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Best Practice & Research Clinical Gastroenterology

Vol. 20, No. 6, pp. 1085e1101, 2006


doi:10.1016/j.bpg.2006.03.002
available online at http://www.sciencedirect.com

Symptoms, diagnosis and endoscopic


management of common bile duct stones

Grant R. Caddy* MD, MRCP


Consultant Gastroenterologist

Tony C.K. Tham MD, FRCP


Consultant Gastroenterologist
Department of Gastroenterology, Ulster Hospital, Dundonald, Belfast, Northern Ireland, UK

Bile duct stones (BDS) are often suspected on history and clinical examination alone but symptoms
may be variable ranging from asymptomatic to complications such as biliary colic, pancreatitis, jaun-
dice or cholangitis. The majority of BDS can be diagnosed by transabdominal ultrasound, computed
tomography, endoscopic ultrasound or magnetic resonance cholangiography prior to endoscopic
or laparoscopic removal. Approximately 90% of BDS can be removed following endoscopic retro-
grade cholangiography (ERC) þ sphincterotomy. Most of the remaining stones can be removed
using mechanical lithotripsy. Patients with uncorrected coagulopathies may be treated with
ERC þ pneumatic dilatation of the sphincter of Oddi. Shockwave lithotripsy (intraductal and extra-
corporeal) and laser lithotripsy have also been used to fragment large bile duct stones prior to
endoscopic removal. The role of medical therapy in treatment of BDS is currently uncertain.
This review focuses on the clinical presentation, investigation and current management of BDS.

Key words: bile duct stones; choledocholithiasis; ERCP; Endoscopic retrograde cholangio-
graphy; sphincterotomy; endoscopic biliary stenting; lithotripsy; ESWL; MRCP; mechanical
lithotripsy; chemical dissolution; ursodeoxycholic acid; review.

SYMPTOMS AND SIGNS OF COMMON BILE DUCT STONES

The symptoms and signs of common bile duct stones (CBDS) are variable and can range
from being completely asymptomatic to complications such as biliary colic, jaundice,
cholangitis or pancreatitis. Whilst complications of retained bile duct stones (BDS)
are common, a proportion of CBDS remain asymptomatic and do not result in any

* Corresponding author. Tel.: þ44 28 90484511x2479; Fax: þ44 28 90564785.


E-mail addresses: grant.caddy@ucht.n-i.nhs.uk (G.R. Caddy), tony.tham@ucht.n-i.nhs.uk (T.C.K. Tham).
1521-6918/$ - see front matter ª 2006 Elsevier Ltd. All rights reserved.
1086 G. R. Caddy and T. C. K. Tham

complications. However, the natural history of asymptomatic BDS is difficult to deter-


