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PO Box 2345, Beijing 100023, China World J Gastroenterol 2006 May 28; 12(20): 3162-3167
www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327
wjg@wjgnet.com © 2006 The WJG Press. All rights reserved.
Choledocholithiasis: Evolving standards for diagnosis and
management
Marilee L Freitas, Robert L Bell, Andrew J Duffy
www.wjgnet.com
Marilee L Freitas, Robert L Bell, Andrew J Duffy, Department
of Surgery, Yale University School of Medicine, 40 Temple Street,
Suite 3A, New Haven, CT 06510, United States
Correspondence to: Andrew J Duffy, MD, Department of
Surgery, Yale University School of Medicine, 40 Temple Street,
Suite 3A, New Haven, CT 06510,
United States. andrew.duffy@yale.edu
Telephone: +1-203-7469060 Fax: +1-203-7469066
Received: 2006-03-29 Accepted: 2006-04-16
Abstract
Cholelithiasis, one of the most common medical condi-
tions leading to surgical intervention, affects approxi-
mately 10 % of the adult population in the United States.
Choledocholithiasis develops in about 10%-20% of pa-
tients with gallbladder stones and the literature suggests
that at least 3%-10% of patients undergoing cholecys-
tectomy will have common bile duct (CBD) stones.
CBD stones may be discovered preoperatively, intraop-
eratively or postoperatively Multiple modalities are avail-
able for assessing patients for choledocholithiasis includ-
ing laboratory tests, ultrasound, computed tomography
scans (CT), and magnetic resonance cholangiopancrea-
tography (MRCP). Intraoperative cholangiography during
cholecystectomy can be used routinely or selectively to
diagnose CBD stones.
The most common intervention for CBD stones is
ERCP. Other commonly used interventions include intra-
operative bile duct exploration, either laparoscopic or
open. Percutaneous, transhepatic stone removal other
novel techniques of biliary clearance have been devised.
The availability of equipment and skilled practitioners
who are facile with these techniques varies among insti-
tutions. The timing of the intervention is often dictated
by the clinical situation.
© 2006 The WJG Press. All rights reserved.
Key words: Choledocholithiasis; Laparoscopy; Diagnosis;
Treatment; Cholangiogram
Freitas ML, Bell RL, Duffy AJ. Choledocholithiasis: Evolving
standards for diagnosis and management. World J
Gastroenterol 2006; 12(20): 3162-3167
http://www.wjgnet.com/1007-9327/12/3162.asp
INTRODUCTION
Symptomatic gallstone disease is a very common indica-
tion for abdominal surgery. It is estimated that around
500 000 cholecystectomies are performed a year in the
United States. Gallstones, alone, are rarely an indication
for surgery, but 10% of the adult population are believed
to carry them. Furthermore, up to one-third of the popu-
lation over 70 years of age will have gallstones. Gallstone
formation is a multifactorial process but is undoubtedly
associated with family history, diabetes mellitus, pregnancy,
obesity, significant weight loss, and hemolytic diseases. As
many as 35% of patients with gallstones will ultimately be-
come symptomatic and require cholecystectomy[1]
.
Common indications for surgical treatment for chole-
lithiasis include biliary colic, acute cholecystitis, gallstone
pancreatitis, and other presentations of choledocholithiasis
including bile duct obstruction and cholangitis. Other rela-
tive indications include gallstones in patients undergoing
splenectomy for hemolytic anemia, high risk patients in
the pretreatment phase for other conditions such as bone
marrow transplant. Cholecystectomy is no longer routinely
performed for asymptomatic gallstones in those undergo-
ing bariatric surgery or aortic surgery.
Common bile duct (CBD) stones may be discovered
preoperatively, intraoperatively or postoperatively. The
standard preoperative workup for patients presenting with
symptoms attributable to cholelithiasis includes liver func-
tion tests, and abdominal ultrasound. These tests, com-
bined with clinical exam and history, constitute the entire
workup for most patients. Abnormalities in these tests may
suggest the presence of choledocholithiasis. Choledocholi-
thiasis may occur in up to 3%-10% of all cholecystectomy
patients[1]
, or as high as 14.7% in some series[2]
. This in-
cludes some patients without classic preoperative findings
suggestive of choledocholithiasis. Of these asymptomatic
patients, it is believed about 15% will eventually become
symptomatic[3]
and require further interventional treat-
ment.
Since the advent of routine laparoscopic cholecystecto-
my, the debate has continued about the utility of intraoper-
ative bile duct assessment, primarily with cholangiography
or intraoperative ultrasonography. This debate continues
to some degree, with most surgeons either selectively or
routinely evaluating the bile duct intraoperatively. A smaller
subset relies only on preoperative assessment tools, includ-
ing magnetic resonance cholangiopancreatography (MRCP)
TOPIC HIGHLIGHT
John Geibel, MD, Dsc and Walter Longo, MD, Series Editors
and endoscopic retrograde cholangiopancreatography
(ERCP), as a complement to routine laboratory and imag-
ing studies. The most common intervention for common
bile duct (CBD) stones is ERCP. Other procedures for
CBD stone extraction include percutaneous, transhepatic
stone removal and intraoperative CBD exploration, wheth-
er laparoscopic or open. The availability of equipment and
skilled practitioners who are facile with these techniques
varies among institutions. The timing of the intervention
is often dictated by the clinical situation.
PREOPERATIVE EVALUATION AND THERAPY
Diagnosis of choledocholithiasis is not always straight-
forward and clinical evaluation and biochemical tests are
often not sufficiently accurate to establish a firm diagnosis.
