the liver. The fundus of the GB lies close to the anterior abdominal wall and near the hepatic flexure of the colon. The surface marking of the GB fundus is in the region of the costal cartilage. At this point, it is covered by peritoneum, and its proximity to the hepatic flexure of the colon may obscure it. The body of the GB is adjacent to the duodenum, which indents and produces a frequent ultrasonographic artifact that mimics gallstones or a mass in the GB. An inflamed GB may perforate into the colon or duodenum because of the close proximity of the GB to these structures. The mucosa of the GB neck is thrown into folds, giving an echogenic appearance that may also mimic gallstones. A small pouch, known as the Hartmann pouch, projects from the right side of the GB neck. When visible, this finding is frequently associated with pathology, particularly dilatation. The GB fundus is often folded over, and the GB then assumes a double-barrel appearance. Pseudoseptation of the GB fundus caused by kinking or, occasionally, a true septum called the phrygian cap is seen in 2-6% of GBs. The phrygian cap is of no pathologic significance. A cystic artery supplies the GB, and it is usually a branch of the right hepatic artery. The artery lies in the triangle made by the liver, the cystic duct, and the common hepatic duct (CHD). Other, smaller tributaries supply the GB through the right hepatic artery via the GB bed through the liver. Usually, the right hepatic artery passes behind the CHD and the cystic artery crosses behind the cystic duct. In 25% of cases, the common hepatic artery passes in front of the CHD and the cystic artery in front of the cystic duct. Recognition of GB blood supply is gaining increased importance because of vascular intervention in the liver, particularly chemoembolization. Catheters should be placed distal to the cystic artery to prevent embolic material from entering the cystic artery and causing GB ischemia. Ultrasonographic anatomy The GB is a pear-shaped anechoic structure indenting the inferomedial aspect of the right lobe of the liver. A linear echogenic line representing fat in the main interlobar fissure is interposed between the GB and the right main portal vein. The GB mucosa is hyperechoic, the submucosa and the muscle layer are hypoechoic, and the serosal surface fatty layer is hyperechoic. A linear fold is present on the posterior GB wall at the junction of the body and neck. Called the junctional fold, this structure is of no pathologic significance. Sound waves from the spiral valve of the neck may cast an acoustic shadow and mimic a gallstone. The normal thickness of the GB wall is usually less than 3 mm. Provided that the patient has been fasting for 8-12 hours, visualization of the normal GB should be nearly complete. In a truly fasting patient, nonvisualization of the GB is a pathologic finding in 96% of patients. GB dimensions The normal GB usually measures 7-10 X 2-3.5 cm. In the fasting patient, the normal dimensions of the GB seldom exceed 4 X 10 cm. The size of the GB generally increases with age, but the GB wall thickness is unaffected by age. The normal wall thickness is 2-3 mm. Neonatal GB dimensions are 0.5-1.6 cm (mean, 0.9 cm) X 2.5 cm. The wall thickness is usually 1 mm. GB anomalies Many anatomic anomalies affect the GB. The recognition of these anomalies is important in the context of GB disease. Errors in GB surgery are frequently a result of the failure to appreciate variations in the anatomy of the biliary system. Anomalous positioning or orientation of the GB includes situs inversus when the GB is in the left upper quadrant. A GB in the left lobe of the liver without situs inversus is rare. Heterotaxia, which represents an intermediate situs with GB in the midline, may be associated with asplenia, polysplenia, pulmonary isomerism, and congenital heart disease. An anomalous orientation may be present when the GB is vertical or horizontal. It may descend into the right iliac fossa, particularly in the presence of the Riedel lobe. Unusual locations include intrahepatic, suprahepatic, lateral, anterior abdominal wall, and retrorenal sites. The GB may also be present in the thorax, in the falciform ligament and/or interlobular fissure, and in the transverse mesocolon. A wandering GB results when the GB is suspended on its own mesentery. Recognition of this anomaly is important because such a GB is prone to torsion. Agenesis is a rare anomaly found in 0.04-0.07% of autopsies. Agenesis may be associated with biliary atresia, imperforate anus, CHD, and common bile duct (CBD) anomalies. Rarely, the GB opens separately into the duodenum. The most common anomalous shape is due to the phrygian cap, in which the fundus of the GB is folded back on itself, producing a kink in the fundus. The GB may rarely appear as a diverticulum with no cystic duct. Other anomalies include a fishhook, a siphon, and