Chapter 49. Choledocholithiasis and Cholangitis

With advanced endoscopic and laparoscopic techniques being readily accessible to the treating surgeon, determining the wisest path to the successful treatment of choledocholithiasis and cholangitis has become more challenging. Nevertheless, a large number of options allow one to tailor-specific therapy to each individual clinical situation so as to achieve the highest probability of success. In this chapter we attempt to give the reader a better understanding of the methods available for the diagnosis and treatment of common bile duct (CBD) stones and cholangitis so that treatment plans are developed that are patient-specific and have the highest chance of success.

Classification and Epidemiology

A common entity in Western societies, gallstones are found in approximately 15% of Americans and result in 700,000 cholecystectomies a year. The annual cost of medical care for gallstones is almost $6.5 billion (1.3% of US health care costs) compared with chronic liver disease and cirrhosis ($1.6 billion), chronic hepatitis C ($0.8 billion), and diseases of the pancreas ($2.2 billion).1 CBD (downstream of the confluence of the hepatic ducts) stones have been noted in 10–15% of patients with cholelithiasis, and this incidence increases with age to over 80% in those who are over 90 years old.2 Choledocholithiasis in Western countries usually results from stones originating in the gallbladder and migrating through the cystic duct. These secondary bile duct stones are cholesterol stones in 75% and black pigment stones in 25% of patients. Cholesterol stones are formed in the presence of cholesterol saturation, biliary stasis, and nucleating factors. Behavioral factors associated with cholesterol gallstones include nutrition, obesity, weight loss, and physical activity. Biologic factors linked to gallstones include increasing age, female sex and parity, serum lipid levels, and the Native American, Chilean, and Hispanic race.1 The formation of black pigment stones is associated with hemolytic disorders, cirrhosis, ileal resection, prolonged fasting, and total parenteral nutrition.2

Primary bile duct stones, on the other hand, form within the bile ducts and usually are of the brown pigment variety. These tend to be lower in cholesterol content and higher in bilirubin content as compared with secondary stones. Unlike secondary stones, primary stones are associated with biliary stasis and bacteria.3 In fact, in the pathogenesis of brown pigment stones, bile infection appears to be the initial event leading to stone formation.4 Moreover, bacteria have been found in brown pigment stones by electron microscopy but not in black pigment stones. Primary bile duct stones are more common in Asian populations, and these often are associated with primary intrahepatic stones in this population.1 These intrahepatic stones usually are calcium bilirubinate and mixed stones and contain more cholesterol and less bilirubin than the extrahepatic bile duct pigmented stones. The pathogenesis of these intrahepatic stones appears to involve bile infection; biliary stasis; low-protein, low-fat diets and malnutrition; and parasitic infections. However, the role of Ascaris lumbricoides and Clonorchis sinensis in the formation of intrahepatic stones is controversial. While these parasites are found in many geographic areas, primary intrahepatic stones are found mainly in Southeast Asia. Therefore, in addition to parasitic infections, other factors must play a role in the formation of these stones.1

Clinical Presentation and Natural History

Asymptomatic bile duct stones may be found incidentally during evaluation of patients with suspected gallstones. In fact, 5% of common duct stones found during surgery may be unsuspected by preoperative findings and discovered only during intraoperative evaluation of the biliary tree. In one autopsy study of 615 patients over age 60, 1% were found to have bile duct stones.2 Patients with choledocholithiasis may present with biliary colic, bile duct obstruction, bilirubinuria (or tea-colored urine), pruritus, acholic stools, and jaundice. However, the biliary obstruction usually is incomplete. There may be nausea and vomiting with intermittent or constant epigastric or right upper quadrant pain.5 The clinical course may be complicated by acute gallstone pancreatitis, cholangitis, or rarely, hepatic abscess. Infected patients may present with back pain, fever, hypotension, and mental status changes suggestive of cholangitis and ascending cholangitis. An asymptomatic state is also recognized.

CBD stones are covered by a bacterial biofilm of adherent quiescent bacteria residing in a hermetic environment. When stones cause obstruction of the ducts, cytokines released by epithelial cells activate these bacteria to the planktonic and virulent forms.1 Therefore, bile duct obstruction secondary to stones often is accompanied by bacterial sepsis resulting from activation of the bacterial biofilm on these stones. Sepsis is much less likely to occur in the context of malignant obstruction without choledocholithiasis.

Although a majority of stones will pass spontaneously into the duodenum within hours, prolonged biliary obstruction can lead to biliary cirrhosis and portal hypertension. The average time for choledocholithiasis to lead to biliary cirrhosis is about 5 years, depending on the extent of obstruction.1 Even with cirrhosis, however, the obstruction should be relieved because some reversal of portal hypertension and secondary biliary cirrhosis may be possible.

Physical examination of patients with choledocholithiasis may be normal or reveal jaundice, scleral icterus, and abdominal tenderness over the right upper quadrant without peritoneal signs. Early in the course, physical examination may not be very different from that of patients with cholecystitis. Severe tenderness may point to acute gallstone pancreatitis, whereas fever, hypotension, and confusion may suggest cholangitis.6

Blood tests may reveal elevation of serum alkaline phosphatase, gamma-glutamyl transpeptidase, and bilirubin. Mild elevations of aspartate aminotransferase and alanine aminotransferase can be seen, whereas these are particularly abnormal in the situation of cholangitis. Although bilirubin and aminotransferase levels are high in 70–90% of patients at the onset of symptoms, almost all patients have elevation of alkaline phosphatase and gamma-glutamyl transpeptidase.6 Elevated amylase and lipase may suggest pancreatitis. Leukocytosis may be seen with cholangitis, pancreatitis, or associated acute cholecystitis. It is worth noting that laboratory evaluation of patients with bile duct stones can be normal repeatedly, and this should not dissuade further evaluation of patients suspected to harbor duct stones.7

Evaluation and Management

The evaluation and treatment of choledocholithiasis are best discussed by considering the three clinical circumstances in which patients who may have bile duct stones are seen prior to cholecystectomy, during cholecystectomy, or some time after cholecystectomy.

Preoperative

The diagnosis of choledocholithiasis cannot be made on the basis of history, physical examination, and laboratory investigations alone. Moreover, the distinction between the symptoms of bile duct stones and gallbladder stones often is difficult. Increasing age, history of fever, cholangitis, and pancreatitis are risk factors for bile duct stones, whereas elevations of serum bilirubin, aspartate aminotransferase, or alkaline phosphatase are independent positive predictors.1,8

Transcutaneous ultrasound has been the traditional method of evaluating patients with biliary disease. It is highly accurate in identifying acute calculous cholecystitis and the presence of gallstones greater than 2 mm. Sensitivities and specificities of 48–100% and 64–100%, respectively, have been reported.9 However, the ability of transcutaneous ultrasound to establish the diagnosis of choledocholithiasis is only about 50%, varying from 30 to 90%.6,10 The role of ultrasound as a screening test for bile duct stones was evaluated prospectively by Gross and colleagues.11 Patients who were about to undergo endoscopic retrograde cholangiopancreatography (ERCP) were examined by right upper quadrant sonography to assess the size of the intra- and extrahepatic ducts and for the presence or absence of bile duct stones. The findings were compared with ERCP, percutaneous transhepatic cholangiography, or surgical follow-up. Ultrasound was not found to be accurate in the diagnosis (sensitivity of 25%) or the exclusion (73% negative predictive value) of choledocholithiasis.

