Acute Calculous Cholecystitis

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 Cholelithiasis, sonographic Murphy sign, and GB wall thickening

• CT findings

image Distended GB (measuring > 5 cm in short axis)
image GB wall thickening (> 3 mm) with mural and mucosal hyperenhancement and pericholecystic fat stranding
image Calcified gallstones may be visualized (15% of cases)
image Hyperenhancement of adjacent liver parenchyma
• Hepatobiliary scintigraphy (Tc99-HIDA)

image Nonvisualization of GB 4 hours after injection of radiotracer (or 30 minutes after administration of morphine)
• Complications

image Gangrenous cholecystitis: GB wall necrosis with ↑ morbidity/mortality
image Perforated cholecystitis: Most often occurs due to progressive GB distension with eventual rupture
image Emphysematous cholecystitis: Secondary infection of GB with gas-forming organisms
image Hemorrhagic cholecystitis: Hemorrhage within GB lumen or wall

TOP DIFFERENTIAL DIAGNOSES

• Acalculous cholecystitis
• Nonspecific GB wall thickening
• Peptic ulcer disease
• Acute pancreatitis
• Hepatic flexure diverticulitis

CLINICAL ISSUES

• Immediate cholecystectomy in patients who are good surgical candidates
• Percutaneous cholecystostomy with antibiotics in patients who are high-risk surgical candidates
image
(Left) Transverse US shows a large echogenic stone image with an acoustic shadow image and a thickened gallbladder (GB) wall. These findings, along with a positive sonographic Murphy sign, suggested acute cholecystitis, confirmed at surgery.

image
(Right) This hepatobiliary scan is of a 48-year-old woman with RUQ pain and surgically confirmed acute cholecystitis. Note the presence of bowel image, absence of GB activity, and a subtle GB fossa rim sign image. Persistent pericholecystic activity may be due to tissue edema and biliary stasis.
image
(Left) Axial CECT demonstrates a tiny stone image within the gallbladder, with thickening of the GB wall, pericholecystic free fluid image, and fat stranding image, a constellation of findings diagnostic of acute cholecystitis.

image
(Right) Axial CECT of a 37-year-old woman shows GB wall thickening and GB fossa hyperenhancement image. This surrounding hepatic parenchymal hyperemia is analogous to the rim sign of hepatobiliary scintigraphy.

TERMINOLOGY

Definitions

• Acute inflammation of gallbladder (GB) precipitated by an obstructing calculus within GB neck or cystic duct

IMAGING

General Features

• Best diagnostic clue

image Cholelithiasis, with an impacted, immobile stone within GB neck or cystic duct
image GB wall thickening
image Positive sonographic Murphy sign: Pain with insonation directly over GB (accentuated during deep inspiration)

– May be absent in elderly, anesthetized, or diabetic patients, or those with GB necrosis
• Location

image Stone impacted in GB neck or cystic duct
• Size

image Distended GB (> 5 cm transverse diameter)
• Morphology

image Distended GB more rounded than normal pear-shaped configuration

Fluoroscopic Findings

• ERCP

image No filling of GB with contrast as result of cystic duct/GB neck obstruction by stone
image May document common bile duct (CBD) stones in patients with associated choledocholithiasis

CT Findings

• Uncomplicated cholecystitis

image Distended GB (measuring > 5 cm in short axis)
image GB wall thickening (> 3 mm) with mural and mucosal hyperenhancement and pericholecystic fat stranding
image Cholesterol/bilirubin stones typically not visible, but calcified gallstones may be visualized (15% of cases)

– Stone visualization may improve at higher kVp settings (140 kVp)
image Hyperenhancement of liver parenchyma adjacent to inflamed GB (particularly in arterial phase)
• Complicated cholecystitis

image Gangrenous cholecystitis:Focal interruption or lack of enhancement of GB wall due to necrosis

– Small ulcerations or outpouchings of GB wall may occur at these sites
– Intraluminal linear membranes (secondary to sloughed mucosa)
– Intramural or pericholecystic abscesses
image Emphysematous cholecystitis: Gas in lumen/wall of GB 

– CT is best modality to identify ectopic gas and make diagnosis of emphysematous cholecystitis
image Hemorrhagic cholecystitis: High-attenuation intraluminal clot ± active extravasation of contrast

– Blood within GB lumen or bile ducts
image Gallbladder perforation:Focal pericholecystic fluid collection or abscess adjacent to disrupted GB wall; extraluminal gallstones