an hourglass configuration. A diverticulum of the GB is extremely rare and usually located at the neck of the GB. This is rarely symptomatic unless it is complicated by calculus disease. Regarding GB duplication, true duplication is rare, but it has been reported in as many as 1 in 3000-4000 people, with a male-to-female ratio of 2:1. Triplication is even rarer, and it may be an incidental finding at autopsy. In duplication, each GB may have a separate cystic duct or there may be 1 shared cystic duct. A septate GB may have an isolated transverse septum. True duplication has a longitudinal septum. A multiseptate GB is extremely rare, with multiple loculi connected by small pores; patients with this condition are particularly prone to bile stasis and calculus formation. With an anomalous cystic duct insertion, the cystic duct may insert into the CBD or CHD high or low. The cystic duct is often intramural, running for some distance in the wall of the CBD within a common sheath. Congenital stenosis of the cystic duct is extremely rare, and it may be complicated by calculus disease. Heterotopic tissue may be present within the GB, where gastric or pancreatic tissue has been described within the GB wall. This tissue may mimic tumors. Clinical DetailsClinical findings AC usually occurs with right upper quadrant pain and tenderness. The abdominal pain increases with time. The site of pain is usually the right subcostal region, although the pain may begin in the epigastrium or the left upper quadrant and then shift to the right subcostal region to the area of the GB inflammation. Referred pain to the right shoulder or the interscapular region may be experienced. Approximately 70% of patients have had previous attacks of similar pain that spontaneously resolved. Anorexia, nausea, and vomiting may occur, but vomiting is seldom severe. Most patients are afebrile and have no leukocytosis. When fever occurs, the patient's temperature is seldom higher than 38°C. Chills are unusual, and their presence suggests a complicated cholecystitis (abscess or associated cholangitis). Palpation of the right subcostal area reveals muscle spasm. During deep inspiration, the tenderness becomes suddenly worse and produces an inspiratory arrest called the Murphy sign. The Murphy sign cab be elicited with an ultrasound probe. In approximately 35% of patients, a distended, tender GB may be palpable as a distinct mass. This is an important clinical finding and may confirm the diagnosis. Approximately 20% patients with AC may have mild jaundice, which may be related to common hepatic and/or bile duct edema or to the presence of calculi within the CBD.22 Most patients improve within 24 hours after hospitalization, and signs and symptoms gradually subside. However, persistent pain, fever and leukocytosis, chills, and more severe localized or generalized tenderness may indicate complicated disease such as abscess formation or GB perforation. The development of empyema of the GB can produce systemic toxicity, and it may be a predictor of GB perforation. Leukocytosis is pronounced with empyema and is usually in the range of 10,000-15,000/μL. The clinical differential diagnosis includes acute pancreatitis, perforated peptic ulcer, gonococcal perihepatitis (Fitz-Hugh-Curtis syndrome) in women, acute hepatitis, pneumonitis, pyelonephritis, cardiac disease, sickle cell crises, and leptospirosis. AAC is difficult to diagnose clinically. It occurs often in children (50%) and in patients who are critically ill or who have recently undergone stress from severe trauma, burns, or surgery. Predisposing factors include prolonged fasting, immobility, and hemodynamic instability. Often, these patients cannot express pain; however, fever, jaundice, vomiting, abdominal tenderness, leukocytosis, and hyperbilirubinemia should lead to a high index of clinical suspicion. Children with AAC more often present in the outpatient setting than in other settings, and they usually present with right upper quadrant pain in the absence of gallstones. These patients are usually treated by means of cholecystectomy. Some elderly patients have few signs during their initial presentation with AC. A minority of adult patients, mostly elderly patients with AAC, also present in the outpatient setting. These cases are diagnosed and treated early and are associated with a good prognosis. Causes
