Acalculous Cholecystitis

Published on 19/07/2015 by admin

Filed under Radiology

Last modified 22/04/2025

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 Findings identical to calculous cholecystitis (except gallstones)

image Thickening of gallbladder wall > 3 mm
image Positive sonographic Murphy sign

– May be absent or impossible to elicit in critically ill patients at highest risk
image Gallbladder distention (> 5 cm in transverse plane)
image Gallbladder wall hyperemia on color Doppler
• CT and MR

image Gallbladder wall thickening (> 3 mm) with mural/mucosal hyperenhancement

– May be associated with intramural lucency on CT caused by wall edema (subserosal halo sign)
image Dilated gallbladder (> 5 cm) with pericholecystic fluid and fat stranding
image Hyperenhancement of liver adjacent to gallbladder
• Hepatobiliary scintigraphy

image Nonvisualization of gallbladder 4 hours after injection of radiotracer (or 30 minutes after morphine)

TOP DIFFERENTIAL DIAGNOSES

• Acute calculous cholecystitis
• Gallbladder wall edema
• Hyperplastic cholecystoses
• Gallbladder carcinoma
• AIDS cholangiopathy

PATHOLOGY

• Not associated with obstruction of cystic duct by stones
• Most often result of bile stasis and gallbladder ischemia
• Typically occurs in critically ill patients (trauma, surgery, sepsis, mechanical ventilation, immunosuppression, etc.)

CLINICAL ISSUES

• Higher risk of morbidity/mortality compared to calculous cholecystitis with ↑ risk of complications

image More likely than calculous cholecystitis to present atypically
image Insidious presentation in critically ill patients and diagnosis is often delayed
• Preferred treatment: Cholecystectomy and broad spectrum intravenous antibiotics
• Cholecystostomy used as bridge to definitive cholecystectomy in critically ill, unstable patients
image
(Left) Coronal CECT in a critically ill ICU patient demonstrates severe gallbladder (GB) wall thickening and edema with pericholecystic fat stranding and fluid. Note the lack of clear enhancement of the GB wall near the fundus image, concerning for gangrenous cholecystitis.

image
(Right) Coronal CECT acquired a day later shows placement of a cholecystostomy tube image, a common temporizing measure in critically ill patients too unstable for cholecystectomy.
image
(Left) CECT of a diabetic septic female 4 days post laparotomy for a perforated duodenal ulcer shows a distended GB, wall thickening image, and pericholecystic fat infiltration image. No gallstones were identified at ultrasound.

image
(Right) Hepatobiliary scan of the same patient shows progressive small bowel filling image but no GB activity 30 minutes post tracer administration. No GB activity was shown after morphine administration (an observation that increases exam specificity).

TERMINOLOGY

Definitions

• Acute inflammation of gallbladder (GB) unrelated to gallstones

IMAGING

General Features

• Best diagnostic clue

image Combination of imaging features and clinical history

– Ultrasound: Distended GB with wall thickening, pericholecystic fluid, and positive sonographic Murphy sign but no gallstones
– Hepatobiliary scintigraphy: Nonvisualization of GB
– Typical clinical history: Critically ill patient

Ultrasonographic Findings

• Findings identical to acute calculous cholecystitis (except for absence of gallstones)

image Ultrasound often equivocal due to inability to elicit sonographic Murphy sign in intubated/unconscious patients
• Thickening of GB wall > 3 mm

image Higher thresholds increase specificity, but decrease sensitivity

– Using cutoff value of 3 mm leads to better sensitivity but lower specificity
– Using cutoff value of 4 mm (or 5 mm) leads to better specificity at the cost of having more false-negative cases
image Striated appearance of wall is common (no longer thought to be suggestive of gangrenous cholecystitis)
• Positive sonographic Murphy sign (pain with insonation over GB that is accentuated with deep breathing)

image May be absent or impossible to elicit in critically ill ICU patients at highest risk for acalculous acute cholecystitis
• GB distention (> 5 cm in transverse plane)
• Pericholecystic echogenic fat (due to inflammation)
• GB wall hyperemia on color Doppler images
• Complications

image Gangrenous cholecystitis: Asymmetric wall thickening, intraluminal linear membranes, and echogenic material due to sloughed mucosa and irregularity/ulcerations of GB wall

– May not be associated with wall hyperemia due to necrosis
image Emphysematous cholecystitis: Intramural and intraluminal gas with multiple bright echogenic reflectors and “dirty” posterior acoustic shadowing

– Champagne sign: Tiny, nonshadowing echogenic foci rising up in real-time from dependent portion of GB
image Perforated GB: Collapsed GB with discrete wall defect and adjacent pericholecystic fluid collection ± complex fluid in peritoneal cavity

– Most common site of perforation is fundus, which can be difficult to visualize in some patients
– Sonographic hole sign: Visualization of defect in GB wall is more easily diagnosed on CT
image Hemorrhagic cholecystitis: Echogenic clot within GB

