Editor: Peter B. Cotton
3. Common bile duct stones and cholangitis
Enders K. W. Ng & Sydney Chung
Common bile duct (CBD) stones can be classified into primary stones (those that form within the bile ducts) and secondary
stones (those that originate from the gall-bladder). They can cause pain, jaundice, cholangitis, or biliary pancreatitis.
Endoscopic sphincterotomy is an established method for the removal of CBD stones. Stones <1 cm in diameter can be extracted easily with baskets or balloon catheters. Large (>2 cm) or giant stones require some form of lithotripsy (mechanical or intraductal with laser/electrohydraulic lithotripsy) to facilitate duct clearance.
Patients presenting with acute cholangitis secondary to biliary stones carry a significant morbidity and mortality. Broad
spectrum antibiotics therapy is necessary to cover against the mixed bacterial infection. The presence of complete biliary
obstruction and infection may lead to suppurative cholangitis with an increase risk of fatality. The clinical outcome is improved
with urgent endoscopic biliary decompression using a nasobiliary catheter or an indwelling biliary stent. Successful removal
of CBD and intrahepatic stones may require stricture dilation and lithotripsy. Combined percutaneous and endoscopic drainage
procedures assure complete duct clearance and prevent stone recurrence.
Incidence of CBD stones
Choledocholithiasis is a common clinical problem worldwide. It has been estimated that 1015% of patients undergoing cholecystectomy for symptomatic gallstones harbour concomitant stones in their common bile duct
. Primary ductal stones formed de novo also add a further small percentage to the overall prevalence.
After the first successful common bile duct exploration by Courvoisier in 1890, surgical lithotripsy was the treatment of
choice for choledocholithiasis for nearly a century .
Non-operative approach to CBD stones
The introduction of endoscopic sphincterotomy in 1974  and the rapid development of minimal access surgery in the late 1980s have completely revolutionized the approach to CBD
stones. As laparoscopic cholecystectomy is the first-line treatment for gallstones nowadays, endoscopic removal of biliary
tree calculi has become the most appealing and widely embraced technique for removal of choledocholithiasis.
Classification of CBD stones
Bile duct stones can be broadly classified into two types according to the site of origin.
Primary CBD stones
Primary ductal stones are stones that develop de novo in the intrahepatic ducts or common duct. They are far more common in the Asian populations than in the West. The reason
for such a geographical difference is enigmatic. These stones are often brownish-yellow in color with a soft muddy consistency
(Fig. 1); biochemically, they consist of calcium bilirubinate mixed with variable amounts of cholesterol and calcium salts. While
the etiology remains conjectural, bacterial infections and biliary stasis are considered the two most important causative
Bacteriology of primary CBD stones
Gastrointestinal tract microorganisms such as Escherichia coli, Klebsiella, Proteus, Bacteroides, and Clostridium have been isolated from the bile of patients with primary duct stones . In addition, bacterial cytoskeletons are invariably seen in primary duct stones under electronic microscope . These bacteria may have a contributory role by producing enzymes that catalyze deconjugation of bilirubin and lysis of phospholipids,
which in turn promote the precipitation of calcium bilirubinate and initiate stone formation. Among all the bacteria isolated,
Clostridium perfringens has been found to produce the highest beta-glucuronidase enzyme activity, which is 34-fold higher than that for E. coli, Corynebacterium spp., Enterococcus spp., and Klebsiella spp. . On the other hand, the biliary stasis theory is supported by the fact that intrahepatic ductal strictures and proximal dilatation
are commonly seen among patients with primary duct calculi . Nevertheless, whether these strictures are the cause or consequence of the intrahepatic ductal calculi remains unresolved.
Secondary CBD stones
Secondary common duct stones are supposed to have originated from the gallbladder. Conceivably their composition is identical
to that of gallstones, which are mainly yellowish cholesterol or black pigment calculi with a hard and crispy consistency.
It is unclear why gallstones migrate into the common duct in some patients. In one study the size of the cystic duct has been
reported as the single most important determinant .
Asymptomatic biliary stones
A considerable proportion of patients with common or intrahepatic ductal calculi are asymptomatic. The stones may be found
incidentally during investigation for unrelated abdominal conditions. The presence of coexisting ductal stones is sometimes
noted by abdominal ultrasound scan when patients are being worked up for cholelithiasis.
Symptomatic biliary stones
Intermittent jaundice is said to be a typical feature of choledocholithiasis, when the stone impacts and disimpacts at the
papilla or the distal common bile duct leading to fluctuating jaundice and serum bilirubin levels. Continuous obstruction
from stone impaction in the distal common duct may manifest as progressive jaundice.
Dull right upper abdominal pain due to increased biliary tree pressure may also be experienced as a result of stone impaction.
When bacterial infection superimposes in the obstructed biliary system, the patient presents with the typical Charcot's triad
(fever, pain, and jaundice) of cholangitis. Nevertheless, cholangitis may not necessarily present with all three features,
and the diagnosis should not be dismissed lightly just because the patient is afebrile or not jaundiced.
Small stones may pass spontaneously through the ampulla of Vater. The passage of stones across the papilla may induce a transient
rise in the pancreatic duct pressure and trigger intrapancreatic activation of enzymes resulting in acute pancreatitis. Patients
with acute pancreatitis typically present with epigastric pain radiating to the back, associated with nausea and vomiting.
A serum amylase level exceeding 1000 IU/liter is considered to be diagnostic of pancreatitis.
Oriental cholangitis or recurrent pyogenic cholangitis
Patients with primary intrahepatic duct stones may present with recurrent attacks of cholangitis. Characteristically there
are multiple strictures, with stone formation proximal to the stricture in the dilated portion of one or more segments of
the intrahepatic ducts. Jaundice may not be obvious if only segmental branch ducts of one liver lobe are involved. This condition
is more commonly seen in South-East Asia and thus is called oriental cholangitis or cholangiohepatitis (Fig. 2).