Costi and colleagues studied the usefulness of the number and size of gallbladder stones for predicting asymptomatic choledocholithiasis.12 Ultrasound data of 300 consecutive patients undergoing laparoscopic cholecystectomy were analyzed. Patients were divided into two groups: those with multiple small (<5 mm) gallbladder stones or variable (≤5 mm and >5 mm) stones and those with large (>5 mm) stones only. The classification of stone size was confirmed by surgery in 95% of patients. Moreover, the presence of multiple small and variable gallbladder stones represented a risk factor for synchronous asymptomatic bile duct stones (9.5%) as compared with large stones only (2.5%). In another study, ultrasonography was found to have a positive predictive value (PPV) of 69% and a negative predictive value (NPV) of 78% for choledocholithiasis in patients suspected to have bile duct stones.13 This compared with serum transaminase tests having predictive values of 68 and 93%, respectively. In comparison to elevated serum transaminases and/or increased amylase levels, ultrasonographic evidence of common bile duct dilatation (>7 mm) has been described to be the best predictor of choledocholithiasis.14 Nonetheless, it is worth noting that almost half the patients with CBD stones do not have dilated ducts by ultrasonography, hence a negative study has limited value.15

In order to predict the presence of bile duct stones more accurately, the combination of clinical, laboratory, and ultrasound risk factors has been used by several investigators.1,16,17 By multivariate logistic regression analysis, the combination of dilated CBD with evidence of stones by ultrasonography, clinical evidence of cholangitis, elevated aspartate transaminase and bilirubin, the likelihood of having stones in the bile duct was 99%.17 In the absence of all four of these findings, the probability of synchronous choledocholithiasis in patients with cholelithiasis was only 7%.17 Unfortunately, many patients present with only some of these findings, and the prediction of bile duct stones based on these criteria becomes difficult. Moreover, ultrasound sensitivity is in part operator-dependent and altered by bowel gas, making the findings inconsistent.18

In 1968, ERCP was introduced as a diagnostic tool to aid in the management of biliary and pancreatic diseases.19 Five years later, with the development of endoscopic sphincterotomy, ERCP was transformed into a therapeutic modality.20 Currently, more than 150,000 endoscopic biliary sphincterotomies are performed annually in the United States. Short of intraoperative examination, ERCP has long been considered the standard reference for the diagnosis of CBD stones.18 The specificity and sensitivity of ERCP were reported in 1982 by Frey and colleagues.21 ERCP was compared with findings on common duct exploration or cystic duct cholangiography in 72 patients and was found to have a sensitivity of 90%, specificity of 98%, and a 96% accuracy. Interestingly, the interval between performance of the procedure and operation was particularly important in patients with multiple small stones. Since small stones pass more readily from the gallbladder to the common duct and from the common duct to the duodenum, the longer the interval between ERCP and operation, the greater was the chance of discordant findings. With improvements in technique and better radiological equipment, ERCP certainly has improved over time.

Along with the ability to diagnose bile duct stones, ERCP has the advantage of offering therapeutic intervention options in the same setting of diagnosis (Figs. 49-1 and 49-2). That is, after stones in the bile duct are identified, endoscopic sphincterotomy and stone extraction can be performed at the same setting. If stones are not found, bile can be collected to test for microlithiasis if clinically appropriate.18 ERCP stone extraction is successful 80–90% of the time using the techniques of sphincterotomy and balloon catheter or Dormia basket stone retrieval.20,22 The addition of mechanical, electrohydraulic, laser, or extracorporeal shockwave lithotripsy for large stones increases the success rate to over 95%.

Sphincterotomy entails division of the papilla and sphincter muscles to widen the distal end of the CBD with the use of a sphincterotome, a device consisting of a Teflon catheter with exposed cautery wire at the tip. The length of the intraduodenal part of the CBD limits the extent of the cut. Balloon sphincteroplasty is a sphincter-preserving alternative to sphincterotomy that uses a high-pressure hydrostatic balloon of either 6 or 8 mm diameter to dilate the papilla. One drawback of sphincteroplasty is the limited size of the papillary opening created as compared with sphincterotomy. Failure rates of 22% for stone extraction with balloon dilatation and the need for mechanical lithotripsy in 31% have been reported.22 Furthermore, sphincteroplasty has been associated with a pancreatitis rate of 19 times greater than the rate associated with sphincterotomy.23 A recent study evaluating the use of sphincteroplasty, on the other hand, found that severe pancreatitis only occurred in 1 patient out of 63, whereas the successful stone extraction rate was 84%.24

Once the sphincter has been divided, most stones can be removed using a Dormia basket or a balloon catheter. The Dormia basket has better traction than the balloon and consequently is recommended for larger stones (>1 cm). The balloon catheter occludes the bile duct lumen after inflation and therefore is useful for removal of small stones and gravel. The catheter also can be inserted over a guidewire, making it useful for intrahepatic duct stones. Three situations that may lead to a difficult extraction are stone size greater than 1.5 cm, stone location proximal to a stricture, and multiple stones that are impacted. Alternative approaches to these situations include mechanical lithotripsy, electrohydraulic or laser lithotripsy, and extracorporeal shock wave lithotripsy. Mono-octanoin and methyl tertiary butyl ether (MTBE) have been used in the past to dissolve bile duct stones through nasobiliary drainage catheters or T-tubes. The practice largely has been abandoned because of high complication rates, poor results, and the technical difficulty of performing the dissolution.22

Mechanical lithotripsy is the most commonly used and simplest means of fragmenting large bile duct stones or when a significant discrepancy between the stone size and the diameter of the exit passage exists.25 A large, strong basket is used to trap the stone. The stone then is crushed against a metal sheath by applying tension to the wires by the use of a crank handle. Reimann and colleagues first described the technique in 1982, and since then, many variations in design have become available.26,27 When stones are extremely large, repeat application of the technique may be needed to further break the stone fragments and thus allow removal. Success rates between 80 and 90% have been reported for clearing the bile duct using the procedure.28–30 One retrospective study of 162 patients undergoing mechanical lithotripsy found that the probability of bile duct clearance was over 90% for stones less than 1 cm diameter versus 68% for stones greater than 2.8 cm diameter.31 Garg and colleagues recently presented data on 87 patients with stones greater than 1.5 cm that required mechanical lithotripsy.32 They analyzed various predictive factors, including size and number of stones, stone impaction, serum bilirubin, presence of cholangitis, and bile duct diameter, in relation to the success or failure of lithotripsy. Impaction of the stones in the bile duct was found to be the only significant factor that predicted failure of mechanical lithotripsy and subsequent bile duct clearance. The composition of the stone also has been found to affect the success of stone removal. Soft stones, such as those found in Oriental cholangitis, are large but amenable to crushing, sometimes even with the Dormia basket.25 However, calcified stones are hard and resist mechanical crushing.

When mechanical lithotripsy fails, intraductal shock wave lithotripsy can be performed using a cholangioscope that is inserted into the bile duct through the instrument channel of the duodenoscope. A flexible lithotripsy probe then is passed into the bile duct through the working channel of the cholangioscope. Shock waves are generated at the tip of the lithotripsy probe using electrical (electrohydraulic lithotripsy) or light energy (laser lithotripsy).22 Impulses are fired on the surface of the stones under cholangioscopic guidance until the needed fragmentation is achieved. The main risk of intraductal shock wave therapy is bile duct injury resulting from a misguided shock wave. The avoidance of this complication makes cholangioscopic guidance necessary. Newer devices have a scattered light sensor located at the tip of the probe that allows automatic interruption of the laser pulse when tissue is detected. Nevertheless, the cost of intraductal shock wave lithotripsy and the requirement for two endoscopists experienced in the mother-baby scope system makes the availability of this technique limited to a few major referral centers.22 Success rates of electrohydraulic and laser lithotripsy have been in the 80–95% range.33 In a recent report by Arya and colleagues, the use of electrohydraulic lithotripsy was evaluated in 94 patients, with 81 having large stones and 13 having average-sized stones located above a narrow bile duct.34 A total of 96% had successful fragmentation of their stones, with fragmentation failure secondary to hard stones in two patients and trouble with targeting in two patients. Seventy-six percent of the patients required one treatment session, 14% needed two sessions, and 10% underwent three or more treatments. Complications included cholangitis and/or jaundice in 13 patients, hemobilia in one, mild post-ERCP pancreatitis in one, biliary leak in one, and bradycardia in one patient. No deaths were reported, and the final stone clearance achieved was 90%.

