REVIEWS Advances in the endoscopic management of common bile duct stones Guru Trikudanathan, Mustafa A. Arain, Rajeev Attam and Martin L. Freeman Abstract | Extraction of common bile duct stones by endoscopic retrograde cholangiopancreatography generally involves biliary sphincterotomy, endoscopic papillary balloon dilation or a combination of both. Endoscopic papillary large-balloon dilation after sphincterotomy has increased the safety of large stone extraction. Cholangioscopically directed electrohydraulic and laser lithotripsy using single-operator mother– daughter systems or direct peroral cholangioscopy using ultraslim endoscopes are increasingly utilized for the management of refractory stones. In this Review, we focus on advances in endoscopic approaches and techniques, with a special emphasis on management strategies for ‘difficult’ common bile duct stones. Trikudanathan, G. et al. Nat. Rev. Gastroenterol. Hepatol. 11, 535–544 (2014); published online 27 May 2014; doi:10.1038/nrgastro.2014.76
Introduction
Common bile duct (CBD) stones are found in ~7–12% of patients undergoing cholecystectomy for sympto matic cholelithiasis and often present de novo after cholecystectomy. The introduction of endoscopic retro grade cholangiopancreatography (ERCP) with biliary sphincterotomy in 19741,2 ushered in a new era in the management of patients with CBD stones, such that ERCP has now become the primary method for treat ing choledocholithiasis in most circumstances. With continual advances in endoscopic extraction techniques and instruments, keeping current with the latest devel opments is essential to optimize outcomes. This Review covers advances in endoscopic approaches and tech niques, with a special emphasis on management strategies for ‘difficult’ CBD stones.
Conventional management of CBD stones
Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, MMC 36, 406 Harvard Street SE, Minneapolis, MN 55455, USA (G.T., M.A.A., R.A., M.L.F.) Correspondence to: M.L.F. [email protected]
Management of CBD stones by ERCP routinely involves enlarging the papillary orifice, either by dividing the biliary sphincter via endoscopic biliary sphincterotomy (EBS) or by endoscopic papillary balloon dilation (EPBD). EPBD without sphincterotomy is performed by dilating the intact papilla with a wire-guided smalldiameter balloon catheter (usually 6, 8 or 10 mm, depend ing on the diameter of the native distal bile duct).3 EPBD is intended to preserve the function of the biliary sphinc ter, because its function might recover after balloon dilation; however, the clinical benefits of sphincter preservation remain uncertain.4 Bleeding and perforation are theoretically less likely with EPBD than EBS; however, EPBD, particularly of an intact sphincter, is associated with an increased risk of post-ERCP pancreatitis. 5,6 Competing interests M.L.F. has received speaking honoraria from Cook Endoscopy and Boston Scientific, and is an unpaid consultant for Hobbs Medical Inc. The other authors declare no competing interests.
A disparity seems to exist in the risk of pancreatitis across studies depending on the country of origin, which might be attributable to differences in patient popula tions, study methods, or perhaps to a certain degree of difference in technique.4 The duration of balloon dilation in EPBD has also been suggested to be a cause for the disparity in the risk of pancreatitis.7 Although initially described as dilating the papilla for 45–60 s, a longer duration of dilation seems to be safer, contrary to intu ition. A randomized trial concluded that EPBD of 5 min duration was associated with a lower incidence of pan creatitis than EPBD of 1 min duration.7 A meta-analysis has shown similar results.8 Brief dilation is hypothesized to be inadequate and produce excessive post-procedure oedema, whereas a longer dilation creates a wider orifice, which not only guarantees better success at stone extrac tion but also reduces the risk of pancreatitis.7 However, in the above studies no prophylactic pancreatic stents were placed, which is in contrast to current practice, making extrapolation of the results somewhat limited (Figure 1). Most meta-analyses have shown that EBS and EPBD have comparable success rates (94.3% versus 96.5%) and similar rates of cholangitis, perforation, mortal ity and overall complications (10.5% versus 10.3%), but that EPBD is more likely to cause pancreatitis than EBS (7.4% versus 4.3%)6,7 with one exception.8 Thus, if the patient does not have major risk factors for bleeding, EBS is still the initial procedure of choice to facilitate stone extraction. An ample EBS will separate the pancre atic and biliary orifices and create a wide enough orifice to facilitate successful extraction of stones. If bile duct access is challenging and involves pancreatic instrumen tation, particularly in patients who have other risk factors for post-ERCP pancreatitis, a pancreatic stent should be placed during the procedure.9 Along with pancreatic duct stenting, rectally administered indomethacin has been shown to decrease the risk of post-ERCP pancreatitis.10
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REVIEWS Key points ■■ Endoscopic papillary large-balloon dilation after sphincterotomy appears to reduce complications and the need for mechanical lithotripsy during extraction of large bile duct stones; mechanical lithotripsy is the mainstay of difficult stone removal ■■ Cholangioscopically directed electrohydraulic and laser lithotripsy enables fragmentation of refractory stones ■■ Cholangioscopy can be performed using single-operator mother–daughter systems or by direct peroral cholangioscopy using ultraslim endoscopes ■■ Percutaneous cholangioscopy enables visualization, fragmentation and removal of intrahepatic stones ■■ Balloon-enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) has limited efficacy for stone removal in patients with altered surgical anatomy ■■ Laparoscopic-access ERCP and percutaneous and endoscopic ultrasonographyguided access provide alternatives to ERCP for patients who have undergone Roux-en‑Y gastric bypass
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Figure 1 | Pancreatic stent placement prior to endoscopic papillary balloon dilatation. a | Pancreatic stent in place. b | Large-balloon (15 mm) dilatation showing compression against pancreatic stent and orifice. c | After large-balloon dilatation with pancreatic drainage preserved.
Difficult CBD stones
10–15% of stones are not amenable to conventional extraction techniques.11 Challenges include difficulties in accessing the papilla (for example, owing to peri ampullary diverticulum, sigmoid-shaped CBD or Billroth type II anatomy), large stone size (stones with a diameter of >10–15 mm that cannot be readily extracted with a conventional balloon or basket), multiple stones, unusu ally shaped stones (barrel shaped), difficult location of stones (for example, intrahepatic, in the cystic duct, or proximal to strictures), Mirizzi syndrome, a poor general condition of the patient and the presence of bleeding diathesis (Figure 2).12 Kim et al.13 prospectively evalu ated factors contributing to technical difficulties during ERCP and observed that older age (>65 years), previous gastrojejunostomy, large stone size (≥15 mm diameter), impaction of stones, short length of distal CBD arm (≤36 mm), and more-acute distal CBD angulation (≤135°) are all contributors to difficulty with endoscopic removal of CBD stones.13 After biliary sphincterotomy, mechanical basket lithotripsy has usually been the first approach for such difficult stones, with a variable success rate of up to 90% (Figure 3).12 Many other techniques have evolved to deal with difficult stones and are reviewed later.
