This document discusses functional hepatobiliary diseases, including chronic acalculous cholecystitis, gallbladder ejection fraction testing, and sphincter of Oddi dysfunction. It provides details on protocols for gallbladder ejection fraction testing using cholecystokinin cholescintigraphy or fatty meal stimulation. An abnormal ejection fraction below 35% may indicate gallbladder dyskinesia. Sphincter of Oddi dysfunction can cause post-cholecystectomy pain and be diagnosed using cholescintigraphy by detecting delayed biliary clearance after CCK administration. Therapies may include sphincterotomy or drugs to relax the sphincter of Oddi.

1. Functional hepatobiliary
disease
Done by : Dr. Mahmoud Alzoubi
Supervised by : Dr. Ola Attieh

3. Chronic Acalculus
Cholecystitis
 relatively uncommon in comparison to
chronic calculous cholecystitis
 RUQ pain and biliary colic, but have a
completely normal work-up, including
a normal ultrasound and hepatobiliary
study

4. Gallbladder Ejection Fraction
 Abnormal gallbladder ejection
response to CCK : Patients with
chronically inflamed, partially
obstructed, or functionally impaired
gallbladders (gallbladder dyskinesia).
 An abnormal gallbladder ejection
fraction is considered less than 35%
and is not affected by age

5. Protocol for Cholecystokinin
Cholescintigraphy for
Gallbladder Ejection Fraction

6.  Routine cholescintigraphy:
1. The patient should have nothing by
mouth for 4 hours before the exam. If
fasting over 24 hours, the patient should
receive a slow infusion of CCK before
initiating the study. After CCK infusion, wait
30 min before radiopharmaceutical injection
to allow time for the gallbladder to relax.
2. Camera: Large field of view, anterior
projection
3. Computer set-up: 60 one minute frames
4. Patient set-up: Supine
5. Inject Tc-99m-mebrofenin or Tc-99m-
disofenin 5 mCi (185 MBq) I.V.
6. After the gallbladder has filled, usually at
60 minutes, commence setup for CCK
cholescintigraphy

7.  CCK Cholescintigraphy:
1. Computer set-up: 30 one minute frames
2. Place camera in the left anterior oblique
projection to minimize overlap of gallbladder,
small bowel, and common duct activity.
3. Infuse 0.02 ug/kg sincalide diluted in a 30-mL
volume continuously over 30 minutes using a
constant infusion pump or volutrol for
intravenous rate control. Recently, a 60 minute
infusion has been suggested to provide more
consistent gallbladder contractility with imaging
and quantification over the entire 60 minute
period .
4. On the computer, draw a region of interest
around the gallbladder and adjacent liver
background.
5. Generate a gallbladder back-ground corrected
time-activity curve.
6. Calculate the percentage of gallbladder

15.  Rapid injection of Sincalide may cause
spasm of the cystic duct/gallbladder
neck which will impair emptying of the
gallbladder and falsely lower
gallbladder ejection fraction
 abdominal cramping and nausea can
be seen in 50% of healthy subjects

16.  An alternative to the use of sincalide is to
have the patient consume a fatty meal (at
least 10 gm of fat).
 fatty meal ejection fractions can vary widely
(from 24% to 92%) and can be affected by
the meal content and the duration of imaging.
 maximal gallbladder emptying is generally
seen 55 to 60 minutes following consumption
of the meal.
 For a lactose-free Ensure Plus meal the
normal gallbladder ejection fraction is greater
than 33%

17.  An abnormal gallbladder ejection fraction is
not necessarily diagnostic of chronic
cholecystitis. Chronic diseases such as
sprue, diabetes, achalasia, sickle cell
disease, and irritable bowel syndrome have
also been associated with a low GBEF.
Certain drugs can also falsely lower GBEF
including morphine, atropine, octreotide,
nifedipine, progesterone, and phentolamine.
It is very important to ensure that the patient
has not taken opioids during the 24 hours
prior to the exam as these agents can result
in a falsely decreased GBEF.