– CT better than US for visualizing GB wall defect

MR Findings

• Distended GB with wall thickening, gallstones, and pericholecystic fat stranding/fluid
• Hyperenhancement of GB wall and mucosa on T1WI C+, with possible enhancement of surrounding liver parenchyma (rim sign)
• Stones in GB or cystic duct on T2WI or MRCP
• Interrupted GB wall/focally absent mucosal enhancement → gangrenous or perforated GB
• Use of hepatobiliary contrast agents (such as Eovist), which are normally secreted into bile, may be helpful

image Lack of filling or delayed filling (> 60 minutes) of GB supports diagnosis of acute cholecystitis
image Normal filling (< 60 minutes) does not exclude cholecystitis
image GB usually fills with contrast in chronic cholecystitis

Ultrasonographic Findings

• Grayscale ultrasound

image Uncomplicated cholecystitis

– Cholelithiasis (usually an immobile, impacted stone in GB neck or cystic duct), sonographic Murphy sign, and GB wall thickening > 3 mm
– GB distension > 5 cm in short axis
– Increased vascularity of GB wall on color Doppler images
image Complicated cholecystitis

– Perforated cholecystitis: Pericholecystic abscess with collapsed GB

image High-frequency transducer may allow better visualization of GB fundus to help exclude early perforation
image Sonographic hole sign: Visualization of GB wall defect on US
– Gangrenous cholecystitis: Asymmetric wall thickening, intraluminal linear membranes, and irregularity and ulcerations of GB wall

image Striated GB, contrary to prior teaching, not convincingly associated with gangrene
image GB wall hyperemia may be absent on color Doppler images as result of wall necrosis
– Emphysematous cholecystitis: Gas in GB lumen and wall (brightly echogenic reflectors with dense “dirty” posterior acoustic shadowing)

image GB itself may be difficult to visualize as result of shadowing from gas
– Hemorrhagic cholecystitis: Echogenic clot within GB lumen or visualized biliary tree
• Color Doppler

image Increased vascularity of GB wall (flow may be absent in gangrenous cholecystitis)

Nuclear Medicine Findings

• Hepatobiliary scintigraphy

image Tc-99m iminodiacetic acid derivatives
image Nonvisualization of GB 4 hours after radiotracer injection (or 30 minutes after morphine administration)
image Increased uptake in GB fossa (rim sign) due to hyperemia in 35% of patients

– Very specific (but not sensitive) for acute cholecystitis
– Positive predictive value of 57% for gangrenous cholecystitis
image Hepatobiliary scintigraphy more sensitive (97%) and specific (90%) compared to US (88% and 80%, respectively)
image False-positive results in patients who have recently eaten, undergone prolonged fasting (> 24 hours), received hyperalimentation, have severe concurrent illness, or who have severe hepatocellular dysfunction

Imaging Recommendations

• Best imaging tool

image US is best screening tool
image Hepatobiliary scintigraphy for confirmation (particularly when US is equivocal)
image CECT to evaluate potential complications
• Protocol advice

image Measure GB wall thickness adjacent to liver
image Move patient during ultrasound to assess stone mobility

DIFFERENTIAL DIAGNOSIS

Acalculous Cholecystitis

• Non stone-related GB inflammation due to ischemia and stasis usually diagnosed in critically ill patients

Nonspecific Gallbladder Wall Thickening

• Most common causes: Hepatitis, hypoalbuminemia, congestive heart failure, ascites, renal failure, etc.
• Negative Murphy sign

Acute Pancreatitis

• Enlarged pancreas with peripancreatic fluid or inflammatory changes
• GB may show reactive wall thickening

Peptic Ulcer Disease

• Thickened duodenum with periduodenal inflammatory changes and ectopic gas (with perforation)
• GB may show reactive wall thickening

Hepatic Flexure Diverticulitis

• Colonic diverticulosis with colonic wall thickening and pericolonic inflammation
• GB may show reactive wall thickening

Liver Abscess

• CECT

image Cluster sign of multiloculated pyogenic abscesses
image Gas-fluid level from gas-forming organism
• US

image Complex, hypoechoic mass
image Little through transmission

PATHOLOGY

General Features

• Etiology

image Impacted stone within GB neck/cystic duct
• Pathophysiology

image Not fully explained by cystic duct obstruction alone
image Epithelial injury due to stone impaction → release of proinflammatory mediators (such as lysolecithin) → production of additional inflammatory mediators (prostaglandins) → GB inflammation
image Secondary infection also plays a role, although not all patients have infected bile

– Seen in 22-46% of cases
– Escherichia  coli, Enterococcus, Klebsiella, Enterobacter

