Diffuse Gallbladder Wall Thickening


Diffuse gallbladder wall thickening is commonly encountered in diagnostic settings. The ability of ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) to directly visualize the thickened gallbladder wall ascertains the importance of this condition. Ultrasound is the initial imaging technique for evaluation of suspected gallbladder disease. CT plays the role of a problem-solving tool in inconclusive ultrasound examinations, in staging of diseases, and as the initial modality in cases of acute abdomen. MRI is emerging as a modality of choice in the evaluation of pain, jaundice, and gallbladder masses. The current widespread use of abdominal CT and MRI has resulted in the detection of causes of gallbladder wall thickening.

Diffuse gallbladder wall thickening is a nonspecific finding. It is the most common finding in either acute calculus or acalculus cholecystitis. Although a thickened gallbladder wall is considered a hallmark feature of acute cholecystitis, it can be encountered in a wide variety of disease processes such as gallbladder cancer and extracholecystic benign conditions such as hepatitis, heart failure, hypoalbuminemia, and acute severe pyelonephritis. It can be found in both symptomatic and asymptomatic patients.

Normal Gallbladder Wall

The normal gallbladder wall is composed of four layers: the mucosa, lamina propria, an irregular muscle layer, and serosa of loose connective tissue.

On ultrasonography, the normal gallbladder wall appears as a pencil-thin echogenic line. Sonographic depiction of gallbladder wall thickening depends on the degree of gallbladder distention, and pseudo-thickening can occur in the postprandial state. A thickened gallbladder wall measures more than 3 mm and has a layered appearance.

On CT, the normal gallbladder wall is visible as a thin rim of soft tissue density that enhances after injection of a contrast agent. The thickened gallbladder wall on CT frequently contains a hypodense layer of subserosal edema that mimics pericholecystic fluid.

On MRI, the gallbladder wall shows an inner layer of low signal intensity representing mucosal and muscular layers and outer layer of high signal intensity of the serosa on high-resolution T2-weighted images. However, these layers may not be discernible in the nonthickened normal gallbladder wall on half-Fournier acquisition single-shot turbo spin echo (HASTE) images. The portion of the gallbladder wall adjacent to liver is not identified as a separate structure owing to its lower signal intensity on T2-weighted images. On T1-weighted images, the wall has intermediate signal intensity and enhances uniformly after the administration of gadolinium-based contrast material. Because of similar enhancement of the gallbladder wall and the liver parenchyma, the portion of the wall adjacent to the liver is not well appreciated.

Thickened Gallbladder Wall

Although its thickness depends on the degree of gallbladder distention, 3 mm is regarded as the upper limit of normal; and mural thickening is defined as a transverse wall measurement of 4 mm or greater.

On CT, the thickened gallbladder wall is of soft tissue density. It may manifest as a layered, “sandwich-like” appearance formed by an inner enhancing layer of mucosa and an outer enhancing layer of serosa with an intervening hypodense layer made up of subserosal edema, or it may have a halo of low-attenuation subserosal edema surrounding the enhancing mucosa. Occasionally, the enhanced mucosa of the thickened gallbladder wall may mimic a large rim-calcified stone or a gallbladder wall surrounded by pericholecystic fluid. The differentiation of the halo of edema from pericholecystic fluid is possible on CT by demonstrating small enhancing punctate structures within the edematous wall. The focal pericholecystic fluid also can be differentiated from the diffusely thickened gallbladder wall. Ultrasonography may be required at times to exclude these simulations.

On MRI, four different patterns of gallbladder wall thickening have been described based on the definition of the gallbladder layers.

  • Type 1 refers to a well-demarcated two-layered appearance with an inner layer showing thin uniform and low signal intensity and an outer layer demonstrating thick high signal intensity.

  • Type 2 refers to an ill-defined two-layered pattern with a broadened or interrupted inner layer and a heterogeneous outer layer showing intermediate signal intensity.

  • Type 3 is characterized by the presence of multiple high signal intensity cystic spaces within a thickened wall; layering may or may not be evident.

  • Type 4 incorporates diffuse nodular wall thickening without layering and with a homogeneous low signal intensity.

A wide variety of conditions can cause diffuse gallbladder wall thickening. Gallbladder wall thickening from conditions intrinsic to the gallbladder are referred to as primary, whereas wall thickening resulting from conditions not related to gallbladder disease are considered secondary ( Box 56-1 and Figure 56-1 ).

