Endoscopic Managment of Common Bile Duct Stones

Best Practice & Research Clinical GastroenterologyVol. 20, No. 6, pp. 1085e1101, 2006

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

8

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 symptomsmay 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, computedtomography, endoscopic ultrasound or magnetic resonance cholangiography prior to endoscopicor laparoscopic removal. Approximately 90% of BDS can be removed following endoscopic retro-grade cholangiography (ERC)þ sphincterotomy. Most of the remaining stones can be removedusing mechanical lithotripsy. Patients with uncorrected coagulopathies may be treated withERCþ 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 toendoscopic 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; mechanicallithotripsy; 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 rangefrom 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: [email protected] (G.R. Caddy), [email protected] (T.C.K. Tham).

1521-6918/$ - see front matter ª 2006 Elsevier Ltd. All rights reserved.

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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 thanthat 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 to13 years. Forty-five per cent of the patients became asymptomatic but 55% developedcomplications such as biliary colic, jaundice and cholangitis.6 More recently Johnsonand Hosking reported similar outcomes with over 50% of patients with retained ductstones 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 groupwere discovered to have bile duct stones. It was assumed that a similar percentage ofpatients in the group without cholangiography had stones, but no patients developedsymptoms in over 3 years of follow-up.2 We found similar results in our local populationin a non-randomised study.8

A common presentation of CBDS is biliary colic. The pain is often situated in the righthypochondrium or epigastrium lasting 30 min to several hours. Associated symptomswith nausea and vomiting are common. Biliary colic typically is not eased by change inbody position and is not specifically related to food intake. The pain is thought to becaused by distension of the common bile duct due to an increase in pressure causedby 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 threestones more likely associated with cholangitis, biliary colic and higher bilirubin levels thanpatients 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 Stonesup to 8 mm may pass without problems as suggested by a study in which bile duct stoneswere 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 mayoccur. Frequently the obstructed bile becomes infected resulting in cholangitis.CBDS often contain bacteria embedded within their matrix. When obstruction ofthe bile duct occurs, the rise in biliary pressure results in the translocation of bacteriafrom the bile duct to the blood-stream. Approximately one-fifth of patients presentingwith 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 ofjaundice, 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 biliaryobstruction results in secondary biliary cirrhosis after approximately 5 years.15

Between 4% and 8% of patients with gallstones will develop gallstone pancreatitissecondary to migratory gallstones.16 Developing gallstone pancreatitis is more likelywith smaller stones than with larger stones. In a study by Venneman, it was foundthat patients presenting with gallstone pancreatitis had mean diameter bile duct stonesize 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 stillremains around 10%.18 There have been several scoring systems devised to predict theseverity of pancreatitis including the Ranson system, modified Imrie system, Apache IIscore and Balthazar grading system. These scoring systems are based on organdysfunction and local complications.19,20

Symptoms, diagnosis and endoscopic management of common bile duct stones 1087

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 previousepisodes 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 thepresence of a bile duct stone while painless jaundice is more likely to be associatedwith biliary strictures. Courvoisier’s law states that in the presence of jaundice, apalpable gallbladder is likely to be due to malignant obstruction of the bile duct ratherthan choledocholithiasis. Other differentials include sclerosing cholangitis, parasiticinfection of the biliary tree, primary biliary cirrhosis, alcoholic liver disease and bileduct injuries during laparoscopic cholecystectomy, e.g. inadvertent ligation of biliarystructures.

Biliary colic

Differential diagnoses of patients presenting with pain caused by CBDS without biliaryobstruction (biliary colic) include cholecystitis, sphincter of Oddi dysfunction, acutepancreatitis, 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 (benignand malignant e as above), ampullary carcinoma, primary biliary cirrhosis, sclerosing

Practice points

� The natural history of asymptomatic bile duct stones appears to be more benignthan 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%) painalone may be the only presenting feature of cholangitis


cholangitis, medication induced, congenital ductopenic syndromes, granulomatoushepatitis, malignant infiltration of the liver e.g. lymphoma, amyloidosis, alcoholic liverdisease and non alcoholic fatty liver disease (NAFLD).

DIAGNOSTIC INVESTIGATIONS

Laboratory tests

Patients presenting with CBDS often have cholestatic liver function tests (LFT’s). In thestudy by Anciaux, elevated serum gamma glutamyl transpeptidase (GGT) and alkalinephosphatase (ALP) were the most frequent biochemical abnormalities in patients withsymptomatic 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, bilirubinlevels and transaminases were found to decrease over the subsequent 10 days inpatients with CBDS following admission to hospital.

