Margaret R. Khouri, Adrian Marcus, MD
MD
#{149} Jeannete
B. Goldszmidt, Wisniewski, RT
#{149} Frances
Intact Stones in the Imaging Extracorporeal
MD #{149} Olle
#{149}Igor Okberg,
Laufer, MD MD #{149} Peter
#{149} Peter Arger, F. Malet, MD
or Fragments? Potential of Patients after Biliary Shock Wave Lithotripsy’
MD
Pitfalls
Ultrasound is used after extracorporeal shock wave lithotripsy of gallbladder stones to assess f ragmentation. In many patients with apparently successful fragmentation, the posttreatment studies show an intraluminal, echogenic focus within
the
gallbladder,
with
poste-
nor acoustic shadowing characteristic of an intact stone. Cholesterol gallstones were fragmented in vitro by means of lithotripsy, and the sonographic appearance of the f ragmented stones was followed up over time to study factors that might affect the process. After lithotripsy, fragments settled and produced an echogenic focus with posterior shadowing indistinguishable from the appearance of an intact stone. These experimental observations led to the development of a clinical maneuver to overcome the diagnostic pitfalls posed by the reaggregation of stone fragments in situ. This rollover maneuver helps distinguish between intact stones and fragments, and prevents both diagnostic errors in follow-up and unnecessary retreatment. Index terms: Gallbladder, sy
Gallbladder, calculi, US studies, 762.12981
762.2897. Lithotrip-
#{149}
Figure 1. Sonographic stone. Cursors indicates 10 shock waves, but this indistinguishable from
E
1990;
den stones is a promising new py for patients with cholelithiasis In evaluating results of ESWL, sound
(US)
cult
and
Treat-
of Medicine
and Radiology (J.B.G., IL., PA., AM., F.W., 0.0.), University of Pennsylvania and Veterans Administration Medical Center (M.R.K., P.F.M.), University and Wood(M.R.K.,
P.F.M.)
land Ayes,
Philadelphia,
PA 19104. From
the
1989 RSNA scientific assembly. Received May 18, 1989; revision requested June 20; revision received April 6, 1990; accepted April 16. Ad-
dress reprint requests See also the articles
to M.R.K.
by Zeman et al (pp 157161), Zeman et al (pp 163-166), and Shapiro and Winsberg (pp 153-156) in this issue. c RSNA, 1990
the
the
posttreatment
US
studies
shown an intraluminal, echofocus within the gallbladder, posterior acoustic shadowing,
characteristic 2). These
the
be-
intact and fragmented stones US (Fig 1). In many patients apparently successful fragmen-
have genic with From the Gallstone Evaluation ment Center of the Departments
ultra-
to distinguish
of an aggregates
immediate
in some
complete 2 mm
patients.
intact are
post-ESWL In other
fragmentation or less
in diameter
stone detected
ing
the
and
suggesting
appearance
ments
(1).
to determine
or impossible
tation,
I
is used
thera-
extent of fragmentation and the need for netreatment. However, the accuracy of sonography in this setting has not, to our knowledge, been validated. In in vitro studies, it may be diffi-
with with
177:147-151
b. images of in vitro fragmentation. (a) Appearance of an intact gallfocal point of shock waves. (b) The stone in a was fragmented with image shows an echogenic focus with posterior shadowing that is an intact stone.
XTRACORPOREAL shock wave lithotripsy (ESWL) of gablblad-
tween
Phantoms
#{149}
Radiology
a.
(Fig on
US studies patients,
to particles is docu-
mented with immediate posttneatment US studies of the gallbladder. However, in the latter patients, an echogenic focus with posterior acoustic shadowing is detected within the gallbladder 24 hours after ESWL, giv-
have
ped.”
of an
that
the
intact
meaggmegated,
We define
stone
stone
frag-
on “clum-
neaggregation
as the
reversible phenomenon by which fragments of gallstones form a mass that has the sonognaphic features of an intact stone: an echogenic focus within the gallbladder, with postemior acoustic shadowing. The purpose of this
was
(a) to examine
sonographic fragmented lithotnipsy,
course
experiment
the
sequential
appearance of gallstones in vitro with shock wave (b) to study the time
of aggregation
fragments,
cal maneuver
and
on clumping
(c) to develop
to overcome
tial diagnostic pitfalls clumping phenomenon.
MATERIALS
AND
the
posed
of
a clini-
potenby
the
METHODS
Twenty gallstones were collected from three gallbladders (gallbladder A, gallbladder B, and gallbladder C) obtained at
Abbreviations:
ESWL
wave
UDCA
lithotripsy.
extracorporeal ursodeoxycholic
shock
acid.
147
a.
b.
Figure
2.