Box 56-1
Various Conditions Causing Diffuse Gallbladder Wall Thickening

Primary Causes

  • Acute cholecystitis

    • Acute calculus cholecystitis

    • Acute acalculus cholecystitis

    • Gangrenous cholecystitis

    • Emphysematous cholecystitis

  • Chronic cholecystitis

  • Adenomyomatosis

  • Xanthogranulomatous cholecystitis

  • Gallbladder carcinoma

Secondary Causes

  • Systemic disease

    • Liver dysfunction

    • Congestive heart failure

    • Renal failure

    • Hypoalbuminemic states

  • Extracholecystic inflammatory process

    • Acute hepatitis

    • Peritonitis

    • Acute pancreatitis

    • Acute pyelonephritis

  • Others

    • Peptic ulcer

    • Infectious mononucleosis, typhoid

    • Acquired immunodeficiency syndrome cholangiopathy

    • Pregnancy

    • Total parenteral nutrition

Figure 56-1, The various causes of diffuse gallbladder wall thickening. AIDS, Acquired immunodeficiency syndrome.

Primary Gallbladder Wall Thickening

Acute Cholecystitis

Etiology

Acute Calculus Cholecystitis.

Mechanical obstruction of the cystic duct by gallstones (90% of cases) or on rare occasions by helminths (Ascaris, Clonorchis) may occur. Risk factors include female sex, obesity or rapid weight loss, certain drugs, pregnancy, and increasing age.

Acute Acalculus Cholecystitis.

Acute acalculus cholecystitis frequently occurs in those who are critically ill from trauma, sepsis, or burns, presumably because of increased bile viscosity from fasting and taking medication that causes cholestasis. Other risk factors include vascular disease, systemic vasculitides, human immunodeficiency virus infection, diabetes mellitus, acute renal failure, immunosuppression, prolonged fasting, and total parenteral nutrition.

Prevalence and Epidemiology

Acute cholecystitis is defined as acute inflammation of the gallbladder. It is the fourth most common cause of hospital admissions for patients presenting with an acute abdomen. Acute acalculus cholecystitis accounts for 2% to 12% of cholecystitis.

Clinical Presentation

Acute Calculus Cholecystitis.

Acute calculus cholecystitis is right upper quadrant pain increasing in frequency and intensity, radiating to the interscapular area or shoulder, and increasing with deep inspiration. The pain is often accompanied by nausea, vomiting, and loss of appetite. Fever with chills and rigor also occur.

On physical examination, right upper quadrant tenderness and guarding are noted. Murphy's sign is the characteristic physical finding in these patients and is considered highly sensitive (97%) and predictive (93%) of calculus cholecystitis. Murphy's sign refers to pain elicited by palpation in the right upper quadrant during mid-inspiration.

Acute Acalculus Cholecystitis.

Acute acalculus cholecystitis mostly affects patients with prolonged fasting or protracted immobility and those experiencing hemodynamic instability.

Pyrexia may be the only symptom, and up to 75% of patients may have no symptoms referable to the right upper quadrant. This disorder can occur as a manifestation of acquired immunodeficiency syndrome (AIDS) cholangiopathy, usually caused by pathogens such as Cryptosporidium followed by microsporidia such as Enterocytozoon bieneusi .

Pathophysiology

Acute Calculus Cholecystitis.

The initial event in acute calculus cholecystitis is obstruction of the cystic duct by a gallstone. The trapped concentrated bile has an irritant effect on the gallbladder wall, in turn causing increased secretions. This leads to a series of events resulting in increased intraluminal pressure, gallbladder distention, and wall edema that progress to cause venous and lymphatic obstruction, ischemia, and necrosis. Bacterial colonization, perforation, and abscess formation soon ensue. The bile is sterile in early stages, and infection occurs as a secondary event. Bile cultures are positive in only 20% to 75% of patients, and the organisms most commonly cultured are enteric bacteria, including Escherichia coli, Klebsiella, and Enterococcus.

If untreated, acute cholecystitis is complicated by hemorrhage, necrosis, empyema, and perforation. The complications include gangrenous cholecystitis, which complicates 2% to 38% of patients with acute cholecystitis and has increased incidence of perforation and resultant peritonitis. Perforation of the gallbladder wall is present in 3% to 10% of patients. Emphysematous cholecystitis is a rare complication most commonly seen in elderly diabetic men secondary to infection of the gallbladder wall with gas-forming organisms such as Clostridium welchii and Escherichia coli.

Acute Acalculus Cholecysitis.

The pathogenesis of acute acalculus cholecystitis is multifactorial, with gallbladder stasis, paresis, and ischemia considered to play a role. The concentrated and stagnant bile along with reduced gallbladder perfusion leads to chemical and ischemic injury of the gallbladder epithelium, resulting in cholecystitis. Cholecystectomy specimens demonstrate impaired gallbladder microcirculation, possibly resulting from splanchnic vasoconstriction and intravascular coagulation. Infection is a secondary event complicating the ischemic injury.