CT Findings

• Imaging findings are identical to acute calculous cholecystitis (except for absence of gallstones)
• Uncomplicated acalculous cholecystitis

image GB wall thickening (> 3 mm) with mural and mucosal hyperenhancement

– May be associated with intramural lucency caused by wall edema (subserosal halo sign)
image Pericholecystic fluid and fat stranding
image Hyperenhancement of liver adjacent to GB (most apparent in arterial phase)
image Dilated GB (> 5 cm in diameter)
• Complicated acalculous cholecystitis

image Gangrenous cholecystitis: Hypoenhancement or nonenhancement of portions of GB wall

– May be associated with small sites of ulceration or outpouchings in GB wall
– Often associated with asymmetric wall thickening
– Intraluminal linear strands due to sloughed mucosa
image Emphysematous cholecystitis: Intramural or intraluminal gas with other findings of cholecystitis
image Hemorrhagic cholecystitis: High-density blood within GB ± blood in intrahepatic/extrahepatic ducts

– May be associated with active extravasation (usually best visualized on arterial phase)
image GB perforation: Collapsed GB with pericholecystic fluid collection &/or free fluid in peritoneal cavity

– Usually fluid collections are directly contiguous with site of nonenhancement in GB wall

MR Findings

• Distended GB with wall thickening, pericholecystic fluid, and surrounding fat stranding
• Hyperenhancement of GB wall on T1WI C+ images ± hyperenhancement of adjacent liver surrounding GB fossa  (rim sign)

image Interrupted rim sign with sites of nonenhancement of GB wall in gangrenous cholecystitis

Nuclear Medicine Findings

• Hepatobiliary scintigraphy

image Nonvisualization of GB 4 hours after injection of radiotracer or 30 minutes after morphine

– May be associated with rim sign: Increased uptake in liver adjacent to GB fossa due to reactive hyperemia
image Frequent false positives in critically ill patients due to GB dysfunction, prolonged fasting, hyperalimentation, bile stasis, and sludge

– False-positive rate reduced with reimaging after injection of morphine

Imaging Recommendations

• Best imaging tool

image Combination of ultrasound and hepatobiliary scintigraphy

– Ultrasound useful as initial screening tool, with hepatobiliary scintigraphy utilized in patients with equivocal ultrasound
• Protocol advice

image Sequential ultrasound examinations may improve ultrasound specificity
image Morphine increases specificity of cholescintigraphy

DIFFERENTIAL DIAGNOSIS

Acute Calculous Cholecystitis

• Imaging findings are identical, except for presence of gallstones

Gallbladder Wall Edema

• Multiple underlying causes, including cirrhosis, congestive heart failure, ascites, hypoalbuminemia, hepatitis, etc.
• Nonspecific finding which is present in many ICU patients due to concurrent comorbidities and illnesses
• Clinical history and additional imaging (hepatobiliary scintigraphy) may be needed to differentiate from acalculous cholecystitis

Hyperplastic Cholecystoses

• Adenomyomatosis: Different population with no underlying risk factors and no signs of sepsis or fever
• Rokitansky-Aschoff sinuses can mimic microabscesses
• Sites of wall thickening often associated with “comet tail” artifact on ultrasound

Gallbladder Carcinoma

• Eccentric GB wall thickening, invasion of adjacent liver, and enlarged regional lymph nodes

AIDS Cholangiopathy

• GB wall thickening ± bile duct strictures

PATHOLOGY

General Features

• Etiology
• Not associated with obstruction of cystic duct or GB neck by stones or sludge

image Most often due to bile stasis and GB ischemia
image Rarely GB involved in setting of systemic infection

– Common pathogens: Candidiasis, leptospirosis, salmonella, cholerae
image Very rarely due to non-stone-related obstruction of cystic duct (e.g., lymph node, hemobilia, choledochal cyst, etc.)
• Pathophysiology

image Predisposing risk factor(s) → bile stasis in GB → alteration in chemical composition of bile → local inflammatory response in GB wall → mucosal injury
image GB ischemia due to hypotension, dehydration, vasoactive drugs resulting in bile stasis
image Reperfusion injury after ischemia may also play role
• Risk factors (most patients have multiple risk factors)

image Major trauma and burn injuries
image Major surgery (↑ risk for colorectal/gastric surgery)
image Sepsis, hypotension, and mechanical ventilation
image Immunosuppression
image Total parenteral nutrition (TPN) and fasting
image Diabetes mellitus, coronary artery disease, and end-stage renal disease
image Childbirth
image Cholesterol emboli, vasculitis, medications (opioids, etc.)
• Common risk factors in pediatric population

image Dehydration, acute bacterial/viral infection, and enlarged portal lymph node (extrinsic obstruction of cystic duct)
• Infections associated with ↑ risk of acalculous cholecystitis

image Campylobacter jejuni, Candida, C lostridium perfringens, Cryptosporidium, cytomegalovirus (CMV), EBV, hepatitis A & B, leptospirosis, Q fever, Salmonella, Vibrio cholera
• ↑ risk of superimposed infection

image Typically  Escherichia  coli, Enterococcus faecalis, Klebsiella, Pseudomonas, Proteus, Bacteroides
• AIDS/immunocompromised patients at risk for opportunistic infections

image Microsporidia, Cryptosporidium, and CMV

Gross Pathologic & Surgical Features

• GB enlarged and tense
• No specific morphological differences between calculous and acalculous cholecystitis (except for absence of stones)
• GB filled with cloudy or turbid bile that may contain fibrin, pus, or hemorrhage

