Gangrenous Cholecystitis

Usefulness of contrast-enhanced ultrasound
(CEUS) in the diagnosis of acute gangrenous
cholecystitis: a comparative study with
surgical and pathological findings.
T Ripollés MD, J Blay MD, MJ Martínez-Pérez MD,
L Navarro MD, R Martínez-García MD, E Martí MD
Hospital Universitario Dr. Peset
Valencia Spain
Introduction
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Gangrenous cholecystitis is a severe form of acute cholecystitis,
which results from marked distension of the gallbladder with
increased tension in the wall and associated inflammation that leads
to ischemic necrosis of the gallbladder wall.
Early diagnosis and emergent intervention are critical in gangrenous
cholecystitis since it is associated with increased morbidity and
mortality compared with uncomplicated acute cholecystitis.
However, it is often difficult to diagnose gangrenous cholecystitis
preoperatively because clinical and laboratory characteristics are
often nonspecific and indistinguishable from those in patients with
acute cholecystitis without gangrene.
Introduction
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The increase of morbidity and mortality in gangrenous cholecystitis
is due to the complications of wall perforation and abscess
formation.
CEUS examination allows to assess the enhancement of the
gallbladder wall and to detect possible areas of absence of
enhancement (Fig 1).
B
A
CEUS
CEUS
Fig 1. A) Nongangrenous acute cholecystitis. Image before and after contrast agent injection
(CEUS) shows homogeneus gallbladder wall enhancement.
B) Gangrenous cholecystitis. Image before and after contrast agent injection (CEUS) shows lack
of enhancement in several zones (arrows) of the gallbladder wall indicative of necrosis.
Objective
The purpose of this study was to determine the usefulness
of contrast-enhanced ultrasound (CEUS) for the diagnostic
assessment of acute gangrenous cholecystitis, with
histopathology as the reference method.
Material and Methods
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During a 15 month period, from December 2011 to March 2013, all
patients with a diagnosis of acute cholecystitis defined by presence of 3
Tokyo criteria (clinical, laboratory and sonographic) subsequently
underwent a CEUS examination.
CEUS examination was performed in 79 patients.
In the analysis we included only sixty–four patients who underwent
cholecystectomies within 24 hours of CEUS. There were 32 men and 32
women who ranged in age from 29 to 89 years old (mean, 70 years).
Fifteen patients were removed of the study because of surgery
performed after 24-hours (n=6) or cholecystostomy (n=9).
The local ethics committee approved the study, and all patients at
enrollment signed a written informed consent.
Material and Methods
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B-mode sonographic findings
prospectively evaluated were:
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wall thickness (fig 1)
fluid-sludge level (fig 2)
lithiasis (fig 1)
wall striations (fig 3)
sloughed membranes (fig 4)
wall interruption (fig 2)
pericholecystic fluid
mural hyperemia (fig 5)
4
3
1
2
+
+
5
Material and Methods
CEUS examination:
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We use a 3-6 MHz convex transducer with a low mechanical
index (MI<0.10). The US machines were an Acuson
Sequoia 512 with CPS software (Siemens, Mountain View,
Calif.) or an Aplio XV with CHI software (Toshiba, Tokio,
Japan)
We employ the sulfur-hexafluoride based, a second
generation echo-signal enhancer (BR-1) injected as a bolus
in units of 2.4 ml through a three-way 20 gauge catheter in
a forearm vein followed by 10 ml of normal saline solution
(0.9% NaCl)
For each examination a recording is begun a few seconds
before the intravenous administration of the contrast agent
and continuous imaging is performed for 60 seconds
The whole examination is stored on the scanner as a video
clip and subsequently sent to a personal computer
Material and Methods
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Before surgery, US and CEUS images were interpreted by four
radiologists in the course of routine clinical care. At the end of the
examination, the radiologist filled out a questionnaire to evaluate
each US feature.
An original on-site CEUS diagnosis of gangrenous cholecystitis was
made when discontinuity of gallbladder wall enhancement was seen
after contrast agent injection (Figure).