Imaging

The combination of prolonged, constant right upper quadrant pain and tenderness with fever is highly suggestive of acute cholecystitis. Leukocytosis, increased neutrophils, and band forms are usually present. Occasional elevated levels of liver transaminases or bilirubin can occur.

Radiography.

The role of conventional radiography in the evaluation of acute cholecystitis is limited ( Table 56-1 ). Gallstones may be visualized occasionally. In patients with emphysematous cholecystitis, intraluminal or intramural air within the gallbladder may be seen. Staging of emphysematous cholecystitis on conventional radiography is as follows :

  • Stage 1: Gas within the gallbladder lumen

  • Stage 2: Gas within the gallbladder wall

  • Stage 3: Gas within the pericholecystic tissues

TABLE 56-1
Accuracy, Limitations, and Pitfalls of the Modalities Used in Imaging of Acute Cholecystitis
Modality Accuracy Limitations Pitfalls
Radiography Data not available to specify accuracy Insensitive
Nonspecific
Unable to directly visualize the soft tissues of gallbladder
CT Accuracy: 94% Radiation exposure
Not ideal in pregnant patients
Murphy's sign cannot be elicited as in ultrasonography.
CT misses 20% of gallstones because they have the same density as bile
MRI Sensitivity: 95% Not preferred in critically ill patients
Ultrasonography Sensitivity: 48%-100%
Specificity: 64%-100%
Inability to image cystic duct
Decreased sensitivity for choledocholithiasis
Air within gallbladder may be mistaken for calcifications
Gallbladder sludge in acute calculus cholecystitis may mimic gallbladder carcinoma
Nuclear medicine Accuracy: 92%
Gold standard for diagnosis of acute cholecystitis
Reduced specificity in the presence of hepatic impairment, parenteral nutrition, or patient fasting
Does not give information about nonobstructing cholelithiasis and cannot detect other pathology
False-negative and false-positive results
PET/CT Data not available to specify accuracy Decreased sensitivity in patients with diabetes Differentiation from gallbladder cancer not always possible
CT, Computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography.

Computed Tomography.

CT is used for the evaluation of patients with acute right upper quadrant complaints with inconclusive ultrasound findings or with a perplexing clinical presentation when acute cholecystitis is not the first diagnostic choice.

Acute Calculus Cholecystitis.

The most common CT finding in acute cholecystitis is gallbladder wall thickening and gallstones and is noted in 75% of cases ( Figure 56-2 ). Indistinct interface of the gallbladder wall and the juxtaposed liver is regarded as highly suggestive of acute cholecystitis.

Figure 56-2, Acute calculus cholecystitis. Axial (A) and coronal (B) contrast-enhanced computed tomography images in a febrile 45-year-old woman with right upper quadrant abdominal pain show diffuse wall thickening and enhancement with marked distention of the gallbladder ( arrows, A ). Associated pericholecystic stranding is also seen with mild wall thickening of the adjacent transverse colon on the coronal image (arrow).

Pericholecystic stranding, which represents inflammatory changes within the fat surrounding the gallbladder, is another CT feature. Extensive changes may cause reactive mural thickening and edema in the adjacent colon or duodenum (see Figure 56-2 ).

Transient focal hyperattenuation in the hepatic parenchyma adjacent to the inflamed gallbladder is probably related to hepatic arterial hyperemia. The thick gallbladder wall may mimic pericholecystic fluid, particularly if the gallbladder lies oblique to the axial plane of imaging.

Major criteria for acute calculus cholecystitis include calculi, thickened wall, pericholecystic fluid, and subserosal edema. Minor criteria are gallbladder distention and gallbladder sludge. The presence of one major and two minor criteria helps to make the diagnosis.

Acute Acalculus Cholecystitis.

Major CT criteria include gallbladder mural thickening (≥4 mm), pericholecystic fluid, subserosal edema in the absence of ascites, intramural gas, or sloughed mucosa. Minor criteria are a distended gallbladder and hyperdense bile. Presence of two major criteria or one major and two minor criteria suggests the diagnosis.

Gangrenous Cholecystitis.

Lack of mural enhancement, a greater degree of gallbladder distention, and wall thickening are features of gangrenous cholecystitis ( Figure 56-3 ). Discontinuous and/or irregular mucosal enhancement has been described. Pericholecystic abscess is another specific sign of mural necrosis indicating gangrenous cholecystitis, a severe form of acute cholecystitis.