Imaging tests, particularly abdominal ultrasound, are used
routinely to confirm the diagnosis. Liver function tests
(LFT) can be used to predict CBD stones[4,5]
. Elevated
serum bilirubin and alkaline phosphatase typically reflect
biliary obstruction but these are neither highly sensitive
nor specific for CBD stones. Excepting obvious jaundice,
a raised GGT level has been suggested to be the most
sensitive and specific indicator of CBD stones. A value of
greater than 90 U/L has been proposed to indicate a high
risk of choledocholithiasis[4]
. However, laboratory data
may be normal in as many as a third of patients with cho-
ledocholithiasis, warranting further evaluation of the CBD
by imaging studies to clarify the diagnosis.
In order to help select from the various diagnostic and
therapeutic options, patients may be classified preopera-
tively into high, moderate or low risk groups. The high risk
(> 50% risk) group includes those patients with obvious
clinical jaundice or cholangitis, choledocholithiasis or a
dilated CBD on ultrasonography. Patients with a history
of pancreatitis or jaundice, elevated preoperative bilirubin
and alkaline phosphatase levels or multiple small gallstones
carry a moderate (10%-50%) risk of choledocholithiasis.
Patients with large gallstones, without a history of jaundice
or pancreatitis and with normal liver function tests are
considered unlikely to have CBD stones and therefore at
low risk (< 5%)[6-8]
.
The transabdominal ultrasound examination (US) is the
most commonly used screening modality. In patients who
present with symptoms attributable to gallstone disease,
US may be the only radiologic study ordered. It has the
advantages of being widely available, non-invasive, and
inexpensive. Ultrasonography, however, is highly operator
dependent, but it can provide useful information in ex-
perienced hands. For a diagnosis of cholecystitis, in most
circumstances, gallbladder stones need to be visualized.
The sonographic presence of wall thickening, perichole-
cystic fluid, and a Murphy’s sign, may be helpful but are
not required for a diagnosis of acute cholecystitis. The
ultrasonographer should routinely report indirect informa-
tion suggestive of the presence or absence of CBD stones,
specifically the CBD diameter or any signs of intrahepatic
bile duct dilation. The sensitivity of US for detecting bili-
ary dilatation, as reported in various studies, varies from 55
to 91 percent[9]
. A CBD diameter of greater than 6 mm on
US is associated with a higher prevalence of choledocholi-
Freitas ML et al. Diagnosis and management of choledocholithiasis 3163
www.wjgnet.com
thiasis[10]
.
Computed tomography (CT) may have some role in
diagnosis of gallstone disease and choledocholithiasis.
Many patients presenting with acute abdominal pain will
undergo a diagnostic CT scan as part of the acute workup.
A diagnosis of acute cholecystitis may be evident based on
signs of gallbladder inflammation. Cholelithiasis may be
detected on CT[11]
and often the diameter of the CBD can
be measured. In the clinical setting, US may not be neces-
sary for preoperative evaluation if the CT scan provides
this information. The role of helical CT cholangiography
is still in evolution, particularly in the United States. Intra-
venously administered contrast agents, combined with high
resolution helical scans and three dimensional reconstruc-
tions that can be very useful in diagnosing choledocholi-
thiasis[12,13]
. The sensitivity of this technique can be as high
as 95.5%[12]
. This technique is not widely utilized in the U.S.
as the available contrast agents often cause significant nau-
sea on administration. The availability of MRCP also limits
the need for this modality.
MRCP has emerged as an accurate, non-invasive diag-
nostic modality for investigating the biliary and pancreatic
ducts[14]
and has been recommended in some circles as
the preoperative procedure of choice for the detection of
CBD stones[4,15,16]
. MRCP provides excellent anatomic de-
tail of the biliary tract and has a sensitivity of 81%-100%
and a specificity of 92%-100% in detecting choledocho-
lithiasis[14]
. The accuracy of MRCP in diagnosing CBD
stones is comparable with that of ERCP and IOC[14,17]
. It
thus avoids the need for a potentially high risk, invasive
procedure in more than 50% of patients, allowing selec-
tive use of ERCP or surgical CBD exploration in those
patients who require a therapeutic intervention. These
results have led some practitioners to consider MRCP the
new gold standard for biliary imaging[14,18]
. MRCP may,
however, miss stones less than 5 mm in diameter. MRCP
is an expensive option that requires significant expertise
for interpretation; this modality may not always be readily
available.
Endoscopic techniques such as endoscopic ultrasound
(EUS) and ERCP can also be useful tools in preoperative
diagnosis and, in the case of ERCP, management of cho-
ledocholithiasis. Both procedures are more invasive than
strictly radiologic techniques, and carry the low, but inher-
ent risks of upper gastrointestinal tract endoscopy. ERCP
also carries the risks associated with biliary instrumenta-
tion, such as pancreatitis. Endoscopic ultrasound (EUS)
can been used to evaluate the CBD and identify calculi.
Studies comparing the accuracy of EUS to US, CT and
ERCP for detecting choledocholithiasis show a sensitiv-
ity of EUS ranging from 88%-97%, with a specificity of
96%-100%[19]
. This is comparable to ERCP and avoids the
risks of pancreatitis, cholangitis and radiation exposure[19]
.
The role of EUS, however, is not well established espe-
cially when cost and availability of less invasive modalities
such as MRCP are considered. EUS may be combined
with ERCP at the same endoscopy session if biliary calculi
are identified, allowing it to be a bridge to therapeutic in-
tervention.