Endoscopic techniques Endoscopic papillary large-balloon dilatation Endoscopic papillary large-balloon dilatation (EPLBD) with a large-diameter (12–20 mm) dilatation balloon has 536 | SEPTEMBER 2014 | VOLUME 11
evolved as an adjunctive technique to enlarge the papil lary orifice after EBS in order to facilitate extraction of large stones (Figure 4). The rationale behind EPLBD is that it combines the advantages of EBS and EPBD.14 In EPLBD, the risk of perforation and bleeding can be reduced by avoiding an excessively large sphinctero tomy, and the risk of pancreatitis from balloon dilata tion can be decreased by first separating the biliary and pancreatic orifices with EBS, so that the pancreatic orifice is not effaced with significant force during biliary balloon dilatation.14 In 2003, Ersoz et al.15 first reported the use of a largediameter balloon (12–20 mm) in 58 patients (with distal biliary stricture and stones that were square, barrelshaped and/or >15 mm diameter) in whom EBS alone was unsuccessful. Complete stone removal was possible in 54 of the 58 patients (93.1%), with the other 4 (6.9%) needing mechanical lithotripsy. Complications were reported in 15.5% of patients, including mild cholangitis, pancreatitis and bleeding.15 Since this initial report, multi ple studies have reported the efficacy and safety of EPLBD combined with EBS, with a high success rate (94–100%) and a fairly low complication rate (0–17%).16–28 Heo and colleagues reported a trial involving 200 patients with bile duct stones who were randomly allo cated to EBS plus EPLBD (12–20 mm balloon diameter) or EBS alone.18 Outcomes were similar in terms of overall success (97% versus 98%), large (>15 mm diameter) stone removal (94.4% versus 96.7%), the use of mechanical lithotripsy (8% versus 9%), and rate of complications (5% versus 7%).18 Although the study did not show any clear benefit of EPLBD, it has been pointed out that the investigators did not select patients who were most likely to benefit from EPLBD (namely those with large, multiple or difficult stones).14 Teoh and colleagues performed a randomized trial of limited EBS with large-balloon dilata tion versus endoscopic sphincterotomy alone for removal of bile duct stones.29 Although no significant difference was noted between the two groups for the percentage of stones cleared (EBS versus EBS plus EPLBD: 88.5% versus 89%, respectively), patients in the EBS plus EPLBD group needed less mechanical lithotripsy and had a lower cost of hospitalization than those who underwent EBS alone.29 A meta-analysis of EPLBD after EBS compared with EBS alone included six randomized controlled trials involving 835 patients.30 The authors found that EPLBD after EBS caused fewer overall complications than EBS alone (OR 0.53, 95% CI 0.33–0.85, P = 0.008), a significantly lower risk of perforation (OR 0.14, 95% CI 0.20–0.98, P = 0.05) and significantly less need for mechanical lithotripsy (OR 0.26, 95% CI 0.08–0.82, P = 0.02), particularly in patients with a stone size of >15 mm in diameter (OR 0.15, 95% CI 0.03–0.68, P = 0.01). No significant differences were noted between the two groups regarding complete stone removal, stone removal in the first session, post-ERCP pancreatitis, bleeding, infection of the biliary tract or procedure time. The length of sphincterotomy prior to EPLBD varies between studies.14 A Chinese study showed that EPLBD after a limited EBS was safe and effective. Some
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Figure 2 | Difficult bile duct stones. a | Large impacted stone. b | Square and completely impacted stone. c | Stone above stricture. a
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Figure 3 | Basket mechanical lithotripsy of a large stone. a | 2 cm stone. b | Capture with litotripsy basket. c | Fragmented stones. d | Cleared duct.
experts have even questioned the role of EBS preceding EPLBD.14 In a small pilot study involving 37 patients, a South Korean group showed complete duct clear ance by EPLBD alone without the need for mechani cal lithotripsy in 29 (76.3%) patients.31 They speculated that EPLBD enables decreased use of mechanical litho tripsy and thereby causes decreased risk of post-ERCP pancreatitis.28 EPLBD alone has been shown to be safe in elderly patients and in patients who have undergone Billroth type II gastrectomy.32,33 The choice of balloon size varies substantially among studies, but experts recom mend limiting the size of the balloon to the size of the native distal duct within a few centimetres of the papilla.12 A prototype device combining a large-diameter balloon and sphincterotome has been described as a safe and effective accessory for removal of large bile duct stones.34 EPLBD has been shown to have a complication rate of 0–17% across different studies.15–28 In a multicentre
study specifically performed to identify predictors of adverse events after EPLBD, perforation was reported to be the most serious adverse event.35 On multivariate analysis, the authors found that distal CBD stricture was an independent risk factor for perforation and suggested that it should be considered as a relative contraindication to EPLBD.35 In the same study, bleeding was the most common adverse event and the presence of cirrhosis, full EBS and a stone size of >16 mm were independent predic tors of bleeding following EPLBD.35 Surprisingly, none of the patients developed severe post-ERCP pancreatitis, and large balloon size (balloon size ≥14 mm) was identified to be protective against pancreatitis.35 As EPLBD enlarges the biliary orifice to a great extent, the physiology of the sphincter of Oddi is lost; subsequent duodenobiliary reflux could theoretically cause long-term recurrence of stones, although the real risk remains unclear.31,35–37 In summary, the use of EPLBD minimizes the need for mechanical lithotripsy, shortens procedure and fluoro scopy times, and might reduce adverse events associated with prolonged lithotripsy procedures.35 EPLBD might be particularly useful in patients who have a difficult papil lary anatomy, such as those with small or peridiverticular papilla or surgically altered anatomy.36 When consider ing EPLBD, careful consideration should be accorded to the size of the native bile duct, the size and number of stones, the shape and size of the papillary mound, the presence of intradiverticular or peridiverticular papilla, and the patients’ comorbid conditions.14 The presence of coagulopathy or need for anticoagulation favour more emphasis on dilation and less on sphincterotomy. 14 Consideration should be given to placing a pancreatic stent if pancreatic instrumentation is used or if the orifice is effaced during EPBLD.
Cholangioscopy-guided lithotripsy Large stones (especially those ≥2 cm in diameter), stones that are impacted in the bile ducts and those above strictures might be refractory to mechanical lithotripsy and need fragmentation before retrieval.12 Electrohydraulic lithotripsy works on the principle that sparks generated underwater produce high-frequency hydraulic pressure waves whose energy is absorbed by stones and results in their disintegration.38 In laser litho tripsy, pulsed laser energy at a particular wavelength is focused on the stone to induce wave-mediated frag mentation.12 Electrohydraulic lithotripsy or laser litho tripsy are best performed under direct visual control using a cholangioscope to avoid direct application of the shock waves or laser on the duct wall, which could cause perforation or bleeding (Figure 5). Traditionally, peroral cholangios copy involved a mother–daughter system in which a cholangioscope is inserted through the instrument channel of the duodenoscope. Mother– daughter cholangioscopy involves complex equipment and usually requires coordination between two experi enced endoscopists. Fragility, poor optical resolution and the limited ability to steer traditional cholangio scopes hamper their utility for therapeutic biliary inter ventions.12,37,39 Introduction of the SpyGlass® Direct
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Figure 4 | Endoscopic papillary large-balloon dilatation. a | After ample sphincterotomy. b | Large-balloon (15 mm) dilatation. c | Very large papillary orifice enabling a view up the duct. d | Fluoroscopic view of large-balloon dilation. e | Basket capture of stone. f | After removal of intact stone into duodenum.
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Figure 5 | Very large stone requiring direct cholangioscopy and laser lithotripsy. a | 3 × 4 cm stone. b | SpyGlass® (Boston Scientific, Natick, MA, USA) cholangioscopy. c | Direct peroral cholangioscopy. d | After fragmentation of the stone. e | Laser lithotripsy of large stone using direct peroral cholangioscopy.