For patients presenting with jaundice, acute cholangitis, or pancreatitis, the diagnosis of CBD or intrahepatic duct stones
is not difficult because the pathology often declares itself with typical clinical or biochemical features.
However, it may be difficult to diagnose asymptomatic biliary stones, and these may be suspected or identified because of
a subtle derangement of liver function tests. Some patients may only have a mild elevation of serum alkaline phosphatase,
without any changes in the bilirubin level.
The presence of CBD stones can be determined by non-contrast or contrast studies.
Abdominal ultrasound scan
Abdominal ultrasound is the first-line imaging investigation if biliary tree calculi are suspected. In addition to seeing
echogenic materials within the biliary tree, the status of the common bile duct, intrahepatic bile ducts, and gallbladder
can be determined.
Endoscopic retrograde cholangiopancreatography (ERCP)
The diagnosis is confirmed by contrast studies of the biliary system with ERCP or other forms of imaging. Though ERCP has
been the gold standard for demonstrating biliary tract calculi, the procedure itself is invasive and carries a considerable
risk of complications (Fig. 3).
Magnetic resonance cholangiogram (MRC) for CBD stones
MRC has evolved over the last decade and may potentially replace or supplement ERCP in the diagnosis of choledocholithiasis.
In a recent prospective study by Calvo et al., 61 patients with suspected biliary tree calculi according to Cotton's criteria (high probability in 49 patients, intermediate
probability in 9 patients) were subjected to MRC within 72 h prior to diagnostic ERCP. MRC correctly identified CBD stones
in all 3 patients with choledocholithiasis in the intermediate probability group, as well as 29 out of the 32 patients in
the high-probability group . Overall sensitivity and specificity of MRC were 91 and 84%, respectively. The global efficacy was estimated at 90%. It appears
to be a promising technique, especially in cases with equivocal serum biochemistry or sonographic findings (Fig. 4). However, MRC is purely diagnostic and a separate therapeutic session needs to be arranged if choledocholithiasis is found,
rendering it a less favored option for patients with a high suspicion for CBD stones.
Endoscopic ultrasonography (EUS) for CBD stones
There is now supporting evidence that the accuracy of EUS is as good as, or comparable to ERCP in diagnosing bile duct stones
(Fig. 5), with a sensitivity of 84100% and specificity of 76100% [10,11]. These data were largely generated by the use of a radial scanning transducer . Whether a linear scanner can achieve similar accuracy in the diagnosis of choledocholithiasis is still under investigation
. One major disadvantage of EUS is that it is highly operator-dependent, which may account for the wide variations in sensitivity
and specificity being reported in the literature, and which makes the interpretation of data difficult.
Management for CBD stones
While some may advocate the use of medical treatment such as chemical dissolution for removal of biliary tree calculi, endoscopic
or surgical approaches remain the preferred treatments because they are more effective and reliable.
ERCP, sphincterotomy, and stone extraction
CBD stones <5 mm in diameter may pass spontaneously or can be removed without a sphincterotomy. For stones >5 mm, endoscopic sphincterotomy is the most commonly performed procedure for their retrieval.
Choice of endoscopes
The preparation, positioning, and sedation of the patient are the same as those for diagnostic ERCP. The choice of duodenoscopes
is determined by the anticipated size of the CBD stones. For small stones, where a complex lithotripsy instrument is unnecessary,
a regular duodenoscope with a 2.8 mm channel is adequate. However, when the stone is >1 cm or there is a strong likelihood that lithotripsy will be needed, a bigger duodenoscope, with a 3.2 or 4.2 mm channel, should be used.
Cannulation with sphincterotome
Cannulation of the common duct is the same as for diagnostic ERCP. Some patients may have stones impacted at the lower end
of the common duct (Fig. 6), and the resultant bulging papilla could render cannulation more difficult. A cannulating sphincterotome with an adjustable
tip may facilitate cannulation of the bile duct in this situation by lifting the roof of the papilla. The use of a hydrophilic
guidewire under such circumstances may also help in selective cannulation. Deep cannulation of the bile duct should be confirmed
by injecting a small amount of contrast through the sphincterotome or by gently wiggling the sphincterotome under fluoroscopy.
A guidewire is inserted through the lumen of the cannulotome once deep cannulation is confirmed so that access to the bile
duct can be assured in subsequent exchange maneuvers. The cutting wire is then bowed so that it is in contact with the roof
of the papilla. The incision is made in a stepwise manner in the 111 o'clock direction along the longitudinal fold. To avoid an uncontrolled 'zipper' cut, minimal tension is applied to the wire. The electrocautery unit should be set with a high cutting current blended with
a low coagulation current. The size of the sphincterotomy can vary but it should be limited to the junction between the duodenal
wall and the intraduodenal portion of the ampulla of Vater, which often appears as a semicircular mucosal fold above the papilla.
After endoscopic sphincterotomy, stones in the biliary tree can be removed with either a basket or a balloon catheter. The
authors prefer a dormia basket because it is in general more durable than the fragile retrieval balloons.
Basket stone extraction
In brief, the closed basket covered by its plastic sheath is inserted into the common duct through the therapeutic channel
of the duodenoscope. Inside the bile duct, the basket is gently opened and contrast is injected to confirm its position and
relation to the biliary calculi. Care must be taken when opening the basket because stones in the main duct may be displaced
upward and become trapped in one of the intrahepatic ducts. It is also advisable to remove stones lying in the distal common
bile duct before making any attempts to retrieve stones located in the proximal duct. Vigorous shaking of the fully open basket
inside the bile duct may help to bring the stones into the basket. Once the stones are captured, the basket is withdrawn slowly
without closure. Closure of the basket at this juncture may disengage the stones. When the basket and stones are withdrawn
to the level of papillotomy, the duodenoscope is gently pushed in with a right rotational movement. This maneuver helps straighten
the tip of the duodenoscope, and exerts a traction force along the axis of the common bile duct which facilitates the removal
of the stones, and avoids damage to the papilla or duodenum. By repeating the above maneuver, multiple ductal stones <1 cm in diameter can be removed in the same ERCP session (Fig. 7).