Figure 56-3, Acute gangrenous cholecystitis in three patients. A, Axial contrast-enhanced computed tomography scan of the abdomen in a 74-year-old man shows marked distention of the gallbladder with asymmetric wall thickening and areas of absent mural enhancement (thin white arrow) . Small irregular nonenhancing foci are noted within the thickened wall, suggesting necrosis (shorter white arrows). A slender intraluminal membrane is also seen (black arrow). B, Axial contrast-enhanced computed tomography scan in a 56-year-old woman shows marked irregularity of the gallbladder wall with irregular mural enhancement and break in the mucosal lining (arrows). C, Coronal reformatted image from the same patient shows marked pericholecystic fat stranding and thickening of the adjacent colonic wall at the hepatic flexure. Also seen is the thickening and loss of definition of the adjacent lateral abdominal wall muscles. Transverse (D) and sagittal (E) ultrasonograms obtained in a 63-year-old woman show irregular gallbladder wall thickening ( within calipers, D ) with intraluminal sludge, membranes, and gallstones.

A hyperdense gallbladder wall on unenhanced CT has been reported as a sign of acute gangrenous cholecystitis. Because mucosa is prone to ischemia, mucosal necrosis and hemorrhage result in high density that is detectable on CT. Other additional features include the presence of intraluminal membranes and an irregular wall.

Emphysematous Cholecystitis.

The presence of gas in the gallbladder wall represents another variant of acute cholecystitis known as emphysematous cholecystitis ( Figure 56-4 ). Gas also may appear within the gallbladder lumen and pericholecystic tissue. CT has a critical role in detecting the gas because it mimics calcifications or cholesterol deposits on ultrasonography. CT is the most sensitive and specific imaging modality for identifying gas within the gallbladder lumen or wall. The presence of pneumoperitoneum indicates perforation, which requires emergent surgical intervention.

Figure 56-4, Emphysematous cholecystitis. Axial contrast-enhanced CT scan of the abdomen in a 48-year-old patient with diabetes shows multiple pockets of intramural gas and an intraluminal air/fluid level. Mild pericholecystic fat stranding is seen.

Magnetic Resonance Imaging.

Sensitivity of MRI for the diagnosis and differentiation of acute cholecystitis is 95%. The common MRI features include wall thickening (≥4 mm) and distended gallbladder (long axis dimension >8 cm and short axis dimension >4 cm) ( Figure 56-5 ). The type 2 layered pattern of wall thickening is seen. Other features include wall irregularity or defect and intraluminal membranes that are irregular or have intraluminal linear soft tissue signal intensities. On gadolinium administration there is gallbladder wall enhancement with increased transient pericholecystic hepatic enhancement that is best seen during the hepatic arterial dominant phase. Mural striation representing a layered pattern of gallbladder wall with different alternating signal intensities sometimes can be seen. Increased transient pericholecystic hepatic enhancement is highly specific and helps in differentiation from chronic cholecystitis.

Figure 56-5, Acute calculus cholecystitis. Coronal fat-suppressed T2-weighted magnetic resonance image in a 47-year-old woman shows distended gallbladder with diffuse wall thickening and a rounded low signal intensity calculus seen lodged at the gallbladder neck.

Pericholecystic fat signal intensity changes are seen as decreased signal intensity on T1-weighted images and as increased signal on T2-weighted images. Pericholecystic fluid is seen as a high signal intensity collection on T2-weighted images.

Gas in the wall or lumen is seen as signal void gas bubbles in the gallbladder wall or lumen on T1-weighted or T2-weighted images. Air/fluid levels sometimes can be seen.

Ultrasonography

Acute Calculus Cholecystitis. *

Diffuse gallbladder wall thickening (≥4 mm) and a distended gallbladder (long axis dimension >8 cm and short axis dimension >4 cm) are seen ( Figure 56-6 ). The presence of gallstones is the most common and sensitive finding, particularly the presence of an obstructing stone at the gallbladder neck or cystic duct.

Figure 56-6, Acute calculus cholecystitis with emphysematous change. A, Sagittal ultrasound image of the abdomen in a 42-year-old man with right upper quadrant pain shows a distended gallbladder with wall thickening and a calculus seen at the gallbladder neck. Multiple tiny echogenic reflectors corresponding to gas bubbles are seen along the antidependent portion of the gallbladder wall with “comet tail” artifact. B, Axial contrast-enhanced computed tomography scan confirmed the presence of gas within the gallbladder. Significant fat stranding and fluid collections are seen in the pericholecystic region. GB, Gallbladder; SAG, sagittal.

* References .