Visualization System (Boston Scientific, Natick, MA, USA) has enabled increased applicability of cholangio scopy. SpyGlass®is a fairly simple, single-operator, peroral system with four-way steerability and with separate chan nels for the optical probe, irrigation and electrohydraulic or laser lithotripsy probes.40 Fishman and colleagues reported the use of SpyGlass®-directed electrohydraulic lithotripsy in 38 patients, with a technical success rate of 87% after one session and with complete clearance after a second session.41 They reported the often observed dif ficulty in passing the electrohydraulic lithotripsy probe through the SpyGlass®cholangioscope and targeting of 538 | SEPTEMBER 2014 | VOLUME 11
the lesion.41 The authors noted a deterioration in optical resolution after an average of 10 uses.41 Similar success with SpyGlass®-guided electrohydraulic lithotripsy has been reported in other studies.40,42 Laser lithotripsy of difficult biliary stones has been reported through SpyGlass® with a high degree of success (83%) after a single session.39 Holmium laser lithotripsy was found to be effective for both pigment and cholesterol stones.39 Inherent limitations of laser lithotripsy include the fragility of the probe and expense of the equipment. In a prospective multinational study involving 15 endoscopy centres, 66 patients underwent SpyGlass®-guided electrohydraulic or laser lithotripsy treatment, with a 1 month follow-up.43 Impacted stones were present in 30 of 50 patients (60%). All stones were treated by electrohydraulic lithotripsy and/or laser litho tripsy with minimal adverse events, which all resolved without sequelae.43 Experts have criticized the inferior quality of the fibreoptic image of the SpyGlass®system, as well as its inability to perform enhanced endoscopy.44 In addition, the small 1.2 mm working channel limits the range of therapeutic accessories and makes passage of even very small devices such as lithotripsy probes potentially dif ficult. An increased risk of cholangitis of up to 7–10% has been noted with SpyGlass®, most likely from intraductal irrigation in an obstructed duct required for visualiza tion during the procedure.45 Antibiotic prophylaxis is imperative in all cases and in selected cases biliary drain age with stents should be considered after cholangioscopy to minimize the risk of cholangitis.44,45
Direct peroral cholangioscopy In direct peroral cholangioscopy (DPOC), an ultraslim upper endoscope is manoeuvred through the biliary sphincterotomy and into the CBD for direct visualization, resulting in high-resolution digital imaging and four-way steerability.46,47 The 2 mm working channel of the ultra slim endoscope enables passage of larger accessories than through dedicated cholangioscopes, thus facilitat ing advanced therapeutic procedures (Figure 5). DPOC enables simultaneous irrigation and therapeutic capabili ties, and involves use of a readily-available multipurpose endoscope, and thus represents an attractive alternative to conventional mother–daughter endoscope systems.47 The biggest challenge associated with DPOC is diffi culty in passing the ultraslim endoscope into the proximal biliary system. Large loop formation of the slim scope is common within the gastric fundus or the deep portion of the duodenum, which can impede advancement into the biliary system.44 Specialized techniques are often neces sary to enhance success, including passing a wire and/or balloon antegrade into the intrahepatic ducts to anchor and pull the endoscope into the duct. Dislodgement of the guidewire is common. Moon et al.47 proposed the ‘ropeway technique’ with use of an intraductal 5 French balloon catheter that can be anchored within a branch of the intrahepatic duct to advance an ultraslim endo scope into the biliary tree. The balloon and/or guide wire must be withdrawn from the working channel for
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REVIEWS interventional procedures, which might create technical difficulties in maintaining the desired scope position. Overtube balloon-assisted cholangioscopy might be useful to circumvent these difficulties.48 However, cur rently available overtubes are excessively large relative to ultraslim endoscopes, resulting in difficulty manipulat ing both instruments, looping of the endoscope in the duodenum, difficulty in accessing the proximal bile duct and discomfort for the patient.48,49 Efforts are currently underway to develop appropriate accessories to enhance the interventional performance of DPOC.44 DPOC is useful for identifying and extracting residual stones that might have been missed during cholangio graphy.50–52 A prospective study evaluated the usefulness of DPOC in patients thought to have complete stone clearance (as confirmed by balloon-occluded cholangio graphy after mechanical lithotripsy).51 DPOC detected residual stones in 28% of the 48 patients, 85% of which were immediately removed under direct visualization.51 Most importantly, DPOC is useful for performing electro hydraulic or laser lithotripsy under direct high-resolution digital cholangioscopic visualization to ensure safety and precise targeting during fragmentation. Moon et al.53 reported successful electrohydraulic or laser lithotripsy using DPOC in 16 of 18 patients (90%) who had failed conventional lithotripsy, including mechanical lithotripsy, with an average of 1.6 s essions per patient. Laser litho tripsy was successful in 11 of 13 (85%) patients who failed conventional lithotripsy involving mechanical lithotripsy.54 A feared complication of DPOC is air embolism. Use of carbon dioxide instead of air and minimizing gas insuf flation are sufficient to avoid this complication.44 Current DPOC endoscopes lack a dedicated high-volume irriga tion channel separate from the working channel, other than the insufflation/irrigation channel standard on any endoscope, so that a separate nasobiliary tube might be ideal for continuous irrigation with infusion of saline solution or contrast medium for efficient lithotripsy and cleansing of fragmented stones; these ideas have been used, but not yet reported. EPLBD to create a very large sphincterotomy orifice might not only aid with biliary access using the ultraslim endoscope, but enable egress of any excessive pressure built up by insufflation or irrigation, and thus further reduce risk of complications.
Difficult clinical presentations Mirizzi syndrome Mirizzi syndrome is an atypical presentation of gall stone disease in which impaction of a gallstone in the cystic duct or in the Hartmann pouch causes stenosis of the extrahepatic bile duct by extrinsic compression, fibrosis or direct erosion of a stone into the common hepatic duct. McSherry classified Mirizzi syndrome into two types on the basis of ERCP findings: type I involves external compression of the common hepatic duct by a stone impacted in the cystic duct; type II occurs when a stone produces a cholecystocholedochal fistula and migrates into the common hepatic duct. Successful entrapment of impacted stones in the common hepatic duct with conventional baskets is technically challenging,
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Figure 6 | SpyGlass®(Boston Scientific, Natick, MA, USA) access to cystic duct stump with electrohydraulic lithotripsy of retained cystic duct stump stone. a | Radiopaque stone in cystic duct stump. b | SpyGlass®introduced into cystic duct stump. c | Electrohydraulic lithotripsy. d | Clearance of cystic duct stump. e | SpyGlass®view of electrohydraulic lithotripsy probe against cystic duct stump stone.
as even passing a guidewire alongside the impacted stone is difficult.37 Treatment of cystic duct stones can be even more challenging after cholecystectomy as very limited space exists upstream of the stone to pass guidewires or devices through (Figure 6). Extracorporeal shockwave lithotripsy (ESWL) has been utilized for stone fragmentation in patients with Mirizzi syndrome, but complete ductal clearance was achieved in only 56–83% of patients.55,56 A report of cholangioscopic electrohydraulic and laser lithotripsy for 122 consecu tive patients with difficult bile duct stones included 53 patients with Mirizzi syndrome (3 type I and 50 type II), 50 patients with impacted stones, and 19 patients with large stones.57 Successful stone removal was achieved in 96% of patients with Mirizzi syndrome (96% type-II Mirizzi syndrome, 0% type-I Mirizzi syndrome) and 100% of patients with impacted stones and large stones.57 Thus type-II Mirizzi syndrome seems to be more amenable to endoscopic therapy than type I. However, SpyGlass® might represent a viable method for directing a small calibre cholangioscope into the cystic duct and deliver ing electrohydraulic lithotripsy to patients with Mirizzi syndrome of all types (Figure 6).
Hepatolithiasis Hepatolithiasis—or the presence of stones in the intra hepatic ducts (also known as intrahepatic choledocho lithiasis)—is most prevalent in South-East Asia, but occurs throughout the world. Ethnic factors, bacterial infection, parasitic infestation, and anomalies of bile duct anatomy have all been implicated in its aetiopatho genesis.58 Complications of hepatolithiasis include sup purative cholangitis, liver abscess, secondary biliary cirrhosis and cholangiocarcinoma; hence early clearance
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Figure 7 | Percutaneous cholangioscopy with basket and balloon extraction of intrahepatic stones above stenotic Roux-en‑Y hepaticojejunostomy. a | Percutaneous cholangiogram via left hepatic duct with multiple intrahepatic stones (arrows). b | Digital ultraslim videoendoscope advanced via percutaneous tract into right posterior sectoral duct. c | Videoendoscope advanced into right anterior sectoral duct. d | Clearance of stones. e | High-resolution digital view of intrahepatic ducts.