ERCP has been the gold standard for preoperative diag-
nosis of CBD calculi. When compared to other tests such
as ultrasonography and MRCP, ERCP has the advantage
of providing a therapeutic option when a CBD stone is
identified. Stone retrieval and sphincterotomy has sup-
planted surgical treatment of choledocholithiasis in many
institutions[14,20]
. Successful cholangiography by an experi-
enced endoscopist is achieved in greater than 90% of pa-
tients. Complications associated with ERCP can be as high
as 15% and include pancreatitis, cholangitis, perforation of
the duodenum or bile duct, and bleeding. These individual
complications can occur in 5%-8% of patients. The mor-
tality rate from ERCP is 0.2%-0.5%[21,22]
INTRAOPERATIVE EVALUATION AND
THERAPY
Since laparoscopic cholecystectomy became a routine pro-
cedure in the early 1990’s, debate has continued about the
role of intraoperative bile duct assessment. The interest in
intraoperative cholangiography (IOC) came from both the
desire to detect CBD stones and to potentially identify any
bile duct abnormalities, including iatrogenic injuries at the
time of surgery. Routine cholangiography is not generally
considered to be the standard of care but still has its pro-
ponents[3]
. Most surgeons selectively evaluate the bile duct
intraoperatively. A smaller subset relies only on preopera-
tive assessment tools including magnetic resonance chol-
angiopancreatography (MRCP) and endoscopic retrograde
cholangiopancreatography (ERCP) as a complement to
routine laboratory and imaging studies.
Intraoperative cholangiography can be a useful tool to
identify choledochal calculi but its application remains con-
troversial. Proponents often believe that IOC enables clear
definition of the biliary tree anatomy[3,23,24]
, thus reducing
the risk of bile duct injury during cholecystectomy. Most
studies on the subject show no significant difference in the
rates of ductal injury between routine and selective IOC.
Routine IOC has been found to yield little benefit over the
selective approach in the detection of symptomatic CBD
stones[3]
Cholangiography is a relatively straight forward
procedure to perform. It does add to the operative time,
approximately an additional 15 min[25,26]
, but surgeon and
operative team experience can minimize this. Dynamic
fluoroscopic imaging is the technique of choice and can
provide a specificity and sensitivity of 94% and 98%, re-
spectively, in experienced hands[27]
. This technique may be
somewhat less sensitive for patients presenting with biliary
pancreatitis[27]
. A complete IOC should demonstrate the
cannulation of the cystic duct, filling of the left and right
hepatic ducts, CBD and common hepatic duct diameter,
the presence or absence of filling defects in the biliary tree,
and free flow of contrast into the duodenum (Figure 1).
Obstruction or other biliary abnormality should be sus-
pected if these findings are not clear.
The overall safety profile of IOC is very good. The inci-
dence of pancreatitis, in contrast to ERCP, is negligible[28]
.
The reliability, ease to perform, and low complication rate
of IOC suggest that, at least in cases where choledocho-
lithiasis is not proven, IOC during a cholecystectomy is a
better choice than preoperative ERCP assessment of the
bile ducts. More recently intraoperative ultrasonography
3164 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol May 28, 2006 Volume 12 Number 20
www.wjgnet.com
of the CBD during laparoscopic cholecystectomy has
been shown to satisfactorily demonstrate stones and the
biliary tree. Use of intraoperative ultrasound requires a
significant learning curve, but in experienced hands takes
less operative time than traditional IOC[25,26]
. Laparoscopic
ultrasound compares well with intraoperative cholangiog-
raphy. With a sensitivity of 96% and a specificity of 100%,
and the advantages of saved time and lack of radiation,
intraoperative ultrasound may be a superior diagnostic mo-
dality when compared to IOC[23]
. The use of intraoperative
laparoscopic ultrasound is limited by the availability of
equipment and surgeon training and experience. Efforts
to incorporate ultrasonography training in to surgical resi-
dency curricula should aid its acceptance and use.
When CBD stones are detected intraoperatively, a sur-
geon must make a clinical decision on how to proceed.
This decision is often dictated by the availability of equip-
ment, surgeon preference and skill, and the availability of
ERCP at a facility. Available options include laparoscopic
CBD exploration, intraoperative ERCP, open CBD explo-
ration, or postoperative therapy. Many surgeons are reluc-
tant to proceed with an open procedure when other, less
invasive, options are generally available. However, a deci-
sion to delay therapy to the postoperative period risks en-
countering procedural difficulties that preclude endoscopic
therapy. Options for intraoperative CBD clearance include
variations of laparoscopic exploration. Laparoscopic CBD
exploration is most commonly performed with acholedo-
choscope. The scope, attached to a second video camera
and light source, is inserted into the CBD via either the
cystic duct (Figure 2) or via a choledochotomy. Placement
of the choledochoscope directly into the CBD via a cho-
ledochotomy is generally reserved for patients with ducts
dilated to greater than 6 mm in diameter on cholangio-
gram[20]
. A continuous saline infusion through the choledo-
choscope dilates the duct and clears debris. CBD stones
can be directly visualized (Figure 3) and instrumented.
Between 66 and 82.5% of laparoscopic CBD explorations
can be performed via the cystic duct[20,29]
. In experienced
hands, the CBD clearance rate is as high as 97%[2,29]
. In one
large series of laparoscopic CBD exploration, the overall
morbidity rate of this procedure is approximately 9.5%,
with a 2.7% retained stone rate[2]
. These data are equivalent
to the experience with ERCP.
An alternate technique of laparoscopic CBD clearance
involves stone extraction under fluoroscopic guidance.
Figure 1 Intraoperative
cholangiogram via the
cystic duct demonstrating
proximal biliary dilation and
two filling defects in the
CBD (Arrows).