There have been many studies attempting to predict the likelihood of concomitantCBDS in patients going on to have laparoscopic cholecystectomy.21e28 In a retrospec-tive study by Onken and colleagues in 465 patients with confirmed choledocholithiasisat time of cholecystectomy, multivariable analysis identified serum bilirubin, AST, andALP, in addition to common bile duct diameter and age as independent predictors ofcholedocholithiasis.27 Most of the studies have emphasised that laboratory investiga-tions must be used in addition to other imaging modaslities to predict the likelihoodof CBDS and the multivariate analysis models have found a dilated bile duct as anindependent variable in predicting CDBS.25e28

Transabdominal ultrasonography

Transabdominal ultrasonography (TUS) remains the first line radiological investigationin 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, thesensitivity of TUS compared to endoscopic retrograde cholangiopancreatography(ERCP) in detecting common bile duct dilatation was 96%.29 However, the sensitivityof TUS in detecting choledocholithiasis is much lower with sensitivities of between25% and 63% when compared to endoscopic ultrasound (EUS) and ERCP.30,31 Al-though with a specificity of approximately 95%, TUS remains an extremely usefultest 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 CTfor detection of choledocholithiasis has similar sensitivities of 67e88%.36e39 Oralenhanced CT cholangiography has an increased sensitivity of 92%.36


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 decisionto 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 criteriathat have already been discussed. The use of EUS may be best suited for patientsthat fall into the intermediate risk category and thereby reducing the risk to thepatient of pancreatitis and cholangitis that could potentially occur following ERCP.Patients in the low risk category should be referred for laparoscopic cholecystectomyand patients in the high risk category should undergo ERCPþ sphincterotomy or chol-ecystectomyþ intraoperative cholangiogram with laparoscopic extraction of anystones detected.42

Magnetic Resonance Cholangiography (MRC)

Magnetic Resonance Cholangiography (MRC) has become an accepted method ofimaging the bile duct with a high sensitivity and specificity for choledocholithiasis.One such study by Ainsworth and colleagues found the accuracy rates of detectionof choledocholithiasis comparable between EUS and MRC (accuracy rate 93% and91%, respectively).43 In addition, several studies have found MRC to be comparableto 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 EUSwere comparable in their sensitivities, specificities and accuracy rates for detectionof choledocholithiasis.45

Endoscopic retrograde cholangiography (ERC)

ERC has sensitivities between 90% and 95% in detecting choledocholithiasis.44,46 It isoften the gold standard test to which other modalities are compared in the detectionof 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 andtherefore ERC is recommended in patients with a high probability of CBDS. In patientswith 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 inpatients with symptomatic choledocholithiasis, increased in 94% and 91% ofcases, 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%)


IS THERE ALWAYS AN INDICATION TO TREAT CBD STONES?

As previously discussed, CBDS detected in symptomatic patients, have a high rate ofcomplications if left in situ (approximately 50% of patients will subsequently developjaundice, cholangitis, biliary colic or pancreatitis). The true natural history of asymp-tomatic bile duct stones is unknown but they appear to cause fewer complicationsthan CBDS detected in symptomatic patients. In contrast, in asymptomatic gallstones,a cholecystectomy would not be recommended, as the cumulative risk of developingsymptoms is not as great as that of asymptomatic CBDS. In addition, complications willdevelop after the emergence of symptoms. However, with asymptomatic CBDS, com-plications usually develop before symptoms. In an increasing litigious society, themajority of gastroenterologists would recommend attempted removal of CBDSonce detected for fear that any subsequent complications that may ensue may be asa consequence of leaving the stones in situ. Small stones may pass spontaneously aspreviously mentioned. There may be clinical situations in which the risk of performingan ERC to remove identified CBDS may outweigh the benefits. For example, patientswith a short life expectancy e.g. severe end stage dementia or with severe co-morbiditymaking 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 makingprocess 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). Therole 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 dissolvecholesterol containing stones. However, approximately 85e95% of patients in theWestern World will have cholesterol stones. The first report of using bile salt acidsto dissolve cholesterol stones was reported in 1927.47 It wasn’t until half a centurylater that larger studies were performed to investigate the use chenodeoxycholicacid on the dissolution of gallstones.48 To date the majority of these studies havebeen performed on patients with gallstones rather than on patients with CBDS.The studies that have been performed in this patient group contain small numbers

� 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 ofcholedocholithiasis


of patients and are statistically underpowered. Salvioli and colleagues investigated theeffect 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 duringa 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 failedextraction of CBDS. Johnson and colleagues studied 24 patients with difficult toextract CBDS and randomised the patients to either UDCAþ stent or stent alonewith follow up ERC and attempted stone removal. In the UDCA group, 90% of thepatients subsequently had ductal clearance at repeat ERCs compared with none ofthe patients in the stent alone group at the end of the study period.50 Ros andcolleagues studied a group of patients with recurrent pancreatitis caused by microli-thiasis and found that patients treated with UDCA (10 mg/kg) eliminated gallbladdermicrolithiasis and reduced the episodes of further pancreatitis. Continuing therapywith UDCA appeared to prevent recurrence of gallbladder microlithiasis.51

Currently there are no large randomised controlled trials providing convincingevidence 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, gastroenterologistswill continue to use UDCA in patients with difficult to extract CBDS. Larger andmore robust studies are required to determine any overall benefit of UDCA onretained CBDS.