of the stones is important to prevent further liver damage and improve long-term prognosis.58 The association of hepatolithiasis with intrahepatic biliary strictures ham pers the removal of stones and increases the risk of recur rence.59 Surgical resection of the liver segments or lobe that contains stones, strictures or atrophy is the mainstay of treatment, especially for recurrent pyogenic cholan gitis and is effective in reducing the risk of cholangio carcinoma and recurrence of stones. However, surgical resection might be contraindicated in patients who have medical comorbidities, or in those who have cirrhosis from repeated episodes of cholangitis.59 Transpapillary extraction of intrahepatic stones is generally challenging because of frequent biliary strictures in the downstream bile duct, with stone impaction and ductal angulation of the hilar and intrahepatic bile ducts.37 Peroral cholangio scopic lithotripsy using the mother–daughter endoscope as described for difficult CBD stones, with use of electro hydraulic lithotripsy and/or ESWL, has been reported as an option for the treatment of hepatolithiasis: a clear ance rate of 64% was reported, with a recurrence rate of 21.7% after complete removal.60 Technical challenges include insertion of the instrument into the right post erior sectoral ducts (segments VI and VII) and left lateral hepatic duct segments (II and III) because of the sharp anatomic angulations.60 Percutaneous transhepatic cholangioscopic lithotripsy offers a less invasive alternative to hepatectomy for the extraction of intrahepatic stones that cannot be managed endoscopically. Percutaneous approaches are particularly useful in patients who have undergone previous biliary tract surgery (such as Roux-en-Y hepaticojejunostomy) 540 | SEPTEMBER 2014 | VOLUME 11
and those with stone distribution in multiple segments, and also in patients who have already had percutaneous biliary drainage. After the transhepatic percutaneous drainage tract has matured (usually ≥4 weeks), the tract is dilated and a small-calibre digital video endoscope is inserted into the intrahepatic ducts (Figure 7). The entire intrahepatic tree can usually be accessed with a flexible small-calibre endoscope through any percutaneous access. A percutane ous drain must be kept in place throughout the treatment period.61 Laser lithotripsy, electrohydraulic lithotripsy via cholangioscopy, or ESWL can be used to disintegrate stones that are too large to be removed using routine percutaneous transhepatic cholangioscopy. Studies have demonstrated a complete clearance rate of hepatic stones of 80–85% using percutaneous trans hepatic cholangioscopic lithotripsy; the major compli cation rate is 0–2.1% and such complications include liver lacerations, intra-abdominal abscess, disruption of the percutaneous transhepatic fistula, transient hemo bilia and septic shock.37,58,62–64 In some cases, the frag ments produced by electrohydraulic lithotripsy do not spontaneously pass into the duodenum owing to the resistance offered by the sphincter of Oddi, resulting in biliary obstruction, pancreatitis and recurrence of stones. Percutaneous transhepatic papillary balloon dilatation followed by pushing the fragments into the duodenum with the tip of the choledochoscope was shown to be successful in 75% of patients (12 of 16).65 This method was shown to be simple and effective with no procedurerelated pancreatitis or other major complications.65 The use of fully-covered expandable metallic internal stents in the management of intrahepatic biliary strictures has been shown to decrease the recurrence of cholangitis and stones, simplify further treatment and result in fewer limitations of ordinary activities.59 Given the complicated nature of intrahepatic stone disease, no single treatment is definitive and a multidisciplinary approach is essential.
Endoscopic biliary stenting In elderly or frail patients who have serious comorbid conditions and endoscopically irretrievable stones, surgi cal procedures might confer an unacceptably high risk. In this cohort of patients, placement of plastic biliary stents for definitive management of choledocholithiasis might be an acceptable option. In an Italian study, plastic stent exchange every 3 months was prospectively compared with ‘on demand’ stent exchange at the onset of symp toms.66 The authors concluded that the rate of cholan gitis was significantly lower in the group in whom stent exchange was performed at defined intervals (3 months) (P = 0.03).66 Biliary stenting is mandatory if duct clear ance cannot be achieved during ERCP or in between procedures in patients who require multiple sessions for ductal clearance. Mechanical grinding of the stents against stones is thought to reduce stone size, increase stone fragmentation and create space around the stones, thereby facilitating mechanical lithotripsy and extrac tion during follow-up procedures. Placement of multi ple double-pigtail stents (coiled at both ends) around the stones might facilitate stone fragmentation and prevent
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REVIEWS inward or outward migration, which is frequent with conventional straight stents. The combination of two oral dissolution agents— ursodeoxycholic acid (UDCA; 60 mg daily) and 300 mg of a terpene preparation—daily for 6 months, along with placement of multiple 7 French plastic double-pigtail stents was found to be superior to stents alone for success ful bile duct clearance in a randomized, controlled study.67 Similar results were obtained in an earlier study.68 Thus, combination therapy with choleretic agents should be considered in patients with significant comorbidities or intolerance to repeated endoscopic treatment modalities.
Patients with surgically altered anatomy Bile duct stones can occur in patients with a surgi cally altered anatomy, which is increasingly common. In patients with an intact gallbladder, laparoscopic or open extraction of CBD stones can be combined with cholecystectomy. In many cases, though, patients either have complex bile duct stone disease or have already undergone cholecystectomy, such that ERCP is required. Before undertaking ERCP, having thorough knowledge of the specific surgical reconstruction is mandatory. Certain types of post-surgical anatomy feature a conventionally accessible biliary system (Billroth type 1 gastrectomy and sleeve gastrectomy) and advancement of the duo denoscope is fairly straightforward, such that cannula tion of the major papilla is possible with the usual ERCP accessories.37,69 However, the post-surgical anatomy with many procedures, such as Billroth type II gastrectomy or Roux-en-Y reconstruction, results in a long gastrointesti nal tract to traverse and also an inverted approach to the papilla.69 Roux-en-Y reconstruction, especially includ ing gastric bypass (RYGB), poses a particular challenge owing to the extreme length of the Roux limbs, often >300 cm combined. If ERCP is to be undertaken for the management of CBD stones in patients who have an altered anatomy, magnetic resonance cholangiopancreatography (MRCP) is generally recommended to estimate the number and size of stones, and a review of the operative report is essential to estimate the length of the small bowel that needs to be traversed. ERCP in patients who have under gone Billroth type II surgery can be performed with a forward-viewing endoscope or a side-viewing duodeno scope.69 Although the forward-viewing endoscope is easier to advance, the lack of an elevator at the opera tive channel on reaching the papillary area impedes fine control of cannulation tools and accessories.69 The use of a cap over the end of the forward-viewing scope has been shown to facilitate successful cannulation.70 Intrahepatic stones can occur after Roux-en-Y hepati cojejunostomy. ERCP for stone extraction in this setting can be performed by a couple of routes: one option is ante grade passage of the endoscope through a stoma created in the jejunal loop; the alternative is the passage of an endoscope retrograde up the afferent limb to the hepatico jejunostomy. With the proliferation of deep entero scopy techniques, balloon-enteroscopy-assisted ERCP —such as double‑balloon enteroscopy, single-balloon
enteroscopy71–74 and spiral-assisted ERCP75,76—has become popular, with multiple reports of its use in patients with a surgically altered anatomy. Shah and colleagues 77 reported results from a multicentre series of 129 patients undergoing 180 enteroscopy-ERCPs. The anatomy of the patients was RYGB (n = 63), hepaticojejunostomy (n = 45), post-gastrectomy (n = 6), Whipple procedure (n = 10) and other (n = 5). Successful access to the papilla or hepaticopancreaticojejunal anastomosis was achieved in 71% of patients; ERCP was successfully performed in 88% of those patients, to give an overall ERCP success rate of 63%. ERCP success rates were similar between RYGB and other long-limb surgical bypass procedures and among single-balloon enteroscopy, double-balloon enteroscopy and rotational overtube enteroscopy. Complications were seen in 12.4% of patients.77 However, this series represents a select group of patients deemed appropriate and selected by the endoscopists for an attempt at long-limb enteroscopic ERCP; it is possible that these patients had short Roux limbs or fewer comorbidities than other patients. In patients with RYGB anatomy, reliable access to the duodenum with a side-viewing endoscope can almost always be obtained via laparoscopy-assisted ERCP.78–83 This technique is particularly preferable in patients undergoing simultaneous cholecystectomy who are found to have CBD stones by preoperative imaging, such as MRCP or intraoperative cholangiography, and for situa tions in which expertise in laparoscopic CBD exploration and clearance is not locally available. After laparoscopic access to the gastric remnant (excluded stomach) is created, the endoscopist inserts the side-viewing duo denoscope to be passed through a 15 mm trocar in ante grade fashion to reach the papilla. This approach enables a full range of complex endoscopic techniques includ ing selective duct access, protective pancreatic stenting, sphincterotomy, large-balloon dilatation and mechanical and intraductal lithotripsy techniques. A logical question is whether enteroscopic ERCP is worth attempting in patients who have undergone RYGB. In patients who have undergone bariatric surgery, laparoscopy can additionally diagnose and treat internal hernias.82 Schreiner et al.84 compared balloon-enteroscopy- assisted ERCP with laparoscopy-assisted ERCP in patients post-RYGB. Laparoscopy-assisted ERCP resulted in superior outcomes compared with balloon-enteroscopyassisted ERCP (100% versus 59% cannulation rate), with similar rates of post-procedure complications and length of hospitalization. Success rates of enteroscopic ERCP were very low in patients in whom the length of the Roux limb and biliopancreatic limb was ≥150 cm, which is almost universal for gastric bypasses performed within the past 10 or more years. Laparoscopy-assisted ERCP was, however, more expensive. The authors concluded that in centres with expertise in deep enteroscopy and ERCP, patients with a Roux and ligament of Treitz to jejunojejunal anastomosis length of
Introduction
Common bile duct (CBD) stones are found in ~7–12% of patients undergoing cholecystectomy for sympto matic cholelithiasis and often present de novo after cholecystectomy. The introduction of endoscopic retro grade cholangiopancreatography (ERCP) with biliary sphincterotomy in 19741,2 ushered in a new era in the management of patients with CBD stones, such that ERCP has now become the primary method for treat ing choledocholithiasis in most circumstances. With continual advances in endoscopic extraction techniques and instruments, keeping current with the latest devel opments is essential to optimize outcomes. This Review covers advances in endoscopic approaches and tech niques, with a special emphasis on management strategies for ‘difficult’ CBD stones.