mine. Studies have estimated the prevalence of asymptomatic BDS to be between 5.2%
and 12%.1e4 The natural history of asymptomatic BDS appears to be more benign than
that of symptomatic BDS.5 A study by Millbourn of 38 patients presenting with symptom-
atic BDS, who were unfit for surgery or refused surgery, were followed for 6 months to
13 years. Forty-five per cent of the patients became asymptomatic but 55% developed
complications such as biliary colic, jaundice and cholangitis.6 More recently Johnson
and Hosking reported similar outcomes with over 50% of patients with retained duct
stones developing symptoms over time with 25% developing serious complications.7
Conversely, a study by Murison and colleagues randomised patients undergoing chole-
cystectomy, but without symptoms of bile duct stones, to intraoperative or no intrao-
perative cholangiography. Twelve per cent of patients in the cholangiography group
were discovered to have bile duct stones. It was assumed that a similar percentage of
patients in the group without cholangiography had stones, but no patients developed
symptoms in over 3 years of follow-up.2 We found similar results in our local population
in a non-randomised study.8
A common presentation of CBDS is biliary colic. The pain is often situated in the right
hypochondrium or epigastrium lasting 30 min to several hours. Associated symptoms
with nausea and vomiting are common. Biliary colic typically is not eased by change in
body position and is not specifically related to food intake. The pain is thought to be
caused by distension of the common bile duct due to an increase in pressure caused
by partial or complete obstruction by a CBDS. One study has suggested that presenta-
tion of CBDS may depend on the number of stones situated in the CBD (e.g. one to three
stones more likely associated with cholangitis, biliary colic and higher bilirubin levels than
patients presented with four or more stones who were more likely to present with pain-
less jaundice).9 In addition to the number of stones, the diameter of CBDS is also impor-
tant. The likelihood of stones passing spontaneously may be dependent on size.10 Stones
up to 8 mm may pass without problems as suggested by a study in which bile duct stones
were shown to pass spontaneously when ERCP was later performed.11,12
When a stone becomes impacted in the bile duct, obstructive jaundice ensues.
Often the obstruction of the bile duct is incomplete but complete obstruction may
occur. Frequently the obstructed bile becomes infected resulting in cholangitis.
CBDS often contain bacteria embedded within their matrix. When obstruction of
the bile duct occurs, the rise in biliary pressure results in the translocation of bacteria
from the bile duct to the blood-stream. Approximately one-fifth of patients presenting
with cholangitis from CBDS will have a bacteraemia, usually with gram negative organ-
isms being cultured.13 The symptoms of cholangitis are described by Charcot’s triad of
jaundice, fever and pain in up to 75% of patients. However, in a minority of patients
(12%) pain alone may be the only presenting feature of cholangitis.14 Prolonged biliary
obstruction results in secondary biliary cirrhosis after approximately 5 years.15
Between 4% and 8% of patients with gallstones will develop gallstone pancreatitis
secondary to migratory gallstones.16 Developing gallstone pancreatitis is more likely
with smaller stones than with larger stones. In a study by Venneman, it was found
that patients presenting with gallstone pancreatitis had mean diameter bile duct stone
size of 4 mm compared to that of 9 mm for patients presenting with obstructive jaun-
dice.17 The majority of these patients will have a self limiting disease but mortality still
remains around 10%.18 There have been several scoring systems devised to predict the
severity of pancreatitis including the Ranson system, modified Imrie system, Apache II
score and Balthazar grading system. These scoring systems are based on organ
dysfunction and local complications.19,20
Symptoms, diagnosis and endoscopic management of common bile duct stones 1087

Practice points

 The natural history of asymptomatic bile duct stones appears to be more benign
than that of symptomatic bile duct stones
 Up to 50% of patients presenting with symptomatic bile duct stones will develop
complications such as biliary colic, cholangitis, pancreatitis or jaundice if left in situ
 The symptoms of cholangitis are described by Charcot’s triad of jaundice, fever
and pain in up to 75% of patients. However, in a minority of patients (12%) pain
alone may be the only presenting feature of cholangitis

CLINICAL DIFFERENTIAL DIAGNOSIS

The differential diagnosis of CBDS will be dependant on the clinical presentation.

Jaundice with or without pain

The differential of patients presenting with obstructive jaundice include bile duct stric-
tures (both benign and malignant). Benign strictures often result from previous
episodes of pancreatitis or cholangitis, whilst malignant strictures can be due to intrin-
sic obstruction due to a cholangiocarinoma or extrinsic compression due to pancre-
atic or gallbladder carcinoma. The presence of jaundice with pain suggests the
presence of a bile duct stone while painless jaundice is more likely to be associated
with biliary strictures. Courvoisier’s law states that in the presence of jaundice, a
palpable gallbladder is likely to be due to malignant obstruction of the bile duct rather
than choledocholithiasis. Other differentials include sclerosing cholangitis, parasitic
infection of the biliary tree, primary biliary cirrhosis, alcoholic liver disease and bile
duct injuries during laparoscopic cholecystectomy, e.g. inadvertent ligation of biliary
structures.

Biliary colic

Differential diagnoses of patients presenting with pain caused by CBDS without biliary
obstruction (biliary colic) include cholecystitis, sphincter of Oddi dysfunction, acute
pancreatitis, peptic ulcer disease, duodenitis, oesophageal spasm and inferior myocar-
dial infarction.

Pancreatitis

The differential diagnosis of acute pancreatitis includes a perforated gastric or duode-


nal ulcer, mesenteric infarction, strangulating intestinal obstruction, ectopic pregnancy,
dissecting aneurysm, biliary colic, appendicitis, diverticulitis, inferior myocardial infarc-
tion and haematoma of abdominal muscles or spleen.

Abnormal cholestatic liver function tests

The differential includes mechanical obstruction caused by biliary strictures (benign


and malignant e as above), ampullary carcinoma, primary biliary cirrhosis, sclerosing
1088 G. R. Caddy and T. C. K. Tham

cholangitis, medication induced, congenital ductopenic syndromes, granulomatous


hepatitis, malignant infiltration of the liver e.g. lymphoma, amyloidosis, alcoholic liver
disease and non alcoholic fatty liver disease (NAFLD).