A
B
Figure. Gangrenous cholecystitis. Image before (A) and after contrast agent injection (B) shows
lack of enhancement in several zones (arrows) of the gallbladder wall indicative of necrosis.
Material and Methods
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Once the diagnosis of acute cholecystitis was confirmed at surgery,
the video CEUS sequences were retrospectively reviewed by two
experienced abdominal radiologists who were blinded to the first
interpretation and to the final diagnosis, for the presence or absence
of parietal enhancement defects on CEUS.
Homogeneous
enhancement:
Nongangrenous
cholecystitis
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Discontinuity of
gallbladder wall
enhancement:
Gangrenous
cholecystitis
Sonographic diagnosis was compared with macroscopic
intraoperative findings and the histopathology analysis of the
gallbladder specimen. The diagnosis fell into one of three
categories: chronic cholecystitis, acute cholecystitis and gangrenous
cholecystitis.
Material and Methods
Statistical Analysis
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Chronic cholecystitis and acute cholecystitis were fused in one single
category, which we refer to as “non-gangrenous cholecystitis”.
Prospective US data were used to assess the overall sensitivity,
specificity and accuracy of each of the individual B-mode or CEUS
findings for a US diagnosis of acute gangrenous cholecystitis.
Age and thickness wall differences between gangrenous versus nongangrenous patient groups were evaluated with the Student t test
Interobserver agreement was calculated using the kappa statistics.
Results
64 patients: final histological diagnoses were 6 chronic cholecystitis
(9,4%), 10 acute cholecystitis (15,6%) and 48 acute gangrenous
cholecystitis (75%)
Pathological Findings
50
45
40
35
30
Frequency
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25
20
15
10
5
0
Acude
cholecystitis
Chronic
cholecystitis
Chronic
cholecystitis
Acute
cholecystitis
Acude gangrenous
Acute
gangrenouscholecystitis
cholecystitis
Results
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The most common B-mode sonographic findings in gangrenous
cholecystitis were: lithiasis in 95,8% of cases, fluid-sludge level in
72,9%, mural striations in 68,8%, mural hyperemia in 47,9%,
intraluminal membranes in 22,9% and pericholecystic fluid with
hepatic abscess in 4,2%
Gangrenous Cholecystitis
B-mode sonographic findings
hepatic abscess
intraluminal membranes
mural hyperemia
wall striations
biliary sludge
lithiasis
0,00%
20,00%
40,00%
60,00%
80,00%
100,00%
Results
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Wall thickness was greater in patients with nongangrenous cholecystitis than in those with gangrenous
form (6.44±3.41 versus 5.85±2.21), without statistical
significant differences (p=0.429)
Results:
associations between diagnoses and sonographic findings
Non-Gangrenous
Cholecystitis
Acute Gangrenous
Cholecystitis
16
10 (62.5%)
6 (37.5%)
48
15 (31.3%)
33 (68.8%)
0.028
16
12 (75%)
4 (25%)
48
13 (27.1%)
35 (72.9%)
0.01
Lithiasis
Absent
Present
16
3 (18.8%)
13 (81.3%)
48
2 (4.2%)
46 (95.8%)
0.09
Intraluminal membranes
16
15 (93.8%)
1 (6.3%)
48
37 (77.1%)
11 (22.9%)
0.13
Mural hyperemia
Absent
Present
16
9 (56.3%)
7 (43.8%)
48
25 (52.1%)
23 (47.9%)
0.5
Pericholecystic fluid
Absent
Present
16
12 (75%)
4 (25%)
48
27(56%)
21 (44%)
0.18
16
48
<0.001
13 (81.3%)
3 (18.7%)
1
2
10 (20.8%)
38 (79.2%)
5
33
Sonographic features
Gallbladder wall striations
Absent
Present
Fluid-sludge level
Absent
Present
Absent
Present
Wall interruption
(defect of enhancement)
Absent
Present
One
More
p value
Results
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Wall interruption in CEUS was reported in 38 (79,2 %) patients with
gangrenous cholecystitis and in three cases of non-gangrenous
cholecystitis.
n  five cases (10,4%) had only one or two defects of enhancement
n  In 33 cases (68,8%) were reported multiple defects of enhancement
A
B
Figure. Gangrenous cholecystitis. (A) B-mode US: signs of emphysematous cholecystitis; gas in
the gallbladder lumen (arrow), cholelithiasis (curved arrow), pericholecystic fluid (curved arrow).