Preferred ExaminationClinically, few signs differentiate uncomplicated AC from complicated AC. Complications of AC may have serious clinical implications. These complications include perforation, pericholecystic abscess, and development of empyema and bilioenteric fistula. Therefore, radiologic imaging makes a substantial contribution to the differential diagnosis. Ultrasonography significantly aids in the diagnosis of AC, although most ultrasonographic signs are not typical but suggestive of AC. Inflammatory pericholecystic reaction in the GB fossa is better depicted with CT than with other techniques. Also, CT is useful in making the differential diagnosis when obesity or gaseous distention limits the use of ultrasonography. MRI can demonstrate the same morphologic changes as CT, displaying inflammatory changes in the GB wall, pericholecystic fat, and intrahepatic periportal tissues. Plain radiography greatly contributes to the diagnosis of emphysematous pyelonephritis, and ultrasonographic and CT scan results can further confirm the diagnosis (although CT scanning is not strictly needed to make the diagnosis). Cholescintigraphy is an extremely sensitive diagnostic modality in diagnosing AC, although the findings are nonspecific. Oral cholecystography is of historical interest and has no role in the diagnosis of AC. Arteriography is seldom required for AC. Limitations of TechniquesPlain radiographic findings may be entirely normal. Radiolucent calculi are visible. Opaque calculi in the right upper quadrant on plain abdominal radiographs may be an incidental finding and is not necessarily related to AC. Oral cholecystography is of historical interest and has a low sensitivity and specificity in the diagnosis of AC. The main features of AC on ultrasonography are all nonspecific findings. Examples include GB thickening, calculi in the GB, a positive ultrasonographic Murphy sign, and pericholecystic fluid. The sonographic Murphy sign is negative in as many as 70% of patients with AC. In a perforated GB, the wall of the GB is not well delineated, and a localized interruption of the wall may not be noted at the site of perforation. Ultrasonography has problems in making the diagnosis in obese patients and in patients with gaseous distention. The technique remains operator dependent. CT exposes the patient to a radiation burden, which may not be necessary. Arteriography is invasive and is seldom indicated. MRI has a limited availability; it is expensive; and it has problems in making the diagnosis in patients with certain prosthetics, surgical clips, cardiac pacemakers, or claustrophobia. Although cholescintigraphy is sensitive, it has a low specificity and involves the use of ionizing radiation. DIFFERENTIALSSection 3 of 12
Cholecystitis, Acalculous Cholelithiasis Pancreatitis, Acute Other Problems to Be ConsideredCholangitis
RADIOGRAPHSection 4 of 12
FindingsIn AC, an acute plain abdominal radiograph is obtained primarily to exclude other diagnoses. Entities such as empyema of the GB and gallstone ileus can be suggested on plain radiographs. Likewise, porcelain GB and milk-of-calcium bile have fairly characteristic appearances. The plain radiograph may also reveal dilated loops of the small bowel in the right upper quadrant; these may mimic small-bowel obstruction. Rarely, the GB is identified as a soft-tissue mass. On abdominal plain radiographs, the following signs should be assessed: opacities projected over the GB, linear calcifications in GB walls, GB enlargement, focal gas collections within the GB, and air-fluid levels in the GB lumen. Plain radiographs may reveal gallstones, which are known to be radiopaque in 15-20% of patients.7 Gallstones appear as single or multiple, pyramidal, faceted, or cuboidal calcifications located in the right upper quadrant. Calcification may be central, homogeneous, or rimlike. When multiple gallstones are seen, the stones are clustered and usually faceted. On erect images, stones may be layered in the dependent portion of the GB. Occasionally, stellate radiolucencies are seen in the area of GB. These reflect gas-containing fissures within the GB calculi. This finding is referred to as the Mercedes-Benz sign. Gas in the GB wall or lumen is a feature of emphysematous cholecystitis. Calcification of the GB wall, or porcelain GB, may be seen as an indicator of chronic cholecystitis. A high calcium content in the biliary sludge, or limy bile, is also a feature of chronic cholecystitis. Gas may be seen in the bile ducts in cystocutaneous or cystoenteric forms with fistulous complications. The gallstone may pass through such a fistula into the gut and cause gallstone ileus. The stone usually has to be 25 mm in diameter to cause ileus. The ileum near the ileocecal junction is the most common site. Emphysematous cholecystitis may occur as a complication of AAC in more than 50% of cases. Air is readily seen on plain abdominal radiographs. On upright radiographs, if obtained, an air-fluid level in the right upper quadrant may be seen. This finding represents gas within the GB lumen admixed with inflammatory fluid and/or sludge. Air within the wall of the GB appears more curvilinear. Gas visualized in the GB in the setting of AAC is highly associated with complications such as gangrene and perforation. The use of oral cholecystography is largely historical, and it has no role in the diagnosis of AC. Nonvisualization of the GB is seen in the