On ultrasonography, a positive Murphy's sign refers to maximal tenderness elicited by pressure over the sonographically located gallbladder during inspiration. Pericholecystic fat inflammation and/or fluid are secondary findings. Hyperemia of the gallbladder wall demonstrated on color and power Doppler imaging improves the accuracy of ultrasound in diagnosing acute cholecystitis.

Acute Acalculus Cholecystitis.

The imaging features of acalculus cholecystitis are similar to those of acute cholecystitis except for the absence of gallstones and the presence of gallbladder sludge ( Figure 56-7 ).

Figure 56-7, Acute acalculus cholecystitis. Sagittal ultrasound image in a 45-year-old woman with sepsis shows distended gallbladder filled with echogenic sludge and diffuse wall thickening. No calculus was identified on the scan.

Gangrenous Cholecystitis.

Gangrenous cholecystitis is characterized by asymmetric gallbladder wall thickening or the presence of intraluminal membranes (see Figure 56-3 ). Murphy's sign is negative in up to 66% of cases because of denervation of the gallbladder wall.

Emphysematous Cholecystitis.

Ultrasonography demonstrates highly echogenic reflectors with low-level posterior shadowing and reverberation artifact (“dirty shadowing”) emanating from the gallbladder lumen (see Figure 56-6 ). The “champagne sign” refers to the finding of small, nonshadowing echogenic foci rising up from the dependent portions of the gallbladder lumen, similar to effervescing bubbles in a glass of champagne.

Nuclear Medicine.

Biliary scintigraphy is the gold standard for diagnosis of acute cholecystitis resulting from cystic duct obstruction. Cholescintigraphy using technetium-99m ( 99m Tc)-diisopropyl iminodiacetic acid, also known as a hepatobiliary iminodiacetic acid (HIDA) scan, is 86% to 100% sensitive and 94% to 100% specific for acute cholecystitis with an accuracy of 92%.

HIDA scan criteria for acute cholecystitis include persistent nonvisualization of the gallbladder 3 hours after administration of a radiotracer or 30 minutes after morphine sulfate augmentation. Filling of the gallbladder within 60 minutes can occur and is a false-negative finding. False-negative rates are decreased by administering morphine. A false-positive result is nonvisualization of the gallbladder in the absence of obstruction. This can occur in patients who are fasting, are receiving total parenteral nutrition, or have severe liver disease.

The role of HIDA scan in acute acalculus cholecystitis is debatable.

In emphysematous cholecystitis, there is nonvisualization of the gallbladder, along with a region of increased hepatic activity adjacent to the gallbladder fossa (“rim sign”).

Positron Emission Tomography With Computed Tomography.

On positron emission tomography (PET), acute cholecystitis is seen as a hypermetabolic lesion with a ringlike radiotracer uptake in the gallbladder area.

Classic Signs
Acute Cholecystitis

  • Diffuse gallbladder wall thickening (≥4 mm) with gallstones

  • Positive sonographic Murphy's sign

  • Pericholecystic fat stranding and fluid collections

  • Irregular wall thickening with lack of mural enhancement or discontinuous mucosal enhancement with intraluminal membranes (suggestive of gangrenous cholecystitis)

  • Air within the gallbladder wall or lumen

  • Champagne sign on ultrasonography for emphysematous cholecystitis

  • Persistent nonvisualization of the gallbladder 3 hours after administration of radiotracer on hepatobiliary scintigraphy

Differential Diagnosis

The differential diagnosis includes choledocholithiasis, pancreatitis, peptic ulcer disease, acute hepatitis, liver abscess, liver neoplasm with complications, pneumonia, and heart disease. Sympathetic thickening of the gallbladder wall secondary to an acute inflammatory process in the right upper quadrant, including acute pancreatitis, perforated duodenal ulcer, hepatitis, right-sided diverticulitis, and even acute right-sided pyelonephritis can cause confusion with acute cholecystitis.

Treatment

Medical Treatment.

Medical treatment includes restriction of oral intake, intravenous fluid and electrolyte resuscitation, and parenteral (narcotic) analgesia. Indomethacin and diclofenac have been reported to reduce the rate of progression of acute cholecystitis. Intravenous antibiotic therapy is often administered.

Surgical Treatment

Acute Calculus Cholecystitis.

Open/laparoscopic cholecystectomy is performed.

Acute Acalculus Cholecystitis.

Open cholecystectomy is the traditional approach for surgical treatment of acalculus cholecystitis. Percutaneous cholecystostomy is the treatment of choice in critically ill and elderly patients as both a diagnostic and therapeutic procedure.

Chronic Cholecystitis

Etiology

Chronic cholecystitis is often associated with cholelithiasis. It is a result of chronic irritation of the gallbladder wall by recurrent attacks of cholecystitis secondary to transient obstruction by gallstones.

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