Conventional management of CBD stones
Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, MMC 36, 406 Harvard Street SE, Minneapolis, MN 55455, USA (G.T., M.A.A., R.A., M.L.F.) Correspondence to: M.L.F. [email protected]
Management of CBD stones by ERCP routinely involves enlarging the papillary orifice, either by dividing the biliary sphincter via endoscopic biliary sphincterotomy (EBS) or by endoscopic papillary balloon dilation (EPBD). EPBD without sphincterotomy is performed by dilating the intact papilla with a wire-guided smalldiameter balloon catheter (usually 6, 8 or 10 mm, depend ing on the diameter of the native distal bile duct).3 EPBD is intended to preserve the function of the biliary sphinc ter, because its function might recover after balloon dilation; however, the clinical benefits of sphincter preservation remain uncertain.4 Bleeding and perforation are theoretically less likely with EPBD than EBS; however, EPBD, particularly of an intact sphincter, is associated with an increased risk of post-ERCP pancreatitis. 5,6 Competing interests M.L.F. has received speaking honoraria from Cook Endoscopy and Boston Scientific, and is an unpaid consultant for Hobbs Medical Inc. The other authors declare no competing interests.
A disparity seems to exist in the risk of pancreatitis across studies depending on the country of origin, which might be attributable to differences in patient popula tions, study methods, or perhaps to a certain degree of difference in technique.4 The duration of balloon dilation in EPBD has also been suggested to be a cause for the disparity in the risk of pancreatitis.7 Although initially described as dilating the papilla for 45–60 s, a longer duration of dilation seems to be safer, contrary to intu ition. A randomized trial concluded that EPBD of 5 min duration was associated with a lower incidence of pan creatitis than EPBD of 1 min duration.7 A meta-analysis has shown similar results.8 Brief dilation is hypothesized to be inadequate and produce excessive post-procedure oedema, whereas a longer dilation creates a wider orifice, which not only guarantees better success at stone extrac tion but also reduces the risk of pancreatitis.7 However, in the above studies no prophylactic pancreatic stents were placed, which is in contrast to current practice, making extrapolation of the results somewhat limited (Figure 1). Most meta-analyses have shown that EBS and EPBD have comparable success rates (94.3% versus 96.5%) and similar rates of cholangitis, perforation, mortal ity and overall complications (10.5% versus 10.3%), but that EPBD is more likely to cause pancreatitis than EBS (7.4% versus 4.3%)6,7 with one exception.8 Thus, if the patient does not have major risk factors for bleeding, EBS is still the initial procedure of choice to facilitate stone extraction. An ample EBS will separate the pancre atic and biliary orifices and create a wide enough orifice to facilitate successful extraction of stones. If bile duct access is challenging and involves pancreatic instrumen tation, particularly in patients who have other risk factors for post-ERCP pancreatitis, a pancreatic stent should be placed during the procedure.9 Along with pancreatic duct stenting, rectally administered indomethacin has been shown to decrease the risk of post-ERCP pancreatitis.10
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REVIEWS Key points ■■ Endoscopic papillary large-balloon dilation after sphincterotomy appears to reduce complications and the need for mechanical lithotripsy during extraction of large bile duct stones; mechanical lithotripsy is the mainstay of difficult stone removal ■■ Cholangioscopically directed electrohydraulic and laser lithotripsy enables fragmentation of refractory stones ■■ Cholangioscopy can be performed using single-operator mother–daughter systems or by direct peroral cholangioscopy using ultraslim endoscopes ■■ Percutaneous cholangioscopy enables visualization, fragmentation and removal of intrahepatic stones ■■ Balloon-enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) has limited efficacy for stone removal in patients with altered surgical anatomy ■■ Laparoscopic-access ERCP and percutaneous and endoscopic ultrasonographyguided access provide alternatives to ERCP for patients who have undergone Roux-en‑Y gastric bypass
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Figure 1 | Pancreatic stent placement prior to endoscopic papillary balloon dilatation. a | Pancreatic stent in place. b | Large-balloon (15 mm) dilatation showing compression against pancreatic stent and orifice. c | After large-balloon dilatation with pancreatic drainage preserved.
Difficult CBD stones
10–15% of stones are not amenable to conventional extraction techniques.11 Challenges include difficulties in accessing the papilla (for example, owing to peri ampullary diverticulum, sigmoid-shaped CBD or Billroth type II anatomy), large stone size (stones with a diameter of >10–15 mm that cannot be readily extracted with a conventional balloon or basket), multiple stones, unusu ally shaped stones (barrel shaped), difficult location of stones (for example, intrahepatic, in the cystic duct, or proximal to strictures), Mirizzi syndrome, a poor general condition of the patient and the presence of bleeding diathesis (Figure 2).12 Kim et al.13 prospectively evalu ated factors contributing to technical difficulties during ERCP and observed that older age (>65 years), previous gastrojejunostomy, large stone size (≥15 mm diameter), impaction of stones, short length of distal CBD arm (≤36 mm), and more-acute distal CBD angulation (≤135°) are all contributors to difficulty with endoscopic removal of CBD stones.13 After biliary sphincterotomy, mechanical basket lithotripsy has usually been the first approach for such difficult stones, with a variable success rate of up to 90% (Figure 3).12 Many other techniques have evolved to deal with difficult stones and are reviewed later.
Endoscopic techniques Endoscopic papillary large-balloon dilatation Endoscopic papillary large-balloon dilatation (EPLBD) with a large-diameter (12–20 mm) dilatation balloon has 536 | SEPTEMBER 2014 | VOLUME 11
evolved as an adjunctive technique to enlarge the papil lary orifice after EBS in order to facilitate extraction of large stones (Figure 4). The rationale behind EPLBD is that it combines the advantages of EBS and EPBD.14 In EPLBD, the risk of perforation and bleeding can be reduced by avoiding an excessively large sphinctero tomy, and the risk of pancreatitis from balloon dilata tion can be decreased by first separating the biliary and pancreatic orifices with EBS, so that the pancreatic orifice is not effaced with significant force during biliary balloon dilatation.14 In 2003, Ersoz et al.15 first reported the use of a largediameter balloon (12–20 mm) in 58 patients (with distal biliary stricture and stones that were square, barrelshaped and/or >15 mm diameter) in whom EBS alone was unsuccessful. Complete stone removal was possible in 54 of the 58 patients (93.1%), with the other 4 (6.9%) needing mechanical lithotripsy. Complications were reported in 15.5% of patients, including mild cholangitis, pancreatitis and bleeding.15 Since this initial report, multi ple studies have reported the efficacy and safety of EPLBD combined with EBS, with a high success rate (94–100%) and a fairly low complication rate (0–17%).16–28 Heo and colleagues reported a trial involving 200 patients with bile duct stones who were randomly allo cated to EBS plus EPLBD (12–20 mm balloon diameter) or EBS alone.18 Outcomes were similar in terms of overall success (97% versus 98%), large (>15 mm diameter) stone removal (94.4% versus 96.7%), the use of mechanical lithotripsy (8% versus 9%), and rate of complications (5% versus 7%).18 Although the study did not show any clear benefit of EPLBD, it has been pointed out that the investigators did not select patients who were most likely to benefit from EPLBD (namely those with large, multiple or difficult stones).14 Teoh and colleagues performed a randomized trial of limited EBS with large-balloon dilata tion versus endoscopic sphincterotomy alone for removal of bile duct stones.29 Although no significant difference was noted between the two groups for the percentage of stones cleared (EBS versus EBS plus EPLBD: 88.5% versus 89%, respectively), patients in the EBS plus EPLBD group needed less mechanical lithotripsy and had a lower cost of hospitalization than those who underwent EBS alone.29 A meta-analysis of EPLBD after EBS compared with EBS alone included six randomized controlled trials involving 835 patients.30 The authors found that EPLBD after EBS caused fewer overall complications than EBS alone (OR 0.53, 95% CI 0.33–0.85, P = 0.008), a significantly lower risk of perforation (OR 0.14, 95% CI 0.20–0.98, P = 0.05) and significantly less need for mechanical lithotripsy (OR 0.26, 95% CI 0.08–0.82, P = 0.02), particularly in patients with a stone size of >15 mm in diameter (OR 0.15, 95% CI 0.03–0.68, P = 0.01). No significant differences were noted between the two groups regarding complete stone removal, stone removal in the first session, post-ERCP pancreatitis, bleeding, infection of the biliary tract or procedure time. The length of sphincterotomy prior to EPLBD varies between studies.14 A Chinese study showed that EPLBD after a limited EBS was safe and effective. Some
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Figure 2 | Difficult bile duct stones. a | Large impacted stone. b | Square and completely impacted stone. c | Stone above stricture. a
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Figure 3 | Basket mechanical lithotripsy of a large stone. a | 2 cm stone. b | Capture with litotripsy basket. c | Fragmented stones. d | Cleared duct.