Balloon stone extraction
Biliary stones in the CBD of <1 cm diameter can be removed with a balloon catheter. The balloon is deflated and inserted into the CBD through the sphincterotomy,
and advanced above the stones. The balloon is gently inflated to the size of the bile duct and pulled back gently, displacing
the CBD stone distally. With an adequate sphincterotomy, the stone can be pulled against the cut orifice and then expelled
by traction on the balloon catheter followed by downward angulation of the tip of the endoscope. The maneuver is repeated
and complete clearance of the CBD is confirmed by an occlusion cholangiogram.
Bleeding, perforation, pancreatitis, and cholangitis are potential complications of endoscopic sphincterotomy (ES) and stone
extraction. The reported incidence varies markedly in the literature, but bleeding is generally the most common complication
encountered. Previous studies failed to identify predicting factors for these complications. Most of these studies were univariate
or bivariate analyses, which generated inconsistent and often contradictory results [14,15]. Two multicenter studies based on multivariate regression models, however, have shed new light on this complex issue.
In a prospective survey conducted in the United States between 1992 and 1994, acute pancreatitis was found to be significantly
more common if the ES was performed for suspected dysfunction of sphincter of Oddi, in young patients, using a precut technique,
after difficult cannulation, or with repeated and excessive pancreatic contrast injections (Fig. 8) . Similar findings were reported in an Italian multicenter study, in which acute pancreatitis was independently predicted
by young patient age, pancreatic duct opacification, and a non-dilated common bile duct .
Significant post-sphincterotomy bleeding happened more readily if the patient had associated coagulopathy, had cholangitis,
or the procedure was done by an inexperienced endoscopist. Interestingly, bleeding and cholangitis were again associated with
small centers with low case volume. These two large-scale and multivariate studies have two points in common: sphincterotomy
complications are closely related to indications for the procedure and to the experience or case volume of individual endoscopists
Sphincterotomy vs. balloon sphincteroplasty
The reported complication rates of ES ranged from 610%, with a mortality resulting from these complications of 0.41.2% [18,19]. Though the percentages appear to be small, the actual number of patients suffering from these complications, as well as
the associated prolonged hospitalization, is considerable. Since complications are mostly related to the sphincterotomy, some
have advocated the use of endoscopic balloon dilatation (EBD) as an alternative procedure prior to stone extraction.
EBD was first described by Staritz et al. in 1983 . In addition to the lower risk of bleeding and perforation, another apparent advantage of EBD is that the sphincter of Oddi
function can be preserved. This has been demonstrated in a number of studies involving sphincter of Oddi manometry [21,22]. However, when EBD was first proposed in the early 1980s, it was not widely embraced due to skepticism concerning its efficacy
and the fear of precipitating acute pancreatitis. The incidence of acute pancreatitis reported then was as high as 25% according
to some earlier series in which EBD was performed mainly for sphincter of Oddi dysfunction [23,24].
Balloon sphincteroplasty for CBD stones
More recent studies have revealed that EBD is a safe and effective procedure for patients with biliary stones [25,26]. In a randomized trial by Bergmen et al. 202 patients were assigned to either EBD or ES prior to removal of the CBD stones . There was no significant difference in overall duct clearance rate, procedure time, early complications, and death associated
with the two procedures. The drawback for EBD is that mechanical lithotripsy was more frequently required in these patients.
Besides, a considerable number of patients in the EBD group eventually required an ES for ductal clearance.
Sphincterotomy for CBD stones
Though there is concern regarding the safety of ES, a multicenter prospective database study in the United States based on
standard criteria for defining complications revealed that morbidities only occurred in 5.8% of the 1921 patients studied
. Two-thirds of the events were graded as mild, which required less than 3 days of hospitalization. In addition, this study
disproved the dogma that complications are more likely to occur in young patients with normal size ducts. Out of the 238 patients
aged younger than 60 years, only one developed severe complications and there were no fatalities.
Long-term complications of sphincterotomy
As the short-term outcome of endoscopic sphincterotomy is no longer in question, there is an increasing concern about the
long-term effects of sphincterotomy on the biliary system. In a retrospective study by Costamagna et al. 529 patients with successful sphincterotomy and bile duct clearance were evaluated after a follow-up of at least 5 years
. Recurrent biliary symptoms or duct stones occurred in only 11.1% of the patients, while the remaining were either asymptomatic
or died of unrelated causes. A dilated bile duct >22 mm was found to be the only independent predictive factor for recurrence. In another population-based cohort study by Karlson
et al. the cancer risk of 992 patients who had undergone sphincterotomy over a median follow-up time of 1011 years were estimated, and it was found to be almost the same as that of the normal population.
In conclusion, there is no evidence that endoscopic sphincterotomy is unsafe in either the short or long term provided that
it is being performed by, or under stringent supervision of, experienced endoscopists. Endoscopic balloon dilatation can be
an alternative to ES, but currently it should be limited to patients with no more than three stones, each <10 mm in diameter .