Sonographic
images
before
intact gallstone, 27 mm in diameter, successful ESWL with 1,500 shock ance (cursors indicate stone size).
stone
fragments?
and
after
ESWL
in a patient.
before treatment. (b) After waves, there is little change Does this represent a treatment
(For the answer,
(a) The appearance
of an
the completion of apparently in the sonogmaphic appearfailure or clumping of
see Fig 7.)
a. cholecystectomy. bladder
A
tainers
and
The
10 stones
from
gall-
were stored dry in airtight conwere rehydrated for 1 week in
saline before the experiment. The stones from gallbladders B and C were stored in physiologic saline (0.9% sodium chloride) in airtight containers. Chemical analysis of gallstone composition was performed on representative stones from each gallbladder, according to the method of Trotman et al (2). The cholesterol content of each of the representative stones was determined to be greater than 95%. The diameter and weight of all stones were measured. The 20 representative gallstones (10 stones from gallbladder A, five stones from gallbladder B, and five stones from gallbladder C) selected for the experiment had a mean diameter of 10.85 mm ± 0.26 (mean ± standand error of the mean) and a weight of 49.8 g ± 0.01. Punfied mucin was obtained from Sigma Chemical Company, St Louis. Ursodeoxycholic acid (UDCA) was a gift from Ciba Pharmaceutical Company, Summit, NJ. Latex condoms were obtained from Carter Products (Carter-Wallace, New York, NY).
In Vitro
Experimental
Design
If cholesterol stones do reaggregate after ESWL, then the physical properties of gallbladder bile that promote on inhibit the formation of cholesterol gallstones might affect the clumping phenomenon. Two important factors that enhance cholestenol gallstone formation are the saturation of bile with cholesterol and its glycoprotein content (3-9). UDCA, the adjuvant bile salt administered to individuals undergoing ESWL, decreases the saturation of cholesterol in bile (10-12) and might be expected to inhibit the reaggregation of cholesterol stones after ESWL. Conversely, mucin, a glycoprotein that promotes the nucleation of cholesterol monohydrate crystals in saturated bile (69), might be expected to accelerate the meaggregation of cholesterol stones after ESWL. Because UDCA and mucin in the gallbladder might affect the reaggrega148
#{149} Radiology
tion
or clumping
these
ESWL,
of gallstones
chemicals
after
were
added
to a
solution of physiologic saline for the in vitro experiment. Each gallstone was placed in a condom containing 75 mL of physiologic saline with various concentrations of UDCA and a mucin concentration of 4 mgidL. Saline was chosen as the basic test solution
instead
of a model
bile
solution
to
limit the number of variables studied in this series of experiments. The concentration of UDCA was varied from 25 mM to 100 mM to study the effect of UDCA over the
range
of concentrations
of UDCA
found in the bile of patients treated with oral UDCA (13,14). The mucin concentration (4 mgidL) was used to approximate the physiologic concentration of mucin within the gallbladder in vivo (15). The control
solution
was
0.9%
saline
b. Figure 3. Experimental device for in vitro fragmentation. (a) A chamber filled with degassed water is situated the water cushion. (b)
without
a single
UDCA on mucin. The pH of all test solutions was 8.0 to approximate the pH of gallbladder bile (16). Five experimental conditions
were
created:
(a)
0.9%
C were
tested
mental
solutions.
Shock
Wave
in
in
each
of the
Lithotripsy
expeni-
of Stones
Gallstones were fragmented with a Donnien MPL 9000 lithotniptor (Dornier Medical Systems, Marietta, Ga). Shock waves were generated via an underwater spank discharge and were focused with ellipsoid.
The
electrode
is suspended
with-
The gallstone of the shock
is
wave.
Vitro
rotating
stone chamber. focal point
saline
(the contnol), (b) 0.9% saline with 4 mgi dL mucin, (c) 25 mM UDCA in 0.9% saline with 4 mgidL mucin, (d) 50 mM UDCA in 0.9% saline with 4 mgidL mucin, and (e) 100 mM UDCA in 0.9% saline with 4 mgi dL mucin. Stones from gallbladders A, B, and
cholesterol
in the water-filled positioned at the
and secured above A condom containing
was
a
dis-
carded after 1,500 discharges. A single gallstone was placed in a condom contaming 75 mL of one of the experimental solutions. The condom was immersed in a chamber of degassed water, with the gallstone positioned in the shock wave focus of the underwater spank discharge (F2, or the point of greatest energy) (Fig 3). The course of fragmentation was monitored
continuously
with
US.
The
stones
were
fragmented to a particle diameter of 1 mm on less with 100 shock waves genenated at an energy of 16 kV. Fragment size was assessed with a superimposed measure. After delivery of 100 shock waves, the condoms were removed from the Waten bath and manipulated so that stone fragments were dispersed throughout the volume of the solution in the condoms. At 1 hour, 24 hours, 7 days, and 14 days after the lithotnipsy procedure, the condoms
were
stone
fragments
sonographic was repeated.
again
manipulated
were
that
and
imaging in the water bath For each of the intervals
tween sonognaphic doms were suspended at room temperature.
US
so
dispersed,
be-
observations, the conin Styrofoam cups
Scanning
The course of fragmentation was monitored continuously with the in-line and side-arm transducers of the Donniem lithotniptor. The entire procedure was recordOctober
1990
l
Figure
4. Sonognaphic images of progresof in vitro fragmentation. (a) Appearance of the intact stone in the experimental setup. The cursors represent the focal point of the shock wave. (b) Appearance after fragmentation of the stone with 100 shock waves generated at 16 kV. There is a large echogenic focus with acoustic shadowing in the dependent portion of the condom. sion
b.
a.
a.
b.
Figure 5. Sonographic images of the rollover (b) The “cloud of dust” appearance represents are confined to the fundus of the gallbladder. neuver.
maneuver in situ. (a) Intact stones as seen fragmentation of the stones after treatment (c) Dispersion of the fragments throughout
ed on videotape, with the video camera focused on the condom within the water bath. For each procedure, a static sonographic image was obtained after 50 and 100 shock waves were delivered. US scanning of each stone was then performed at
showed a “cloud of dust” appearance due to the swirling of stone fragments in the solution. US scanning
5 minutes, days
after
1 and the
24 hours,
procedure,
nipulation of the the condoms.