obstructed cystic duct. In patients who have recovered from an episode of AC, an oral cholecystogram may show single or multiple lucent-filling defects due to calculi in an opacified GB. These usually are gravity-dependent; however, stones with a high cholesterol content and those containing air may float. Mobility is demonstrated by a change in the position on supine and upright images. Compression images may be necessary to displace bowel gas. Degree of ConfidencePlain abdominal radiographic findings are nonspecific in patients with GB disease and are not useful in differentiating between biliary colic and AC. The role of plain radiography has been superseded by ultrasonography. Nevertheless, it still retains its specific value when the GB is not definitively identified with sonography. Emphysematous cholecystitis can be recognized easily on plain films. Sonography can be used in cases in which calcifications in the right upper quadrant are not typical in appearance or location. Oral cholecystography has no role to play in the diagnosis of AC. However, in a more chronic setting in the detection of gallstones, the described findings are characteristic and no further imaging is required. Oral cholecystographic assessment of the number and size of gallstones is more accurate than sonography. The accuracy of oral cholecystography in the detection of gallstones is 85-90%.8 False Positives/NegativesAs seen on plain abdominal radiographs, small-bowel dilatation in the right upper quadrant caused by AC may be confused with small-bowel obstruction. The differential diagnosis for gallstones include renal calculi, which are related to renal outline and which can be separated on oblique images if necessary. Only 50% of pigment stones and 20% of cholesterol stones contain sufficient calcium to be visible on plain radiographs. Gas in the biliary system must be differentiated from abscess or gas-forming collections in the GB fossa. Ultrasonography may prove useful in such cases. Porcelain GB is characteristic in appearance, presenting as eggshell calcification in the right upper quadrant. Other right-upper-quadrant calcifications, such as hepatic granulomas, tumor calcification, costal cartilage calcification, calcified mesenteric lymph nodes, and hepatic or renal artery aneurysms, are rarely confused with GB calculi. A nonmobile filling defect on an oral cholecystogram may be an adherent stone but must be differentiated from polyps, adenomyomas, or, rarely, primary or metastatic tumors, heterotopic gastric mucosa, or pancreatic mucosa. Calcified stones may be obscured by contrast material in the GB. Nonvisualization of the GB may have various causes, including drug-compliance failure or a change of drugs, intestinal resections, liver diseases, poor timing, cholestasis, and acute pancreatitis. CT SCANSection 5 of 12
FindingsThe CT findings of AC include the following: gallstones within the GB and or cystic duct; more than 3 mm of focal or diffuse thickening of the GB wall in a noncontracted GB; indistinct liver-GB interface; fluid in the GB fossa in the absence of ascites; enlargement of the GB, with a transverse diameter of more than 5 cm; infiltration of the surrounding fat; increased bile attenuation due to biliary sludge; and GB mucosal sloughing. A low-attenuating ring surrounding the GB may be indicative of edema of the outer layer of the GB wall, or it may suggest the accumulation of fluid in the GB fossa. In hemorrhagic cholecystitis, the attenuation values of the GB contents may be abnormally elevated. Contrast-enhanced CT shows enhancement of the GB wall and the adjacent liver. Inflammatory reaction in the pericholecystic fat is well seen on contrast-enhanced CT scans. This is a specific CT sign for AC. The inflammatory reaction is seen as streaky or bandlike soft-tissue areas of attenuation extending from the GB wall into the surrounding fat. CT may be useful in the diagnosis of acalculous cholecystitis by showing the various signs described. However, CT may be difficult to perform because of the patients' poor condition. CT can demonstrate intramural and intraluminal air within the GB in emphysematous cholecystitis better than a plain abdominal radiograph. However, CT is not strictly needed for the diagnosis. CT signs in AC may be classified into major and minor criteria. The diagnosis of AC requires the presence of 2 major or 1 major and 2 minor criteria. This classification is particularly helpful in the diagnosis of acalculous AC. Major criteria include the following: (1) GB wall thickening greater than 3 mm, (2) a halo surrounding the GB because of edema of the GB, (3) extension of inflammation to the GB fossa, (4) pericholecystic fluid in the absence of ascites, (5) GB mucosal sloughing, and (6) intramural GB gas. Minor criteria include GB dilatation, with the transverse diameter greater than 5 cm and sludge in the GB. Degree of ConfidenceMucosal sloughing and intramural gas are specific signs of AC, but these are seen infrequently. The reported sensitivity and specificity of CT findings are 90-95%. CT is more sensitive than ultrasonography in the depiction of a pericholecystic inflammatory response and in localizing pericholecystic abscesses, pericholecystic gas, and calculi outside the GB lumen. False Positives/NegativesCT features of complicated AC can mimic those of GB carcinoma. The features that are confused with a carcinoma include diffuse or focal thickening of the GB wall and inflammatory infiltrate of the surrounding fat. MRISection 6 of 12