←
←
This technique, as described by Traverso et al, does not use
a choledochoscope, but can be highly effective in CBD
clearance for single stones (87%), with an overall 59% suc-
cess rate[30]
. In this technique, instruments, including stone
extraction baskets, are passed into the CBD (usually via
the cystic duct) under fluoroscopy. The fluoroscopic im-
ages facilitate stone capture and removal. This technique
simplifies the operating room set up for CBD exploration
because additional video equipment is not required. In this
series, patients whose ducts were not cleared laparoscopi-
cally, underwent ERCP. The authors noted a significantly
lower complication rate in patient who did not undergo
ERCP[30]
. Likewise, the overall associated costs were lower
in these patients[31]
.
Laparoscopic techniques can be very effective at clearing
CBD stones, but significant expertise and experience is re-
quired to achieve high success rates. Stones impacted at the
sphincter of Oddi are often the most difficult to extract by
this technique. Long term follow up does not demonstrate
a significant risk of CBD stricture or other complications
for these procedures[2,29,30]
. This technique is also advocated
in the pediatric population by some practitioners as a way
of avoiding an ERCP[32]
. Intraoperative ERCP, although
often limited by the immediate availability of a qualified
endoscopist, is a technique that can be very useful. This
takes advantage of the preexisting anesthetic and does
not prolong hospital stay by delaying the procedure[33,34]
.
In some instances, cooperation between the surgeon and
the endoscopist can expedite the procedure[35]
. Guidewire
placement, throught the sphincter of Oddi, into the duo-
denum via the IOC catheter can facilitate cannulation, es-
pecially for patients with difficult duodenal anatomy[34]
. In
the case of an unsuccessful extraction, open CBD explora-
tion or drainage of the duct should be considered.
POSTOPERATIVE EVALUATION AND
THERAPY
Postoperative ERCP is commonly used modality for CBD
clearance when a stone is detected intraoperatively. This
technique is highly effective[20]
, but can be complicated
when anatomic variables such as duodenal diverticulae or
unusual biliary anatomy, are encountered[36]
. On the occa-
www.wjgnet.com
sion that ERCP fails, a primary option includes returning
to the operating room for a laparoscopic or open explora-
tion. However, other less invasive options may be available.
In selected patients, percutaneous transhepatic (PTH)
therapies should be considered for CBD clearance. Ac-
cess to the biliary system can be obtained percutaneously,
under ultrasound guidance. Via this access point, stones
can be extracted, a sphincterotomy can be performed, or
lithotripsy can be used over a single, or multiple sessions
to ensure duct clearance[37,38]
. A percutaneous drain can be
used to decompress the system between procedures or for
temporary stenting after the duct is clear.
Novel approaches have been performed in other ana-
tomic settings which preclude ERCP, such as prior gas-
tric surgery. The most common gastric surgery currently
performed is the Roux-Y gastric bypass. In this surgery, a
small gastric pouch is created and anastomosed to a limb
of jejunum. The majority of the stomach, duodenum, and
proximal jejunum are bypassed, making endoscopic access
technically difficult. Combined laparoscopic surgical and
endoscopic procedures have been described. Endoscopic
access can be achieved via a gastrostomy[39]
or jejunos-
tomy[40]
. The endoscope can be passed under surgical
guidance, and an ERCP can be performed in the standard
fashion. These procedures are only described in short case
reports, but will undoubtedly become more common place
with the prevalence of gastric bypass.
In conclusion, given the various diagnostic and thera-
peutic options available for managing choledocholithiasis,
clinical judgment is paramount. The surgeon and the pa-
tient are best served by accurate laboratory and radiologic
assessment prior to cholecystectomy. In the setting of high
preoperative suspicion for choledocholithiasis, preopera-
tive imaging with MRCP may help guide subsequent treat-
ment. If CBD stones are present on MRCP or in the set-
ting of clinical jaundice or cholangitis, preoperative ERCP
is the first line option. However, preexisting anatomic
abnormalities may influence this decision. Laparoscopic
IOC with a CBD exploration is a reliable approach in ex-
perienced hands and if an ERCP is unsuccessful.
Cholangiography during cholecystectomy is recom-
mended for patients with a history of gallstone pancreati-
tis, LFT abnormalities, or an enlarged CBD on preopera-
tive imaging who have not undergone MRCP or ERCP.
IOC is also recommended when intraoperative findings
suggest anatomic abnormalities or unsuspected CBD calculi.
Intraoperative laparoscopic CBD exploration is the first
Figure 3 CBD stone
as seen through the
choledochoscope.
Figure 2 Laparoscopic view of a choledochoscope (CS) entering the CBD via the
cystic duct. The gallbladder (GB) is retracted to the left of the image.
←
Cystic duct CBD
GB
CS
Liver
Freitas ML et al. Diagnosis and management of choledocholithiasis 3165
option for choledocholithiasis detected in the operating
room. Intraoperative or postoperative ERCP are options
for incompletely cleared ducts. Percutaneous treatment or
combined laparoendoscopic options are available in some
centers for patients who cannot undergo ERCP or laparo-
scopic choledochotomy. Open CBD exploration is a safe
option, but usually limited to the setting of concomitant
open surgery or as a last resort when other therapeutic
modalities fail.