Clinical Vivo
stone
Fragment
and
7 and
following
fragments
14 ma-
within
Dispersion
in
In patients who had undergone gallstone ESWL, a clinical maneuver was deveboped to disperse stone fragments within the gallbladder. Patients were notated 360#{176}, with sonographic imaging of the gallbladder performed before and after rotation. This procedure, termed the “rollover maneuver,” is now routinely used in all patients who have undergone gallstone ESWL at our institution.
RESULTS Before in vitro lithotmipsy, the image of the intact stone revealed
US an
echogenic focus with posterior acoustic shadowing (Fig 4a). During the course of lithotmipsy, US monitoring Volume
177
#{149} Number
1
after
50 shock
waves
showed
c. before ESWL treatment (cursors indicate size). with 1,500 shock waves. Note that the fragments the gallbladder can be seen after the rollover ma-
multi-
pie echogenic foci scattered throughout the condom, with greater echogenicity in the dependent portion. Successful fragmentation of gallstones to a fragment diameter of 1 mm on less was achieved after 100 shock waves were applied to all sampies. After 100 shock waves, fragments settled rapidly, producing increasing echogenicity in the dependent portion of the condoms (Fig 4b). US scanning 5 minutes after the pro-
cedure
showed
a single
echogenic
fo-
cus in all 20 condoms, with sharp posterior acoustic shadowing in one. At 1 hour, a round, echogenic focus with acoustic shadowing was observed in 12 of 20 specimens. Sonographic evaluation at 24 hours after lithotnipsy showed an echogenic focus with acoustic shadowing in all 20 specimens. At 7 and 14 days after the procedure, the US appearance of fragments was unchanged from that seen on the 24-hour images. There was no difference in the US appear-
ance
of the
suits
for
fragments
stones
when
from
the
me-
gallbladdems
A,
B, and C were compared. Neither the concentration of UDCA non the presence of mucin affected the results. When the condoms were invented, the fragments were easily dispersed, reproducing the US appearance of the cloud of dust until the fragments settled and me-created of the intact stone. These results were
the applied
treatment
undergoing
of patients
gallbladder
image
ESWL.
of the
was obtained (Fig 5a). After shock waves,
were
confined
within
fundus
creating
appearance
of the
the
gall-
before treattreatment with the fragments
to the
gallbladder,
to the
A sonognaphic
stones
bladder ment 1,500
appearance
the
of the
sonognaphic
cloud
of dust
(Fig
5b). The patient was then asked to notate 360#{176}to disperse the stone fragments throughout the gallbladder,
and
scanning
This technique tinely in all ESWL.
was has patients
A retrospective rollover
maneuver
repeated
(Fig
been applied undergoing
evaluation was
done Radiolov
5c). rou-
of the by
re-
149
#{149}
a.
b.
Figure 6. Value of the rollover pearance 1 day after apparently rollover
later,
maneuver,
numerous
the echogenic
focus
maneuver successful small
and
fragments
posterior
The
valuable
rollover
maneuver
in dispersing
ments
and
about
the
of stone studies.
size,
was
clumped
providing
frag-
information
number,
fragments
and
mobility
in 30 of the
54
DISCUSSION Sonogmaphy
is routinely
used
evaluate the results of ESWL bladder stones to determine fragmentation has occurred. patients with successful tion, posttreatment US
an echogenic focus acoustic shadowing, an
intact
stone,
fragments “clumped.”
fect
with posterior characteristic
finding in vivo
of clumped
diffithe ef-
on the
accuracy of sonographis unknown. Since
of gallstone
after the miare based on the
fragments
sonographically, able to distinguish ments from intact
ments
on of this
has been because
criteria for metreatment tial ESWL procedure
fragments. In this
of
the
fragments
precision and ic measurements
size
fragmentastudies show
have meaggregated, The significance
sonographic cult to assess
to
of gallwhether In many
suggesting
study,
of 1 mm
depicted
it is important to be clumped fmagstones and large
when
gallstone
or less
fmag-
in diameter
pooled in the dependent portion of the condoms, they met the sonographic criteria of a gallstone (17). Specifically,
they
were
echogenic focus within with posterior acoustic After
manipulation
to disperse throughout 150
#{149} Radiology
the the
seen
fluid
as an
the lumen, shadowing.
of the
stone
condoms
fragments volume,
are
seen
shadowing
viewing 54 sonographic studies performed in 20 patients before and at 24 hours and 3 and 6 months after ESWL.
C.
in distinguishing ESWL treatment
the
between suggests dispersed
intact and fragmented stones, as seen on sonographic that there is a large stone fragment (cursors indicate
throughout
the
gallbladder.
There
was
no
large
images. (a) Apsize). (b) After the
fragment.
(c) Five
minutes
reappear.
cloud-of-dust
ance
sonographic
was
appear-
reproduced.