Staging, Grading, & Classification

• Uncomplicated cholecystitis

image GB wall intact on CT &/or US
• Gangrenous cholecystitis

image GB wall necrosis and gangrene: 1/4 of patients
image US: Pericholecystic fluid, intraluminal membranes, asymmetric GB wall thickening, absent color Doppler flow
image ↑ morbidity/mortality
image Most common in elderly, diabetic, and immunocompromised patients
• Perforated cholecystitis

image More likely with acute acalculous cholecystitis
image CECT: Pericholecystic abscess, focal GB wall necrosis and lack of enhancement
image Most often occurs due to progressive GB distension with eventual rupture 

– May also be secondary to dilation and infection of Rokitansky-Aschoff sinuses, which leads to perforation
image Perforated cholecystitis can result in pericholecystic abscess (including within liver)
• Emphysematous cholecystitis

image Secondary infection of GB with gas-forming organisms (e.g., Clostridium welchii)
image Strong male predominance, especially in diabetics
image Carries 5x greater risk of GB perforation
• Hemorrhagic cholecystitis

image Hemorrhage itself may cause cholecystitis by obstructing cystic duct with blood products
image Can be caused by calculous or acalculous cholecystitis
image Also occurs with trauma, anticoagulation, or malignancy

Gross Pathologic & Surgical Features

• Gallstones in GB neck or cystic duct
• Thickened, hyperemic GB wall
• Omental adhesions

Microscopic Features

• Lumen: Gallstones, sludge
• GB mucosa: Ulcerations
• GB wall: Acute polymorphonuclear (PMN) infiltration

CLINICAL ISSUES

Presentation

• Most common signs/symptoms

image Acute right upper quadrant pain that may radiate to shoulder or back

– Positive Murphy sign: Patient asked to inspire deeply when GB fossa area is palpated by examiner, resulting in pain and patient catching their breath
image Fever, nausea, vomiting, and anorexia
• Other signs/symptoms

image Sepsis and peritonitis depending on severity and presence of complications
• Lab data

image Increased WBC + bandemia
image May have mild ↑ in AST/ALT and amylase
image ↑ alkaline phosphatase/bilirubin raises concern for complication (Mirizzi syndrome, cholangitis, choledocholithiasis)

– Not commonly elevated in uncomplicated acute cholecystitis

Demographics

• Age

image Typically > 25 years
• Gender

image M:F = 1:3
• Epidemiology

image Gallstones cause 90% of cases of acute cholecystitis
image Increased incidence of gallstones in selected populations

– Latinos, Pima Indians, and Scandinavians
image Incidence of acute cholecystitis parallels prevalence of gallstones

– 25 million Americans have gallstones
– 120,000 cholecystectomies performed in US each year for acute cholecystitis

Natural History & Prognosis

• Excellent prognosis for uncomplicated cases treated with prompt surgery

image Overall mortality from acute cholecystitis is 3% (< 1% in young patients and 10% in high-risk patients)
• May progress to gangrenous cholecystitis and perforation if untreated
• Complications

image Gangrene, perforation, emphysematous cholecystitis
image Cholecystoenteric fistula; gallstone ileus
image Mirizzi syndrome: Common hepatic duct obstruction caused by extrinsic compression from impacted stone in cystic duct or Hartmann pouch (seen in 0.7-1.8% of cases)
image Bouveret syndrome: Gallstone erodes into duodenum, causing obstruction

Treatment

• Immediate cholecystectomy in patients who are good surgical candidates

image Laparoscopic approach preferred: Reduces postoperative pain and shortens hospital stay
image Delaying surgery increases complications and risk of open conversion due to local inflammation
• Percutaneous cholecystostomy with antibiotics in patients who are high-risk surgical candidates

image Temporary bridge for patients with high operative risk
• Percutaneous drainage

image Well-defined pericholecystic abscesses

DIAGNOSTIC CHECKLIST

Consider

• Perforated duodenal ulcer or pancreatitis when inflammation is primarily centered around duodenum/pancreas with secondary GB wall thickening

Image Interpretation Pearls

• Stone impacted in cystic duct or GB neck
• Sonographic Murphy sign must be appropriately assessed and unequivocal to be considered positive
image
(Left) Axial CECT in a patient with right upper quadrant pain demonstrates a thickened, irregular GB wall image with adjacent fat stranding image, suggesting acute cholecystitis.