FindingsIn AC, MRI can depict the same pathologic features as CT does. Increased blood flow and capillary leakage due to inflammatory change are best reflected by using gadolinium enhancement, particularly with fat-suppression techniques. Various morphologic changes may be observed. T1-weighted gadolinium-enhanced images show prominent enhancement along the mucosal layer of the GB wall, which progresses to involve the whole thickness of the GB wall on delayed images. A greater than normal degree of enhancement of the GB wall is well correlated with the presence of AC. GB wall thickening is well depicted on both T1- and T2-weighted images. Transient liver enhancement is shown on immediate postgadolinium images, particularly T1-weighted and fat-suppressed images of the GB fossa. GB calculi are well seen on T2-weighted images, as is pericholecystic fluid. Intramural abscesses appear as high signal foci on T2-weighted and fat-suppressed images. Periportal high signal intensity is a nonspecific finding that is occasionally seen. In hemorrhagic cholecystitis, which is more common with acalculous cholecystitis, the blood breakdown products can be identified on nonenhanced MRIs. Because of the specific signal-intensity characteristics of blood products on T1- and T2-weighted images, the age of the hemorrhage can be determined. A magnetic resonance cholangiopancreatography (MRCP) protocol may show calculi in the GB, cystic duct, and CBD. Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape. Degree of ConfidenceGadolinium-enhanced MRI techniques have higher sensitivity and accuracy in the diagnosis of AC than ultrasonographic techniques. The MRI techniques can also detect pericholecystic fluid with greater accuracy than ultrasonography can. CBD calculi can be detected with much greater sensitivity with MRI than with ultrasonography. False Positives/NegativesA multitude of causes of increased thickness of the GB wall are known (see Ultrasound). Both GB polyps and gallstones may float and appear as signal voids. However, unlike gallstones, polyps may be enhanced with the use of a gadolinium-based contrast agent. Contrast enhancement may also occur with chronic cholecystitis, but mural enhancement is more pronounced on delayed images than on other images, and pericholecystic enhancement is minimal. ULTRASOUNDSection 7 of 12
FindingsSonographic features of AC include the following:
In children, AC may be acalculous, with increased GB-wall thickening, signs of hydrops, a positive sonographic Murphy sign, and an increased diameter of the CBD with sludge. In empyema of the GB, ultrasonography may reveal calculi within the lumen of the GB. Occasionally, the impacted calculus may be identified. The GB may be distended and tender to pressure from the sonographic probe. Within the GB lumen, gravity-dependent layering of pus, debris, or bile may be observed. Particulate matter may appear as bright medium-to-coarse echoes without shadowing. With acute emphysematous cholecystitis, gas in the lumen of the GB is hyperreflective, with a distal reverberation artifact in the GB lumen. Intramural gas is characterized by hyperreflective foci in the GB wall with or without a reverberation artifact. An effervescent GB may be seen, with a large number of bubbles rising like gas bubbles in a glass of champagne from the dependent part of the GB. The differential diagnosis includes other causes of pneumobilia. The ultrasonographic diagnostic criteria for the diagnosis of AC can be classified into major and minor criteria. Two major or 1 major and 2 minor criteria need to be present to achieve a diagnosis. This classification is particularly useful with AAC. The major criteria include (1) GB-wall thickening of more than 3 mm, (2) a striated GB wall, (3) a positive sonographic Murphy sign, (4) mucosal sloughing, (5) pericholecystic fluid, and (6) intramural gas. Minor criteria include sludge within the GB and GB dilatation greater than 5 cm in its transverse diameter. Degree of ConfidenceIn the diagnosis of AC, ultrasonography is rapid, noninvasive, affordable, and sensitive. Because ultrasonography can be performed at the bedside, it is particularly useful in making the diagnosis of AC in hospitalized patients, who may be very ill; dependent on a respirator; or