DIAGNOSTIC INVESTIGATIONS

Laboratory tests

Patients presenting with CBDS often have cholestatic liver function tests (LFT’s). In the
study by Anciaux, elevated serum gamma glutamyl transpeptidase (GGT) and alkaline
phosphatase (ALP) were the most frequent biochemical abnormalities in patients with
symptomatic choledocholithiasis (increased in 94% and 91% of cases, respectively).14
Serum bilirubin levels may be markedly elevated depending on whether the obstruc-
tion of the bile duct is complete or incomplete. In the same study by Anciaux, bilirubin
levels and transaminases were found to decrease over the subsequent 10 days in
patients with CBDS following admission to hospital.
There have been many studies attempting to predict the likelihood of concomitant
CBDS in patients going on to have laparoscopic cholecystectomy.21e28 In a retrospec-
tive study by Onken and colleagues in 465 patients with confirmed choledocholithiasis
at time of cholecystectomy, multivariable analysis identified serum bilirubin, AST, and
ALP, in addition to common bile duct diameter and age as independent predictors of
choledocholithiasis.27 Most of the studies have emphasised that laboratory investiga-
tions must be used in addition to other imaging modaslities to predict the likelihood
of CBDS and the multivariate analysis models have found a dilated bile duct as an
independent variable in predicting CDBS.25e28

Transabdominal ultrasonography

Transabdominal ultrasonography (TUS) remains the first line radiological investigation


in patients with suspected CBDS. TUS has a high sensitivity of detecting both intra-
hepatic and extrahepatic biliary dilatation. In the study by Stott and colleagues, the
sensitivity of TUS compared to endoscopic retrograde cholangiopancreatography
(ERCP) in detecting common bile duct dilatation was 96%.29 However, the sensitivity
of TUS in detecting choledocholithiasis is much lower with sensitivities of between
25% and 63% when compared to endoscopic ultrasound (EUS) and ERCP.30,31 Al-
though with a specificity of approximately 95%, TUS remains an extremely useful
test if CBDS are detected.30 A negative TUS in a patient with suspected choledocho-
lithiasis does not rule out CBDS.32

Computed tomography

Conventional computed tomography (CT) studies have found sensitivities between 70%
and 90% in the detection of choledocholithiasis.33e35 The use of unenhanced helical CT
for detection of choledocholithiasis has similar sensitivities of 67e88%.36e39 Oral
enhanced CT cholangiography has an increased sensitivity of 92%.36
Symptoms, diagnosis and endoscopic management of common bile duct stones 1089

EUS

EUS is an accurate test for detection of CBDS, with a sensitivity range between 94%
and 98%.40,41 Due to a significant complication rate associated with ERCP, the decision
to use EUS to detect choledocholithiasis depends on the probability of CBDS in symp-
tomatic patients. The probability of CBDS being detected can be stratified into low,
intermediate or high probability based on clinical, biochemical and imaging criteria
that have already been discussed. The use of EUS may be best suited for patients
that fall into the intermediate risk category and thereby reducing the risk to the
patient of pancreatitis and cholangitis that could potentially occur following ERCP.
Patients in the low risk category should be referred for laparoscopic cholecystectomy
and patients in the high risk category should undergo ERCP þ sphincterotomy or chol-
ecystectomy þ intraoperative cholangiogram with laparoscopic extraction of any
stones detected.42

Magnetic Resonance Cholangiography (MRC)

Magnetic Resonance Cholangiography (MRC) has become an accepted method of


imaging the bile duct with a high sensitivity and specificity for choledocholithiasis.
One such study by Ainsworth and colleagues found the accuracy rates of detection
of choledocholithiasis comparable between EUS and MRC (accuracy rate 93% and
91%, respectively).43 In addition, several studies have found MRC to be comparable
to ERCP. The study by Laokpessi and colleagues found both MRC and ERCP compa-
rable in detection of CBDS (sensitivity and specificity 93% and 100%; 94% and 100%,
respectively).44 A recent NIH consensus statement found that ERC, MRC and EUS
were comparable in their sensitivities, specificities and accuracy rates for detection
of choledocholithiasis.45

Endoscopic retrograde cholangiography (ERC)

ERC has sensitivities between 90% and 95% in detecting choledocholithiasis.44,46 It is


often the gold standard test to which other modalities are compared in the detection
of CBDS. The benefit of ERC is that therapeutic removal of the stone(s) can be per-
formed immediately. However, the risks of ERC have been well documented and
therefore ERC is recommended in patients with a high probability of CBDS. In patients
with an intermediate probability of CBDS, other imaging modalities should be consid-
ered as discussed above.