The
cloud-of-
dust appearance corresponded visuably to the swirling of fragments within the medium. Within minutes, the fragments settled and re-created the sonogmaphic image of an intact stone. These in vitro results suggest that there may be pitfalls in the interpretation of the sonographic images of the gallbladder after ESWL. Although gallbladder mucin has been reported to promote the nudeation of cholesterol in solution (6-9),
we found
that
mucin
had
no effect
on the clumping phenomenon in vitro. Similarly, UDCA, a bile salt that promotes the solubilization of cholesterol in solution (10-12), had no effect on development of clumping. These results, however, must be intenpmeted with caution. More infonmation is needed on the frequency of clumping in patients treated with
UDCA
after
ESWL
the frequency with a placebo,
cance into
the
of this
compared
with
in patients treated before the signifi-
phenomenon
can
be put
perspective.
The phenomenon of clumping and resulting overestimation of fmag-
ment
size
Choyke
was
also
et al (18)
evaluation
observed in the
of patients
by
renal
stone
from
a clump
fragments, in practice this distinction may be difficult. Our clinical experience and that others indicate that the evaluation
patients
of
of of
after
be subject
gallbladder
ESWL
to sonographic
pitfalls
may
sim-
ilar to those encountered in the evaluation of renal calculi after ESWL. Our in vitro experimental observations led to the development of a clinical maneuver to overcome the diagnostic pitfalls posed by the clumping phenomenon in situ. For imaging the gallbladder after ESWL,
an initial
US scan
patient
sition
ESWL. They demonstrated that a densely packed clump of fragments in the renal calyx may exhibit sharp acoustic shadowing, which is chanactemistic of intact renal calculi. The authors state that while sonography theoretically should help differenti-
ate an intact
7. Sonographic image of same patient as in Figure 2, after ESWL treatment. After the rollover maneuver, dispersion of fragments in the gallbladder can be seen.
the
sonographic
after
Figure
lying
(either
prone
is obtained in the
or supine)
6a). The patient is then tate 360#{176}, and scanning
with
treatment
po(Fig
asked to nois repeated.
With this maneuver, clumps dispense and reproduce the sonographic cloud of dust (Fig 6b). When an echogenic focus is due to fragment clumping, the rollover maneuver is valuable in dispersing fragments. Within mmutes, fragments reaggregate and may mimic the sonographic appearance of an intact stone (Fig 6c).
It was Figure
impossible 2b whether
to determine the
in
sonographic October
1990
image
represented
an intact
stone
within the gallbladder on an aggregation of fragments. However, a rollover maneuver in this patient demonstrated the dispersion of fragments throughout the gallbladder (Fig 7). In summary, this study demonstrates that (a) fragmented stones clump after ESWL, (b) clumped fragments may resemble an intact stone, and (c) the rollover maneuver helps distinguish between intact stones and fragments and prevents diagnostic errors in the follow-up and unnecessary retreatment. U
4.
5.
6.
7.
8.
References 1.
Sackmann
al.
M, Delius M, Sauerbruch T, et wave lithotnipsy of gallbladder the first 175 patients. N Engl J Med
9.
Shock
stones:
Invest
1988; 318:393-397.
2.
3.
Vnlume
Trotman BW, Morris TA III, Sanchez HM, Soloway RD. Ostrow JD. Pigment versus cholesterol cholelithiasis: identification and quantification by infrared spectroscopy. Gastroenterology 1 977; 72:495-498. Holzbach RT, Marsh M, Olszewski M, Holan K. Cholesterol solubility in bile: evidence that supersaturated bile is frequent in healthy man. J Clin Invest 1973; 52: 1467-1479.
177
#{149} Number
Carey MC. Small DM. The physical chemistry of cholesterol solubility in bile: relationship to gallstone formation and dissolution in man. J Clin Invest 1978; 61:998-1026. Womack NA. The development of gallstones. Surg Gynecol Obstet 1971; 133: 937-945. Freston JW, Bouchief IA, Newman J. Biliary mucous substances in dihydrocholesterol-induced cholelithiasis. Gastroenterology 1969; 57:670-678. Levy PF, Smith BF, LaMont JT. Human gallbladder mucin accelerates nucleation of cholesterol in artificial bile. Gastroenterology 1984; 87:270-275. Gallinger S. Taylor RD. Harvey PR, Petrunka CN. Strasberg SM. Effect of mucous glycoprotein on nucleation time of human bile. Gastroenterology 1985; 88:937-945. Lee SP, LaMont JT, Carey MC. Role of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones. J Clin
1
10.
11.
1981;
12.
13.
14.
15.
16.
67:1712-1723.
Bachrach WH, Hofman AF. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Dig Dis Sci 1982; 27: 833-856. Nilsell K. Angelin B, Leijd B, Einarsson K. Comparative effects of ursodeoxycholic acid and chenodeoxycholic acid on bile acid kinetics and biliary lipid secretion in humans: evidence for different modes of action on bile acid synthesis. Gastroenterology 1983; 85:1248-1256.
17.
18.
