Endoscopic sphincterotomy (EST) and associated techniques of stone fragmentation and extraction are now widely used for the removal of stones from the common bile duct (CBD). These techniques are generally safe and effective in the management of patients with choledocholithiasis, although more than one session may be needed to clear the ducts in difficult cases. The risk of late complications such as stone recurrence is an important issue, especially for relatively young, otherwise healthy, patients with many years of future exposure time. In more elderly, frail or immunosuppressed patients recurrent stones and cholangitis are serious and life threatening events. If patients at significant risk for stone recurrence could be identified, closer follow-up, earlier intervention, and possible preventive measures could theoretically decrease stone recurrence, biliary sepsis, biliary cirrhosis, or even death.
Recurrence of bile duct stones has been reported ranging from 4 to 24% [1–3] during follow-up intervals of up to 15 years. Most series report fewer than 10 years follow-up. True total recurrence rates involve life-long follow-up and include symptomatic and asymptomatic recurrences. In a study  of 51 patients with recurrent stones after mean follow-up of 2 years, 39% of stone recurrences were asymptomatic and detected initially only by surveillance serum liver chemistries or ultrasonography.
Recurrent versus residual stones
Most series report that bile duct stones recurred within 3 years [4,5]. Such relatively early recurrences suggest that part of the cause of ‘recurrent’ bile duct stones is failure to remove all fragments of stones at the original endoscopic retrograde cholangiopancreatography (ERCP). Residual and truly recurrent stones may have differing composition. The final cholangiogram obtained immediately after stone removal may underestimate residual stones due to numerous air bubbles entering the bile duct from the sphincterotomy. Several methods have been advocated for improved clearance of stone fragments in the bile duct. Placement of a nasobiliary catheter with follow-up cholangiograms in the prone and supine positions can detect residual stones (and requires repeat ERCP if stones are seen). Recently, intraductal ultrasonography has been used to detect residual stones, particularly when the bile duct is dilated . Intraductal ultrasonography can accurately differentiate air bubbles from bile duct stones. Intraductal cholangioscopy can be used to check for residual stones but the technique is tedious to perform.
The risk factors for true recurrence of bile duct stones after EST and stone clearance are suboptimally defined. Table 1 lists many of the factors with some association with stone recurrence. True total recurrence rates are difficult to define. Many patients become symptom-free and have no follow-up. Secondly, a large number of patients (several thousand) must be followed for many decades to have adequate numbers to carry out optimal multivariate statistical analysis. Most reports to date involve relatively small samples of patients for a relatively short follow-up period of time. Life-long follow-up is needed to fully define risk factors.
Value of identifying risk factors
Identifying risk factors for stone recurrence is of little importance unless, once defined, management can be altered to give more favourable outcomes. Potentially, some risks of late complications could be prevented by earlier intervention. Second, if follow-up evaluations are restricted to high risk groups, the cost of subsequent examinations may be reduced. In a selected group of patients with multiple CBD stone recurrences, annual surveillance ERCP with stone removal may be beneficial in preventing serious recurrent episodes of ascending cholangitis .
Correctable risk factors
Correctable risk factors include in-situ gallbladder with stones, biliary strictures and papillary stenosis. Can cholecystectomy after EST prevent the recurrence of bile duct stones? The need for elective cholecystectomy in patients with intact gallbladder with stones before or after EST is still controversial. Development of acute cholecystitis and frequency of cholecystectomy has been observed to be higher in patients with gallstones or in whom there was nonvisualization of the gallbladder during a ductogram [8,9]. It is believed that patients with gallbladder in situ after EST run the risk of CBD stone recurrence secondary to stone migration from the gallbladder [5,9]. Several authors have shown significant improvement in gallbladder motility after EST [10,11]. Gallbladders (without gallstones) after EST may flush away early sediment and prevent new stone formation. Generally cholecystectomy is indicated only if the gallbladder contains stones [5,12].
The decision to perform cholecystectomy must also take into consideration the operative risk to the patient. Although laparoscopic cholecystectomy is the less invasive procedure, complications such as bile duct injury still occur. In younger or middle-aged patients with choledocholithiasis and cholecystolithiasis, laparoscopic cholecystectomy before or after EST is commonly recommended.