Practice points

 Elevated GGT and ALP were the most frequent biochemical abnormalities in
patients with symptomatic choledocholithiasis, increased in 94% and 91% of
cases, respectively.
 The sensitivity of TUS in detecting common bile duct dilatation was 96%
but the sensitivity of TUS in detecting choledocholithiasis is much lower
(25e63%)
1090 G. R. Caddy and T. C. K. Tham

 Conventional CT have found sensitivities between 70% and 90% in the detec-
tion of choledocholithiasis
 Oral enhanced CT cholangiography has an increased sensitivity of 92%
 EUS is an accurate test for detection of CBDS, with a sensitivity range between
94% and 98%
 The accuracy rates of detection of choledocholithiasis are comparable
between EUS and MRC
 ERC has sensitivities between 90% and 95% in detecting choledocholithiasis
 NIH consensus statement found that ERC, MRC and EUS were comparable
in their sensitivities, specificities and accuracy rates for detection of
choledocholithiasis

IS THERE ALWAYS AN INDICATION TO TREAT CBD STONES?

As previously discussed, CBDS detected in symptomatic patients, have a high rate of


complications if left in situ (approximately 50% of patients will subsequently develop
jaundice, cholangitis, biliary colic or pancreatitis). The true natural history of asymp-
tomatic bile duct stones is unknown but they appear to cause fewer complications
than CBDS detected in symptomatic patients. In contrast, in asymptomatic gallstones,
a cholecystectomy would not be recommended, as the cumulative risk of developing
symptoms is not as great as that of asymptomatic CBDS. In addition, complications will
develop after the emergence of symptoms. However, with asymptomatic CBDS, com-
plications usually develop before symptoms. In an increasing litigious society, the
majority of gastroenterologists would recommend attempted removal of CBDS
once detected for fear that any subsequent complications that may ensue may be as
a consequence of leaving the stones in situ. Small stones may pass spontaneously as
previously mentioned. There may be clinical situations in which the risk of performing
an ERC to remove identified CBDS may outweigh the benefits. For example, patients
with a short life expectancy e.g. severe end stage dementia or with severe co-morbidity
making ERCP hazardous. In these situations the risk assessment is the duty of the endo-
scopist and it may be deemed appropriate not to perform ERC. The decision making
process should be carefully explained and documented with the patient (if possible)
and family members.

ROLE OF MEDICAL THERAPY?

The role of medical therapy will discuss the role of ursodeoxycholic acid (UDCA). The
role of other non-surgical treatments of CBDS such as extracorporeal shockwave lith-
otripsy (ESWL) will be discussed below.
The use of UDCA (and chenodeoxycholic acid) has only been shown to dissolve
cholesterol containing stones. However, approximately 85e95% of patients in the
Western World will have cholesterol stones. The first report of using bile salt acids
to dissolve cholesterol stones was reported in 1927.47 It wasn’t until half a century
later that larger studies were performed to investigate the use chenodeoxycholic
acid on the dissolution of gallstones.48 To date the majority of these studies have
been performed on patients with gallstones rather than on patients with CBDS.
The studies that have been performed in this patient group contain small numbers
Symptoms, diagnosis and endoscopic management of common bile duct stones 1091

of patients and are statistically underpowered. Salvioli and colleagues investigated the
effect of UDCA (12 mg/kg) on 28 patients with radiolucent CBDS compared with pla-
cebo. None of the patients in the placebo group had resolution of their CBDS during
a 24-month period follow-up compared with seven patients in the UDCA group.49
UDCA is often used in association with ERC and biliary stent insertion for failed
extraction of CBDS. Johnson and colleagues studied 24 patients with difficult to
extract CBDS and randomised the patients to either UDCA þ stent or stent alone
with follow up ERC and attempted stone removal. In the UDCA group, 90% of the
patients subsequently had ductal clearance at repeat ERCs compared with none of
the patients in the stent alone group at the end of the study period.50 Ros and
colleagues studied a group of patients with recurrent pancreatitis caused by microli-
thiasis and found that patients treated with UDCA (10 mg/kg) eliminated gallbladder
microlithiasis and reduced the episodes of further pancreatitis. Continuing therapy
with UDCA appeared to prevent recurrence of gallbladder microlithiasis.51
Currently there are no large randomised controlled trials providing convincing
evidence at this time that UDCA has a role in the management of CBDS. However,
in view of the relative few side effects and good safety profile, gastroenterologists
will continue to use UDCA in patients with difficult to extract CBDS. Larger and
more robust studies are required to determine any overall benefit of UDCA on
retained CBDS.