recovering from surgery or various medical problems. The sensitivity and specificity of ultrasonography in the diagnosis of AC are 81-100% and 60-100%, respectively.9 False Positives/NegativesUltrasonography may be inaccurate in the diagnosis of AC in hospitalized patients, especially in patients who have acalculous cholecystitis. None of the sonographic criteria for diagnosing AC (eg, cholelithiasis, thickened GB wall, nonshadowing echoes, sonolucent stripes, pericholecystic fluid) are specific. Differentiating acute cholecystitis from chronic cholecystitis is possible in only 26% of patients. In 74% of patients, therefore, ultrasonography cannot differentiate between acute and chronic cholecystitis. AC is presumed to be present if there is no other apparent cause of abdominal pain on ultrasound. The ultrasonographic Murphy sign is present in only 33% of patients with acute gangrenous cholecystitis. When gas is prominent, the GB in emphysematous cholecystitis may be mistaken for a bowel loop because of increased echogenicity and shadowing. The following are causes of increased GB wall thickness4:
Mimics of gallstones include the following4:
Nonshadowing mobile intraluminal GB masses may be present4:
The concentration of bile in the fasting patient may give rise to sludge formation. This is slightly echogenic and does not cause shadowing, but it may form a bile/sludge level. The biochemical nature of sludge has been recognized to be predominantly aggregates of cholesterol crystals and liquid crystalline droplets. In some cases of obstructive jaundice and symptomatic liver disease, it is composed of bilirubin granules embedded in a gel matrix of mucous glycoproteins. Biliary sludge is often associated with biliary stasis, as with parenteral nutrition, fasting, pregnancy, and mucous hypersecretion (eg, mucin-secreting bile duct tumors). In most patients, the presence of sludge is a transient phenomenon; as the patient's condition improves, the sludge resolves. If the lumen of the GB is completely filled with sludge that has an echogenicity similar to that of the liver, the GB may not be seen; this process is called hepatization. Causes of pericholecystic fluid may include the following4:
The lack of findings associated with AC and a clinical picture not suggestive of acalculous cholecystitis should suggest the possibility of other causes of pericholecystic fluid. NUCLEAR MEDICINESection 8 of 12
FindingsTechnetium-99m iminodiacetic acid (99mTc-IDA) agents (disofenin and mebrofenin) are routinely used to perform cholescintigraphy. After the intravenous injection, these compounds are rapidly bound to plasma proteins and transported to the liver. There, the IDA compounds dissociate from their protein binding. After dissociation, the compounds are taken up by the hepatocytes through a carrier-mediated non–sodium-dependent membrane transport mechanism. This is the same pathway as that of bilirubin. Therefore, when the serum bilirubin level increases, competition for the carrier molecules occurs, and biliary excretion of IDA compounds is diminished. Unlike bilirubin, IDA compounds do not undergo conjugation in the hepatocytes, and they are rapidly excreted into the bile. The compounds enable excellent visualization of the bile ducts and GB within 30-60 minutes. Because AC is initiated by cystic duct obstruction, nonvisualization of the GB after the intravenous injection of 99mTc-IDA is better correlated with AC than is the detection of gallstones. Normally, the GB is visualized within 60 minutes after tracer injection. Visualization of the GB establishes cystic duct patency and excludes AC with only rare exceptions. Nonvisualization of the GB 3-4 hours after the injection because of cystic duct obstruction is characteristic of an AC. Alternatively, morphine infusion can be used to shorten the examination time. Morphine increases tone in the sphincter of Oddi, increases CBD pressure, and results in a pressure differential between the CBD and the GB; this promotes tracer entry into the GB. Nonvisualization of the GB 30 minutes after the morphine infusion suggests AC cholecystitis in the appropriate clinical setting. The rim sign indicates inflammatory spread into the adjacent liver parenchyma, and this is usually a sign of complicated AC in which GB gangrene has set in with or without perforation. In one study, radionuclide angiography and cholescintigraphy were performed with a bolus injection of 99mTc-disofenin in 65 patients with clinically suspected AC. AC was surgically confirmed in 23 of 25 patients who had positive radionuclide angiographic findings (a positive result was indicated by increased blood flow to the GB fossa). Severe AC and abscesses were present in 3 patients with a scintigraphically visible GB but with positive angiographic findings. All 20 patients who had positive findings on radionuclide angiography and cholescintigraphy