Not approved for bile duct stones in the United States, extracorporeal shock wave lithotripsy (ESWL) has gained popularity in Europe and Japan for the treatment of bile duct stones in patients with major medical comorbidities and technical difficulties encountered using the standard methods of endoscopic stone extraction. A drawback with this technique is the need for multiple sessions to achieve complete stone fragmentation.22 There have been several reports from various countries on ESWL to break down bile duct stones.33,35–41 Shackman and colleagues, from Germany, reviewed their experience with 313 patients who had failed endoscopic stone extraction with mechanical lithotripsy and subsequently underwent high energy extracorporeal shock wave lithotripsy.35 Stone targeting was performed by either fluoroscopy (99%) or ultrasonography. Using the technique, complete clearance of the bile duct was achieved in 90% of the patients, with 80% requiring fragment extraction by endoscopy after the shock wave therapy. Spontaneous passage, however, was observed in 10% of the patients. No difference in outcome was noted with regard to size or number of stones, intrahepatic or extrahepatic stone location, or presence or absence of bile duct strictures. Four cases of cholangitis and one case of acute cholecystitis were the rare adverse effects noted. Conversely, a study from Switzerland found that in their 54 patients treated with extracorporeal shock wave therapy for difficult bile duct stones, an intrahepatic location of stones was significantly associated with treatment failure.37 Interestingly, the study found microhematuria in 95% of the patients treated. In a randomized, prospective study to evaluate ESWL versus laser-induced shock wave lithotripsy for retained bile duct stones, laser therapy achieved stone disintegration more rapidly and with significantly fewer treatment sessions, resulting in a lower cost for therapy.39 Yasuda and colleagues, from Japan, presented the use of ESWL without preliminary endoscopic sphincterotomy for choledocholithiasis.42 Fifty-two patients underwent endoscopic nasobiliary tube insertion followed by extracorporeal therapy. Fragmentation and complete clearance of stones were achieved in 67% without the need for additional treatment. In 25%, fragmentation was not achieved, and endoscopic extraction was required. A favorable response to extracorporeal shock wave therapy was noted in patients with smaller (<1.5 cm) floating stones.

In addition to lithotripsy, large-balloon dilatation of the distal bile duct has been reported as a means of removing difficult bile duct stones after standard extraction has been unsuccessful.43 In a retrospective analysis, 58 patients who failed standard sphincterotomy and standard basket or balloon extraction underwent dilation with a 10–20-mm-diameter balloon (esophageal type) followed by standard basket or balloon extraction. The patients were divided into two groups: 18 patients with a tapered distal bile duct (group 1) and 40 patients with square, barrel-shaped, and/or large (>15 mm) stones (group 2). Stone clearance was successful in 89% of group 1 patients and 95% of group 2 patients. In the two patients in each group in whom extraction was not possible after dilatation alone, mechanical lithotripsy allowed for stone removal. Complication rates were 33% for group 1 and 7.5% for group 2. Complications included mild pancreatitis (two patients), mild cholangitis (two patients), and bleeding (five patients). Although bleeding was mild in two patients, moderate bleeding was noted in three patients in group 1 and was treated without surgery. Interestingly, hyperamylasemia was noted in all patients, and perforation was seen in none. Large-balloon dilatation offers an alternative in managing difficult bile duct stones, and further studies are needed to establish its role as compared with other lithotripsy options.

The management of complicated situations of choledocholithiasis may require several procedures or several sessions of the same procedure for successful clearance of the common bile duct. In such situations, partial stone impaction may lead to biliary stasis and cholangitis. Along with the administration of broad-spectrum antibiotics to cover gram-negative and gram-positive bacteria, it is important to decompress the biliary tree with either a nasobiliary catheter or a biliary stent as a temporizing measure pending more definitive treatment.22,25 By doing this, serum bilirubin levels are allowed to decrease, and the rate of postprocedure cholangitis becomes similar to that after stone clearance. Interestingly, up to 30% of patients in whom a stent has been left in place for large stones have spontaneous disintegration of the stones, as noted on subsequent ERCP.25 This may be secondary to the frictional movement of stone against the stent or as a result of improved bile flow with dissolution effects. Furthermore, by adding oral ursodeoxycholic acid to stent placement, 9 of 10 patients have been reported to become stone-free by this combination as compared with 0 of 40 with stent placement only.44 Although long-term stent placement is an unconventional management option for patients with large, inextricable stones who are at high risk for surgical intervention, this approach should be used with caution. In a long-term follow-up study of 58 elderly patients, 40% of patients treated with permanent stents for endoscopically irretrievable stones developed 34 complications in 23 patients, with cholangitis being the most frequent.45 At median follow-up of 36 months, 44 patients had died, 9 as a result of biliary-related causes. Hui and colleagues prospectively evaluated 36 high-risk patients with difficult common bile duct stones.46 Of these, 19 underwent stent placement, and 17 underwent complete stone clearance with electrohydraulic lithotripsy. The actuarial incidence of recurrent acute cholangitis was 8% in the lithotripsy group versus 63% in the stent group. The actuarial mortality also was higher in the stent group compared with the lithotripsy group, 74 and 41%, respectively.

Although ERCP has developed over the years as a relatively safe endoscopic diagnostic and therapeutic tool, there are well-defined, potentially severe, and life-threatening complications associated with it. The reported rates of complications vary widely in different studies, and this may be related in part to study design, with retrospective studies being prone to under-reporting. Furthermore, the complication rates may diverge depending on the patient mix in the study and may be influenced in part by the definitions used for these complications.19

The mortality rate after diagnostic ERCP is about 0.2%, and this rate is more than doubled by therapeutic interventions, to 0.5%.18,19 Cardiopulmonary complications are the leading cause of death and include cardiac arrhythmia, hypoventilation, and aspiration. These may be the result of premorbid conditions or related to medications used during sedation and analgesia. Other significant complications include perforations (0.3–0.6%), bleeding related primarily to sphincterotomy (0.8–2%), cholecystitis (0.2–0.5%), and cholangitis (1%). In a recent meta-analysis, prophylactic antibiotics were not found to be beneficial in reducing infectious complications of ERCP. Moreover, another study failed to show a decrease in the rate of cholangitis in patients with distal bile duct stones or biliary strictures receiving antibiotic prophylaxis.19

Pancreatitis is the most common complication seen after ERCP. The consensus definition for ERCP-induced pancreatitis is new or worsened abdominal pain, serum amylase that is greater than three times the upper limits of normal at 24 hours postprocedure and a requirement of at least 2 days of hospitalization. Although the transient elevation of serum pancreatic enzyme levels is frequent, based on the consensus definition of ERCP pancreatitis, the expected rate of this complication is typically between 1 and 7%. Risk factors associated with ERCP-induced pancreatitis include a prior history of ERCP pancreatitis, nondilated biliary ducts, normal bilirubin, young age, female gender, and suspected sphincter of Oddi dysfunction. In fact, the risk of pancreatitis in women with normal bilirubin and suspected sphincter of Oddi dysfunction is 18% compared with 1.1% for the low-risk patient.19,47 Moreover, one of five episodes of pancreatitis in this setting will be severe, requiring more than a 10-day hospital stay and/or resulting in necrosis, pseudocyst, or abscess formation needing surgery or percutaneous drainage, or death. Since the highest rate of complications appears to exist in the group of patients that is least likely to benefit from ERCP, the most effective method of reducing post-ERCP pancreatitis would be to avoid unnecessary ERCP.

Pharmacologic methods of pancreatitis prophylaxis have been attempted to reduce this complication after ERCP.19 Although meta-analyses have suggested that somatostatin and gabexate are useful in reducing pancreatitis rates, multicenter randomized, controlled trials have failed to show effect over that of placebo. Meanwhile, interleukin 10 (IL-10) with its anti-inflammatory activity has been found to have conflicting results in two controlled, prospective trials. The use of nonionic contrast agents has not reduced the rate of pancreatitis. On the other hand, glyceryl trinitrate (GTN) administered by both sublingual and transdermal routes has been shown to decrease post-ERCP pancreatitis in two placebo-controlled trials, supposedly by decreasing sphincter of Oddi pressure. Use of nitrates, however, is limited by their hypotensive effects.

The placement of pancreatic stents has been found to reduce the incidence of postbiliary sphincterotomy pancreatitis in patient suspected of sphincter of Oddi dysfunction. However, in a case-controlled evaluation of pancreatic stent placement after balloon dilatation of the major papillae for bile duct stone removal, a decreased postprocedure hyperamylasemia did not result in a decreased pancreatitis rate.19

Based on clinical, laboratory, and ultrasound criteria for common bile duct stones, up to 70% of patients may be found not to have duct stones at the time of preoperative ERCP.17,48,49 Given this, a large number of patients may be subjected to an unnecessary ERCP and suffer its risks and costs. Several methods have become available to diagnose the presence of bile duct stones accurately prior to having patients undergo ERCP or operative interventions. The most important of these are magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), and computed tomography (CT).

Sensitivities of conventional CT for choledocholithiasis in the setting of suspected bile duct stones is 76–90%, whereas unenhanced helical CT has been shown to have a sensitivity of 88%, a specificity of 97%, and an accuracy of 94%.18 When compared with ERCP as the reference standard, CT without biliary contrast material showed poor concordance with ERCP (sensitivity 65% and specificity 84%) but compared better when oral biliary contrast material was given (sensitivity and specificity greater than 90%).50 CT with intravenous (IV) biliary contrast material in other studies has been found to have a sensitivity of 71–85% and a specificity of 88–95%.50 Patel and colleagues reported a comparison between noncontrast-enhanced helical CT and the reference standard of EUS and found that CT had both a sensitivity and a specificity of 83% for the detection of common bile duct dilatation in the setting of choledocholithiasis.51 However, when CT was evaluated for identifying duct stones, it had a sensitivity of only 22% and a specificity of 83%.