Research agenda

 Currently there are no large randomised controlled trials providing convincing


evidence at this time that UDCA has a role in the management of CBDS
 The role of UDCA needs to be defined in the treatment of CBDS

ERC (SPHINCTEROTOMY OR PNEUMATIC DILATATION)

Endoscopic biliary sphincterotomy (EST) at ERC was first described in 1974 and was
initially advocated for elderly patients or patients with other co-morbid illness exclud-
ing them from surgical management. However, since this time, EST has become wide-
spread in the practice for the removal of CBDS. The complications of EST have been
previously well described. The use of EST, particularly in younger patients, led to con-
cern over the long term sequelae of a disrupted sphincter of Oddi caused by chronic
enteric-biliary reflux. However, a review suggests that this theoretical risk of cholan-
gitis is not apparent in long term studies.52
Endoscopic balloon dilatation (EBD) of the sphincter had previously been per-
formed in the 1980s but had subsequently lost favour in clinical practice due to
reports of increased complications (mainly that of pancreatitis). However, several
more recent studies had suggested that the original risk of post-EBD pancreatitis
was overestimated due to recruitment of patients with sphincter of Oddi (SOD) dys-
function (a group with a known increased risk of post-ERC pancreatitis). Subsequently
there have been several randomised controlled trials comparing EBD against EST.53e60
These studies have been recently been reviewed in a meta-analysis by Baron and col-
leagues.61 In their meta-analysis (incorporating eight randomised prospective studies
and over 1000 patients) they found the overall similar rate of complications (10.3%
1092 G. R. Caddy and T. C. K. Tham

and 10.5%, respectively). However, the rates of pancreatitis were significantly higher
for the EBD group (7.4% versus 4.3%) but bleeding complications were reduced
(0% versus 2%). Other complication rates of infection and perforation were similar
between the two groups. Primary clearance of the bile duct was less successful using
EBD compared to EST (70% versus 80%), and the use of mechanical lithotripsy was
more common (21% versus 15%).
A further randomised control trial, not included in the meta-analysis, comparing the
short term complications of EBD versus EST again confirmed an increase rate of
pancreatitis with EBD versus EST (15.4% and 0.8%, respectively).62 The rate of post
EST pancreatitis in this study was lower than that expected, however. Patients were
found to have more frequent invasive procedures, longer hospital stay and more missed
days off work/normal activities of daily living in the EBD group. EBD has been advocated
in patients with coagulopathies where the risk of bleeding from sphincterotomy would
be hazardous. However, if the coagulopathy cannot be corrected prior to the ERCP
procedure then a biliary stent is a safe alternative and is our preference over EBD.
Following endoscopic sphincterotomy (or balloon dilatation), CBDS are removed
using a Dormia-type basket of a balloon catheter. Using either of these techniques
stones can be removed form the bile duct in about 90% of patients.

Practice points

 In a meta-analysis (incorporating over 1000 patients), the overall complication


rate between EST and EBD were similar (10.3% and 10.5% respectively)
 However, rates of pancreatitis are significantly higher for EBD compared to
EST (7.4% versus 4.3%)
 Bleeding complications were reduced in EBD compared to EST (0% versus 2%).
 Patients were found to have more frequent invasive procedures, longer hospi-
tal stay and more missed days off work/normal activities of daily living in the
EBD group compared to EST