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difficult bile duct stones. Endoscopy 2003; 35: S31-S34
37 Nagashima I, Takada T, Shiratori M, Inaba T, Okinaga K.
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38 Itoi T, Shinohara Y, Takeda K, Nakamura K, Sofuni A, Itokawa
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39 Peters M, Papasavas PK, Caushaj PF, Kania RJ, Gagne
DJ. Laparoscopic transgastric endoscopic retrograde
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1106
40 Mergener K, Kozarek RA, Traverso LW. Intraoperative
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Standard for dx & tx for choledocholithiasis

  • 1. PO Box 2345, Beijing 100023, China World J Gastroenterol 2006 May 28; 12(20): 3162-3167 www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327 wjg@wjgnet.com © 2006 The WJG Press. All rights reserved. Choledocholithiasis: Evolving standards for diagnosis and management Marilee L Freitas, Robert L Bell, Andrew J Duffy www.wjgnet.com Marilee L Freitas, Robert L Bell, Andrew J Duffy, Department of Surgery, Yale University School of Medicine, 40 Temple Street, Suite 3A, New Haven, CT 06510, United States Correspondence to: Andrew J Duffy, MD, Department of Surgery, Yale University School of Medicine, 40 Temple Street, Suite 3A, New Haven, CT 06510, United States. andrew.duffy@yale.edu Telephone: +1-203-7469060 Fax: +1-203-7469066 Received: 2006-03-29 Accepted: 2006-04-16 Abstract Cholelithiasis, one of the most common medical condi- tions leading to surgical intervention, affects approxi- mately 10 % of the adult population in the United States. Choledocholithiasis develops in about 10%-20% of pa- tients with gallbladder stones and the literature suggests that at least 3%-10% of patients undergoing cholecys- tectomy will have common bile duct (CBD) stones. CBD stones may be discovered preoperatively, intraop- eratively or postoperatively Multiple modalities are avail- able for assessing patients for choledocholithiasis includ- ing laboratory tests, ultrasound, computed tomography scans (CT), and magnetic resonance cholangiopancrea- tography (MRCP). Intraoperative cholangiography during cholecystectomy can be used routinely or selectively to diagnose CBD stones. The most common intervention for CBD stones is ERCP. Other commonly used interventions include intra- operative bile duct exploration, either laparoscopic or open. Percutaneous, transhepatic stone removal other novel techniques of biliary clearance have been devised. The availability of equipment and skilled practitioners who are facile with these techniques varies among insti- tutions. The timing of the intervention is often dictated by the clinical situation. © 2006 The WJG Press. All rights reserved. Key words: Choledocholithiasis; Laparoscopy; Diagnosis; Treatment; Cholangiogram Freitas ML, Bell RL, Duffy AJ. Choledocholithiasis: Evolving standards for diagnosis and management. World J Gastroenterol 2006; 12(20): 3162-3167 http://www.wjgnet.com/1007-9327/12/3162.asp INTRODUCTION Symptomatic gallstone disease is a very common indica- tion for abdominal surgery. It is estimated that around 500 000 cholecystectomies are performed a year in the United States. Gallstones, alone, are rarely an indication for surgery, but 10% of the adult population are believed to carry them. Furthermore, up to one-third of the popu- lation over 70 years of age will have gallstones. Gallstone formation is a multifactorial process but is undoubtedly associated with family history, diabetes mellitus, pregnancy, obesity, significant weight loss, and hemolytic diseases. As many as 35% of patients with gallstones will ultimately be- come symptomatic and require cholecystectomy[1] . Common indications for surgical treatment for chole- lithiasis include biliary colic, acute cholecystitis, gallstone pancreatitis, and other presentations of choledocholithiasis including bile duct obstruction and cholangitis. Other rela- tive indications include gallstones in patients undergoing splenectomy for hemolytic anemia, high risk patients in the pretreatment phase for other conditions such as bone marrow transplant. Cholecystectomy is no longer routinely performed for asymptomatic gallstones in those undergo- ing bariatric surgery or aortic surgery. Common bile duct (CBD) stones may be discovered preoperatively, intraoperatively or postoperatively. The standard preoperative workup for patients presenting with symptoms attributable to cholelithiasis includes liver func- tion tests, and abdominal ultrasound. These tests, com- bined with clinical exam and history, constitute the entire workup for most patients. Abnormalities in these tests may suggest the presence of choledocholithiasis. Choledocholi- thiasis may occur in up to 3%-10% of all cholecystectomy patients[1] , or as high as 14.7% in some series[2] . This in- cludes some patients without classic preoperative findings suggestive of choledocholithiasis. Of these asymptomatic patients, it is believed about 15% will eventually become symptomatic[3] and require further interventional treat- ment. Since the advent of routine laparoscopic cholecystecto- my, the debate has continued about the utility of intraoper- ative bile duct assessment, primarily with cholangiography or intraoperative ultrasonography. This debate continues to some degree, with most surgeons either selectively or routinely evaluating the bile duct intraoperatively. A smaller subset relies only on preoperative assessment tools, includ- ing magnetic resonance cholangiopancreatography (MRCP) TOPIC HIGHLIGHT John Geibel, MD, Dsc and Walter Longo, MD, Series Editors