ERCP vs. laparoscopic common duct exploration for retained CBD stones
In the era of open cholecystectomy, intraoperative cholangiogram was part of the operation. If CBD stones were suspected with
intraoperative cholangiogram, exploration of the common duct would be performed, and a variety of techniques were used to
remove the ductal calculi. The choledochotomy would be closed around a rubber T-tube, and a check cholangiogram performed
about 10 days after the operation to rule out any residual ductal stones. However, with the rapid acceptance of laparoscopic
cholecystectomy in the last decade, when and how these concomitant choledocholithiase should be managed is become increasingly
To perform ERCP for all patients scheduled for laparoscopic cholecystectomy is impractical and the projected numbers of complications
and mortality are also unacceptable.
Operative removal of CBD stones
An operative laparoscopic cholangiogram can be performed to rule out CBD stones. If stones are found intraoperatively, transcystic
duct lithotripsy or exploration of the common duct is a feasible option with the laparoscope. Success rates for using such
an approach to diagnose and clear the common duct stones have been reported to be close to 90% [31,32]. However, these laparoscopic procedures require a much higher level of skill and expertise, which may not be universally
available except in some tertiary referral centers.
Factors that predict CBD stones
One possible approach is to identify patients at higher risk of concomitant choledocholithiasis and send them for preoperative
cholangiogram and lithotripsy prior to laparoscopic cholecystectomy. A number of studies have reported that deranged liver
function, dilated biliary tree on ultrasound scan, and history of jaundice or pancreatitis predict the presence of common
bile duct stones [33,34]. Unfortunately, these studies were unable to generate concrete data that would allow accurate prediction of the biliary tree
MRC for detection of CBD stones
The emergence of magnetic resonance technology in the 1990s opened new possibilities for solving this clinical dilemma. Earlier
series comparing MRC with conventional ERCP or operative findings had already shown promising data regarding non-invasive
diagnosis of common duct calculi [35,36]. In a recent series by Laokpressi et al. on a group of 147 patients with clinical and biological signs of choledocholithiasis, MRC was shown to have a sensitivity
of 93% and a specificity of 100% in detecting the ductal calculi . MRC is likely to play an important role in preoperative diagnosis of concomitant CBD stones in equivocal cases, and may
allow better planning regarding the mode of stone removal prior to or during laparoscopic cholecystectomy.
Risk scores for prediction of CBD stones
There is as yet no conclusion as to which approach is superior, and the choice of management method depends mainly on the
expertise and support available in individual centers. One of the latest developments is to categorize patients into high-,
intermediate-, and low-risk groups for CBD stones, and the management approach is dependent upon the risk score of each individual
Alternative approaches to CBD stones
Precut sphincterotomy for failed deep cannulation
A needle-knife sphincterotome can be used to incise the lower end of the common duct when guidewire cannulation of the bile
duct fails (Fig. 9). In a recent prospective study by Binmoeller et al., precut papillotomy was performed on 123 out of 327 patients who had an unsuccessful CBD cannulation . Selective cannulation was achieved in all cases after the procedure, without a significant increase in the rate of pancreatitis
and bleeding when compared to those undergoing the conventional pull-type endoscopic sphincterotomy.
Complications of precut sphincterotomy
Today, the overall incidence of complications following precut sphincterotomy has been reported to be 711%, which is not much higher than that quoted for conventional sphincterotomy [40,41]. However, it cannot be overemphasized that these figures were mostly produced by experienced endoscopists in world-renowned
centers. The mortality and morbidity rates could have been higher if the procedure had been done by trainees or by the less
Percutaneous transhepatic cholangiogram and drainage
A percutaneous transhepatic biliary drain (PTBD) can be considered when deep cannulation of the common duct has been unsuccessful.
The procedure is usually done under ultrasound guidance. With the intrahepatic duct punctured, a pigtail catheter of size
7F to 10F can be inserted using the Saldinger technique. This allows immediate decompression and drainage of the system, and
the risk of introducing infections to the biliary tree is low. It may not be a procedure of choice if the patient has underlying
coagulopathy or if the intrahepatic ducts are not dilated. After a successful PTBD, a cholangiogram can be performed in a
later session to delineate the details of the common duct pathology. If stones are found, there are essentially two possible
Rendezvous procedure (two-hands technique)
A guidewire is passed through the percutaneous catheter down to the common duct and duodenum, which is to be picked up by
a snare inserted through a duodenoscope. The guidewire is pulled out from the biopsy valve of the duodenoscope and a wire-guided
sphincterotome is threaded over the guidewire into the common duct. Subsequent endoscopic sphincterotomy and stone extraction
can be performed in the standard manner. In a series reported by Calvo et al. the success rate for clearing the CBD with a rendezvous approach was 93% (13/14) . Only one complication was encountereda retroperitoneal perforation during sphincterotomy. This approach is an extremely good option for patients with poor surgical
risks and refractory choledocholithiasis.
Percutaneous stone extraction
For patients in whom the duodenoscope cannot be advanced into the duodenum, e.g. a history of previous hepatico-jejunostomy,
percutaneous stone extraction after serial dilatation of the PTBD tract can be considered. The tract needs to be dilated up
to at least 18F in order to allow a standard choledochoscope to be inserted into the bile duct. A waiting period of 46 weeks is allowed for the dilated tract to become mature and tough enough for subsequent manipulations. Our preference is
to insert a choledochoscope into the biliary system and perform cholangiogram through the endoscope under fluoroscopy. Stones
are seen as filling defects, and can be removed by dormia basket. An electrohydraulic lithotripsy device is a useful adjunct
for breaking up the stones before they are removed through the percutaneous tract. Another alternative is to dilate the sphincter
of Oddi from above, with the stone fragments then being flushed or pushed down into the duodenum using the choledochoscope.
In a recent series by the Dutch group, the totally percutaneous approach managed to clear the bile duct in 27 out of 31 patients
(87%), and complications only occurred in 3 patients, with no mortality .