MECHANICAL LITHOTRIPSY

Stone removal from the common bile duct may be technically difficult due to factors
such as the size of the stone (>2 cm), impaction of the stone in a non-dilated bile duct,
stones above a bile duct stricture or a narrowed retro-pancreatic portion of the distal
CBD. In these circumstances, mechanical lithotripsy (ML) is commonly used. The stan-
dard ML device is a basket inserted through a plastic and then a metallic sheath, which
is inserted through the scope. The Olympus BML range and Monolith lithotriptor, (Mi-
crovasive Corp) are amongst the most commonly used lithotriptor devices. The CBD
stone is engaged with an open basket and the metallic sheath can then be advanced up
into the bile duct to meet the basket resulting in crushing of the stone. Often the wires
of the basket can become deformed after several ‘crushes’ and the ML device may
need to be removed to reset the wires back into their standard position.
The use of ML was described in 1982 as a method of successfully removing large
CBDS.63 Bile duct clearance rates using ML have been reported to be between 68%
and 98%.64e71 In a retrospective series of 163 patients to investigate a range of param-
eters that may be important in failure to remove CBDS, Cipolletta and colleagues
Symptoms, diagnosis and endoscopic management of common bile duct stones 1093

found that size of the stone was the only factor important in failure of bile duct clear-
ance using ML.66 They found that bile duct clearance rates were 90% for stones with
a diameter less than 10 mm compared to 68% for those greater than 28 mm in diam-
eter. Subsequently a prospective study by Garg and colleagues only identified impac-
tion of CBDS in the bile duct as the only important factor in failure of a ML. This
study did not find the size of CBDS as a significant factor in failure of a ML in the
removal of difficult CBDS.65 The impaction of the stone led to an inability to pass
the basket proximal to the stone or a failure to open fully around the stone to allow
it to be grasped. Often if there is little space between the stone and bile duct wall, the
basket will not fully open and therefore not be able to engage the stone. It has been
found useful in these circumstances to insert the metallic sheath up into the bile duct
and to rotate the basket to try to grasp the stone.72 Even if the stone is partially
engaged, the stone can be fragmented and successfully removed.

Practice points

 The removal of CBDS may be technically difficult due to factors such as the
size of the stone (>2 cm), impaction of the stone in a non-dilated bile duct,
stones above a bile duct stricture or a narrowed retro-pancreatic portion of
the distal CBD
 Bile duct clearance rates using ML have been reported to be up to 98%.
 Impaction of CBDS in the bile duct is an important factor in failure of a ML to
remove stones

Shock waves can be generated with intraendoscopical probes by direct contact (elec-
trohydraulic lithotripsy) or a pulsed dye laser (laser lithotripsy), or outside the bile duct
using an extracorporeal lithotriptor. These techniques are generally reserved for pa-
tients in whom stones cannot be removed with conventional techniques due to factors
such as large size of the stones, impacted stones or the presence of a biliary stricture.

INTRAENDOSCOPICAL LITHOTRIPSY

Pulsated laser lithotripsy

Laser lithotripsy uses an amplified light energy, at a particular wavelength, which is


focused into a single beam and directed onto a stone within the bile duct. This causes
plasma formation on the surface of the stone, allowing more absorption of laser light,
and results in an acoustic shockwave that can fragment the stone. Laser lithotripsy can
be performed under direct vision using cholangioscopy using mini scopes or can be
performed under fluoroscopic control using standard equipment. More recently the
development of software coupled to the laser allows differentiation of light reflected
back from bile duct epithelium compared to light reflected back from a stone. This
causes a discontinuation of the laser pulse, and reduces any potential thermal injury
to the epithelium. The use of this software allows the safe use of laser lithotripsy
under fluoroscopic control and avoids the need for lithotripsy to be performed under
direct vision.
1094 G. R. Caddy and T. C. K. Tham

The experience of laser lithotripsy has been limited to a few centres and the
majority of the published literature on its use has been in a small number of patients
in non-randomised studies. Despite these limitations the success rate of duct clear-
ance for retained bile duct stones using laser lithotripsy in these studies is between
64% and 97%.73e84 In a randomised trial comparing laser lithotripsy versus extracor-
poreal shockwave lithotripsy (ESWL), laser lithotripsy was found to be more effective
in clearing the bile duct (29/30 patients) compared to ESWL group (22/30 patients)
p < 0.05.85