experts have even questioned the role of EBS preceding EPLBD.14 In a small pilot study involving 37 patients, a South Korean group showed complete duct clear ance by EPLBD alone without the need for mechani cal lithotripsy in 29 (76.3%) patients.31 They speculated that EPLBD enables decreased use of mechanical litho tripsy and thereby causes decreased risk of post-ERCP pancreatitis.28 EPLBD alone has been shown to be safe in elderly patients and in patients who have undergone Billroth type II gastrectomy.32,33 The choice of balloon size varies substantially among studies, but experts recom mend limiting the size of the balloon to the size of the native distal duct within a few centimetres of the papilla.12 A prototype device combining a large-diameter balloon and sphincterotome has been described as a safe and effective accessory for removal of large bile duct stones.34 EPLBD has been shown to have a complication rate of 0–17% across different studies.15–28 In a multicentre
study specifically performed to identify predictors of adverse events after EPLBD, perforation was reported to be the most serious adverse event.35 On multivariate analysis, the authors found that distal CBD stricture was an independent risk factor for perforation and suggested that it should be considered as a relative contraindication to EPLBD.35 In the same study, bleeding was the most common adverse event and the presence of cirrhosis, full EBS and a stone size of >16 mm were independent predic tors of bleeding following EPLBD.35 Surprisingly, none of the patients developed severe post-ERCP pancreatitis, and large balloon size (balloon size ≥14 mm) was identified to be protective against pancreatitis.35 As EPLBD enlarges the biliary orifice to a great extent, the physiology of the sphincter of Oddi is lost; subsequent duodenobiliary reflux could theoretically cause long-term recurrence of stones, although the real risk remains unclear.31,35–37 In summary, the use of EPLBD minimizes the need for mechanical lithotripsy, shortens procedure and fluoro scopy times, and might reduce adverse events associated with prolonged lithotripsy procedures.35 EPLBD might be particularly useful in patients who have a difficult papil lary anatomy, such as those with small or peridiverticular papilla or surgically altered anatomy.36 When consider ing EPLBD, careful consideration should be accorded to the size of the native bile duct, the size and number of stones, the shape and size of the papillary mound, the presence of intradiverticular or peridiverticular papilla, and the patients’ comorbid conditions.14 The presence of coagulopathy or need for anticoagulation favour more emphasis on dilation and less on sphincterotomy. 14 Consideration should be given to placing a pancreatic stent if pancreatic instrumentation is used or if the orifice is effaced during EPBLD.
Cholangioscopy-guided lithotripsy Large stones (especially those ≥2 cm in diameter), stones that are impacted in the bile ducts and those above strictures might be refractory to mechanical lithotripsy and need fragmentation before retrieval.12 Electrohydraulic lithotripsy works on the principle that sparks generated underwater produce high-frequency hydraulic pressure waves whose energy is absorbed by stones and results in their disintegration.38 In laser litho tripsy, pulsed laser energy at a particular wavelength is focused on the stone to induce wave-mediated frag mentation.12 Electrohydraulic lithotripsy or laser litho tripsy are best performed under direct visual control using a cholangioscope to avoid direct application of the shock waves or laser on the duct wall, which could cause perforation or bleeding (Figure 5). Traditionally, peroral cholangios copy involved a mother–daughter system in which a cholangioscope is inserted through the instrument channel of the duodenoscope. Mother– daughter cholangioscopy involves complex equipment and usually requires coordination between two experi enced endoscopists. Fragility, poor optical resolution and the limited ability to steer traditional cholangio scopes hamper their utility for therapeutic biliary inter ventions.12,37,39 Introduction of the SpyGlass® Direct
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Figure 4 | Endoscopic papillary large-balloon dilatation. a | After ample sphincterotomy. b | Large-balloon (15 mm) dilatation. c | Very large papillary orifice enabling a view up the duct. d | Fluoroscopic view of large-balloon dilation. e | Basket capture of stone. f | After removal of intact stone into duodenum.
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Figure 5 | Very large stone requiring direct cholangioscopy and laser lithotripsy. a | 3 × 4 cm stone. b | SpyGlass® (Boston Scientific, Natick, MA, USA) cholangioscopy. c | Direct peroral cholangioscopy. d | After fragmentation of the stone. e | Laser lithotripsy of large stone using direct peroral cholangioscopy.