The challenge: giant CBD stones
The ordinary endoscopic methods described above are suitable for stones around 1 cm in size. For stones >1.5 cm diameter, endoscopic retrieval becomes difficult, if not impossible (Fig. 10). Several options are available to tackle the situation.
Basket mechanical lithotripsy (BML)
Mechanical lithotripsy is the most commonly used technique in the authors' center when giant biliary stones are encountered
(Fig. 11). When unexpected stone and basket impaction occurs, soft stones may be crushed by forceful closure of a standard basket
against the Teflon sheath. It is, however, generally not recommended because the basket wire may be distorted or embedded
into the stone surface, resulting in a basket trapped inside the common duct. The Wilson Cook Sohendra lithotriptor or Percy
McGowan 'fishing reel' system is the device of choice for salvaging such a situation.
Through-the-scope BML using a metal sheath
When performing BML, it is imperative to make sure the stone-engaged basket is placed in the most dilated portion of the common
duct. When stone capture is confirmed, the Teflon sheath is gradually withdrawn to facilitate the passage of the metal sheath
into the common duct. After the Teflon sheath is fully withdrawn into the spiral metal sheath, fragmentation of stones is
accomplished by closing the basket wire with the captured stone pressed against the metal sheath. This maneuver is monitored
mainly under fluoroscopic imaging. Caution is taken to avoid ductal injury when the basket is about to close completely into
the metal sheath, as tension on the tip of the BML basket may suddenly change its direction and potentially damage the common
Results of BML
The reported success rate of stone fragmentation by BML ranges from 82100% [44-45]. In a series reported by the authors' center, 55 out of 68 patients (81%) had complete CBD clearance after lithotripsy of
giant stones with BML . Of the remaining 13 patients, 1 had the stone crushed with the Soehendra lithotriptor, 6 were successfully managed by electrohydraulic
lithotripsy through a 'mother and baby' endoscope, 4 received an indwelling stent, and 2 patients underwent surgery. The ductal clearance rate was 92% in another
multicenter study of the efficacy of BML in 116 patients, without any significant increase in the incidence of pancreatitis
or hemorrhage . Thus far the largest series ever reported was by Schneider et al. on a group of 209 patients, in which the overall success rate was 88%, with 79% of the stones >20 mm in diameter . The reasons for failure in the remaining 12% of patients were either unsuccessful insertion of the basket, or failure to
engage the stone because of its size, the common duct diameter, or other technical problems.
Mother and baby choledochoscopy and intraductal lithotripsy
Passing a baby endoscope via the channel of a large-size duodenoscope is another method for the management of giant CBD stones.
Using the baby cholangioscope, an electrohydraulic lithotriptor or laser probe can be applied to shatter the stone under direct
visualization. This approach used to require a standard mother and baby system, but the recent release of a per-oral choledochoscope
(CHF system, XP20, Olympus) that can go through the 4.2 mm working channel of a regular therapeutic duodenoscope has reduced the cost. Caution should be exercised by the endoscopist
controlling the duodenoscope to avoid excessive elevation of the elevator, which may damage the delicate optical fibers inside
the choledochoscope and result in premature failure.
Electrohydraulic lithotripsy (EHL)
EHL was first introduced in the 1950s as a method of fragmenting rocks in mines. It was later adapted for medical use, and
Koch et al. in 1977 were the first to attempt fragmentation of common bile duct calculi . The mechanism is a cracking force transmitted by hydraulic pressure waves generated under water by the high-voltage sparks
discharged across the tip of the EHL probe. Few data are available in the literature regarding the use of EHL for biliary
tract stones. The largest series reported thus far had a success rate of 99% in 65 patients . Other smaller series involving less than 10 patients also claimed CBD clearance in all the patients treated .
Intraductal laser lithotripsy
The other device that can work through the motherbaby system is laser lithotripsy. Essentially there are three types of laser available. The Nd:YAG laser is no longer in use
because of the high risk of ductal injury. The flash lamp pulsed dye lasers, on the other hand, can be delivered with thinner
fibers and are superior to the Nd:YAG lasers for intraductal lithotripsy. The reported success rates range from 8094%, and serious complications are uncommon [52,53]. The latest development includes the 'smart dye laser', which is capable of differentiating stone from normal ductal tissue and thus obviates the need for direct visualization
during the procedure. This new mode of intraductal lithotripsy can be performed under fluoroscopic guidance without the necessity
of a baby cholangioscope. In a series of 38 patients, 37 had successful ductal clearance after being treated by an automatic
stone recognition laser system . A slightly lower success rate was also reported by Hochberger et al. in a group of 50 patients . Major complications were not found in either series.
Stenting and interval endoscopic lithotripsy
For patients whose common duct stones are refractory to endoscopic retrieval, a plastic biliary stent can be inserted as a
temporary or permanent measure. It has been shown in several prospective series that elderly patients with difficult stones
remained symptom-free after insertion of an endoprosthesis, and thus surgery was avoided. There have also been studies reporting
a decrease in the stone size after a period of biliary stenting. In a study by the authors, 46 patients with large CBD stones
received plastic stents . Twenty-eight patients had repeat ERCP for stone extraction after a median of 63 days. Size of stones was significantly reduced,
from 1146 mm (mean 24.9 mm) to 546 mm (mean 20.1 mm), and duct clearance was achieved in 25 patients (89%) during the repeat procedure. Similar findings have been reported
by Maxton et al. and Jain et al. [57,58].
Effects of stenting on CBD stones
The exact mechanism causing the change in the size of stones is unclear, but improvement in the solubility of bile after drainage
as well as the mechanical friction between stents and calculi are thought to be responsible.