Electrohydraulic lithotripsy

Electrohydraulic lithotripsy (EHL) uses direct high voltage to generate a shockwave,


through a liquid medium, to fragment the BDS. The procedure has been performed
successfully under cholangioscopic guidance86,87 or under fluoroscopic control using
a balloon catheter.88 The advantage of direct visualisation is to control the shockwave
being applied to the stone rather than on the ductal wall and thereby potentially
reducing complications. However, the disadvantage is the cost, and the expertise
required in cholangioscopic techniques. In earlier studies, a stone fragmentation
rate of approximately 80% was achieved using EHL.89,90 In the prospective open study
by Adamek and colleagues, a stone fragmentation rate of 93% was achieved and they
were able to remove all stones from the bile duct in 74% of patients.86 In a small rand-
omised trial comparing extracorporeal shockwave lithotripsy versus EHL, no differ-
ence was demonstrated in stone free rates of the bile duct at the end of each
treatment. In addition, both groups of patients required additional endoscopic proce-
dures to remove residual stones.91 Hui and colleagues found a lower incidence of
complications, particularly cholangitis, in a small prospective study of 36 patients,
comparing double pigtail stent insertion versus EHL therapy in difficult to remove
CBD stones (63.2% versus 7.7%).92 In summary, the use of EHL has been used suc-
cessfully in patients with difficult to remove CBD stones but its use is limited to spe-
cialised centres. In addition, most of the published studies are in a small number of
patients and subject to bias, making evidence based recommendations on its use
limited.

STENTING AS DEFINITE TREATMENT OF BILE DUCT STONES?

Insertion of an endoprothesis may be required on a temporary basis for difficult to


retrieve CBDS. Studies have shown that the majority of CBDS reduce in size follow-
ing stenting and therefore should be easier to remove at repeat ERCP.93 However,
insertion of an endoprothesis as a definitive treatment of CBDS, without any further
subsequent intervention, may be considered but should be limited to patients with
severe co-morbid illness. Any such illness should make any subsequent ERC proce-
dures hazardous to be performed and therefore best avoided. The decision regard-
ing a patient’s fitness to undergo an ERCP is that of the endoscopist performing the
procedure but an anaesthetic assessment may also be useful in the decision making
process.
There have been several studies investigating the role of stent insertion as the sole
treatment of CBDS that could not be removed at ERC. In the study by Bergman and
colleagues, 58 of 117 patients had permanent biliary stent insertion as their treatment
for CBDS (i.e. expectant management and stent exchange only if complications
Symptoms, diagnosis and endoscopic management of common bile duct stones 1095

occurred). Sixty percent of these patients were alive at 2 years of follow up and of
these 70% were symptom free. However, overall the complication rate was 40%
and the mortality rate related to complications of the biliary stent was 16%. Cholan-
gitis and jaundice were felt to be the cause attributable to the death of these patients
and occurred after a median time of 42 months.94 These results are similar to a study
by De Palma and colleagues, which followed up 49 patients with stent insertion for
irretrievable CBDS. Their results found a 40% late complication rate and 6% mortality
related to biliary sepsis over a 3-year follow-up period.95 Jain and colleagues carried
out a prospective study on 20 patients with difficult to extract CBDS (mean diameter
of stone was 1.7 cm). In each case a 7F pigtail stent was inserted and ERC repeated at
6 months. In 20% of patients the stones had fragmented and allowed balloon clearance
of the duct. However, in 35% of patients the duct had cleared spontaneously.96 There
is a potential advantage of pigtail stents over straight stents in that the duodenal por-
tion of the stent comes out at an angle and may keep the biliary orifice open more
effectively. If the stent becomes occluded after several months, it still has the potential
to keep the CBDS from impacting. Pigtail stents also have a lower rate of stent migra-
tion. The evidence for the use of pigtail over straight stents for definitive treatment of
CBDS is however limited. In the study by Hui and colleagues, as previously mentioned,
there was a lower incidence of cholangitis and mortality in a small study comparing
double pigtail stent insertion versus EHL therapy.92 In summary, where facilities exist,
alternative forms of treatment should be considered in high risk patients with retained
CBDS such as lithotripsy. However, long term stenting is an alternative in patients with
a poor life expectancy.