Erlinger S. Le Go A, Husson JM, Fevery J. Franco-Belgian cooperative study of ursodeoxycholic acid in the medical dissolution of gallstones: a double-blind, randomized dose-response study, and comparison with cheno acid. Hepatology 1984; 4:308-314. Igimi H, Tamesu N, Ikejiri Y. et al. Ursodeoxycholate in vitro cholesterol solubility and changes of composition of human gallbladder-bile after oral treatment. Life Sci 1977; 21:1373-1380. Makino I, Nakagawa S. Changes in biliary lipid and biliary bile acid composition after administration of ursodeoxycholic acid. J Lipid Res 1978; 19:723-728. Pearson JP, Kaura R, Taylor W, Allen A. The composition and polymeric structure of mucus glycoproteins from human gallbladder bile. Biochem Biophys Acta 1982; 706:221-228. Gollish SH, Burnstein MJ, Ilson RG, et al. Nucleation of cholesterol monohydrate crystals from hepatic and gallbladder bile of patients with cholesterol gallstones. Gut 1983; 24:836-844. Hessler PC, Hill DS, Detorie FM, Rocco AF. High accuracy sonographic recognition of gallstones. AJR 198 1 ; 136:517-520. Choyke PL, Pahira JH, Davros WJ, et al. Renal calculi after shock wave lithotripsy: US evaluation with an in vitro phantom. Radiology 1989; 170:39-44.
Radiology
#{149} 151
MD
#{149} Jeannete
B. Goldszmidt, Wisniewski, RT
#{149} Frances
Intact Stones in the Imaging Extracorporeal
MD #{149} Olle
#{149}Igor Okberg,
Laufer, MD MD #{149} Peter
#{149} Peter Arger, F. Malet, MD
or Fragments? Potential of Patients after Biliary Shock Wave Lithotripsy’
MD
Pitfalls
Ultrasound is used after extracorporeal shock wave lithotripsy of gallbladder stones to assess f ragmentation. In many patients with apparently successful fragmentation, the posttreatment studies show an intraluminal, echogenic focus within
the
gallbladder,
with
poste-
nor acoustic shadowing characteristic of an intact stone. Cholesterol gallstones were fragmented in vitro by means of lithotripsy, and the sonographic appearance of the f ragmented stones was followed up over time to study factors that might affect the process. After lithotripsy, fragments settled and produced an echogenic focus with posterior shadowing indistinguishable from the appearance of an intact stone. These experimental observations led to the development of a clinical maneuver to overcome the diagnostic pitfalls posed by the reaggregation of stone fragments in situ. This rollover maneuver helps distinguish between intact stones and fragments, and prevents both diagnostic errors in follow-up and unnecessary retreatment. Index terms: Gallbladder, sy
Gallbladder, calculi, US studies, 762.12981
762.2897. Lithotrip-
#{149}
Figure 1. Sonographic stone. Cursors indicates 10 shock waves, but this indistinguishable from
E
1990;
den stones is a promising new py for patients with cholelithiasis In evaluating results of ESWL, sound
(US)
cult
and
Treat-
of Medicine
and Radiology (J.B.G., IL., PA., AM., F.W., 0.0.), University of Pennsylvania and Veterans Administration Medical Center (M.R.K., P.F.M.), University and Wood(M.R.K.,
P.F.M.)
land Ayes,
Philadelphia,
PA 19104. From
the
1989 RSNA scientific assembly. Received May 18, 1989; revision requested June 20; revision received April 6, 1990; accepted April 16. Ad-
dress reprint requests See also the articles
to M.R.K.
by Zeman et al (pp 157161), Zeman et al (pp 163-166), and Shapiro and Winsberg (pp 153-156) in this issue. c RSNA, 1990
the
the
posttreatment
US
studies
shown an intraluminal, echofocus within the gallbladder, posterior acoustic shadowing,
characteristic 2). These
the
be-
intact and fragmented stones US (Fig 1). In many patients apparently successful fragmen-
have genic with From the Gallstone Evaluation ment Center of the Departments
ultra-
to distinguish
of an aggregates
immediate
in some
complete 2 mm
patients.
intact are
post-ESWL In other
fragmentation or less
in diameter
stone detected
ing
the
and
suggesting
appearance
ments
(1).
to determine
or impossible
tation,
I
is used
thera-
extent of fragmentation and the need for netreatment. However, the accuracy of sonography in this setting has not, to our knowledge, been validated. In in vitro studies, it may be diffi-
with with
177:147-151
b. images of in vitro fragmentation. (a) Appearance of an intact gallfocal point of shock waves. (b) The stone in a was fragmented with image shows an echogenic focus with posterior shadowing that is an intact stone.
XTRACORPOREAL shock wave lithotripsy (ESWL) of gablblad-
tween
Phantoms
#{149}
Radiology
a.
(Fig on
US studies patients,
to particles is docu-
mented with immediate posttneatment US studies of the gallbladder. However, in the latter patients, an echogenic focus with posterior acoustic shadowing is detected within the gallbladder 24 hours after ESWL, giv-
have
ped.”
of an
that
the
intact
meaggmegated,
We define
stone
stone
frag-
on “clum-
neaggregation
as the
reversible phenomenon by which fragments of gallstones form a mass that has the sonognaphic features of an intact stone: an echogenic focus within the gallbladder, with postemior acoustic shadowing. The purpose of this
was
(a) to examine
sonographic fragmented lithotnipsy,
course
experiment
the
sequential
appearance of gallstones in vitro with shock wave (b) to study the time
of aggregation
fragments,
cal maneuver
and
on clumping
(c) to develop
to overcome
tial diagnostic pitfalls clumping phenomenon.
MATERIALS
AND
the
posed
of
a clini-
potenby
the
METHODS
Twenty gallstones were collected from three gallbladders (gallbladder A, gallbladder B, and gallbladder C) obtained at
Abbreviations:
ESWL
wave
UDCA
lithotripsy.
extracorporeal ursodeoxycholic
shock
acid.
147
a.
b.