The need for stone extraction after stenting
Temporary drainage and decompression of the biliary system by a plastic stent is a valid option for high surgical risk patients
whose stones are too big for endoscopic retrieval at the outset. However, in a prospective randomized trial by Chopra et al. significantly more long-term biliary complications were observed in patients treated with endoprosthesis as compared to
those with complete ductal clearance . Thus it is highly advisable to clear all common duct calculi and reserve stenting as a definitive treatment for only those
who are extremely unfit for other procedures.
Extracorporeal shock-wave lithotripsy (ESWL)
ESWL can be used for giant stones not amenable to regular ERCP or mechanical lithotripsy. The latest models of ESWL is more
patient-friendly and the procedure can be performed under sedation. ERCP and papillotomy are still required in most cases
for localization of the stones. A nasobiliary catheter is placed for cholangiography. Alternatively, percutaneous cholangiography
can be employed for stone localization. Even if fragmentation by ESWL is successful, the resultant stone fragments are often
too big to pass out spontaneously and must be removed by either ERCP or percutaneous cholangioscopy.
Results of ESWL for CBD stones
There are many studies reporting high ductal clearance rates. In a multicenter study conducted in Germany, the success rate
was 86%, with a mortality rate of only 1.8% . Other series also reported similar outcomes, with cholangitis being the most frequent complication. The most recent report
by Ellis et al. studied 83 patients with retained bile duct stones treated by the third-generation lithotriptor. Complete stone clearance
was achieved in 69 (83%) patients. Complications included six cases of cholangitis, and one perinephric hematoma which resolved
For patients with giant or inaccessible CBD stones who have failed all the treatment modalities described above, surgical
exploration and clearance of the common duct should be contemplated if the general condition of the patient allows.
Intrahepatic duct stones
Primary intrahepatic duct calculi, or hepatolithiasis, is a distinct condition that is predominately found in the Far East.
It is characterized by the presence of multiple strictures and brown or black pigment calculi in the intrahepatic ducts. For
unknown reasons, it tends to affect the left lobe of the liver more than the right side. Surgical resection of the affected
liver segment and creation of drainage are the preferred treatment if the pathology is localized to one side. However, due
to the multiple segment involvement and peripheral location of the strictures and stones, management of this condition remains
formidable, and surgical resection is only possible in a small percentage of the patients.
ERCP and basket removal
Stones located in the intrahepatic ducts close to the bifurcation of the common hepatic duct can be removed with an ordinary
dormia basket. The accessibility of specific segmental ducts is largely dependent on the technique and experience of the endoscopist.
More sophisticated endoscopic maneuvers may be required to retrieve intrahepatic calculi lying proximal to a relative stenosis
or stricture. Balloon dilators or through-the-scope graded dilators can be applied to dilate these strictures so as to facilitate
complete clearance of stones endoscopically.
Endoscopic retrieval of intrahepatic calculi with conventional baskets can be difficult if the stones are located deeply inside
the tortuous segmental ducts with multiple or tight strictures. The development of a wire-guided basket has helped to overcome
this problem. Earlier prototypes had the guidewire going through the center of the basket, rendering engagement of stones
inefficient. The guidewire needed to be removed to permit entrapment of the stones, but repeated cannulation of the same segmental
duct sometimes became technically difficult. The wire-guided basket used nowadays has the guidewire passed along the side
instead of the center of the basket (Fig. 12). Access to the same segmental duct can be guaranteed during capture and retrieval of the intrahepatic stones. Our preliminary
experience with this device on four patients with intrahepatic calculi was very good and successful stone retrieval was achieved
in all .
Percutaneous transhepatic cholangioscopy (PTC)
Though the preferred treatment of primary intrahepatic stones has been removal of the stones via resection of the stenotic
bile duct and atrophic segments, surgery may be impossible in patients with multisegmental distribution of the stones. PTC
lithotripsy is definitely one possible option whereby the intrahepatic duct stones can be removed from above a stricture using
a more straightforward approach .
Results of percutaneous treatment of intrahepatic stones
In a study on 165 patients treated with PTC lithotripsy for intrahepatic duct stones, the success rate of complete stone clearance
was 80% . Three major causes of incomplete removal of stones were identified: (1) angulation or stricture of the intrahepatic ducts;
(2) sludgy bile and stones; and (3) a peripheral location rendering access impossible. After a mean follow-up of 58 months,
43 (32.6%) of the 132 patients with initial clearance developed recurrent stones. Other investigators have reported similar
results, and it appeared that the risk of stone recurrence tends to increase with time . In a more recent series reported by the Korean group, recurrence of intrahepatic stones after percutaneous cholangioscopic
treatment was strongly associated with severe biliary stricture, advanced biliary cirrhosis, and Tsunoda types III and IV
hepatolithiasis . As a whole, PTC lithotripsy is an option for patients whose stones are not amenable to endoscopic treatment but who at the
same time are not suitable candidates for surgical resection due to poor anesthetic risk.
ERCP and sphincterotomy in Billroth II gastrectomy
ERCP is considered to be more difficult in patients with previous Billroth II gastrectomy. The overall complication rates
reported in the literature ranged from 813% [67,68]. The problems include difficulties in (1) maneuvering the side-view duodenoscope through the afferent loop in a retrograde
manner, (2) cannulating the common bile duct from an inverted position, and (3) carrying out a papillotomy in an upside-down
position. Among all the morbidities reported, bowel perforation involving in particular the afferent loop is a considerable
and unique complication for ERCP. In one of our recent series, there were 11 perforations in 185 ERCP procedures for patients
with a history of previous Billroth II gastrectomy . Nine perforations occurred when the afferent loop was entered; one occurred after sphincterotomy, and another during cannulation.
The majority of perforations were found near the duodenojejunal flexure area. The likely mechanism is that the endoscope loops
excessively in the jejunum when it is being inserted across the relatively fixed duodenojejunal flexure. Mucosal tear or perforation
happens as a result of overstretching of the proximal jejunum during retrograde advancement of the endoscope.