had transmural cholecystitis. Of the 9 patients with AC and false-negative angiographic findings, none had abscess or gangrene of the GB. Radionuclide angiography may therefore allow the determination of AC severity. In one study, 9 of 25 patients with positive findings had gangrenous cholecystitis or a pericholecystic abscess. Positive findings on radionuclide angiograms may also shorten the patient examination, and delayed images (>1 h) may not be necessary. Gallium-67 (67Ga) has been shown to accumulate in both inflammatory and infective processes. In one study of 10 patients with cholecystitis examined with 67Ga scanning, images in 5 patients with AC showed significant accumulation in the GB. Degree of ConfidenceCholescintigraphy is highly sensitive in the diagnosis of AC, and it is especially valuable when ultrasound results are equivocal. The negative predictive value of a normal cholescintigram is greater than 98%.10 The rim sign is not sensitive (35% sensitivity), but it is reasonably specific for complicated cholecystitis; however, the specificity is not high enough to obviate delayed or postmorphine images.10 In a meta-analysis, cholescintigraphy displayed a sensitivity of 97% and a specificity of 90% for AC, as compared with 91% sensitivity and 79% specificity for ultrasonography. Although cholescintigraphy is more accurate than ultrasonography, the latter has the advantages of evaluating all the abdominal structures (possibly arriving at an alternative diagnosis in patients with right-upper-quadrant pain without AC). In patients who do have AC, ultrasonography can provide anatomic information regarding gallbladder size, stone size, gallbladder wall, and bile duct size. Cholescintigraphy is less accurate in diagnosing acalculous AC than it is in diagnosing calculous AC. Sensitivities are 68-100%; specificities, 38-100%. Morphine administration may be particularly helpful in preventing false-positive results in patients with suspected acalculous AC. Use of cholecystokinin before the study empties viscous bile from the gallbladder and helps prevent false-positive results. Although 67Ga scanning is noninvasive, it has not found acceptance in the diagnosis of AC. False Positives/NegativesSpontaneous resolution of an AC may occur in 5-7 days after onset of symptoms because of reestablishment of cystic duct patency. In such circumstances, cholescintigraphy may result in normal visualization of the GB. In a small number of patients with acalculous cholecystitis, the GB visualization may be normal. Most patients with AAC, however, have a functional cystic duct obstruction due to vasculitis or edema; therefore, GB visualization is unusual. The presence of tracer in the duodenal cap, dilated cystic duct, or duodenal diverticulum may be misinterpreted as GB filling. Chronic cholecystitis may appear identical to AC. Only 4-8% of GBs are not visualized, especially in symptomatic patients with chronic cholecystitis. False-positive results with hepatic iminodiacetic acid (HIDA) scanning (eg, lack of GB visualization) are possible with the following:
Serial 67Ga scanning is needed to rule out gallium accumulation in the hepatic flexure of the colon, which is a potential false-positive result. The accumulation of 67Ga has also been reported in chronic cholecystitis. ANGIOGRAPHYSection 9 of 12
FindingsPatients with AC are rarely examined with angiography. Described angiographic findings are historical. Marked hypervascularity with dilatation of the cystic artery may be observed, but the inflammatory process also acquires blood from the right hepatic arterial supply. Arterial blush is present with increased accumulation of contrast material in the GB, the GB fossa, and the associated inflammatory mass. In the subacute phase of disease, the hypervascularity persists, but parenchymal accumulation of contrast material may occur early and may be prominent, demonstrating a thickened GB wall. GB veins are seldom seen with a normal GB, but in the subacute stage of AC, the GB veins may be particularly prominent. Degree of ConfidenceAngiography has no role in the diagnosis of AC. Angiography is an invasive procedure, and there are risks associated with the contrast material and radiation exposure, as well as other complications. False Positives/NegativesEmpyema of the GB, which may arise de novo or as a complication of AC, can have angiographic findings similar to those of subacute AC. INTERVENTIONSection 10 of 12