Figure
2.
Sonographic
images
before
intact gallstone, 27 mm in diameter, successful ESWL with 1,500 shock ance (cursors indicate stone size).
stone
fragments?
and
after
ESWL
in a patient.
before treatment. (b) After waves, there is little change Does this represent a treatment
(For the answer,
(a) The appearance
of an
the completion of apparently in the sonogmaphic appearfailure or clumping of
see Fig 7.)
a. cholecystectomy. bladder
A
tainers
and
The
10 stones
from
gall-
were stored dry in airtight conwere rehydrated for 1 week in
saline before the experiment. The stones from gallbladders B and C were stored in physiologic saline (0.9% sodium chloride) in airtight containers. Chemical analysis of gallstone composition was performed on representative stones from each gallbladder, according to the method of Trotman et al (2). The cholesterol content of each of the representative stones was determined to be greater than 95%. The diameter and weight of all stones were measured. The 20 representative gallstones (10 stones from gallbladder A, five stones from gallbladder B, and five stones from gallbladder C) selected for the experiment had a mean diameter of 10.85 mm ± 0.26 (mean ± standand error of the mean) and a weight of 49.8 g ± 0.01. Punfied mucin was obtained from Sigma Chemical Company, St Louis. Ursodeoxycholic acid (UDCA) was a gift from Ciba Pharmaceutical Company, Summit, NJ. Latex condoms were obtained from Carter Products (Carter-Wallace, New York, NY).
In Vitro
Experimental
Design
If cholesterol stones do reaggregate after ESWL, then the physical properties of gallbladder bile that promote on inhibit the formation of cholesterol gallstones might affect the clumping phenomenon. Two important factors that enhance cholestenol gallstone formation are the saturation of bile with cholesterol and its glycoprotein content (3-9). UDCA, the adjuvant bile salt administered to individuals undergoing ESWL, decreases the saturation of cholesterol in bile (10-12) and might be expected to inhibit the reaggregation of cholesterol stones after ESWL. Conversely, mucin, a glycoprotein that promotes the nucleation of cholesterol monohydrate crystals in saturated bile (69), might be expected to accelerate the meaggregation of cholesterol stones after ESWL. Because UDCA and mucin in the gallbladder might affect the reaggrega148
#{149} Radiology
tion
or clumping
these
ESWL,
of gallstones
chemicals
after
were
added
to a
solution of physiologic saline for the in vitro experiment. Each gallstone was placed in a condom containing 75 mL of physiologic saline with various concentrations of UDCA and a mucin concentration of 4 mgidL. Saline was chosen as the basic test solution
instead
of a model
bile
solution
to
limit the number of variables studied in this series of experiments. The concentration of UDCA was varied from 25 mM to 100 mM to study the effect of UDCA over the
range
of concentrations
of UDCA
found in the bile of patients treated with oral UDCA (13,14). The mucin concentration (4 mgidL) was used to approximate the physiologic concentration of mucin within the gallbladder in vivo (15). The control
solution
was
0.9%
saline
b. Figure 3. Experimental device for in vitro fragmentation. (a) A chamber filled with degassed water is situated the water cushion. (b)
without
a single
UDCA on mucin. The pH of all test solutions was 8.0 to approximate the pH of gallbladder bile (16). Five experimental conditions
were
created:
(a)
0.9%
C were
tested
mental
solutions.
Shock
Wave
in
in
each
of the
Lithotripsy
expeni-
of Stones
Gallstones were fragmented with a Donnien MPL 9000 lithotniptor (Dornier Medical Systems, Marietta, Ga). Shock waves were generated via an underwater spank discharge and were focused with ellipsoid.
The
electrode
is suspended
with-
The gallstone of the shock
is
wave.
Vitro
rotating
stone chamber. focal point
saline
(the contnol), (b) 0.9% saline with 4 mgi dL mucin, (c) 25 mM UDCA in 0.9% saline with 4 mgidL mucin, (d) 50 mM UDCA in 0.9% saline with 4 mgidL mucin, and (e) 100 mM UDCA in 0.9% saline with 4 mgi dL mucin. Stones from gallbladders A, B, and
cholesterol
in the water-filled positioned at the
and secured above A condom containing
was
a
dis-
carded after 1,500 discharges. A single gallstone was placed in a condom contaming 75 mL of one of the experimental solutions. The condom was immersed in a chamber of degassed water, with the gallstone positioned in the shock wave focus of the underwater spank discharge (F2, or the point of greatest energy) (Fig 3). The course of fragmentation was monitored
continuously
with
US.
The
stones
were
fragmented to a particle diameter of 1 mm on less with 100 shock waves genenated at an energy of 16 kV. Fragment size was assessed with a superimposed measure. After delivery of 100 shock waves, the condoms were removed from the Waten bath and manipulated so that stone fragments were dispersed throughout the volume of the solution in the condoms. At 1 hour, 24 hours, 7 days, and 14 days after the lithotnipsy procedure, the condoms
were
stone
fragments
sonographic was repeated.
again
manipulated
were
that
and
imaging in the water bath For each of the intervals
tween sonognaphic doms were suspended at room temperature.