Precaution and alternatives for Billroth II gastrectomy
We believe that the experience of the endoscopist is the key factor for avoiding perforation in this clinical setting. The
passage of the endoscope through the afferent loop has to be monitored under fluoroscopy. Excessive looping of the duodenoscope
should be avoided. If resistance is encountered, the procedure should be stopped and alternative methods for gaining access
to the biliary system considered. One option is to drain the bile ducts by percutaneous transhepatic biliary drain (PTBD)
and have the calculi fragmented and removed through the PTBD tract in subsequent sessions. This approach is likely to lengthen
the course of treatment because the PTBD tract requires serial dilatation, to a size of 16F or 18F, before lithotripsy is
possible. Another option is to enter the afferent loop with a forward-viewing endoscope instead of a side-viewing duodenoscope.
Side-viewing vs. forward-viewing scope for ERCP in Billroth II gastrectomy
In a comparative study by Kim et al. on the use of these two types of endoscopes in patients with previous Billroth II gastrectomies, significantly less bowel
perforation was observed in the group having the forward-viewing endoscope, yet the success rate in cannulating the CBD was
comparable . However, due to the lack of the bridge elevator, maneuverability of various devices is compromised with the forward-viewing
endoscope. Thus we still prefer to use a side-viewing duodenoscope whenever possible because it allows the operator to view
the papilla en face. Recently, a special wire-guided B-II papillotome with the cutting wire on the reverse side has been introduced . Whether it helps the safety of sphincterotomy in gastrectomized patients remains to be seen.
In the obstructed biliary tree, stagnant bile is a favorable culture medium for bacteria. Ascending infection in the biliary
system is one of the mechanisms leading to acute cholangitis.
Effect of biliary obstruction on the reticuloendothelial system
It has been shown in both clinical and animal studies that the phagocytic function of the reticuloendothelial cells surrounding
the canaliculi are severely affected in complete bile duct obstruction. Clearance of the bacteria coming along in the portal
venous blood is therefore compromised, and infection of the stagnant bile inside the obstructed system may take place.
Bacteriology of cholangitis
The infected bile contains a large quantity of bacteria, mostly Gram-negative bacilli, with E. coli, Klebsiella spp., Enterobacter spp., and Pseudomonas sometimes mixed with anaerobes such as Clostridium perfringens and Bacteroides fragilis, or Gram-positive enterococci.
Effect of raised intrabiliary pressure and cholangiovenous reflux
The intraductal pressure in the biliary tree may rise in the presence of obstruction. As the terminal ends of bile canaliculi
are in direct contact with the hepatic sinusoids, a raised intrabiliary pressure will facilitate cholangiovenous reflux of
infected materials into the hepatic venous circulation. Under such circumstances the patient may develop bacteraemia as well
as endotoxaemia. The septicemia then triggers a systemic response from the patient's own immune system, including a variety
of cytokines, complements, and vasodilators. In severe cases the reaction may be overwhelming, with deleterious effects towards
other internal organs, resulting in a phenomenon known as systemic inflammatory response syndrome (SIRS), with multiorgan
failure, and considerable mortality.
Simple cholangitis: Charcot's triad
Charcot's triad of acute cholangitis includes acute right upper abdominal pain, fever, and jaundice. Nevertheless, not every
patient having cholangitis manifest all these features. Jaundice can be subtle if the onset is acute or the obstruction is
incomplete, yet the patient could be very ill and septic if there is considerable endotoxemia. Frail or old patients may not
experience or complain of any pain even if they are suffering from cholangitis. Overall, fever has been the most common and
consistent symptom, present in more than 90% of patients. Chills and rigor are not as frequent but their presence is suggestive
of bacteremia or septicemia.
Suppurative cholangitis: Reynold's pentad
In the presence of profound septicemia, the patient may develop hemodynamic instability and mental confusion. When added to
Charcot's triad described above, hypotension and coma are collectively known as Reynold's pentad, which signifies a severe
attack of suppurative cholangitis associated with significant mortality. As the condition can be rapidly fatal, vigorous resuscitation,
intensive care support, and urgent biliary decompression should be provided in order to minimize mortality.
Of patients with clinical cholangitis, 8090% may respond to conservative treatment; the remaining 510% with suppurative cholangitis will need urgent biliary decompression.
Initial conservative management
Patients with suspected acute cholangitis should be admitted to hospital for further management. It is imperative to control
the sepsis as early as possible. Aggressive fluid resuscitation and high-dose intravenous broad spectrum antibiotics are the
key initial measures. Close monitoring of the vital signs, including urine output, is necessary. With such initial treatment,
control of sepsis is achieved in 90% of patients. Further intervention and drainage for the obstructing lesion can be performed
on a semielective or elective basis in the next available session.
Urgent biliary decompression
Some 510% of patients, especially those with Reynold's pentad, may not respond to the initial resuscitation. Emergency decompression
of the obstructed biliary system is mandatory. In case of unstable patients with compromised hemodynamic status and respiratory
function, intensive-care monitoring, including use of inotropes and/or ventilatory support, should be sought before biliary drainage.
Role of ERCP
Endoscopic sphincterotomy with stone extraction is considered to be the procedure of choice in patients with acute cholangitis.
It is often performed when the initial treatment was to control the sepsis. However, in patients with severe cholangitis not
responding to the initial medical therapy, the only possible option is decompression and drainage of the infected biliary
system. In one of our earlier series, endoscopic drainage of the biliary tree was attempted in 105 patients with severe cholangitis
. The success rate was 97%, resulting in rapid resolution of fever and improvement in liver function tests in most of the
patients. Mortality was found to be associated with a delay in drainage. In another subgroup of 40 patients with severe cholangitis
managed by urgent ERCP, we have demonstrated that endoscopic drainage is an effective method of lowering bile and serum endotoxin
levels and aborting the process of SIRS .