19. Medications and Physiologic
States which can alter
gallbladder contractility:
 Morphine: Produces spasm of the sphincter of Oddi.
Morphine has a 4 to 6 hour half-life, but approximately 50% of
patients who receive sincalide subsequent to having been
administered morphine during cholescintigraphy have normal
gallbladder contraction.
 Atropine: Inhibits gallbladder emptying
 Calcium channel blockers: Reduce contractility by interfering
with calcium mediated smooth muscle contraction
 Diabetes: Neuropathy has been associated with decreasing
contractility
 Truncal vagotomy: Results in decreased gallbladder
contractility and increased gallbladder volume due to
disruption of the cholinergic pathway.
 Achalasia- decreases ejection fraction by 50%
 Octreotide therapy
 Cholinergic medications: Enhance gallbladder emptying
 Hypercalcemia: Enhances contraction

20. Sphincter of Oddi Dyskinesia:
(Biliary Dyskinesia)
 A functional disorder of the biliary tract
which is felt to be related to a
paradoxical response of the sphincter of
Oddi to CCK (Contraction rather than
relaxation). Patients complain of RUQ
pain and the disorder can be found in
both pre- and post cholecystectomy
patients.
 On manometry, these patients are found
to have elevated sphincter of Oddi
pressures (over 20 mm Hg).
 Treatment is sphincterotomy or
sphincteroplasty.

21.  Scintigraphic findings in this
syndrome include delayed biliary-to-
bowel transit and a dilated common
duct sign (due to failure of the
sphincter of Oddi to relax) after CCK
administration.
 Paradoxical filling of the gallbladder
following sincalide administration can
also be seen.
 These patients, however, tend to have
a normal gallbladder ejection fraction.

22.  Partial biliary obstruction after cholecystectomy. HIDA images at 1
hour (left) and 2 hours (right). At 1 hour considerable retained
activity in the common duct and proximal ducts is seen. At 2 hours,
the liver has cleared but, the common duct continues to retain
activity. This patient had sphincter of Oddi obstruction that required
subsequent sphincterotomy.

23. Sphincter of Oddi Dysfunction
 Sphincter of Oddi dysfunction occurs in
approximately 10% of patients with the
postcholecystectomy pain syndrome.
 It presents as intermittent abdominal pain and
sometimes transient liver function
abnormalities.
 It is a partial biliary obstruction at the level of
the sphincter of Oddi, not caused by stones
or stricture.
 It presents after cholecystectomy, possibly
because the gallbladder had been acting as a
pressure release valve, decompressing the
biliary ducts with increases in pressure,
preventing pain.

24.  Patients have been classified clinically into 3
categories.
 In type I, enzyme elevations are seen, with
pain episodes and dilated biliary ducts.
 In type II, either enzyme elevations or dilated
biliary ducts occur.
 Type III presents with only pain.
 Patients with type I are the most easily
diagnosed.
 Patients with types II and III are more
diagnostically challenging; cholescintigraphy
may have a role in these cases.

25.  Therapy is usually sphincterotomy, particularly for a
fixed obstruction (papillary stenosis), whereas a
functional and reversible obstruction (biliary
dyskinesia) may temporarily respond to drugs (e.g.,
nifedipine) and toxins (e.g., Botox).
 Sonography, CT, and MRCP often are not
diagnostic.
 Sphincter of Oddi manometry has been regarded as
the gold standard, with an elevated sphincter
pressure (>40 mm Hg) being diagnostic. However,
this technique is invasive, not widely available,
technically difficult, prone to interpretative errors,
and associated with a significant incidence of
adverse effects, notably pancreatitis.
 ERCP is ultimately used to exclude cholelithiasis or
stricture; however, it is invasive and associated with
a high Incidence of postprocedure complications,

26.  The value of cholescintigraphy is
controversial. Evidence- based data are
lacking. However, multiple singlecenter
studies have shown it to be useful and is
routinely performed at some biliary
referral centers.
 Early studies suggested that image
analysis alone can be diagnostic with
findings of a partial biliary obstruction—
that is, delayed biliary duct clearance at
60 minutes with no further clearance
between 1 and 2 hours

28.  Thank you 