Since its introduction over a decade ago, MRCP has significantly influenced the way in which CBD stones are detected and excluded. With sensitivities and specificities that approach those of ERCP, MRCP has emerged as a diagnostic alternative to ERCP for the detection and exclusion of choledocholithiasis.18 Performed with T2-weighted sequences, the biliary tract is seen as a bright structure with high-signal intensity without the use of contrast material, instrumentation, or ionizing radiation. Common duct stones are seen as low-signal-intensity filling defects surrounded by high-intensity bile. Improvements in hardware and software for MRCP over the past decade have resulted in the ability to image the entire biliary tract in a single breath-hold of 20 seconds with a resolution that allows visualization of fourth-order intrahepatic bile ducts and small stones. Stones as small as 2 mm can be detected even in the absence of biliary dilatation.18 In one study of 97 patients, sensitivity of MRCP was 100% for stone diameters of 11–27 mm, 89% for stone diameters of 6–10 mm, and 71% for stone diameters of 3–5 mm.47 In this study, MRCP had a 91% sensitivity compared with 100% for ERCP, whereas both tests had a specificity of 100%. Although earlier studies reported MRCP sensitivities ranging from 81 to 92% and specificities from 91 to 100% for choledocholithiasis, recent studies with state-of-the-art techniques have found sensitivities of 90–100% with specificities of 92–100%.18 In a prospective analysis by Ke and colleagues, 267 patients felt to have CBD stones were evaluated by MRCP and ERCP.52 MRCP was found to have a sensitivity of 100%, a specificity of 96%, and a NPV of 100%. Kejriwal and colleagues retrospectively examined patients with cholelithiasis who underwent MRCP for suspected choledocholithiasis.53 Patients were considered not to have clinically relevant common duct stones if they had a negative MRCP and did not present for readmission for choledocholithiasis after treatment of their cholelithiasis. MRCP was negative for bile duct stones in 74% of patients (60 of 81) and missed clinically relevant stones in two patients, resulting in a PPV of 95% and a NPV of 97%. With its ability to exclude bile duct stones, MRCP may allow the avoidance of unnecessary diagnostic ERCP. Demertines and colleagues found that even in patients with high and moderate risk of common bile duct stones based on laboratory findings, the performance of MRCP could have resulted in the avoidance of ERCP in 52 and 80% of patients, respectively.54

One of the limitations of MRCP is that its resolution remains less than that of ERCP, and therefore, it cannot detect small stones and crystals consistently. Claustrophobia also may influence the use of MRCP, and patients may need sedation or even general anesthesia for its performance. Open magnetic resonance imaging (MRI) may soon alleviate this problem. Patient obesity may diminish the quality of images, whereas morbid obesity, pacemakers, and aneurysm clips preclude entry into the scanner.18 Conversely, ERCP may be limited by an inability to access and cannulate the papilla and opacify the ductal system. Failed ERCP rates vary greatly among endoscopists and vary from 5 to 20%.18 Moreover, alterations in the gastrointestinal tract anatomy, such as a Billroth II gastrojejunostomy, may preclude access to the ampulla. MRCP offers a method of evaluating the biliary system for bile duct stones with sensitivities and specificities that approach those of ERCP in a manner that is noninvasive and avoids the risks and limitations of ERCP. Patients with a positive MRCP then may be considered for more invasive therapeutic procedures.

Another sensitive method of evaluating the biliary system for common bile duct stones is EUS. EUS has been shown to have a diagnostic accuracy of 95% for bile duct stones.55 With the high ultrasound frequencies used (7.5 and 12 MHz), EUS has a resolution of less than 1 mm, making it the best imaging technique available for the extrahepatic biliary tract. Several studies have found EUS to be similar to ERCP in sensitivity and specificity for the evaluation of choledocholithiasis, with some showing ERCP to be better and others showing EUS to be better.50 Compared with ERCP, EUS is semi-invasive with almost no procedure-related complications and a negligible failure rate. In fact, several series comprising over 1000 patients have reported no complications.55 In a prospective study by Buscarini and colleagues, 485 patients suspected to have choledocholithiasis based on clinical, laboratory, and ultrasound, or CT findings underwent EUS.55 Positive EUS findings were confirmed by surgery or ERCP with sphincterotomy; negative findings were confirmed by clinical follow-up of at least 6 months. EUS findings were verified in 463 patients as follows: 237 true positive, 216 true negative, 2 false positives, and 4 false negatives, and in 4 patients EUS was incomplete (sensitivity 98%, specificity 99%, PPV 99%, NPV 98%, accuracy 97%). No complications were noted in the study. EUS offers higher resolution than MRCP and therefore is better able to detect small stones. It is able to identify bile duct stones as well as microlithiasis and is able to detect pathology that is not seen by ERCP. EUS prior to performing invasive diagnostic or therapeutic techniques would lower the rate of procedure-related complications in patients suspected of having bile duct stones. Cost analysis of EUS followed by ERCP versus ERCP alone is also in favor of EUS as a pretherapeutic procedure.55

In patients for whom ERCP is not available, not possible secondary to anatomic considerations, or not successful, an alternative method of cholangiography and nonsurgical therapy is percutaneous transhepatic cholangiography (PTC) followed by transhepatic methods of stone removal. A needle is introduced into the intrahepatic bile ducts through the skin, and a cholangiogram is performed, followed by wire insertion and then a catheter over the wire for external biliary drainage and access to the biliary system. The method was introduced in Denmark in the 1970s and has been refined over the years with the addition of several therapeutic options.56 This technique is particularly useful for evaluating intrahepatic stones or other proximal bile duct disease. After diagnosis of bile duct stones, several therapeutic options are available through the percutaneous route. In 1981, the removal of an 8-mm common bile duct stone by percutaneous transhepatic technique was reported by Fernstrom and colleagues.57 In 1990, Stokes and colleagues, from Boston, reported a series of 53 patients in whom surgery was contraindicated and ERCP unsuccessful.58 By inserting a modified Dormia basket via a percutaneous transhepatic route, stones were advanced whole or after fragmentation into the duodenum. Mono-octanoin or MTBE were used in 30 patients to reduce stone size or remove debris. Morbidity and mortality were 12 and 4%, with a success rate of 93%. Transhepatic cholangioscopy and lithotripsy can be performed after PTC and dilatation of the intrahepatic channel with success rates of 90–100% and 5–8% complications.59 In a series of 12 patients with bile duct stones, PTC in combination with laser or electrohydraulic lithotripsy to deliver stone fragments into the duodenum was found to be successful in all the patients.60 In another series of 13 patients, laser lithotripsy was used with percutaneous cholangioscopy performed either transhepatic (12 patients) or through the T-tube track.61 Stone fragmentation was successful in 92%, and stone clearance was possible in all patients. However, 11 patients required the addition of sphincterotomy (either by ERCP or by antegrade method with fluoroscopic monitoring) or stent insertion. Bleeding in two patients accounted for a 15% severe complication rate. Percutaneous transhepatic papillary balloon dilatation was reported recently by a Japanese group for the management of choledocholithiasis.62 In the five patients in whom the method was used, bile duct stones were able to be pushed into the duodenum in all, with no complications or deaths. Ponchon and colleagues reported percutaneous choledochoscopy for stone extraction in 75 patients, with the transhepatic route used in 48 patients and T-tube tract used in 27 patients.63 Complete clearance of bile duct stones was accomplished in 69 patients (92%).

Role of Cholecystectomy Following Cbd Stone Extraction.