ERC (SPHINCTEROTOMY OR PNEUMATIC DILATATION)

Endoscopic biliary sphincterotomy (EST) at ERC was first described in 1974 and wasinitially 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 beenpreviously 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 chronicenteric-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 toreports of increased complications (mainly that of pancreatitis). However, severalmore recent studies had suggested that the original risk of post-EBD pancreatitiswas overestimated due to recruitment of patients with sphincter of Oddi (SOD) dys-function (a group with a known increased risk of post-ERC pancreatitis). Subsequentlythere 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 studiesand over 1000 patients) they found the overall similar rate of complications (10.3%

Research agenda

� Currently there are no large randomised controlled trials providing convincingevidence 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


and 10.5%, respectively). However, the rates of pancreatitis were significantly higherfor the EBD group (7.4% versus 4.3%) but bleeding complications were reduced(0% versus 2%). Other complication rates of infection and perforation were similarbetween the two groups. Primary clearance of the bile duct was less successful usingEBD compared to EST (70% versus 80%), and the use of mechanical lithotripsy wasmore common (21% versus 15%).

A further randomised control trial, not included in the meta-analysis, comparing theshort term complications of EBD versus EST again confirmed an increase rate ofpancreatitis with EBD versus EST (15.4% and 0.8%, respectively).62 The rate of postEST pancreatitis in this study was lower than that expected, however. Patients werefound to have more frequent invasive procedures, longer hospital stay and more misseddays off work/normal activities of daily living in the EBD group. EBD has been advocatedin patients with coagulopathies where the risk of bleeding from sphincterotomy wouldbe hazardous. However, if the coagulopathy cannot be corrected prior to the ERCPprocedure then a biliary stent is a safe alternative and is our preference over EBD.

Following endoscopic sphincterotomy (or balloon dilatation), CBDS are removedusing a Dormia-type basket of a balloon catheter. Using either of these techniquesstones can be removed form the bile duct in about 90% of patients.

MECHANICAL LITHOTRIPSY

Stone removal from the common bile duct may be technically difficult due to factorssuch 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 distalCBD. 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, whichis inserted through the scope. The Olympus BML range and Monolith lithotriptor, (Mi-crovasive Corp) are amongst the most commonly used lithotriptor devices. The CBDstone is engaged with an open basket and the metallic sheath can then be advanced upinto the bile duct to meet the basket resulting in crushing of the stone. Often the wiresof the basket can become deformed after several ‘crushes’ and the ML device mayneed 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 largeCBDS.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

Practice points

� In a meta-analysis (incorporating over 1000 patients), the overall complicationrate 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 theEBD group compared to EST


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 witha 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. Thisstudy did not find the size of CBDS as a significant factor in failure of a ML in theremoval of difficult CBDS.65 The impaction of the stone led to an inability to passthe basket proximal to the stone or a failure to open fully around the stone to allowit to be grasped. Often if there is little space between the stone and bile duct wall, thebasket will not fully open and therefore not be able to engage the stone. It has beenfound useful in these circumstances to insert the metallic sheath up into the bile ductand to rotate the basket to try to grasp the stone.72 Even if the stone is partiallyengaged, the stone can be fragmented and successfully removed.

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 ductusing an extracorporeal lithotriptor. These techniques are generally reserved for pa-tients in whom stones cannot be removed with conventional techniques due to factorssuch 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 isfocused into a single beam and directed onto a stone within the bile duct. This causesplasma 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 canbe performed under direct vision using cholangioscopy using mini scopes or can beperformed under fluoroscopic control using standard equipment. More recently thedevelopment of software coupled to the laser allows differentiation of light reflectedback from bile duct epithelium compared to light reflected back from a stone. Thiscauses a discontinuation of the laser pulse, and reduces any potential thermal injuryto the epithelium. The use of this software allows the safe use of laser lithotripsyunder fluoroscopic control and avoids the need for lithotripsy to be performed underdirect vision.