EXTRACORPOREAL SHOCKWAVE LITHOTRIPSY

Extracorporeal shockwave lithotripsy (ESWL) was first used treating gallstones


in 1980s following its successful use in fragmenting renal calculi.97 Shock waves
are generated outside the body using electrohydraulic, electromagnetic or piezocer-
amic shockwave systems. First generation lithotriptors required patients to be im-
mersed in a water bath and often required general anaesthesia. Subsequent
generation of lithotriptors do not require immersion in a water bath and can be
performed under intravenous sedation. Complete duct clearance of CBDS following
ESWL range between 83% and 93%.97e100 The majority of patients will require en-
doscopic extraction of the bile stone fragments following ESWL, although approx-
imately 10% of stones may subsequently pass spontaneously following treatment.98
Localisation of CBDS amenable to ESWL is performed under fluoroscopy or
ultrasound.
In a small prospective randomised trial comparing ESWL to EHL, no significant
difference in stone fragmentation rates or final bile duct clearance was demon-
strated.91 A larger prospective non-randomised trial by the same authors found sim-
ilar results of final bile duct clearance rates between the two treatment modalities
(79% versus 74%, respectively).86 Comparison studies between ESWL and laser lith-
otripsy as mentioned previously have demonstrated significantly higher final bile duct
clearance rates, fewer additional interventions required following treatment and
shorter duration of treatment for laser lithotripsy.85,101 The main morbidity associ-
ated with ESWL is sepsis due to bacteria being released into the bloodstream during
shockwave treatment. Pre-procedural antibiotics prior to ESWL are therefore
recommended.
1096 G. R. Caddy and T. C. K. Tham

Practice points

 The success rate of duct clearance for retained bile duct stones using laser lith-
otripsy is between 64% and 97% but large randomised studies are lacking
 Laser lithotripsy may be more effective ESWL in clearing the bile duct of CBDS
but larger studies are required
 Bile duct clearance rates are reported to be approximately 74% using EHL
 One study found no significant difference in the clearance rates of CBDS using
either EHL or ESWL
 Complete duct clearance of CBDS following ESWL range between 83% and
93%
 The majority of patients will require endoscopic extraction of the bile stone
fragments following lithotripsy, although approximately 10% of stones may sub-
sequently pass spontaneously following treatment.

CHEMICAL DISSOLUTION THERAPY

Following published reports of chemical dissolution therapy for gallstones, the tech-
nique of chemical contact dissolution for retained common bile duct stones was first
published in 1947.102 However, due to the side effects of the chemical used (diethyl
ether), the procedure was not widely practiced. The discovery of mono-octanoin as
a cholesterol stone dissolving agent, led to several reports of its use in difficult to
remove CBDS. Palmer and Hofmann collated a series of case reports on its use in treat-
ing CBDS (most of these patients had not had previous sphincterotomy), and therapy
was deemed ‘useful’ in 54% of patients. However, side effects were common and
reported in 67% of patients.103 The chemical is administered via a nasobiliary catheter,
T-tube or percutaneous catheter and therapy is required for at least several weeks mak-
ing therapy less practical. The use of methyl tertiary butyl ether (MTBE) has advantages
over other chemical dissolution agents, mainly that of faster kinetics. In a non-
randomised study by Neoptolemos and colleagues, MTBE was used in 33 patients
with bile duct stones and found to be helpful in removal in 36% of patients. Again com-
plication rates were high (79%) in this study.104 At present the use of chemical dissolu-
tion therapy has a limited role in the treatment of difficult to remove CBDS due to the
length of treatment, continuous access to the bile duct that is required and a high
complication rate.

SUMMARY

Symptomatic BDS commonly cause significant morbidity and attempt at stone removal
should be attempted if possible. Complications of CBDS include biliary colic, jaundice,
cholangitis and pancreatitis. Investigations aimed to predict the presence of stones
within the bile duct include serum bilirubin, AST, ALP, common bile duct diameter
and age as independent predictors of choledocholithiasis. TUS is a sensitive test in de-
tecting bile duct dilatation but the sensitivity is reduced in its ability to detect chole-
docholithiasis. A NIH consensus statement found that ERC, MRC and EUS were
comparable in their sensitivities, specificities and accuracy rates for detection of
Symptoms, diagnosis and endoscopic management of common bile duct stones 1097

choledocholithiasis. ERC and stone removal using a balloon or basket is often per-
formed following EST. EBD may be performed if patients have uncorrected coagulopa-
thies but the risk of pancreatitis is higher than for EST (although the risk of bleeding
complications is lower for EBD). ML is often required in difficult to remove CBDS and
using this device, CBDS can be removed in 90e95% of cases. Other forms of litho-
tripsy including laser lithotripsy and EHL are confined to specialised centres and the
evidence for their use is based on small studies. ESWL may clear stones from the
bile duct in up to 93% of patients but frequently ERC and stone fragment removal
is required post ESWL. The role of medical therapy in difficult to remove CBDS (or
in CBDS in patients with severe co-morbid illness preventing ERC þ stone removal)
is still currently uncertain due to a lack of large randomised control trials.

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