After bile duct clearance is achieved by nonoperative methods, cholecystectomy generally is recommended in younger patients to decrease the risk of future cholecystitis and recurrent biliary colic. As many as 24% of patients have been found to require cholecystectomy at follow-up after endoscopic papillotomy at an average of 14 months.64 Others have argued that sphincterotomy results in gallbladder stasis, bacterial overgrowth, and an increase in bile acids, and these may increase the risk of gallbladder cancer in 10–20 years.2 On the other hand, Dhiman and colleagues studied the changes in gallbladder emptying and lithogenicity of bile following endoscopic sphincterotomy in patients with choledocholithiasis and gallbladder in situ.65 Sphincterotomy was found to decrease stasis of gallbladder bile, improve gallbladder emptying, and decrease the lithogenicity of bile as measured by prolongation of nucleation time. Meanwhile, there is much evidence to support leaving the gallbladder in situ after bile duct clearance in high-risk or elderly patients.66–75 In a study of 191 patients (median age 76 years) in whom the gallbladder was left in situ post-ERCP, only 10 patients (5%) required subsequent uneventful cholecystectomy.69 Twenty-six percent (49 patients) died during the review period from nonbiliary pathology. Kwon and colleagues followed 146 patients without elective cholecystectomy after endoscopic CBD stone removal for a period of 3 months or more to see if they could identify factors that predict subsequent gallbladder-related symptoms and need of cholecystectomy.71 Fifty-nine patients had cholelithiasis, whereas 87 patients had no gallbladder stones. During a mean follow-up of 24 months, seven patients (5%) underwent cholecystectomy, on average, 18 months after ERCP as a result of acute cholecystitis (four patients), biliary pain (two patients), and acute pancreatitis (one patient). Nine patients (6%) died of causes unrelated to biliary disease. Interestingly, Cox regression analysis revealed that the need for subsequent cholecystectomy did not correlate with age, sex, presence of gallbladder stones, number of gallbladder stones, or underlying disease. Kullman and colleagues found that at a median observation time of 42 months, cholecystectomy was needed in 11% (13 patients) of 118 patients with a gallbladder in situ after ERCP bile duct clearance.72 Forty-nine patients (42%) died within 2–87 months after ERCP during the follow-up period. In another study of 33 elderly patients who were followed for an average of 42 months with gallbladder in situ after successful ERCP for choledocholithiasis, 3% (one patient) required cholecystectomy for acute cholecystitis, and 6% (two patients) had mild right upper quadrant pain, whereas 91% remained asymptomatic.73 Over the course of the study, 30% of the patients died from nonbiliary causes. The impact of gallbladder status on patient outcome after ESWL for complicated CBD stones was studied by a German group.70 One-hundred twenty patients with an average age of 68 years (range 28–86 years) were followed for 3–9 years (mean 4 years). Thirty-seven had their gallbladder in situ, 27 had had a cholecystectomy after ESWL, and 56 had already undergone cholecystectomy prior to diagnosis of choledocholithiasis. During the follow-up period, 30% (36 patients) experienced biliary symptoms. However, there was no significant difference in the incidence of these symptoms between the three groups. Repeat ERCP revealed 28 cases of recurrent bile duct stones. Although not reaching statistical significance (p = .077), the recurrences occurred more often in the cholecystectomy groups. Given the multiple studies supporting leaving the gallbladder in situ after CBD clearance, it seems reasonable to perform cholecystectomies on high risk or elderly patients as needed rather than prophylactically following nonoperative treatment of bile duct stones.

Intraoperative

When patients present to the operating room for cholecystectomy, they may either have CBD stones confirmed by preoperative studies (eg, ERCP, MRCP, or EUS), or they are suspected to have CBD stones by clinical presentation, laboratory values, or transabdominal ultrasound, or they have no suspicion of bile duct stones. At the time of surgery, intraoperative cholangiography (IOC) is the method used most often to establish the presence of bile duct stones. IOC was first introduced to open biliary surgery by Mirizzi in the 1930s.76 With the universal acceptance of laparoscopic cholecystectomy as the treatment of choice for symptomatic gallbladder stones, laparoscopic IOC has developed into a very useful method to evaluate the biliary tree. The technique may be performed by injecting contrast material through a catheter introduced into the cystic duct via a variety of techniques.78 14-gauge IV catheter placed through the abdominal wall 3 cm medial to the midclavicular port.77 Cannulation rates with successful cholangiography are from 75 to 100%, and the use of fluoroscopy has become standard because it is faster, more detailed, and allows real-time surgeon interaction.77,78 The reported sensitivity, specificity, PPV, NPV, and accuracy for laparoscopic cholangiography are 80–90%, 76–97%, 67–90%, 90–98%, and 95%, respectively, and these are comparable with the values for open IOC.76 The rate of false-positive IOC results in a recent large review was found to be 0.8% (34 of 4209 patients).

Although approximately 10–15% of patients undergoing laparoscopic cholecystectomy harbor CBD stones, the need for routine IOC is a matter of much debate.79 In a large Medline literature review, Metcalfe and colleagues found a 4% rate of CBD stones in eight laparoscopic cholecystectomy trials in which routine IOC was performed on 4209 patients without suspected bile duct stones preoperatively.78 This finding was felt to be consistent with previous reviews. On the other hand, in a total of 5179 patients without suspicion for bile duct stones that did not undergo IOC during laparoscopic cholecystectomy, 32 (0.6%) proceeded to develop symptoms from residual bile duct stones. By extrapolating this data, it would seem that of the 4% of patients with silent CBD stones at laparoscopic cholecystectomy, only 15% go on to develop symptoms from retained stones. In other words, 167 IOCs would have to be performed during laparoscopic cholecystectomy in order to detect one CBD stone that would go on to cause symptoms in patients without preoperative evidence of duct stones. This would result in eight unnecessary bile duct explorations or ERCPs.78 It is possible that stones that are not manifested preoperatively are of the size that can pass spontaneously into the duodenum, never presenting with symptoms.

Intraoperative ultrasound (IOUS) is a noninvasive way to evaluate the biliary system at the time of surgery. First introduced in the mid-1980s in the time of open cholecystectomy, laparoscopic IOUS came into use in the mid-1990s.76 Recent experience with laparoscopic IOUS has suggested that it is a very sensitive test for CBD stones and roughly equivalent to IOC in evaluating the biliary ductal system. Moreover, it lacks the potential of common bile duct injury that exists with placement of the cholangiography catheter during IOC and will not cause a false-positive test owing to air introduced into the biliary tree.78 The use of laparoscopic IOUS has been limited, however, possibly secondary to equipment availability and cost, as well as the expertise and experience required for its use. There appears to be a considerable learning curve associated with the use of laparoscopic IOUS.80,81

Once the presence of CBD stones has been established at the time of surgery, there are several treatment options. Depending on local availability and expertise, these may include open or laparoscopic duct exploration and postcholecystectomy nonoperative techniques such as ERCP or PTC. However, before embarking on a means of eradicating the biliary tree of stones, it is worth remembering that only 15% of patients with silent bile duct stones at the time of cholecystectomy present with symptoms of retained stones.78 The natural history of choledocholithiasis was revisited in a recent prospective study by Collins and colleagues.82 Operative cholangiography was attempted in 997 patients undergoing laparoscopic cholecystectomy and was successful in 962 patients. Patients with cholangiogram-positive stones were restudied in 48 and 72 hours and 6 weeks after laparoscopic cholecystectomy through a cystic duct cholangiocatheter left in the cystic duct at the time of surgery. Of the 962 patients, 46 (4.6%) had at least one filling defect, but 12 had normal cholangiograms 48 hours later, giving a 26% possible false-positive cholangiogram rate. At 6 weeks, a further 12 patients had a normal cholangiogram, giving a 26% spontaneous passage rate of bile duct stones. This spontaneous passage was not predictable by either the number or size of stones or the diameter of the bile duct. Only 2.2% of the total population (22 patients) required postoperative endoscopic retrograde cholangiopancreatographic retrieval of persistent common duct calculi. Thus a treatment decision based on the findings of IOC alone would have resulted in 52% of patients with positive findings undergoing unnecessary intervention.