US
so
dispersed,
be-
observations, the conin Styrofoam cups
Scanning
The course of fragmentation was monitored continuously with the in-line and side-arm transducers of the Donniem lithotniptor. The entire procedure was recordOctober
1990
l
Figure
4. Sonognaphic images of progresof in vitro fragmentation. (a) Appearance of the intact stone in the experimental setup. The cursors represent the focal point of the shock wave. (b) Appearance after fragmentation of the stone with 100 shock waves generated at 16 kV. There is a large echogenic focus with acoustic shadowing in the dependent portion of the condom. sion
b.
a.
a.
b.
Figure 5. Sonographic images of the rollover (b) The “cloud of dust” appearance represents are confined to the fundus of the gallbladder. neuver.
maneuver in situ. (a) Intact stones as seen fragmentation of the stones after treatment (c) Dispersion of the fragments throughout
ed on videotape, with the video camera focused on the condom within the water bath. For each procedure, a static sonographic image was obtained after 50 and 100 shock waves were delivered. US scanning of each stone was then performed at
showed a “cloud of dust” appearance due to the swirling of stone fragments in the solution. US scanning
5 minutes, days
after
1 and the
24 hours,
procedure,
nipulation of the the condoms.
Clinical Vivo
stone
Fragment
and
7 and
following
fragments
14 ma-
within
Dispersion
in
In patients who had undergone gallstone ESWL, a clinical maneuver was deveboped to disperse stone fragments within the gallbladder. Patients were notated 360#{176}, with sonographic imaging of the gallbladder performed before and after rotation. This procedure, termed the “rollover maneuver,” is now routinely used in all patients who have undergone gallstone ESWL at our institution.
RESULTS Before in vitro lithotmipsy, the image of the intact stone revealed
US an
echogenic focus with posterior acoustic shadowing (Fig 4a). During the course of lithotmipsy, US monitoring Volume
177
#{149} Number
1
after
50 shock
waves
showed
c. before ESWL treatment (cursors indicate size). with 1,500 shock waves. Note that the fragments the gallbladder can be seen after the rollover ma-
multi-
pie echogenic foci scattered throughout the condom, with greater echogenicity in the dependent portion. Successful fragmentation of gallstones to a fragment diameter of 1 mm on less was achieved after 100 shock waves were applied to all sampies. After 100 shock waves, fragments settled rapidly, producing increasing echogenicity in the dependent portion of the condoms (Fig 4b). US scanning 5 minutes after the pro-
cedure
showed
a single
echogenic
fo-
cus in all 20 condoms, with sharp posterior acoustic shadowing in one. At 1 hour, a round, echogenic focus with acoustic shadowing was observed in 12 of 20 specimens. Sonographic evaluation at 24 hours after lithotnipsy showed an echogenic focus with acoustic shadowing in all 20 specimens. At 7 and 14 days after the procedure, the US appearance of fragments was unchanged from that seen on the 24-hour images. There was no difference in the US appear-
ance
of the
suits
for
fragments
stones
when
from
the
me-
gallbladdems
A,
B, and C were compared. Neither the concentration of UDCA non the presence of mucin affected the results. When the condoms were invented, the fragments were easily dispersed, reproducing the US appearance of the cloud of dust until the fragments settled and me-created of the intact stone. These results were
the applied
treatment
undergoing
of patients
gallbladder
image
ESWL.
of the
was obtained (Fig 5a). After shock waves,
were
confined
within
fundus
creating
appearance
of the
the
gall-
before treattreatment with the fragments
to the
gallbladder,
to the
A sonognaphic
stones
bladder ment 1,500
appearance
the
of the
sonognaphic
cloud
of dust
(Fig
5b). The patient was then asked to notate 360#{176}to disperse the stone fragments throughout the gallbladder,
and
scanning
This technique tinely in all ESWL.
was has patients
A retrospective rollover
maneuver
repeated
(Fig
been applied undergoing
evaluation was
done Radiolov
5c). rou-
of the by
re-
149
#{149}
a.
b.
Figure 6. Value of the rollover pearance 1 day after apparently rollover
later,
maneuver,
numerous
the echogenic
focus
maneuver successful small
and
fragments
posterior
The
valuable
rollover
maneuver
in dispersing
ments
and
about
the
of stone studies.
size,
was
clumped
providing
frag-
information
number,
fragments
and
mobility
in 30 of the
54
DISCUSSION Sonogmaphy
is routinely
used
evaluate the results of ESWL bladder stones to determine fragmentation has occurred. patients with successful tion, posttreatment US
an echogenic focus acoustic shadowing, an
intact
stone,
fragments “clumped.”
fect
with posterior characteristic
finding in vivo
of clumped
diffithe ef-
on the
accuracy of sonographis unknown. Since
of gallstone
after the miare based on the
fragments
sonographically, able to distinguish ments from intact
ments
on of this
has been because
criteria for metreatment tial ESWL procedure
fragments. In this
of
the
fragments
precision and ic measurements
size
fragmentastudies show
have meaggregated, The significance
sonographic cult to assess
to
of gallwhether In many
suggesting
study,
of 1 mm
depicted
it is important to be clumped fmagstones and large
when
gallstone
or less
fmag-
in diameter
pooled in the dependent portion of the condoms, they met the sonographic criteria of a gallstone (17). Specifically,
they
were
echogenic focus within with posterior acoustic After
manipulation
to disperse throughout 150
#{149} Radiology
the the
seen
fluid
as an
the lumen, shadowing.
of the
stone
condoms
fragments volume,
are
seen
shadowing
viewing 54 sonographic studies performed in 20 patients before and at 24 hours and 3 and 6 months after ESWL.