  • 2. and endoscopic retrograde cholangiopancreatography (ERCP), as a complement to routine laboratory and imag- ing studies. The most common intervention for common bile duct (CBD) stones is ERCP. Other procedures for CBD stone extraction include percutaneous, transhepatic stone removal and intraoperative CBD exploration, wheth- er laparoscopic or open. The availability of equipment and skilled practitioners who are facile with these techniques varies among institutions. The timing of the intervention is often dictated by the clinical situation. PREOPERATIVE EVALUATION AND THERAPY Diagnosis of choledocholithiasis is not always straight- forward and clinical evaluation and biochemical tests are often not sufficiently accurate to establish a firm diagnosis. Imaging tests, particularly abdominal ultrasound, are used routinely to confirm the diagnosis. Liver function tests (LFT) can be used to predict CBD stones[4,5] . Elevated serum bilirubin and alkaline phosphatase typically reflect biliary obstruction but these are neither highly sensitive nor specific for CBD stones. Excepting obvious jaundice, a raised GGT level has been suggested to be the most sensitive and specific indicator of CBD stones. A value of greater than 90 U/L has been proposed to indicate a high risk of choledocholithiasis[4] . However, laboratory data may be normal in as many as a third of patients with cho- ledocholithiasis, warranting further evaluation of the CBD by imaging studies to clarify the diagnosis. In order to help select from the various diagnostic and therapeutic options, patients may be classified preopera- tively into high, moderate or low risk groups. The high risk (> 50% risk) group includes those patients with obvious clinical jaundice or cholangitis, choledocholithiasis or a dilated CBD on ultrasonography. Patients with a history of pancreatitis or jaundice, elevated preoperative bilirubin and alkaline phosphatase levels or multiple small gallstones carry a moderate (10%-50%) risk of choledocholithiasis. Patients with large gallstones, without a history of jaundice or pancreatitis and with normal liver function tests are considered unlikely to have CBD stones and therefore at low risk (< 5%)[6-8] . The transabdominal ultrasound examination (US) is the most commonly used screening modality. In patients who present with symptoms attributable to gallstone disease, US may be the only radiologic study ordered. It has the advantages of being widely available, non-invasive, and inexpensive. Ultrasonography, however, is highly operator dependent, but it can provide useful information in ex- perienced hands. For a diagnosis of cholecystitis, in most circumstances, gallbladder stones need to be visualized. The sonographic presence of wall thickening, perichole- cystic fluid, and a Murphy’s sign, may be helpful but are not required for a diagnosis of acute cholecystitis. The ultrasonographer should routinely report indirect informa- tion suggestive of the presence or absence of CBD stones, specifically the CBD diameter or any signs of intrahepatic bile duct dilation. The sensitivity of US for detecting bili- ary dilatation, as reported in various studies, varies from 55 to 91 percent[9] . A CBD diameter of greater than 6 mm on US is associated with a higher prevalence of choledocholi- Freitas ML et al. Diagnosis and management of choledocholithiasis 3163 www.wjgnet.com thiasis[10] . Computed tomography (CT) may have some role in diagnosis of gallstone disease and choledocholithiasis. Many patients presenting with acute abdominal pain will undergo a diagnostic CT scan as part of the acute workup. A diagnosis of acute cholecystitis may be evident based on signs of gallbladder inflammation. Cholelithiasis may be detected on CT[11] and often the diameter of the CBD can be measured. In the clinical setting, US may not be neces- sary for preoperative evaluation if the CT scan provides this information. The role of helical CT cholangiography is still in evolution, particularly in the United States. Intra- venously administered contrast agents, combined with high resolution helical scans and three dimensional reconstruc- tions that can be very useful in diagnosing choledocholi- thiasis[12,13] . The sensitivity of this technique can be as high as 95.5%[12] . This technique is not widely utilized in the U.S. as the available contrast agents often cause significant nau- sea on administration. The availability of MRCP also limits the need for this modality. MRCP has emerged as an accurate, non-invasive diag- nostic modality for investigating the biliary and pancreatic ducts[14] and has been recommended in some circles as the preoperative procedure of choice for the detection of CBD stones[4,15,16] . MRCP provides excellent anatomic de- tail of the biliary tract and has a sensitivity of 81%-100% and a specificity of 92%-100% in detecting choledocho- lithiasis[14] . The accuracy of MRCP in diagnosing CBD stones is comparable with that of ERCP and IOC[14,17] . It thus avoids the need for a potentially high risk, invasive procedure in more than 50% of patients, allowing selec- tive use of ERCP or surgical CBD exploration in those patients who require a therapeutic intervention. These results have led some practitioners to consider MRCP the new gold standard for biliary imaging[14,18] . MRCP may, however, miss stones less than 5 mm in diameter. MRCP is an expensive option that requires significant expertise for interpretation; this modality may not always be readily available. Endoscopic techniques such as endoscopic ultrasound (EUS) and ERCP can also be useful tools in preoperative diagnosis and, in the case of ERCP, management of cho- ledocholithiasis. Both procedures are more invasive than strictly radiologic techniques, and carry the low, but inher- ent risks of upper gastrointestinal tract endoscopy. ERCP also carries the risks associated with biliary instrumenta- tion, such as pancreatitis. Endoscopic ultrasound (EUS) can been used to evaluate the CBD and identify calculi. Studies comparing the accuracy of EUS to US, CT and ERCP for detecting choledocholithiasis show a sensitiv- ity of EUS ranging from 88%-97%, with a specificity of 96%-100%[19] . This is comparable to ERCP and avoids the risks of pancreatitis, cholangitis and radiation exposure[19] . The role of EUS, however, is not well established espe- cially when cost and availability of less invasive modalities such as MRCP are considered. EUS may be combined with ERCP at the same endoscopy session if biliary calculi are identified, allowing it to be a bridge to therapeutic in- tervention. ERCP has been the gold standard for preoperative diag- nosis of CBD calculi. When compared to other tests such