Visualization System (Boston Scientific, Natick, MA, USA) has enabled increased applicability of cholangio scopy. SpyGlass®is a fairly simple, single-operator, peroral system with four-way steerability and with separate chan nels for the optical probe, irrigation and electrohydraulic or laser lithotripsy probes.40 Fishman and colleagues reported the use of SpyGlass®-directed electrohydraulic lithotripsy in 38 patients, with a technical success rate of 87% after one session and with complete clearance after a second session.41 They reported the often observed dif ficulty in passing the electrohydraulic lithotripsy probe through the SpyGlass®cholangioscope and targeting of 538 | SEPTEMBER 2014 | VOLUME 11
the lesion.41 The authors noted a deterioration in optical resolution after an average of 10 uses.41 Similar success with SpyGlass®-guided electrohydraulic lithotripsy has been reported in other studies.40,42 Laser lithotripsy of difficult biliary stones has been reported through SpyGlass® with a high degree of success (83%) after a single session.39 Holmium laser lithotripsy was found to be effective for both pigment and cholesterol stones.39 Inherent limitations of laser lithotripsy include the fragility of the probe and expense of the equipment. In a prospective multinational study involving 15 endoscopy centres, 66 patients underwent SpyGlass®-guided electrohydraulic or laser lithotripsy treatment, with a 1 month follow-up.43 Impacted stones were present in 30 of 50 patients (60%). All stones were treated by electrohydraulic lithotripsy and/or laser litho tripsy with minimal adverse events, which all resolved without sequelae.43 Experts have criticized the inferior quality of the fibreoptic image of the SpyGlass®system, as well as its inability to perform enhanced endoscopy.44 In addition, the small 1.2 mm working channel limits the range of therapeutic accessories and makes passage of even very small devices such as lithotripsy probes potentially dif ficult. An increased risk of cholangitis of up to 7–10% has been noted with SpyGlass®, most likely from intraductal irrigation in an obstructed duct required for visualiza tion during the procedure.45 Antibiotic prophylaxis is imperative in all cases and in selected cases biliary drain age with stents should be considered after cholangioscopy to minimize the risk of cholangitis.44,45
Direct peroral cholangioscopy In direct peroral cholangioscopy (DPOC), an ultraslim upper endoscope is manoeuvred through the biliary sphincterotomy and into the CBD for direct visualization, resulting in high-resolution digital imaging and four-way steerability.46,47 The 2 mm working channel of the ultra slim endoscope enables passage of larger accessories than through dedicated cholangioscopes, thus facilitat ing advanced therapeutic procedures (Figure 5). DPOC enables simultaneous irrigation and therapeutic capabili ties, and involves use of a readily-available multipurpose endoscope, and thus represents an attractive alternative to conventional mother–daughter endoscope systems.47 The biggest challenge associated with DPOC is diffi culty in passing the ultraslim endoscope into the proximal biliary system. Large loop formation of the slim scope is common within the gastric fundus or the deep portion of the duodenum, which can impede advancement into the biliary system.44 Specialized techniques are often neces sary to enhance success, including passing a wire and/or balloon antegrade into the intrahepatic ducts to anchor and pull the endoscope into the duct. Dislodgement of the guidewire is common. Moon et al.47 proposed the ‘ropeway technique’ with use of an intraductal 5 French balloon catheter that can be anchored within a branch of the intrahepatic duct to advance an ultraslim endo scope into the biliary tree. The balloon and/or guide wire must be withdrawn from the working channel for
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REVIEWS interventional procedures, which might create technical difficulties in maintaining the desired scope position. Overtube balloon-assisted cholangioscopy might be useful to circumvent these difficulties.48 However, cur rently available overtubes are excessively large relative to ultraslim endoscopes, resulting in difficulty manipulat ing both instruments, looping of the endoscope in the duodenum, difficulty in accessing the proximal bile duct and discomfort for the patient.48,49 Efforts are currently underway to develop appropriate accessories to enhance the interventional performance of DPOC.44 DPOC is useful for identifying and extracting residual stones that might have been missed during cholangio graphy.50–52 A prospective study evaluated the usefulness of DPOC in patients thought to have complete stone clearance (as confirmed by balloon-occluded cholangio graphy after mechanical lithotripsy).51 DPOC detected residual stones in 28% of the 48 patients, 85% of which were immediately removed under direct visualization.51 Most importantly, DPOC is useful for performing electro hydraulic or laser lithotripsy under direct high-resolution digital cholangioscopic visualization to ensure safety and precise targeting during fragmentation. Moon et al.53 reported successful electrohydraulic or laser lithotripsy using DPOC in 16 of 18 patients (90%) who had failed conventional lithotripsy, including mechanical lithotripsy, with an average of 1.6 s essions per patient. Laser litho tripsy was successful in 11 of 13 (85%) patients who failed conventional lithotripsy involving mechanical lithotripsy.54 A feared complication of DPOC is air embolism. Use of carbon dioxide instead of air and minimizing gas insuf flation are sufficient to avoid this complication.44 Current DPOC endoscopes lack a dedicated high-volume irriga tion channel separate from the working channel, other than the insufflation/irrigation channel standard on any endoscope, so that a separate nasobiliary tube might be ideal for continuous irrigation with infusion of saline solution or contrast medium for efficient lithotripsy and cleansing of fragmented stones; these ideas have been used, but not yet reported. EPLBD to create a very large sphincterotomy orifice might not only aid with biliary access using the ultraslim endoscope, but enable egress of any excessive pressure built up by insufflation or irrigation, and thus further reduce risk of complications.
Difficult clinical presentations Mirizzi syndrome Mirizzi syndrome is an atypical presentation of gall stone disease in which impaction of a gallstone in the cystic duct or in the Hartmann pouch causes stenosis of the extrahepatic bile duct by extrinsic compression, fibrosis or direct erosion of a stone into the common hepatic duct. McSherry classified Mirizzi syndrome into two types on the basis of ERCP findings: type I involves external compression of the common hepatic duct by a stone impacted in the cystic duct; type II occurs when a stone produces a cholecystocholedochal fistula and migrates into the common hepatic duct. Successful entrapment of impacted stones in the common hepatic duct with conventional baskets is technically challenging,
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Figure 6 | SpyGlass®(Boston Scientific, Natick, MA, USA) access to cystic duct stump with electrohydraulic lithotripsy of retained cystic duct stump stone. a | Radiopaque stone in cystic duct stump. b | SpyGlass®introduced into cystic duct stump. c | Electrohydraulic lithotripsy. d | Clearance of cystic duct stump. e | SpyGlass®view of electrohydraulic lithotripsy probe against cystic duct stump stone.
as even passing a guidewire alongside the impacted stone is difficult.37 Treatment of cystic duct stones can be even more challenging after cholecystectomy as very limited space exists upstream of the stone to pass guidewires or devices through (Figure 6). Extracorporeal shockwave lithotripsy (ESWL) has been utilized for stone fragmentation in patients with Mirizzi syndrome, but complete ductal clearance was achieved in only 56–83% of patients.55,56 A report of cholangioscopic electrohydraulic and laser lithotripsy for 122 consecu tive patients with difficult bile duct stones included 53 patients with Mirizzi syndrome (3 type I and 50 type II), 50 patients with impacted stones, and 19 patients with large stones.57 Successful stone removal was achieved in 96% of patients with Mirizzi syndrome (96% type-II Mirizzi syndrome, 0% type-I Mirizzi syndrome) and 100% of patients with impacted stones and large stones.57 Thus type-II Mirizzi syndrome seems to be more amenable to endoscopic therapy than type I. However, SpyGlass® might represent a viable method for directing a small calibre cholangioscope into the cystic duct and deliver ing electrohydraulic lithotripsy to patients with Mirizzi syndrome of all types (Figure 6).
Hepatolithiasis Hepatolithiasis—or the presence of stones in the intra hepatic ducts (also known as intrahepatic choledocho lithiasis)—is most prevalent in South-East Asia, but occurs throughout the world. Ethnic factors, bacterial infection, parasitic infestation, and anomalies of bile duct anatomy have all been implicated in its aetiopatho genesis.58 Complications of hepatolithiasis include sup purative cholangitis, liver abscess, secondary biliary cirrhosis and cholangiocarcinoma; hence early clearance
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Figure 7 | Percutaneous cholangioscopy with basket and balloon extraction of intrahepatic stones above stenotic Roux-en‑Y hepaticojejunostomy. a | Percutaneous cholangiogram via left hepatic duct with multiple intrahepatic stones (arrows). b | Digital ultraslim videoendoscope advanced via percutaneous tract into right posterior sectoral duct. c | Videoendoscope advanced into right anterior sectoral duct. d | Clearance of stones. e | High-resolution digital view of intrahepatic ducts.
