Sincalide Cholescintigraphy: The Essentials

Transcription

1/31/2013
Sincalide-stimulated Gallbladder
Ejection Fraction. Dr. Mark Tulchinsky
Sincalide Cholescintigraphy:
g p y
The Essentials
Mark Tulchinsky, MD, FACNP
Professor of Radiology and Medicine
Penn State University College of Medicine
Hershey, Pennsylvania
[email protected]
Disclosure: Investigator, Consultant and Lecturer for
Bracco Diagnostic, Inc.
Postprandial or
Post-CCK
Fasting
Costoff A. Gastrointestinal Physiology: Biliary Secretion and Excretion.
http://www.lib.mcg.edu/edu/eshuphysio/program/section6/6ch5/s6ch5_12.htm
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Radiopharmaceuticals
Proposed bis structure of 99mTc-IDAs
Lidofenin
Disofenin (DISIDA)
[[(2,6-Xylylcarbamoyl)
methyl]-iminodiacetic acid
[[(2,6-Diisopropylphenyl)carbamoyl]
-imino]diacetic acid
Mebrofenin (BromIDA)
[[[(3-Bromomesityl)carbamoyl]
Methyl]-imino]diacetic acid
NCBI PubChem. http://pubchem.ncbi.nlm.nih.gov/
Uptake of IDA is facilitated by carrier-mediated, non-sodium
dependent, organic anionic pathway – similar to bilirubin
IDA (
)
Radiopharmaceutical extracted by hepatocytes and transported without modification
Illustration by M. Tulchinsky
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Preparation for the GB
Examination
1. Select patients who are in their usual state of
health (or illness) – NOT AN INPATIENT
2. Exclude the use of opioids (four half lives of
a drug)
3. A fatty snack at 8-9 PM (empty out the GB)
4. Fasting after the snack (filling phase in AM)
5 Pre-treat with CCK
5.
CCK, if NPO longer than 24
hours (should not be an issue, if #1 is true)
6. Schedule for early AM imaging, if possible
(minimize inconvenience of long fasting)
Tulchinsky M. Hepatobiliary Scintigraphy. In: Diagnostic Nuclear Medicine, 2nd revised
edition. Published 2005 Springer.
Hepatobiliary Scintigraphy:
Imaging Sequence
•
•
Baseline one-hour dynamic imaging depicts
parenchymal uptake,
uptake bile excretion
excretion, and
passage – can be replaced by anterior, right
lateral and left anterior oblique spot static
imaging at 1 hr post-injection
Post sincalide dynamic imaging, carried out
for 60 minutes (optimum protocol), depicts
response to a stimulant (sincalide is
recommended)
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HBS: Digital Set-Up
•
Pre-sincalide Imaging
–
60 minute dynamic
y
acquisition,
q
60 sec/frame, anterior
(posterior is optional) projection(s), 128x128x16 matrix
• Display in 15 frames (4 min/frame)
or
–
2 or 3 static images to determine GB filling
• Anterior, Right Lateral, Left Anterior Oblique (in order of
preference) for 2 min each, 256x256x16 matrix
•
Post-sincalide Imaging
–
–
–
Acquire dynamically for 60 min, 60 sec/frame, in left
anterior oblique projection
Display in 15 frames (4 min/frame)
Calculate gallbladder ejection fraction (GBEF)
In anterior view the activity in the duodenum often
contributes to (interferes with) activity in the
gallbladder region!
Anterior View
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Anterior View
40o
Left Anterior Oblique view separates GB from duodenal
activity – makes good anatomical sense!
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40o LAO – Separates GB from Duodenal Activity
Gallbladder Ejection Fraction
Determination
•
Stimuli:
Cholecystokinin 8 (sincalide) IV
Cholecystokinin-8
– Fatty meal
–
•
GBEF calculation:
Net GB counts max – Net GB counts min x 100%
Net GB counts max
Tulchinsky M, Ciak BW, Delbeke D, et al. SNM practice guideline for hepatobiliary
scintigraphy 4.0. J Nucl Med Technol. 2010;38:210-218.
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Clinical Presentation
•
Chronic disease (including functional) –
often atypical clinical presentation:
Patients often referred for numerous
expensive anatomical imaging procedures,
often negative, over a long period of time
– Stones in the GB may or may not be present –
GB dysfunction is the key diagnostic finding
– Surgery,
Surgery cholecystectomy,
cholecystectomy is the only
treatment option (except in SOD)
–
SOD = Sphincter of Oddi Dysfunction
Chronic Gallbladder or Biliary