C.
in distinguishing ESWL treatment
the
between suggests dispersed
intact and fragmented stones, as seen on sonographic that there is a large stone fragment (cursors indicate
throughout
the
gallbladder.
There
was
no
large
images. (a) Apsize). (b) After the
fragment.
(c) Five
minutes
reappear.
cloud-of-dust
ance
sonographic
was
appear-
reproduced.
The
cloud-of-
dust appearance corresponded visuably to the swirling of fragments within the medium. Within minutes, the fragments settled and re-created the sonogmaphic image of an intact stone. These in vitro results suggest that there may be pitfalls in the interpretation of the sonographic images of the gallbladder after ESWL. Although gallbladder mucin has been reported to promote the nudeation of cholesterol in solution (6-9),
we found
that
mucin
had
no effect
on the clumping phenomenon in vitro. Similarly, UDCA, a bile salt that promotes the solubilization of cholesterol in solution (10-12), had no effect on development of clumping. These results, however, must be intenpmeted with caution. More infonmation is needed on the frequency of clumping in patients treated with
UDCA
after
ESWL
the frequency with a placebo,
cance into
the
of this
compared
with
in patients treated before the signifi-
phenomenon
can
be put
perspective.
The phenomenon of clumping and resulting overestimation of fmag-
ment
size
Choyke
was
also
et al (18)
evaluation
observed in the
of patients
by
renal
stone
from
a clump
fragments, in practice this distinction may be difficult. Our clinical experience and that others indicate that the evaluation
patients
of
of of
after
be subject
gallbladder
ESWL
to sonographic
pitfalls
may
sim-
ilar to those encountered in the evaluation of renal calculi after ESWL. Our in vitro experimental observations led to the development of a clinical maneuver to overcome the diagnostic pitfalls posed by the clumping phenomenon in situ. For imaging the gallbladder after ESWL,
an initial
US scan
patient
sition
ESWL. They demonstrated that a densely packed clump of fragments in the renal calyx may exhibit sharp acoustic shadowing, which is chanactemistic of intact renal calculi. The authors state that while sonography theoretically should help differenti-
ate an intact
7. Sonographic image of same patient as in Figure 2, after ESWL treatment. After the rollover maneuver, dispersion of fragments in the gallbladder can be seen.
the
sonographic
after
Figure
lying
(either
prone
is obtained in the
or supine)
6a). The patient is then tate 360#{176}, and scanning
with
treatment
po(Fig
asked to nois repeated.
With this maneuver, clumps dispense and reproduce the sonographic cloud of dust (Fig 6b). When an echogenic focus is due to fragment clumping, the rollover maneuver is valuable in dispersing fragments. Within mmutes, fragments reaggregate and may mimic the sonographic appearance of an intact stone (Fig 6c).
It was Figure
impossible 2b whether
to determine the
in
sonographic October
1990
image
represented
an intact
stone
within the gallbladder on an aggregation of fragments. However, a rollover maneuver in this patient demonstrated the dispersion of fragments throughout the gallbladder (Fig 7). In summary, this study demonstrates that (a) fragmented stones clump after ESWL, (b) clumped fragments may resemble an intact stone, and (c) the rollover maneuver helps distinguish between intact stones and fragments and prevents diagnostic errors in the follow-up and unnecessary retreatment. U
4.
5.
6.
7.
8.
References 1.
Sackmann
al.
M, Delius M, Sauerbruch T, et wave lithotnipsy of gallbladder the first 175 patients. N Engl J Med
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3.
Vnlume
Trotman BW, Morris TA III, Sanchez HM, Soloway RD. Ostrow JD. Pigment versus cholesterol cholelithiasis: identification and quantification by infrared spectroscopy. Gastroenterology 1 977; 72:495-498. Holzbach RT, Marsh M, Olszewski M, Holan K. Cholesterol solubility in bile: evidence that supersaturated bile is frequent in healthy man. J Clin Invest 1973; 52: 1467-1479.
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Erlinger S. Le Go A, Husson JM, Fevery J. Franco-Belgian cooperative study of ursodeoxycholic acid in the medical dissolution of gallstones: a double-blind, randomized dose-response study, and comparison with cheno acid. Hepatology 1984; 4:308-314. Igimi H, Tamesu N, Ikejiri Y. et al. Ursodeoxycholate in vitro cholesterol solubility and changes of composition of human gallbladder-bile after oral treatment. Life Sci 1977; 21:1373-1380. Makino I, Nakagawa S. Changes in biliary lipid and biliary bile acid composition after administration of ursodeoxycholic acid. J Lipid Res 1978; 19:723-728. Pearson JP, Kaura R, Taylor W, Allen A. The composition and polymeric structure of mucus glycoproteins from human gallbladder bile. Biochem Biophys Acta 1982; 706:221-228. Gollish SH, Burnstein MJ, Ilson RG, et al. Nucleation of cholesterol monohydrate crystals from hepatic and gallbladder bile of patients with cholesterol gallstones. Gut 1983; 24:836-844. Hessler PC, Hill DS, Detorie FM, Rocco AF. High accuracy sonographic recognition of gallstones. AJR 198 1 ; 136:517-520. Choyke PL, Pahira JH, Davros WJ, et al. Renal calculi after shock wave lithotripsy: US evaluation with an in vitro phantom. Radiology 1989; 170:39-44.
Radiology
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