The first surgical exploration of the CBD was done in 1890 by Ludwig Courvoisier, a Swiss surgeon who made an incision in the CBD and removed a gallstone.77,83 Prior to the development of laparoscopic cholecystectomy, patients found to have bile duct stones at surgery underwent open CBD exploration with greater than 90% successful duct clearance. ERCP was used for retained stones postoperatively or for patients who would not be able to tolerate extended general anesthesia. At the time of open cholecystectomy, the common duct is opened in the longitudinal direction so as to not compromise the blood supply to the duct. The bile duct is cleared of stones with the use of Fogarty balloons, saline irrigation, stone forceps, and scoops placed into the biliary tract through the opening. Choledochoscopy is particularly useful in evaluating the duct system during and after the clearance of residual stones and in making sure that there is no other ductal pathology. Moreover, a basket can be passed through the working channel of the scope and used under direct vision for stone removal. Although used commonly in the management of CBD stones in the era of open cholecystectomy, open bile duct exploration is used infrequently in the present age of minimally invasive surgery. In a recent series of 326 patients who underwent laparoscopic common bile duct exploration (LCBDE) for choledocholithiasis at the time of cholecystectomy, only five patients were converted to laparotomy and only two for open bile duct exploration and stone extraction.77

Over a hundred years after Langenbuch performed the first open cholecystectomy in 1882, laparoscopic cholecystectomy was introduced and soon became the standard treatment of cholecystitis and symptomatic gallstones.77,83 In the early years after the development of laparoscopic cholecystectomy, LCBDE was used infrequently, and reliance on alternative methods of duct clearance was widespread.77 With increasing experience in laparoscopic techniques and the demand for single-procedure minimally invasive duct clearance, the use of LCBDE gained greater acceptance among experienced biliary surgeons. Since the development of the technique, thousands of successful LCBDEs have been reported in the literature, and success rates of duct clearance are between 80 and 90%, comparable with the open method of bile duct exploration.76 The morbidities range from 8 to 10% and are typical of laparoscopic procedures, including nausea, diarrhea, ileus, atelectasis, phlebitis, urinary retention and infection, biliary leak, dislodgement of the T-tube, fluid collections, pulmonary embolus, and myocardial infarctions. Reported mortalities are from 0 to 2%.

The technique of LCBDE has been well described by Petelin.76,77 Access to the biliary system, after obtaining a cholangiogram, can be either transcystic or transductal using a choledochotomy. Use of the transcystic approach varies from 5 to 98% depending on the series. With this method, the gallbladder is retracted toward the right hemidiaphragm, and if needed, the cystic duct is dilated with either over-the-wire mechanical or pneumatic dilators. The transductal approach is favored for stones greater than 6 mm in diameter, intrahepatic stones, cystic duct diameter less than 4 mm, and cystic duct entrance either posterior or distal. When using the transductal method, a choledochotomy is made on the anterior surface of the CBD with a scissors or scalpel and is limited to 1 cm or the size of the largest stone.

Once the biliary tree has been accessed, choledocholithotomy is performed using several different techniques and is guided by either fluoroscopy or choledochoscopy. Although separate monitors may be used with a choledochoscope, the use of a video mixer to place the laparoscopic and choledochoscopic images on the same screen is helpful. Newer choledochoscopes with 3 mm diameters even can be passed through the cystic duct. Common bile duct clearance is started with irrigation, which allows the flushing of small, less than 3-mm stones and sludge. The administration of 1–2 mg IV glucagon allows relaxation of the sphincter of Oddi and facilitates the irrigation process. Fogarty-type balloons (4F) then can be inserted into the bile duct for retrograde extraction of stones with withdrawal of the inflated balloon. Stones also may be captured with a Dormia-type basket inserted directly through the cystic duct or choledochotomy or through the working port of the choledochoscope. Intraoperative electrohydraulic or laser lithotripsy is useful for large stones or stones that are impacted and not responsive to other methods. Care is needed, however, to avoid injury to the duct by inaccurate application of the lithotripsy device.

If a choledochotomy is used to perform the LCBDE, a T-tube may be left in place for later study of the biliary system, decompression if the biliary tree was not cleared, or access to the biliary system for recurrent stones. On the other hand, laparoscopic suturing with 4-0 or 5-0 Vicryl can be done instead to close the choledochotomy primarily. A recent study found that hospital stay was shorter in a group of patients who underwent primary closure versus placement of a T-tube (5 vs 9 days).84 There does not appear to be an increase in the incidence of bile leak or peritonitis in patients undergoing primary closure.77 This further abrogates the complications of T-tubes, including dislodgement, bacteremia, fracture of the tube, and the possibility of bile leak and peritonitis at the time of T-tube removal. An alternative to T-tube placement is a stent placed in an antegrade fashion into the duct similar to an ERCP-placed stent.85 An alternative to a T-tube is a modified ureteral catheter placed through the cystic duct and brought out through the abdomen after closure of the choledochotomy.86 In a study of 30 patients undergoing placement of this modified catheter, no complications related to the catheter were found, and removal was possible at a median of 5 days as compared with 29 days when a T-tube was used.

If LCBDE is unsuccessful, a transcystic catheter may be inserted through the abdominal wall to decompress the biliary system and allow for postoperative cholangiography. If the catheter is further advanced into the duodenum, it can aid in bile duct cannulation at the time of postoperative ERCP.76 In addition to treating bile duct stones postoperatively following an incomplete laparoscopic duct clearance, the option of converting to an open duct exploration is also available to the operating surgeon.

There are several alternatives to laparoscopic or open duct exploration for bile duct stones encountered at the time of surgery. At the time of cholecystectomy, a transcystic stent may be placed over a wire antegrade through the sphincter of Oddi as initial treatment.87 This allows for decompression of the biliary tree and can be followed postoperatively by ERCP and sphincterotomy with stent removal. Another option is the use of intraoperative ERCP (IO-ERCP), allowing the same anesthetic to be used for both the cholecystectomy and the ERCP.88–90 In one Swedish study by Enochsson and colleagues, 592 patients underwent IOC during laparoscopic cholecystectomy.90 Thirty-four of these were subjected to IO-ERCP with a 100% common bile duct cannulation rate. This was assisted by the fact that the surgeon, while waiting for the endoscopist, introduced a thin guidewire into the IOC catheter and through the sphincter of Oddi into the duodenum. Bile duct clearance was possible in 94%, and a stent was left in place in the two patients with remaining stones. Operative time was prolonged by 1.5 hours as compared with laparoscopic cholecystectomy, but the length of hospitalization was not significantly longer for IO-ERCP patients. There were no cases of postoperative pancreatitis. In a French report by Meyer and colleagues, 60 patients were treated with laparoscopic cholecystectomy and IO-ERCP for confirmed or suspected CBD stones.89 The mean operative time for laparoscopic cholecystectomy was 60 minutes (range 40–90 minutes), and general anesthesia was prolonged only 40 minutes (range 30–60 minutes) for performing the IO-ERCP, including the time needed for setting up the endoscopic equipment. The papilla could not be catheterized in two patients. In one, postoperative ERCP was possible, and in the second patient, a small stone passed spontaneously. In one patient, secondary to multiple calculi in CBD, open surgery was performed immediately after IO-ERCP. Final duct clearance was achieved in 100% of patients. The argument for using IO-ERCP versus postoperative ERCP is that the former allows the identification of anatomic problems (such as duodenal diverticulum) that could make later ERCP unsuccessful. Thus the surgeon has the option to convert to open bile duct exploration at the same anesthetic.88 If one chooses to use IO-ERCP, performing the cholecystectomy prior to the ERCP is important because this avoids endoscopy-induced small bowel distension from interfering with gallbladder visualization. Moreover, transcystic IOC at the time of cholecystectomy may avoid unnecessary ERCP if no stones are visualized by the cholangiogram.

Postoperative

Patients presenting with CBD stones after cholecystectomy generally are treated with ERCP77 (Fig. 49-3). The noninvasive imaging techniques, such as ultrasound and MRI, are not different from those used preoperatively. If a T-tube (or other transabdominal drainage catheter) had been left in place at prior surgery, a cholangiogram can be obtained after surgery to establish the presence of bile duct stones. In situations in which ERCP is not possible or successful, other nonoperative methods can be used. For patients with T-tubes, percutaneous instrumentation under fluoroscopic guidance through the T-tube tract can be used to remove bile duct stones. In one report, 23 of 25 patients underwent successful duct clearance through the T-tube tract for retained stones.91 A choledochoscope also may be inserted through the T-tube tract to allow for either laser or electrohydraulic lithotripsy and stone extractions.63 Other percutaneous transhepatic options described in the preoperative section of this chapter also may be used. Combinations and repeated techniques may be needed to achieve duct clearance. In the rare incidences where the biliary system cannot be cleared of stones nonoperatively, surgical duct exploration is considered, and the need for surgical drainage procedures must be addressed.

Surgical Biliary Drainage Procedures

Surgical biliary drainage procedures must be considered in situations of multiple stones; incomplete removal of all stones; impacted, irremovable distal bile duct stones; markedly dilated CBD; distal bile duct obstruction from tumor or stricture; and reoccurrence after previous bile duct exploration. The methods of surgical drainage include transduodenal sphincteroplasty, choledochoduodenotomy, and choledochojejunostomy (CDJ).