Disease: Spectrum of Conditions
•
Acalculous
Biliary dyskinesia
– Gallbladder dyskinesia
– Chronic acalculous cholecystitis
– Chronic acalculous biliary disease
– Acalculous biliary disease
– Cystic duct syndrome
– Gallbladder spasm
– Functional Gallbladder Disorder
–
•
Calculous
–
Chronic calculous cholecystitis
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Historical Normal Values
1.
2.
3.
4.
5.
6.
7.
Min/µg per kg (Ref.)
GBEF (M±S.D.)
Range
n
1/0.02 (3)
3/0.04 (1)
3/0.02
/ . ((1))
3/0.02 (5)
3/0.01 (4)
10/0.01 (6)
15/0.02 (2)
30/0.01 (5)
30/0.02 (5)
45/0.015 (3)
45/0.015 (7)
60/0.01 (4)
52±42%
43±26%
35±17%
7%
56±27%
46±20%
76±16%
76±22%
64±20%
70±22%
77±23%
75±12%
68±16%
12-92%
15-88%
17-59%
7 9%
0-100%
12-74%
37-96%
32-98%
26-95%
17-97%
65-96%
65
96%
>40%‡
15-88%
22†
12
6
23
20
13
15
14
23
22†
40
20
Mesgarzadeh M, Krishnamurthy GT, et al. J Nucl Med. 1983; 24 (8):666-71.
Raymond F, Lepanto L, Rosenthall L et al. Eur J Nucl Med. 1988; 14 (7-8):378-81.
Sarva RP, Shreiner DP, Van Thiel D et al. J Nucl Med. 1985; 26 (2):140-4.
Ziessman HA, Muenz LR, Agarwal AK et al. Radiology. 2001; 221 (2):404-10.
Ziessman HA, Fahey FH, Hixson DJ. J Nucl Med. Apr 1992;33(4):537-541.
Krishnamurthy GT, Brown PH. J Nucl Med. Dec 2002;43(12):1603-1610.
Yap L, et. al. Gastroenterology. Sep 1991;101(3):786-793.
† patients rather than normal volunteers
‡ 99% confidence limits
The Pivotal Study of Normal
Values for CCK-HBS
•
Establish which infusion protocol has the
least variabilityy in GBEF:
0.02 µg/kg over 15 min
– 0.02 µg/kg over 30 min
– 0.02 µg/kg over 60 min
–
•
•
Evaluate the methods in healthy
individuals – 60 volunteers
The next step would be to take the best
infusion method and test it in a
randomized controlled clinical trial
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Normal Values – Multicenter Study
of 60 Volunteers
Min/µg per kg GBEF (M±S.D.)
(M±S D ) GBEF Range
GBEF<35%
CV(%)
15/0.02
30/0.02
60/0.02
16/60 (27%)
6/60 (10%)
0/60
52%
35%
19%
56.9±29.4%*
70.9±24.5%*
84.3±15.5% *
-2 to 98%
8 to 99%
38 to 100%
* Significantly different from other 2 infusion rates, p < 0.0001
Current Recommendation:
0.02 mcg/kg of Sincalide over 60 min
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Interpretation of GBEF Results
•
•
GBEF ≥ 38% - normal GB function
GBEF < 38% - Abnormal
Ab
l GB ffunction.
ti
I
In
the proper clinical setting is consistent with
functional gallbladder disorder:
Clinically, suffering from chronic episodes of
biliary pain
– No gallstones on US
–
•
With gallstones the combination would
suggest chronic calculous cholecystitis
Fatty Meal vs. CCK?
• CCK1 = 75.8 ± 16.3%
• CCK2 = 71.3 ± 17.4%
• MEAL = 53.6 ± 20.2%
Excluded were 8/21 prescreened because GBEF <35% after 3 minute injection
Krishnamurthy GT, et al. J Nucl Med. 2002;43:1603-1610.
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CCK vs. Fatty Meal Stimulation
•
CCK infusion has a more predictable rate
of GB contraction
Maximum GB emptying occurs shortly (within
few minutes) after infusion ends
– Independent of gastric emptying
–
•
Fatty meal has a less predictable rate of
GB contraction
It takes longer (variable) time to reach
maximum contraction
– Normal gastric emptying is required
–
Which statement is true about administration
of sincalide or fatty meal for the study of
gallbladder ejection fraction in stable
patients with chronic abdominal pain and
multiple gallstones?
A. It is relatively contraindicated
B. Should be avoided because of high
frequency of abdominal pain during
gallbladder stimulation
C Results in abnormal ejection fraction in
C.
more than 85% of such patients
D. The ejection fraction is normal in over 50%
of such patients
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There are many practitioners who are concerned about giving
sincalide or fatty meal to patients with gallstones. There is no
evidence in the literature to support this concern. Cholelithiasis is
not listed among the contraindications in sincalide package insert (A
is wrong). It makes intuitive sense to expect higher rate of
abdominal p
pain in those p
patients during
g sincalide or fatty