CLINICAL ISSUES

Presentation

• Most common signs/symptoms

image May present similarly to acute calculous cholecystitis: Right upper quadrant pain, fever, leukocytosis
image More likely than calculous cholecystitis to present atypically
• Other signs/symptoms

image Jaundice (∼ 20%) and palpable GB are more common in acalculous cholecystitis
image Mild ↑ in AST/ALT
• Clinical profile

image In critically ill patients, presentation may be insidious and diagnosis is often delayed

– ↑ risk of gangrene and perforation
image In more stable patients, presentation is similar to calculous cholecystitis

Demographics

• Gender

image Slight female predominance (60% of patients)
• Epidemiology

image Encompasses < 10% cases of acute cholecystitis
image Initially described in critically ill patients but can be seen in outpatients with risk factors

– In one study, 77% (36/47) of patients were outpatient
image Prevalence

– 0.7-0.9% after open AAA repair
– 0.05% after cardiac surgery
image Acalculous cholecystitis accounts for 50-70% of cases of acute cholecystitis in children

Natural History & Prognosis

• ↑ morbidity/mortality compared to calculous cholecystitis with ↑ risk (> 40%) of complicated cholecystitis

image ∼ 50% risk of gangrene and ∼ 10% risk of perforation
image Mortality ranges between 10-90%
image Higher morbidity/mortality partially reflects concurrent illness and is likely much lower in outpatients
• Prognosis depends on coexisting medical and surgical conditions and rapidity of diagnosis

Treatment

• Preferred treatment: Cholecystectomy (open or laparoscopic) + broad spectrum intravenous antibiotics is definitive treatment 

image Many patients with acalculous cholecystitis are critically ill and not immediate surgical candidates
image If surgery is possible, cholecystectomy should be performed (associated with less complications, less mortality, and shorter hospital stay than cholecystostomy)
• Cholecystostomy: Used as bridge to cholecystectomy in critically ill, unstable patients who are not surgical candidates

image Drain removal if patient improvement post GB decompression
image Prophylactic GB drainage of ICU patients with sepsis and suspicious ultrasound advocated in several series

DIAGNOSTIC CHECKLIST

Consider

• High degree of suspicion for acalculous cholecystitis in patients with risk factors and unexplained sepsis
image
(Left) Axial CECT after myocardial infarction shows a distended GB with pericholecystic fat stranding image and reactive thickening of the adjacent colon image. Patients recovering from surgical or medical emergencies are at risk for acalculous cholecystitis.

image
(Right) US in an ICU patient 3 weeks after trauma shows a distended GB, sludge, irregular wall thickening, focal perforation image, and a complex pericholecystic fluid collection image. Acalculous cholecystitis was confirmed at surgery.
image
(Left) US in an elderly patient with sepsis and hypotension after laparotomy for an incarcerated hernia shows irregular GB wall thickening image and a linear echogenic band adjacent to the wall image; features compatible with mucosal sloughing and acalculous, gangrenous cholecystitis.

image
(Right) Sagittal US of the GB in a patient with ulcerative colitis shows asymmetric GB wall edema image and no gallstones. A sonographic Murphy sign was elicited. Cholecystectomy revealed gangrenous, acute acalculous cholecystitis.
image
(Left) Axial CECT in a septic ICU patient demonstrates irregular wall thickening of the GB with a focal site of ulceration image.

image
(Right) Axial CECT in the same patient demonstrates irregular, “shaggy” wall thickening of the GB with a focal contained perforation image. The appearance is highly suggestive of gangrenous cholecystitis with contained perforation, a diagnosis confirmed at surgery.
image
Coronal CECT demonstrates an inflamed gallbladder (GB) with a small pericholecystic fluid collection image, suggesting perforation. While no discrete defect was seen on CT, gangrenous cholecystitis was confirmed at surgery.

image
Axial CECT in a septic patient demonstrates GB wall thickening with mild pericholecystic fat stranding, compatible with acute cholecystitis. No stones were seen on ultrasound or at surgery.
image
Axial NECT in a patient with acalculous cholecystitis shows a distended GB image, irregular wall thickening, and pericholecystic fat infiltration. The patient expired 1 day later.
image
Ultrasound of a septic 57-year-old male 3 days post pancreatic debridement for hemorrhagic pancreatitis shows a distended, sludge-filled GB, diffuse wall thickening image, and pericholecystic fluid image.
image
Axial CECT in the same patient shows a hydropic GB, wall thickening image, and adjacent fluid image. Ongoing sepsis and persistent GB thickening on follow-up ultrasound exams prompted a cholecystotomy. The aspirate was positive for E. coli and Enterococcus faecalis.
image
Ultrasound examination of a 64-year-old male with ulcerative colitis, primary sclerosis cholangitis, hairy cell leukemia, fever, right upper quadrant pain, and leukocytosis shows asymmetric GB wall edema image, found to represent acalculous cholecystitis.

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