Transduodenal sphincteroplasty (TDS) is useful in the management of choledocholithiasis when there is stone impaction in the ampulla of Vater, papillary stenosis, and multiple stones, particularly in the presence of a nondilated bile duct.92–94 The duodenum is kocherized completely, and the ampulla is located by passing a biliary Fogarty catheter through the CBD into the duodenum. A longitudinal duodenotomy is made over the ampulla, and the entrance to the pancreatic duct is identified at the 4 o'clock position when possible. Intravenous secretin given at 0.2 g/kg over 1 minute sometimes is helpful in this identification. Absorbable sutures are placed on each side of the ampulla, and the sphincteroplasty is started at 11 o'clock and extended with sequential placement of sutures along the incision. After the opening is wide enough to fit a biliary dilator the size of the common duct, the last ampullary suture is placed at the apex to prevent a duodenal leak. The duodenotomy then is closed in the transverse direction to prevent duodenal stenosis, and a drain is left in the event that the duodenotomy leaks.

In a French review by Suter and colleagues, of the 78 patients who underwent transduodenal sphincterotomy, 26 were operated on urgently.94 Forty-seven (60%) were jaundiced, 15 (19%) had pancreatitis, and 12 (15%) had cholangitis before surgery. Three patients died, one from pulmonary embolism, one from pulmonary sepsis, and the other from multiorgan failure syndrome complicating preoperative necrotizing pancreatitis. Of the 30 patients (38%) with complications, 20 were directly related to the surgery and included 4 cases of bleeding not requiring transfusion, 17 instances of hyperamylasemia with 1 case of clinical pancreatitis, and 1 case of duodenal fistula that healed after conservative therapy. No deaths were noted that were directly attributable to the TDS. In an older review by Meyhoff, a 10% postoperative mortality was noted after TDS, with four patients developing fatal pancreatitis.92

Choledochoduodenostomy (CDD) was first performed by Riedel in 1888 in Europe.95 Unfortunately, the patient died of anastomotic disruption secondary to a missed stone in the distal CBD. The first successful operation was performed by Sprengel in 1891. CDD is indicated in patients with recurrent stones requiring repeated interventions, impacted or giant stones, biliary sludge, and ampullary stenosis. The funnel syndrome in which a distal bile duct stenosis exists in the presence of CBD stones is one of the most classic indications for CDD.95 Most of the CBD stones in this situation are primary biliary stones forming as a result of biliary stasis. Any procedure done to remove only the stones has a temporary benefit if the stenosis is not addressed.

CDD can be performed either as an elective or an emergency operation, such as for cholangitis. The side-to-side anastomosis is the most commonly used technique, but an end-to-side is also an option. A CBD diameter of at least 1.2 cm is important in assessing the feasibility of CDD because this allows a wide enough stoma to ensure good biliary drainage and avert stenosis. The anastomosis is created in the most distal portion of the bile duct to decrease the chance of the well-described sump syndrome.95 After opening the abdomen, the duodenum is kocherized widely to allow for a tension-free anastomosis, and the CBD is dissected completely along its distal anterior surface. A longitudinal duodenotomy is made close to the bile duct along the long axis of the duodenum, perpendicular to the choledochotomy. The CBD incision is made along the long axis of the bile duct as close to the duodenum as possible and of a 2 cm length to prevent stenosis. After performing a CBD exploration and clearing the duct of stones, a side-to-side single-layered anastomosis is made with absorbable suture, and a drain is placed for the possibility of an anastomotic leakage.

The morbidity and mortality rates associated with CDD are 23 and 3%, respectively.95 Mortality is most commonly from medical complications, such as pulmonary embolism, myocardial infarction (MI), or heart failure. Among the specific operative morbidities, cholangitis and sump syndrome are described most commonly.

The incidence of cholangitis ranges from 0 to 6% in the largest long-term follow-up series.95 Although once thought to be caused by ascending reflux of duodenal contents into the biliary tree, cholangitis is now believed to be the result of stenosis of the anastomotic stoma. A wide anastomosis avoids stasis and stone retention by allowing entrance and egression of duodenal and biliary contents. Sump syndrome is caused by food and debris accumulating between the stoma and the papilla of Vater. This leads to contamination of the large and small bile ducts with resulting recurrent cholangitis and even secondary biliary cirrhosis.95 Although the accumulation of debris in the blind segment of the bile duct may cause destruction of the stoma or cholangitis, some believe that the disease is caused by stenosis of the stoma. To avoid the problem, creating a stoma of at least 14 mm, along with placing the anastomosis near the duodenum, is important. Stomal patency is felt to be the most important factor for preventing both cholangitis and sump syndrome.96 Other complications of CDD include wound infection, anastomotic leak, and intra-abdominal abscess. Long-term studies reveal that 70–80% of patients are asymptomatic 5 years after surgery.95 In a review of 126 patients undergoing CDD after CBD exploration over a period of 19 years, Deutsch and colleagues reported a 4% mortality rate, with all deaths occurring in patients over 70 years old.97 Morbidity included wound infections in 18 patients (14%) and bile leak through a drain for over 2 weeks in 4 patients (3%). Ninety-seven patients (94%) were symptom-free at a follow-up of 1–19 years.

Rameriz and colleagues reported their experience with CDD and transduodenal sphincterotomy for the treatment of choledocholithiasis over a period of 10 years.98 Of the 591 patients who underwent choledochotomy for bile duct stones, 240 (40.6%) were treated with primary closure over a T-tube, 126 (21.3%) received primary closure over a T-tube along with a TDS, 216 (36.5%) had a supraduodenal CDD, and 9 (1.5%) had both a CDD and a TDS. CDD was performed when the bile duct was more than 12 mm in diameter, and TDS was used if a stone was impacted in the papilla and/or papillary stenosis was noted. Complications included six abdominal abscesses and three external biliary fistulas in the patients undergoing CDD and four abscesses and two episodes of acute pancreatitis in the patients treated with TDS. There was no difference in mortality between the two groups, and after a mean follow-up of 5.6 years, 71.5% of the CDD group and 75.2% of the TDS group were asymptomatic. Symptoms noted in the remainder included dyspepsia, colicky pain, and episodes of cholangitis and resulted in reoperations for residual stones in nine patients, six from the CDD group and three from the TDS group. The same authors previously reported that of the patients who presented with symptoms after CDD and underwent endoscopy, no problems at the anastomosis were noted in patients who presented with dyspepsia, whereas 27% of those with biliary colic had an anastomotic stenosis or sump syndrome, and all the patients with cholangitis had stenosis and residual stones.99 On the other hand, in a comparison of 190 patients with CDD and 56 patients with TDS over a period of 10 years, Baker and colleagues found an overall mortality of approximately 5% in both groups.93 The morbidity rates were 11.6% for CDD and 21.4% for TDS. With a mean follow-up of 4.5 years, six patients (3.3%) in the CDD group presented with sump syndrome, cholangitis or both and three patients (5.7%) in the TDS group had cholangitis. In another report by the same authors, an elevated serum alkaline phosphatase level was noted in 22% of CDD patients and 3% of the TDS patients, whereas radiological studies showed that the CDD stoma admitted air and barium more often than the TDS stoma.100 Interestingly, neither the biochemical nor the radiological findings correlated with long-term symptomatic results after the two procedures.

An alternative to CDD is CDJ, which can be performed with either a loop of jejunum or using a Roux-en-Y configuration. If a loop is used, a side-to-side jejunojejunostomy is used to divert the flow of intestinal contents from the biliary tree. The Roux-en-Y usually is brought retrocolic using a 60-cm afferent limb to protect against intestinal reflux and secondary cholangitis. In either case, an end-to-side CDJ is created using fine absorbable suture. The anastomosis can be decompressed using a T-tube if the remaining bile duct is long enough to allow one, or a transhepatic stent can be used if the remaining bile duct is short. As in the other methods of surgical drainage, a drain is left in place to guard against possible anastomotic leakage.