y meal
stimulation. However, this concern was not substantiated in clinical
trials. In fact, abdominal pain was experienced by only one out of 67
patients with gallstones during sincalide infusion in one study (1),
hence answer B is wrong. In another study of such patients 77.4%
had normal ejection fraction (2); therefore, answer D is correct and
C is incorrect. Most unselected patients with gallstones who are
referred for gallbladder ejection fraction would be expected to have
a normall ejection
j ti ffraction.
ti
References:
1.
Gani JS. Can sincalide cholescintigraphy fulfil the role of a gall-bladder
stress test for patients with gall-bladder stones? Aust N Z J Surg. 1998;68:514-519.
2.
Hong SN, Lee JK, Lee KT, et al. Usefulness of gallbladder ejection fraction
estimation to predict the recurrence of biliary pain in patients with symptomatic
gallstones who did not undergo cholecystectomy. Dig Dis Sci. 2004;49:820-827.
Multiple GB stones:
Is it safe to give sincalide (CCK)?
Case 3
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Multiple GB stones:
Is it safe to give sincalide (CCK)?
If you do proceed with hepatobiliary study, would the GB fill?
If it does fill, what is your prediction on resulting GBEF?
Case 3
Anterior View
Case 3
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LAO View
Case 3
Case 3
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Which statement is true about gallbladder
nonvisualization during 60 minutes after
radiopharmaceutical injection to a properly prepared
patient with suspected functional gallbladder disorder
and no symptoms during or within past 3 days prior to
hepatobiliary scintigraphy?
A. The patient likely having acute cholecystitis
B. The finding indicates abnormal gallbladder
and no further imaging is needed during this
test
C Morphine augmentation is indicated to make
C.
sure the gallbladder fills during this study
D. The patient should have delayed images until
the gallbladder activity is demonstrated
Not seeing the gallbladder during 60 minutes of cholescintigraphy is an
abnormal finding and can be seen in chronic or acute cholecystitis.
However, acute cholecystitis is associated with symptoms and signs of
this illness, therefore, it is unlikely in the described patient (answer A is
incorrect). Normal individuals who are properly prepared for the
hepatobiliary scintigraphy invariably show gallbladder activity during the
fi t 60 minutes
first
i t off observation.
b
ti
It was found
f
d to
t be
b true
t
in
i 60 normall
volunteers who were imaged three separate times in one study (1),
which amounts to gallbladder visualization by 60 minutes in every one of
180 tests of patients with normal gallbladder function. Therefore, not
seeing the gallbladder during 60 minutes is definitely abnormal (answer
B is correct). There is no further information to be obtained in the
described patient by manipulations aimed at filling the gallbladder
((options
p
C and D are incorrect)) later,, either by
y morphine
p
or delayed
y
imaging. The most that such manipulation can offer is differentiation of
acute from chronic cholecystitis. This would be a senseless exercise in
someone who is having no symptoms or signs of acute cholecystitis.
1. Ziessman HA, Tulchinsky M, Lavely WC, et al. Sincalide-stimulated cholescintigraphy: a
multicenter investigation to determine optimal infusion methodology and gallbladder
ejection fraction normal values. J Nucl Med. 2010;51:277-281.
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29 Y/O FEMALE WITH CHRONIC, INTERMITENT
ABD/P, ASYMPTOMATIC IN THE PAST 5 DAYS
Abdominal CT 5 days ago was normal, patient is
asymptomatic around time of imaging
Activity in the duodenum - no GB visualization at 1 hour =
abnormal study = gallbladder dysfunction
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No GB visualization after morphine
Doesn’t mean acute cholecystitis in asymptomatic pt!
Further imaging after the 1st hour contributes
nothing except possible confusion.
17

Sincalide Cholescintigraphy: The Essentials

Transcription

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