  • 3. as ultrasonography and MRCP, ERCP has the advantage of providing a therapeutic option when a CBD stone is identified. Stone retrieval and sphincterotomy has sup- planted surgical treatment of choledocholithiasis in many institutions[14,20] . Successful cholangiography by an experi- enced endoscopist is achieved in greater than 90% of pa- tients. Complications associated with ERCP can be as high as 15% and include pancreatitis, cholangitis, perforation of the duodenum or bile duct, and bleeding. These individual complications can occur in 5%-8% of patients. The mor- tality rate from ERCP is 0.2%-0.5%[21,22] INTRAOPERATIVE EVALUATION AND THERAPY Since laparoscopic cholecystectomy became a routine pro- cedure in the early 1990’s, debate has continued about the role of intraoperative bile duct assessment. The interest in intraoperative cholangiography (IOC) came from both the desire to detect CBD stones and to potentially identify any bile duct abnormalities, including iatrogenic injuries at the time of surgery. Routine cholangiography is not generally considered to be the standard of care but still has its pro- ponents[3] . Most surgeons selectively evaluate the bile duct intraoperatively. A smaller subset relies only on preopera- tive assessment tools including magnetic resonance chol- angiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) as a complement to routine laboratory and imaging studies. Intraoperative cholangiography can be a useful tool to identify choledochal calculi but its application remains con- troversial. Proponents often believe that IOC enables clear definition of the biliary tree anatomy[3,23,24] , thus reducing the risk of bile duct injury during cholecystectomy. Most studies on the subject show no significant difference in the rates of ductal injury between routine and selective IOC. Routine IOC has been found to yield little benefit over the selective approach in the detection of symptomatic CBD stones[3] Cholangiography is a relatively straight forward procedure to perform. It does add to the operative time, approximately an additional 15 min[25,26] , but surgeon and operative team experience can minimize this. Dynamic fluoroscopic imaging is the technique of choice and can provide a specificity and sensitivity of 94% and 98%, re- spectively, in experienced hands[27] . This technique may be somewhat less sensitive for patients presenting with biliary pancreatitis[27] . A complete IOC should demonstrate the cannulation of the cystic duct, filling of the left and right hepatic ducts, CBD and common hepatic duct diameter, the presence or absence of filling defects in the biliary tree, and free flow of contrast into the duodenum (Figure 1). Obstruction or other biliary abnormality should be sus- pected if these findings are not clear. The overall safety profile of IOC is very good. The inci- dence of pancreatitis, in contrast to ERCP, is negligible[28] . The reliability, ease to perform, and low complication rate of IOC suggest that, at least in cases where choledocho- lithiasis is not proven, IOC during a cholecystectomy is a better choice than preoperative ERCP assessment of the bile ducts. More recently intraoperative ultrasonography 3164 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol May 28, 2006 Volume 12 Number 20 www.wjgnet.com of the CBD during laparoscopic cholecystectomy has been shown to satisfactorily demonstrate stones and the biliary tree. Use of intraoperative ultrasound requires a significant learning curve, but in experienced hands takes less operative time than traditional IOC[25,26] . Laparoscopic ultrasound compares well with intraoperative cholangiog- raphy. With a sensitivity of 96% and a specificity of 100%, and the advantages of saved time and lack of radiation, intraoperative ultrasound may be a superior diagnostic mo- dality when compared to IOC[23] . The use of intraoperative laparoscopic ultrasound is limited by the availability of equipment and surgeon training and experience. Efforts to incorporate ultrasonography training in to surgical resi- dency curricula should aid its acceptance and use. When CBD stones are detected intraoperatively, a sur- geon must make a clinical decision on how to proceed. This decision is often dictated by the availability of equip- ment, surgeon preference and skill, and the availability of ERCP at a facility. Available options include laparoscopic CBD exploration, intraoperative ERCP, open CBD explo- ration, or postoperative therapy. Many surgeons are reluc- tant to proceed with an open procedure when other, less invasive, options are generally available. However, a deci- sion to delay therapy to the postoperative period risks en- countering procedural difficulties that preclude endoscopic therapy. Options for intraoperative CBD clearance include variations of laparoscopic exploration. Laparoscopic CBD exploration is most commonly performed with acholedo- choscope. The scope, attached to a second video camera and light source, is inserted into the CBD via either the cystic duct (Figure 2) or via a choledochotomy. Placement of the choledochoscope directly into the CBD via a cho- ledochotomy is generally reserved for patients with ducts dilated to greater than 6 mm in diameter on cholangio- gram[20] . A continuous saline infusion through the choledo- choscope dilates the duct and clears debris. CBD stones can be directly visualized (Figure 3) and instrumented. Between 66 and 82.5% of laparoscopic CBD explorations can be performed via the cystic duct[20,29] . In experienced hands, the CBD clearance rate is as high as 97%[2,29] . In one large series of laparoscopic CBD exploration, the overall morbidity rate of this procedure is approximately 9.5%, with a 2.7% retained stone rate[2] . These data are equivalent to the experience with ERCP. An alternate technique of laparoscopic CBD clearance involves stone extraction under fluoroscopic guidance. Figure 1 Intraoperative cholangiogram via the cystic duct demonstrating proximal biliary dilation and two filling defects in the CBD (Arrows). ← ←