Practice points

� The removal of CBDS may be technically difficult due to factors such as thesize 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 ofthe 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


The experience of laser lithotripsy has been limited to a few centres and themajority of the published literature on its use has been in a small number of patientsin 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 between64% and 97%.73e84 In a randomised trial comparing laser lithotripsy versus extracor-poreal shockwave lithotripsy (ESWL), laser lithotripsy was found to be more effectivein 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 performedsuccessfully under cholangioscopic guidance86,87 or under fluoroscopic control usinga balloon catheter.88 The advantage of direct visualisation is to control the shockwavebeing applied to the stone rather than on the ductal wall and thereby potentiallyreducing complications. However, the disadvantage is the cost, and the expertiserequired in cholangioscopic techniques. In earlier studies, a stone fragmentationrate of approximately 80% was achieved using EHL.89,90 In the prospective open studyby Adamek and colleagues, a stone fragmentation rate of 93% was achieved and theywere 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 eachtreatment. In addition, both groups of patients required additional endoscopic proce-dures to remove residual stones.91 Hui and colleagues found a lower incidence ofcomplications, particularly cholangitis, in a small prospective study of 36 patients,comparing double pigtail stent insertion versus EHL therapy in difficult to removeCBD 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 ofpatients and subject to bias, making evidence based recommendations on its uselimited.

STENTING AS DEFINITE TREATMENT OF BILE DUCT STONES?

Insertion of an endoprothesis may be required on a temporary basis for difficult toretrieve 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 furthersubsequent intervention, may be considered but should be limited to patients withsevere 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 theprocedure but an anaesthetic assessment may also be useful in the decision makingprocess.

There have been several studies investigating the role of stent insertion as the soletreatment of CBDS that could not be removed at ERC. In the study by Bergman andcolleagues, 58 of 117 patients had permanent biliary stent insertion as their treatmentfor CBDS (i.e. expectant management and stent exchange only if complications


occurred). Sixty percent of these patients were alive at 2 years of follow up and ofthese 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 patientsand occurred after a median time of 42 months.94 These results are similar to a studyby De Palma and colleagues, which followed up 49 patients with stent insertion forirretrievable CBDS. Their results found a 40% late complication rate and 6% mortalityrelated to biliary sepsis over a 3-year follow-up period.95 Jain and colleagues carriedout a prospective study on 20 patients with difficult to extract CBDS (mean diameterof stone was 1.7 cm). In each case a 7F pigtail stent was inserted and ERC repeated at6 months. In 20% of patients the stones had fragmented and allowed balloon clearanceof the duct. However, in 35% of patients the duct had cleared spontaneously.96 Thereis 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 moreeffectively. If the stent becomes occluded after several months, it still has the potentialto 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 ofCBDS 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 comparingdouble pigtail stent insertion versus EHL therapy.92 In summary, where facilities exist,alternative forms of treatment should be considered in high risk patients with retainedCBDS such as lithotripsy. However, long term stenting is an alternative in patients witha poor life expectancy.

EXTRACORPOREAL SHOCKWAVE LITHOTRIPSY

Extracorporeal shockwave lithotripsy (ESWL) was first used treating gallstonesin 1980s following its successful use in fragmenting renal calculi.97 Shock wavesare 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. Subsequentgeneration of lithotriptors do not require immersion in a water bath and can beperformed under intravenous sedation. Complete duct clearance of CBDS followingESWL 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 orultrasound.

In a small prospective randomised trial comparing ESWL to EHL, no significantdifference 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 ductclearance rates, fewer additional interventions required following treatment andshorter 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 duringshockwave treatment. Pre-procedural antibiotics prior to ESWL are thereforerecommended.


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 firstpublished in 1947.102 However, due to the side effects of the chemical used (diethylether), the procedure was not widely practiced. The discovery of mono-octanoin asa cholesterol stone dissolving agent, led to several reports of its use in difficult toremove 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 therapywas deemed ‘useful’ in 54% of patients. However, side effects were common andreported 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 advantagesover other chemical dissolution agents, mainly that of faster kinetics. In a non-randomised study by Neoptolemos and colleagues, MTBE was used in 33 patientswith 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 thelength of treatment, continuous access to the bile duct that is required and a highcomplication rate.

SUMMARY

Symptomatic BDS commonly cause significant morbidity and attempt at stone removalshould be attempted if possible. Complications of CBDS include biliary colic, jaundice,cholangitis and pancreatitis. Investigations aimed to predict the presence of stoneswithin the bile duct include serum bilirubin, AST, ALP, common bile duct diameterand 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 werecomparable in their sensitivities, specificities and accuracy rates for detection of

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.


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 bleedingcomplications is lower for EBD). ML is often required in difficult to remove CBDS andusing 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 theevidence for their use is based on small studies. ESWL may clear stones from thebile duct in up to 93% of patients but frequently ERC and stone fragment removalis required post ESWL. The role of medical therapy in difficult to remove CBDS (orin CBDS in patients with severe co-morbid illness preventing ERCþ stone removal)is still currently uncertain due to a lack of large randomised control trials.

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Endoscopic Managment of Common Bile Duct Stones