Biliary stricture is one risk factor of recurrent stones after endoscopic initial removal. In this issue of the European Journal of Gastroenterology & Hepatology, Jakobs and colleagues address risk factors for symptomatic stone recurrence after laser lithotripsy. Symptomatic stone recurrence developed in 11 of 80 (15.5%) patients with mean follow-up of 1.7 years. They concluded that the presence of a bile duct stenosis was significantly associated with an increased risk for stone recurrence . In their series strictures were 42% intrahepatic including hilum and 58% extrahepatic. Strictures were treated in only 30% of patients. We are not told whether stones recurred in stricture patients who received stricture therapy or not. It is logical that aggressive stricture therapy may be needed to resolve strictures. Some investigators recently reported that multiple plastic stents were needed to optimally resolve strictures .
Intrahepatic strictures are probably the most difficult setting in which to achieve stone removal and resolution of the stricture. The residual stone rates after endoscopic lithotripsy for hepatolithiasis with stricture are higher than without stricture . In Asians, approximately 20%  of ductal stones are intrahepatic. Such higher frequency probably applies to Asians living outside of Asia also.
Another potential factor for stone recurrence is papillary stenosis (i.e., insufficiently patent papillary orifice [3,5]). The cause for this in the postsphincterotomy setting is thought to be excess coagulation current during sphincterotomy or an inadequate incision .
Overall, since strictures promote stone recurrence, aggressive stricture therapy (dilatation, stents, etc.) appears to be needed.
Risk factors that are difficult to correct
These include periampullary diverticulum (PAD) and dilated bile duct without residual obstruction. PAD may contribute to cholangitis and recurrent biliary stone formation [16,17]. Diverticula are thought to distort the terminal bile duct or sphincter. Patients with PAD were found to have slower biliary emptying by quantitative cholescintigraphy than patients without PAD and delay in clearance is probably a significant factor in the recurrence of bile duct stones . Diverticulum removal via surgery is rarely done. Choledochoduodenostomy or choledochojejunostomy will bypass the duodenum and/or diverticulum.
It is well known that bile is frequently colonized with bacteria after EST, with at least 60% having positive bile culture . The markedly dilated CBD (greater than 15 mm) is commonly contaminated with bacteria and also has bile stasis, which may play important roles in the pathogenesis of recurrent stones. Brown pigment stones are generally considered to result from bacterial infection. Prospective randomized controlled trials are needed to determine whether antibiotics, bile salts or other cholerrhoeic agents would prevent recurrent stones in such dilated ducts after EST.
Choledocholithiasis may also form in patients with sickle cell anaemia and other haemolytic disorders. Treatment of such underlying conditions should be done if possible during follow-up after stone removal.
There are four follow-up management alternatives of patients with a ‘clean duct’ after ERCP with sphincterotomy, as follows. (1) Dismiss such patients from follow-up and encourage return only if symptoms recur. This is the most common practice in North America. (2) Periodically repeat serum liver chemistries and/or non-invasive imaging of the ducts. (3) Repeat invasive ductal imaging, usually by ERCP. This alternative is rarely applied to asymptomatic patients. (4) Prophylactic treatment with antibiotics, cholerrhoeic agents or stone solubilizing agents, e.g., ursodiol. Whether patients with recurrent risk factors should be managed differently is largely unknown. We apply options 2 or 3 above only to patients who have already had one or two documented recurrence episodes.
The good news is that repeat ERCP manages most of these episodes of late cholangitis and recurrent choledocholithiasis effectively except in surgically altered anatomy such as Roux-en-Y choledochojejunostomy. One group of investigators  suggests that prophylactic ERCP be performed yearly in patients who have had at least two recurrence events. They reported that annual surveillance ERCP with stone removal decreases the incidence of recurrent episodes of ascending cholangitis. The rationale is to clear recurrent stones before cholangitis and the need for hospitalization occur. Randomized trials would be needed to show cost efficacy of this approval. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive and sensitive test for detection of bile duct lesions, but it is relatively expensive and provides no option for therapy . MRCP is probably of limited value in the air-filled duct after endoscopic stone removal . Dissolution of bile duct stones by oral agents and subsequent endoscopic extraction is logical but not proven. Alternatively, CBD surgical exploration or biliary bypass remain as good options for difficult patients .
In conclusion, the majority of patients with CBD stone who have EST and stone clearance will have no further biliary events during the remainder of their life. Patients with recurrences can usually be readily managed by repeat ERCP. Whether identifying risk factors for recurrence can improve outcomes by prophylactic treatments or earlier interventions needs further prospective study. A large multicentre database with several thousand patients at risk for stone recurrence is needed to more accurately define risk factors for recurrence by multivariate analysis.
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