image
(Right) Axial fat-suppressed T2WI in the same patient demonstrates the irregularity of the thickened GB wall, with subtle sites of ulceration image. This was confirmed to represent gangrenous cholecystitis at surgery.
image
(Left) Axial CECT demonstrates a thickened, inflamed GB with wall thickening and a small amount of free fluid image near the fundus. Most importantly, there is active extravasation image within the GB lumen, in keeping with this patient’s surgically confirmed hemorrhagic cholecystitis.

image
(Right) Axial CECT shows high-density blood distending the GB image, with similar density blood tracking in Morison pouch and medial to the GB image. At surgery, the GB was gangrenous and contained hemorrhagic bile.
image
(Left) CT scout image in a septic patient with abdominal pain after surgery demonstrates gas filling the GB image. There also appears to be a collection of gas more medially image. Ureteral stents image and surgical clips are noted from the patient’s recent surgery.

image
(Right) Axial NECT from the same patient demonstrates findings of emphysematous cholecystitis, with gas image in the GB lumen and wall. The fluid/gas image tracking outward from the GB, as well as the adjacent gas and fluid collection image, are consistent with perforation.
image
Longitudinal color Doppler US image demonstrates a thickened GB wall with hyperemia image, suggesting acute cholecystitis. However, the GB is distended and filled with high-density, heterogeneous blood products image, suggesting hemorrhagic cholecystitis.

image
Axial CECT demonstrates stones image within the GB, which appears thickened and inflamed, in keeping with acute cholecystitis.
image
Axial CECT demonstrates a thickened GB wall with heterogeneous enhancement, as well as a focal blood clot image within the GB lumen, suggesting acute hemorrhagic cholecystitis.
image
Coronal NECT in the same patient acquired a few hours later shows that the blood clot image has grown and now fills much of the GB lumen.
image
Axial CECT in the same patient shows blood products image distending and filling the common bile duct. Hemorrhagic cholecystitis in this patient was thought to be secondary to a recent embolization procedure.
image
This CECT is of a 59-year-old man with clinical and CT features pathognomonic for acute cholecystitis. Note GB wall thickening, mucosal enhancement image, omental infiltration image, and subtle layering of calcified stones image.
image
Ultrasound shows fine, shadowing, layering calculi image, mild GB thickening image, and sludge. Omentum is infiltrated image, and an unequivocal sonographic Murphy sign was easily elicited to make the diagnosis of acute cholecystitis.
image
Ultrasound of a 37-year-old woman with right upper quadrant pain and leukocytosis shows GB wall thickening image and multiple small, weakly shadowing stones image. A sonographic Murphy sign was confidently elicited.
image
MRCP of a 27-year-old man with right upper quadrant pain and fever (and ultimately surgically confirmed acute cholecystitis) shows a hydropic GB, gallstones image, and pericholecystic fluid image.
image
Transverse color Doppler ultrasound of gangrenous cholecystitis demonstrates hyperemia of the omental fat at the fundus of the GB image, a small amount of pericholecystic fluid image, and small gallstones image.
image
Sagittal color Doppler ultrasound of the same patient reveals marked hypertrophy of the cystic artery image and linear membranes in the GB lumen image from fibrous strands of pus.
image
Axial CECT in a patient shows acute gangrenous cholecystitis. Note the distended GB with a thickened wall image.
image
Axial CECT at a more caudal level in the same patient demonstrates focal necrosis of the GB wall with a lack of contrast enhancement image. Note the adjacent inflammatory changes in the omental fat image.
image
Sagittal ultrasound shows gallstones image, but the GB wall was judged to be of normal thickness, and the area above it was not very tender.
image
Axial CECT in the same patient, performed immediately after ultrasound, shows a gallstone image as well as mural thickening and pericholecystic inflammation image. Acute cholecystitis was confirmed at surgery.
image
Anteroposterior radiograph shows the classic appearance of emphysematous cholecystitis, an infection of the GB wall caused by gas-forming organisms. Note the air in oval configuration in the expected location of the GB image.
image
Axial NECT of acute hemorrhagic cholecystitis shows a high-attenuation clot in the GB image.
image
Color Doppler ultrasound of a 71-year-old woman who presented with a high fever, leukocytosis, and abdominal pain shows marked hyperemia image of a thickened GB wall.
image
Biliary scintigram in a 47-year-old woman who presented with RUQ pain and an inconclusive sonogram illustrates acute cholecystitis. Note the isotope filling the common bile duct image and the small bowel image without filling of the GB.
image
Sagittal ultrasound of gangrenous cholecystitis demonstrates intraluminal membranes from fibrinous debris image.
image
Sagittal ultrasound of gangrenous cholecystitis demonstrates sloughed mucosa image.

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