Diagnostic aspiration of the GB Acalculous cholecystitis poses a difficult diagnostic and therapeutic dilemma. It often complicates a serious illness in an already hospitalized patient, and the diagnosis is often overlooked. Percutaneous aspiration of GB bile has been suggested as a means of diagnosis in such patients. The technique involves the transhepatic passage of a 22-gauge needle under ultrasonographic guidance into the GB. Accurate needle-tip placement in the GB is ascertained with the gentle aspiration of bile. The bile is sent for Gram staining and culturing. A Gram stain showing 1 or more bacteria and 1 or more leukocytes and positive bile cultures suggest the diagnosis. A specificity of 87% has been reported for Gram stains and bile cultures, but the sensitivity is low. On the whole, GB bile aspiration is of limited use in the diagnosis of AC. Two reasons have been quoted for the low sensitivity of GB bile aspiration: First, most patients with suspected acalculous cholecystitis are already taking systemic antibiotics that can possibly render their bile cultures negative. Second, in AC, the GB wall may be inflamed but no leukocytes or bacteria may be present in the bile in the early stages of AC. GB aspiration has also been used in the treatment of AC in noncritically ill patients who are at high surgical risk. Chopra et al evaluated GB aspiration and percutaneous cholecystostomy in 53 patients with AC who were at high surgical risk but were not critically ill. There were no significant differences found in the primary clinical outcome measures between those patients who were treated with GB aspiration and those who underwent percutaneous cholecystostomy. The authors recommend that GB aspiration be considered the procedure of choice in high-risk patients with AC who are not critically ill, and they suggest that percutaneous cholecystostomy be reserved as a salvage procedure in cases in which GB aspiration is technically or clinically unsuccessful.11 Emergency percutaneous cholecystostomy Percutaneous cholecystostomy is most often performed in AC patients who are poor surgical risks. Such patients are often hospitalized with major medical or surgical problems, and their existing illness may be complicated by acalculous cholecystitis. Surgical cholecystostomy has been shown to be a valuable technique in achieving decompression of the inflamed GB until the patient's condition allows definitive surgery, but the technique is not without complications. Percutaneous cholecystostomy allows decompression of the inflamed GB and provides a potential route for stone extraction. The GB is localized by sonography or fluoroscopy after oral administration of contrast material. CT-guided access may be of value if no sonographic window is found. Debate continues regarding the extrahepatic approach versus the transhepatic approach, which depends on anatomy and whether stone extraction is planned. A transhepatic route is associated with less risk of bile leakage and catheter dislodgement and increases the likelihood of accessing the nonperitoneal bare area of the liver, whereas a subhepatic or transperitoneal approach provides a more favorable route when stone extraction is planned. The GB is punctured by using a Seldinger technique with traction dilatation and a 12F or 14F catheter placement over a stiff guidewire. Alternatively, a trocar technique with a smaller catheter system may be used. The trocar technique with a smaller catheter is preferred when stone extraction is not planned and when the objective is decompression of the GB at the patient's bedside. A locking pigtail catheter is preferred because it provides anchorage and prevents catheter dislodgement. The procedure is performed with the patient under diazepam or midazolam sedation and local anesthesia. After catheter placement, bile is withdrawn. The final catheter placement is confirmed by ultrasonography, but if doubt exists, iodinated contrast material is gently injected via the catheter and a radiograph is obtained. A forceful or high-volume injection of contrast material poses the risk of ascending cholangitis. After its placement, the catheter is left to drain freely. Flushing with sodium chloride solution may improve catheter patency. Contraindications to percutaneous cholecystostomy include coagulopathy that cannot be corrected and massive ascites that cannot be drained. Complication rates are low, and complications include procedure-related death (<0.5%), vagal reactions, catheter dislodgement, catheter misplacement, bile leakage, delayed GB rupture, and hemorrhage. Definitive percutaneous cholecystostomy Initially, percutaneous cholecystostomy was used as a stopgap procedure to help patients recover from a serious underlying illness. However, in some cases, the procedure has been performed as definitive treatment for patients who are poor candidates for surgery. Both patients with calculous AC and patients with acalculous AC have been treated by percutaneous cholecystostomy. Percutaneous cholecystostomy in GB perforation Percutaneous cholecystostomy has been used as a temporizing procedure in patients with GB perforation. In some patients, no further treatment was required after the procedure. Medical/Legal Pitfalls
Special Concerns
MULTIMEDIASection 11 of 12
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