(B) CEUS: Gallblader wall foci of necrosis (arrows) with lack of enhancement representing
devitalized wall confirmed at surgery.
Results:
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A
Sensitivity, specificity and accuracy of local or widespread absence of
gallbladder wall enhancement on the preoperative CEUS image for a
diagnosis of gangrenous acute cholecystitis were 79,2%, 81,3% and
79,7%, respectively.
B
C
Figure. 77 year-old woman with acute gangrenous cholecystitis. Image before (A) and after
contrast agent injection (B) shows lack of enhancement in several zones (arrows) of the
gallbladder wall indicative of mural necrosis. Corresponding CT scan (C) shows irregular
contour and several defects in gallbladder wall.
Results:
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Interobserver agreement for detection of mural defects of
enhancement was good (k values: 0.592, 0.690 and 0.719).
Sensitivity, Specificity and Accuracy of CEUS for the Diagnosis of
Acute Gangrenous Cholecystitis
CEUS
Gangrenous
Cholecystitis
Reviewer 1
Reviewer 2
On-site lecture
Sensitivity
89.4
88.4
79.2
Specificity
63.7
56.3
81.3
Accuracy
83.9
79.7
79.7
Odds ratio
16.80
10
16,4
Figure. 47 year-old woman with gangrenous cholecystitis. US after
contrast agent injection shows two mural defects of enhancement in
the gallbladder fundus.
Results:
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The radiologic criteria with the highest sensitivity and specificity (and
statistically associated) to the diagnosis of the gangrenous form were
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defects of enhancement (specificity of 81,3%, sensitivity 79,2%)
wall striations (specificity of 62,5%, sensitivity 68,8%)
biliary sludge (specificity of 75%, sensitivity 72,9%)
A
B
Figure. Gangrenous cholecystitis. B-mode sonographic image before (A) and B) after contrast
agent injection show wall striations (A) and defects of enhancement (B).
Results:
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Presence of intraluminal membranes had high specificity (92,8%) but
low sensitivity (22,9%) for detection of gangrenous cholecystitis.
A
B
Figure. Gangrenous cholecystitis. (A) B-mode US scan shows presence of intraluminal
sloughed membranes (arrow), and (B) image after contrast agent injection depicts local
absence of mural enhancement (arrows).
Results:
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No significant differences were found between non-gangrenous
cholecystitis versus gangrenous form in terms of demographic
variables :
Variable
Nongangrenous
cholecystitis
Gangrenous
cholecystitis
p value
Sex
8 men, 8 women
24 men, 24 women
1
Age
60.93±16.6
65.52±19.2
0.38
12426±6178
14170±5302
0.34
WBCC>18000mm3
3 (19%)
12 (25%)
0.75
Duration of symptoms
58.6±38
63±62
0.75
Duration of symptoms>72
7 (44%)
18 (37%)
0.77
White blood cell count
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There were no significant associations between pathologic
diagnosis of gangrenous cholecystitis and the surgical diagnosis
of gangrene (based specially on wall colour)
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Sensitivity 43%, specificity 80%, p = 0.13
Conclusion
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Diagnosis of gangrenous cholecystitis cannot be based
on clinical or laboratory variables.
Local or widespread absence of gallbladder wall
enhancement on CEUS is strongly associated with the
presence of gangrenous acute cholecystitis.
Other sonographic criteria associated with the diagnosis
of gangrenous form are:
q  wall striations and fluid-sludge level.
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