of the stones is important to prevent further liver damage and improve long-term prognosis.58 The association of hepatolithiasis with intrahepatic biliary strictures ham pers the removal of stones and increases the risk of recur rence.59 Surgical resection of the liver segments or lobe that contains stones, strictures or atrophy is the mainstay of treatment, especially for recurrent pyogenic cholan gitis and is effective in reducing the risk of cholangio carcinoma and recurrence of stones. However, surgical resection might be contraindicated in patients who have medical comorbidities, or in those who have cirrhosis from repeated episodes of cholangitis.59 Transpapillary extraction of intrahepatic stones is generally challenging because of frequent biliary strictures in the downstream bile duct, with stone impaction and ductal angulation of the hilar and intrahepatic bile ducts.37 Peroral cholangio scopic lithotripsy using the mother–daughter endoscope as described for difficult CBD stones, with use of electro hydraulic lithotripsy and/or ESWL, has been reported as an option for the treatment of hepatolithiasis: a clear ance rate of 64% was reported, with a recurrence rate of 21.7% after complete removal.60 Technical challenges include insertion of the instrument into the right post erior sectoral ducts (segments VI and VII) and left lateral hepatic duct segments (II and III) because of the sharp anatomic angulations.60 Percutaneous transhepatic cholangioscopic lithotripsy offers a less invasive alternative to hepatectomy for the extraction of intrahepatic stones that cannot be managed endoscopically. Percutaneous approaches are particularly useful in patients who have undergone previous biliary tract surgery (such as Roux-en-Y hepaticojejunostomy) 540 | SEPTEMBER 2014 | VOLUME 11
and those with stone distribution in multiple segments, and also in patients who have already had percutaneous biliary drainage. After the transhepatic percutaneous drainage tract has matured (usually ≥4 weeks), the tract is dilated and a small-calibre digital video endoscope is inserted into the intrahepatic ducts (Figure 7). The entire intrahepatic tree can usually be accessed with a flexible small-calibre endoscope through any percutaneous access. A percutane ous drain must be kept in place throughout the treatment period.61 Laser lithotripsy, electrohydraulic lithotripsy via cholangioscopy, or ESWL can be used to disintegrate stones that are too large to be removed using routine percutaneous transhepatic cholangioscopy. Studies have demonstrated a complete clearance rate of hepatic stones of 80–85% using percutaneous trans hepatic cholangioscopic lithotripsy; the major compli cation rate is 0–2.1% and such complications include liver lacerations, intra-abdominal abscess, disruption of the percutaneous transhepatic fistula, transient hemo bilia and septic shock.37,58,62–64 In some cases, the frag ments produced by electrohydraulic lithotripsy do not spontaneously pass into the duodenum owing to the resistance offered by the sphincter of Oddi, resulting in biliary obstruction, pancreatitis and recurrence of stones. Percutaneous transhepatic papillary balloon dilatation followed by pushing the fragments into the duodenum with the tip of the choledochoscope was shown to be successful in 75% of patients (12 of 16).65 This method was shown to be simple and effective with no procedurerelated pancreatitis or other major complications.65 The use of fully-covered expandable metallic internal stents in the management of intrahepatic biliary strictures has been shown to decrease the recurrence of cholangitis and stones, simplify further treatment and result in fewer limitations of ordinary activities.59 Given the complicated nature of intrahepatic stone disease, no single treatment is definitive and a multidisciplinary approach is essential.
Endoscopic biliary stenting In elderly or frail patients who have serious comorbid conditions and endoscopically irretrievable stones, surgi cal procedures might confer an unacceptably high risk. In this cohort of patients, placement of plastic biliary stents for definitive management of choledocholithiasis might be an acceptable option. In an Italian study, plastic stent exchange every 3 months was prospectively compared with ‘on demand’ stent exchange at the onset of symp toms.66 The authors concluded that the rate of cholan gitis was significantly lower in the group in whom stent exchange was performed at defined intervals (3 months) (P = 0.03).66 Biliary stenting is mandatory if duct clear ance cannot be achieved during ERCP or in between procedures in patients who require multiple sessions for ductal clearance. Mechanical grinding of the stents against stones is thought to reduce stone size, increase stone fragmentation and create space around the stones, thereby facilitating mechanical lithotripsy and extrac tion during follow-up procedures. Placement of multi ple double-pigtail stents (coiled at both ends) around the stones might facilitate stone fragmentation and prevent
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REVIEWS inward or outward migration, which is frequent with conventional straight stents. The combination of two oral dissolution agents— ursodeoxycholic acid (UDCA; 60 mg daily) and 300 mg of a terpene preparation—daily for 6 months, along with placement of multiple 7 French plastic double-pigtail stents was found to be superior to stents alone for success ful bile duct clearance in a randomized, controlled study.67 Similar results were obtained in an earlier study.68 Thus, combination therapy with choleretic agents should be considered in patients with significant comorbidities or intolerance to repeated endoscopic treatment modalities.
Patients with surgically altered anatomy Bile duct stones can occur in patients with a surgi cally altered anatomy, which is increasingly common. In patients with an intact gallbladder, laparoscopic or open extraction of CBD stones can be combined with cholecystectomy. In many cases, though, patients either have complex bile duct stone disease or have already undergone cholecystectomy, such that ERCP is required. Before undertaking ERCP, having thorough knowledge of the specific surgical reconstruction is mandatory. Certain types of post-surgical anatomy feature a conventionally accessible biliary system (Billroth type 1 gastrectomy and sleeve gastrectomy) and advancement of the duo denoscope is fairly straightforward, such that cannula tion of the major papilla is possible with the usual ERCP accessories.37,69 However, the post-surgical anatomy with many procedures, such as Billroth type II gastrectomy or Roux-en-Y reconstruction, results in a long gastrointesti nal tract to traverse and also an inverted approach to the papilla.69 Roux-en-Y reconstruction, especially includ ing gastric bypass (RYGB), poses a particular challenge owing to the extreme length of the Roux limbs, often >300 cm combined. If ERCP is to be undertaken for the management of CBD stones in patients who have an altered anatomy, magnetic resonance cholangiopancreatography (MRCP) is generally recommended to estimate the number and size of stones, and a review of the operative report is essential to estimate the length of the small bowel that needs to be traversed. ERCP in patients who have under gone Billroth type II surgery can be performed with a forward-viewing endoscope or a side-viewing duodeno scope.69 Although the forward-viewing endoscope is easier to advance, the lack of an elevator at the opera tive channel on reaching the papillary area impedes fine control of cannulation tools and accessories.69 The use of a cap over the end of the forward-viewing scope has been shown to facilitate successful cannulation.70 Intrahepatic stones can occur after Roux-en-Y hepati cojejunostomy. ERCP for stone extraction in this setting can be performed by a couple of routes: one option is ante grade passage of the endoscope through a stoma created in the jejunal loop; the alternative is the passage of an endoscope retrograde up the afferent limb to the hepatico jejunostomy. With the proliferation of deep entero scopy techniques, balloon-enteroscopy-assisted ERCP —such as double‑balloon enteroscopy, single-balloon
enteroscopy71–74 and spiral-assisted ERCP75,76—has become popular, with multiple reports of its use in patients with a surgically altered anatomy. Shah and colleagues 77 reported results from a multicentre series of 129 patients undergoing 180 enteroscopy-ERCPs. The anatomy of the patients was RYGB (n = 63), hepaticojejunostomy (n = 45), post-gastrectomy (n = 6), Whipple procedure (n = 10) and other (n = 5). Successful access to the papilla or hepaticopancreaticojejunal anastomosis was achieved in 71% of patients; ERCP was successfully performed in 88% of those patients, to give an overall ERCP success rate of 63%. ERCP success rates were similar between RYGB and other long-limb surgical bypass procedures and among single-balloon enteroscopy, double-balloon enteroscopy and rotational overtube enteroscopy. Complications were seen in 12.4% of patients.77 However, this series represents a select group of patients deemed appropriate and selected by the endoscopists for an attempt at long-limb enteroscopic ERCP; it is possible that these patients had short Roux limbs or fewer comorbidities than other patients. In patients with RYGB anatomy, reliable access to the duodenum with a side-viewing endoscope can almost always be obtained via laparoscopy-assisted ERCP.78–83 This technique is particularly preferable in patients undergoing simultaneous cholecystectomy who are found to have CBD stones by preoperative imaging, such as MRCP or intraoperative cholangiography, and for situa tions in which expertise in laparoscopic CBD exploration and clearance is not locally available. After laparoscopic access to the gastric remnant (excluded stomach) is created, the endoscopist inserts the side-viewing duo denoscope to be passed through a 15 mm trocar in ante grade fashion to reach the papilla. This approach enables a full range of complex endoscopic techniques includ ing selective duct access, protective pancreatic stenting, sphincterotomy, large-balloon dilatation and mechanical and intraductal lithotripsy techniques. A logical question is whether enteroscopic ERCP is worth attempting in patients who have undergone RYGB. In patients who have undergone bariatric surgery, laparoscopy can additionally diagnose and treat internal hernias.82 Schreiner et al.84 compared balloon-enteroscopy- assisted ERCP with laparoscopy-assisted ERCP in patients post-RYGB. Laparoscopy-assisted ERCP resulted in superior outcomes compared with balloon-enteroscopyassisted ERCP (100% versus 59% cannulation rate), with similar rates of post-procedure complications and length of hospitalization. Success rates of enteroscopic ERCP were very low in patients in whom the length of the Roux limb and biliopancreatic limb was ≥150 cm, which is almost universal for gastric bypasses performed within the past 10 or more years. Laparoscopy-assisted ERCP was, however, more expensive. The authors concluded that in centres with expertise in deep enteroscopy and ERCP, patients with a Roux and ligament of Treitz to jejunojejunal anastomosis length of