Endoscopic drainage vs. surgery
In a retrospective series which compared surgery with endoscopic drainage for acute cholangitis, patients undergoing emergency
exploration of the common duct had a significantly higher mortality (21%) than those who underwent endoscopic sphincterotomy
alone (4.7%) . The most concrete evidence favoring endoscopic intervention for acute cholangitis comes from a prospective randomized trial
in which patients were treated either by endoscopic drainage or surgical decompression . There were significantly fewer complications in patients treated endoscopically than in those treated with surgery (34 vs.
66%, P < 0.05). The hospital mortality rate was also significantly lower in those who underwent endoscopy (10 vs. 32%, P < 0.03).
ERCP vs. PTBD
There are relatively little data in the literature comparing ERCP with PTBD drainage procedures for acute cholangitis. Presumably
PTBD may be more suitable for patients who are hemodynamically unstable and not suitable to be transferred to the endoscopy
suite. However, in a non-randomized study comparing different modes of drainage for elderly patients with acute cholangitis,
endoscopic drainage had yielded significantly lower morbidity (16.7%) and mortality (5.6%) than surgical (87.5 and 25.0%,
respectively) and percutaneous drainage (36.4 and 9.1%, respectively) .
Nasobiliary catheter drainage vs. stenting in acute cholangitis
Although nasobiliary catheter drainage has become well established for use in emergency decompression of the biliary system
in patients with severe cholangitis, it is not without problems in real clinical practice. Confused patients may pull the
nasobiliary drain (NBD) out shortly after it has been placed and repeat insertion may be required. It is often cumbersome
and risky, especially in critically ill patients. Inadvertent displacement or kinking of the NBD may happen from time to time
during transfer of patients or other procedures. One way of avoiding these problems is to place an indwelling plastic stent
in lieu of a nasobiliary catheter in such patients. A major drawback of an internal stent is that its patency and adequacy
of drainage cannot be monitored. In a prospective randomized trial of 74 patients conducted in the authors' center, both approaches
were shown to have similar efficacy on initial decompression for the biliary sepsis, with comparable mean procedure times
. Nasobiliary catheter displacement and kinking happened in 5 out of the 40 patients assigned to NBD, while stent blockage
was found in 1 patient among the 34 with endoprosthesis placement. Patients' tolerance was much better in the stent group,
but it had a higher mortality rate than the NBD group (12 vs. 2.5%) though the difference was not statistically significant.
Currently we still prefer NBD for decompression for patients with cholangitis.
Surgery to prevent recurrent cholangitis
Endoscopic or percutaneous transhepatic lithotripsy may not be feasible in some patients, when cholangitis affects the biliary
tree at multiple sites with varying degrees of severity (Fig. 13). Surgery remains the last resort in removing the calculi and preventing stone recurrence in such patients.
Types of operation
Though the details of various operative procedures are beyond the scope of this chapter, surgeons would like to achieve the
following goals: (1) removal of the obstructing stones; (2) improved drainage of the biliary system; and (3) resection of
non-functioning or atrophic liver segments. Transduodenal sphincteroplasty, supraduodenal choledochoduodenostomy, and end-to-side
hepaticojejunostomy are the surgical procedures for improving bile drainage. Liver resection may be suitable for disease confined
to a segment or to one side of the liver, especially if the affected parenchyma is atrophic with little residual function.
It is performed not only to eradicate the source of symptoms and infections, but also to remove the underlying stricture which
carries a malignant potential in the future.
Endoscopic treatment is now the first-line management option for choledocholithiasis. The success rate has increased with
the recent advances in cannulation techniques and instrument design. Although endoscopic balloon dilatation has been proposed
as a replacement for sphincterotomy for stone extraction, it is still restricted to selected cases with small calculi. It
is advisable to refer patients with giant difficult stones to expert centers where advanced lithotripsy techniques are readily
available. With the current endoscopic technology, very few patients with choledocholithiasis will require surgery. However,
surgical resection still has a role for those with intractable intrahepatic stones and cholangitis localized to certain segments
of the liver.
Outstanding issues and future trends
ERCP remains the gold standard for the diagnosis of CBD stones, although EUS has shown its very high sensitivity in identifying
distal CBD stones. With improvements in resolution of MRC technique, this may provide an alternative and non-invasive method
of confirming the diagnosis before intervention. Randomized controlled studies have shown that endoscopic biliary drainage
is the first line of urgent management for patients with suppurative cholangitis who have failed conservative treatment. Part
of the reason for the failure of antibiotic therapy is the inability of most drugs to penetrate a completely obstructed biliary
system with raised intrabiliary pressure. Drugs that can be excreted into bile against a pressure gradient would have considerable
advantages in the management of these sick patients, but they are not a replacement for urgent biliary decompression in sick
patients. For urgent biliary drainage, a prior sphincterotomy is not necessary for the placement of a nasobiliary catheter
or an indwelling stent. The trick is to aspirate bile to decompress the bile ducts as soon as deep cannulation is achieved.
Drainage without sphincterotomy also avoids the risk of pancreatitis and postsphincterotomy bleeding. In principle, a large
10 French stent provides better drainage for the thick infected bile than a 7 or 8 French stent. With improvements in scope
design, we now have reasonably sized duodenoscopes fitted with larger therapeutic channels. This avoids the difficult manipulation
of large therapeutic scopes in an emergency situation. Recognizing the significance of individual bacteria in biliary stone and sludge formation may open a new avenue
for the prevention of stone recurrence. Suppression of bacterial enzymatic activities through the use of enzyme blockers,
or down-regulation of the genetic control of enzyme production, may offer an alternative approach to prevention.
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