  • 4. This technique, as described by Traverso et al, does not use a choledochoscope, but can be highly effective in CBD clearance for single stones (87%), with an overall 59% suc- cess rate[30] . In this technique, instruments, including stone extraction baskets, are passed into the CBD (usually via the cystic duct) under fluoroscopy. The fluoroscopic im- ages facilitate stone capture and removal. This technique simplifies the operating room set up for CBD exploration because additional video equipment is not required. In this series, patients whose ducts were not cleared laparoscopi- cally, underwent ERCP. The authors noted a significantly lower complication rate in patient who did not undergo ERCP[30] . Likewise, the overall associated costs were lower in these patients[31] . Laparoscopic techniques can be very effective at clearing CBD stones, but significant expertise and experience is re- quired to achieve high success rates. Stones impacted at the sphincter of Oddi are often the most difficult to extract by this technique. Long term follow up does not demonstrate a significant risk of CBD stricture or other complications for these procedures[2,29,30] . This technique is also advocated in the pediatric population by some practitioners as a way of avoiding an ERCP[32] . Intraoperative ERCP, although often limited by the immediate availability of a qualified endoscopist, is a technique that can be very useful. This takes advantage of the preexisting anesthetic and does not prolong hospital stay by delaying the procedure[33,34] . In some instances, cooperation between the surgeon and the endoscopist can expedite the procedure[35] . Guidewire placement, throught the sphincter of Oddi, into the duo- denum via the IOC catheter can facilitate cannulation, es- pecially for patients with difficult duodenal anatomy[34] . In the case of an unsuccessful extraction, open CBD explora- tion or drainage of the duct should be considered. POSTOPERATIVE EVALUATION AND THERAPY Postoperative ERCP is commonly used modality for CBD clearance when a stone is detected intraoperatively. This technique is highly effective[20] , but can be complicated when anatomic variables such as duodenal diverticulae or unusual biliary anatomy, are encountered[36] . On the occa- www.wjgnet.com sion that ERCP fails, a primary option includes returning to the operating room for a laparoscopic or open explora- tion. However, other less invasive options may be available. In selected patients, percutaneous transhepatic (PTH) therapies should be considered for CBD clearance. Ac- cess to the biliary system can be obtained percutaneously, under ultrasound guidance. Via this access point, stones can be extracted, a sphincterotomy can be performed, or lithotripsy can be used over a single, or multiple sessions to ensure duct clearance[37,38] . A percutaneous drain can be used to decompress the system between procedures or for temporary stenting after the duct is clear. Novel approaches have been performed in other ana- tomic settings which preclude ERCP, such as prior gas- tric surgery. The most common gastric surgery currently performed is the Roux-Y gastric bypass. In this surgery, a small gastric pouch is created and anastomosed to a limb of jejunum. The majority of the stomach, duodenum, and proximal jejunum are bypassed, making endoscopic access technically difficult. Combined laparoscopic surgical and endoscopic procedures have been described. Endoscopic access can be achieved via a gastrostomy[39] or jejunos- tomy[40] . The endoscope can be passed under surgical guidance, and an ERCP can be performed in the standard fashion. These procedures are only described in short case reports, but will undoubtedly become more common place with the prevalence of gastric bypass. In conclusion, given the various diagnostic and thera- peutic options available for managing choledocholithiasis, clinical judgment is paramount. The surgeon and the pa- tient are best served by accurate laboratory and radiologic assessment prior to cholecystectomy. In the setting of high preoperative suspicion for choledocholithiasis, preopera- tive imaging with MRCP may help guide subsequent treat- ment. If CBD stones are present on MRCP or in the set- ting of clinical jaundice or cholangitis, preoperative ERCP is the first line option. However, preexisting anatomic abnormalities may influence this decision. Laparoscopic IOC with a CBD exploration is a reliable approach in ex- perienced hands and if an ERCP is unsuccessful. Cholangiography during cholecystectomy is recom- mended for patients with a history of gallstone pancreati- tis, LFT abnormalities, or an enlarged CBD on preopera- tive imaging who have not undergone MRCP or ERCP. IOC is also recommended when intraoperative findings suggest anatomic abnormalities or unsuspected CBD calculi. Intraoperative laparoscopic CBD exploration is the first Figure 3 CBD stone as seen through the choledochoscope. Figure 2 Laparoscopic view of a choledochoscope (CS) entering the CBD via the cystic duct. The gallbladder (GB) is retracted to the left of the image. ← Cystic duct CBD GB CS Liver Freitas ML et al. Diagnosis and management of choledocholithiasis 3165
  • 5. option for choledocholithiasis detected in the operating room. Intraoperative or postoperative ERCP are options for incompletely cleared ducts. Percutaneous treatment or combined laparoendoscopic options are available in some centers for patients who cannot undergo ERCP or laparo- scopic choledochotomy. Open CBD exploration is a safe option, but usually limited to the setting of concomitant open surgery or as a last resort when other therapeutic modalities fail. REFERENCES 1 Schirmer BD, Winters KL, Edlich RF. Cholelithiasis and cholecystitis. J Long Term Eff Med Implants 2005; 15: 329-338 2 Riciardi R, Islam S, Canete JJ, Arcand PL, Stoker ME. Effectiveness and long-term results of laparoscopic common bile duct exploration. Surg Endosc 2003; 17: 19-22 3 Metcalfe MS, Ong T, Bruening MH, Iswariah H, Wemyss- Holden SA, Maddern GJ. Is laparoscopic intraoperative cholangiogram a matter of routine? Am J Surg 2004; 187: 475-481 4 Peng WK, Sheikh Z, Paterson-Brown S, Nixon SJ. 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  • 6. www.wjgnet.com difficult bile duct stones. Endoscopy 2003; 35: S31-S34 37 Nagashima I, Takada T, Shiratori M, Inaba T, Okinaga K. Percutaneous transhepatic papillary balloon dilation as a therapeutic option for choledocholithiasis. J Hepatobiliary Pancreat Surg 2004; 11: 252-254 38 Itoi T, Shinohara Y, Takeda K, Nakamura K, Sofuni A, Itokawa F, Moriyasu F, Tsuchida A. A novel technique for endoscopic sphincterotomy when using a percutaneous transhepatic cholangioscope in patients with an endoscopically inaccessible papilla. Gastrointest Endosc 2004; 59: 708-711 39 Peters M, Papasavas PK, Caushaj PF, Kania RJ, Gagne DJ. Laparoscopic transgastric endoscopic retrograde cholangiopancreatography for benign common bile duct stricture after Roux-en-Y gastric bypass. Surg Endosc 2002; 16: 1106 40 Mergener K, Kozarek RA, Traverso LW. Intraoperative transjejunal ERCP: case reports. Gastrointest Endosc 2003; 58: 461-463 S- Editor Pan BR E- Editor Bi L Freitas ML et al. Diagnosis and management of choledocholithiasis 3167