Gouma and colleagues reported their experience with 43 patients undergoing Roux-en-Y CDJ after complex clearance of the biliary tree for choledocholithiasis.101 There were no mortalities and only one major complication. Moreover, 98% of the patients had good long-term results with no signs or symptoms related to biliary obstruction or cholangitis. A comparison of CDD and CDJ for choledocholithiasis was evaluated by a French group.102 One-hundred and thirty patients were included, of which 64 underwent CDD and 66 had a CDJ. No difference in morbidity or mortality was noted between the two groups. Of the 120 patients (58 CDD and 62 CDJ) available for a mean follow-up of 29 months, 107 were symptom-free, 13 patients (6 CDD and 7 CDJ) experienced biliary symptoms suggestive of cholangitis, 8 presented in the first postoperative year, and 5 presented in the second postoperative year. In the CDD group, the cholangitis was secondary to sump syndrome (three patients), anastomotic stricture (one patient), or unknown causes (two patients). Anastomotic strictures (three patient), residual intrahepatic stones (one patient), or unknown causes (three patients) were felt to be the cause of cholangitis in the CDJ group. The authors concluded that CDD is preferable given the similar outcomes because it is easier and faster to perform than CCJ and allows for easy endoscopic interventions if needed in the future. However, often the choice between the two operations is dictated by the anatomy and feasibility of creating a tension-free anastomosis.103

One controversy in performing biliary anastomoses is the use of biliary stents. Earlier studies have argued that stents allow for decompression of the bile duct and decreased risk of bile leak, postoperative radiographic evaluation of the biliary tree, and reduced fibrotic narrowing of the anastomosis during early healing.104 Pitt and colleagues noted a higher success rate with the anastomosis stented for more than 1 month compared with those stented for less than 1 month or not stented at all.105 Others also have noted good results with the use of stents.106,107 However, Bismuth and colleagues showed that excellent results could be obtained in 86% of 123 patients undergoing stentless hepaticojejunostomy for benign biliary disorders.108 Pellegrini and colleagues found that stenting for more than 1 month postoperatively resulted in outcomes no different from anastomoses done without stents.109 The argument has been raised that stents cause an inflammatory reaction that may predispose to stenosis. DiFronzo and colleagues found that of the 97 patients having either a CDD (77%), CDJ (8%), hepaticoduodenostomy (1%), or hepaticojejunostomy (13%) without the use of stents, only one patient developed an anastomotic leak that resolved spontaneously within 1 week.104 In the mean follow-up period of 13 months, no postoperative strictures were noted. Meanwhile, Tocchi and colleagues presented their data on performing hepaticojejunostomy (48 patients), CDJ (34 patients), and intrahepatic cholangiojejunostomy (8 patients) without stents in 84 patients over a period of 15 years for benign biliary strictures.110 Excellent or good results were obtained in 83% of the patients. Anastomotic strictures occurred in 10 patients, 6 within 5 years and 4 at 62, 75, 85, and 96 months. By multivariate analysis, only postoperative complications and the degree of CBD dilatation proved to be significant independent predictors of outcome. A bile duct dilatation of less than 15 mm was noted in 60% of patients with poor outcome. Although not reaching statistical significance, higher complications and restructures were noted in patients having a CDJ versus hepaticojejunostomy, and the authors changed their practice to performing only higher anastomosis during the study period for even low strictures. Peptic ulcers were noted in only 2.3% of the patients in the entire series, which is not higher than the normal population and does not appear to be related to diverting the flow of bile from the duodenum, as others have suggest.

Laparoscopic approaches to both Roux-en-Y CDJ and CDD have been reported recently. Jeyapalam and colleagues reported six patients who underwent laparoscopic choledochoduodenostomy (LCDD).111 While one patient died of comorbidity, the liver laboratory values returned to normal in all the remaining patients, and the average length of postoperative stay was 6 days. Tang and colleagues selected 12 patients to undergo LCDD for recurrent pyogenic cholangitis.112 A successful laparoscopic approach was used in all cases, with a mean operating time of 6 hours and a median postoperative length of stay of 7.5 days. One postoperative bile leak was noted and managed conservatively, whereas no patients developed cholangitis or sump syndrome at a mean follow-up of 38 months. Han and colleagues presented similar results in performing laparoscopic Roux-en-Y CDJ for benign disease.113 One episode of melena that resolved spontaneously was the only postoperative complication in six patients who underwent the surgery. All patients were symptom-free at a 27-month follow up. Despite the proliferation of robotic-assisted surgery, its application to biliary surgery has remained rather limited. The literature thus far includes only two separate case reports. One report describes robotic-assisted CBD exploration.114 The other report describes a robotic CDJ with an intracorporeal Roux limb construction.115 The use of minimally invasive surgical drainage procedures is likely to become more widely used as experience increases and technology improves.

Summary

The evaluation and treatment of choledocholithiasis has evolved over the last 100 years. As newer and less invasive techniques emerge, the surgeons will find a variety of options and many paths that can lead to the successful treatment of a patient with CBD stones. Evaluation and diagnosis may involve an examination and simple laboratory tests or evaluation of the biliary tree with MRCP, ERCP, or an IOC. Treatment may be endoscopic, percutaneous, open, or laparoscopic. Given the multiple alternatives available, sometimes it is difficult to decide on the right one for a particular patient. Frequently, the best path is the one the surgeon is most adept at or the one that local expertise can accomplish most safely. Sometimes, however, the safest approach is a transfer to a center where multiple treatment options are available so that the treatment can be tailored to fit each individual situation.

Figures 49-4 and 49-5 show the treatments followed at our institution for preoperative and intraoperative suspected choledocholithiasis (at cholecystectomy).

Cholangitis is the most rapidly fatal complication of gallstones and occurs as a result of biliary tract bacterial infection in the setting of biliary tree obstruction. Mortality approaches 100% in patients who after failing conservative therapy are not subjected to needed drainage interventions.116 Early diagnosis and treatment are imperative for a successful outcome.

Pathophysiology

Although bile is normally sterile, when the biliary tree is compromised, such as by a stone, stricture, or endoprosthesis, bacteria then often can be cultured from the bile.117 Along with the sphincter of Oddi and the bacteriostatic properties of bile, bile flow is an important component of maintaining sterility. Bile duct obstruction results in decreased antibacterial defenses, allowing bacteria to gain access to the biliary tree. Although the route of infection is unclear, ascent from the duodenum or hematogenous is felt to be the possible source.116 Once colonization has occurred, stasis allows for exponential bacterial growth. As the biliary pressure rises with obstruction, bacteria and their products such as endotoxins leak into the systemic circulation and cause the septicemia of cholangitis.117

Patients with partial obstruction have a higher chance of developing cholangitis than those with complete obstruction, and bile duct stones are associated more often with cholangitis than neoplasms causing obstruction. In the United States, secondary choledocholithiasis is the most common cause of cholangitis. Primary bile duct stones are common in areas where Oriental cholangiohepatitis is endemic, including Hong Kong and Southeast Asia.116 Other causes of cholangitis include obstructing periampullary tumors, tumors metastatic to the porta hepatis or peripancreatic lymph nodes, benign strictures, and primary sclerosing cholangitis. Biliary tract interventions may lead to postprocedural cholangitis, and rare cases of cholangitis may be caused by hemobilia, parasites, and congenital abnormalities of the biliary tree.

Escherichia coli, Streptococcus spp., Klebsiella spp., and Enterobacteriaceae are the most common organisms cultured in cholangitis. Pseudomonas spp. and skin and oral flora are associated with biliary tract interventions, whereas anaerobes are noted most commonly in the elderly after biliary surgery.116

Clinical Presentation and Diagnosis

Charcot's triad of fever, right upper quadrant pain, and jaundice is present in 50–70% of patients with cholangitis at presentation, with fever, abdominal pain, and jaundice occurring in 90, 70, and 60% of patients, respectively. Hypotension (20%) and altered mental status (30%) are seen in septic patients and are known as Reynold's pentad when presenting in the setting of Charcot's triad. Although peritonitis is uncommon, 65% of patients have right upper quadrant tenderness.116 Laboratory and radiological studies are important for distinguishing cholangitis from other conditions such as acute cholecystitis, liver abscesses, and pancreatitis. Elevations of serum alkaline phosphatase, gamma-glutamyl transpeptidase, and bilirubin are typical. Mild increases in transaminases may be seen, whereas hyperamylasemia is found in up to 30% of patients. A discussion of imaging studies for the evaluation of choledocholithiasis has been presented in the section on CBD stones. In a patient presenting with signs of cholangitis, the most widely used imaging modalities are ultrasound and CT scan. Ultrasound is highly accurate in diagnosing acute cholecystitis and identifying gallstones. However, its ability to establish the diagnosis of choledocholithiasis is only 50%, varying from 30 to 90%.6,10 Although the presence of bile duct stones can be inferred by associated bile duct dilatation, a normal ultrasound without duct dilatation does not exclude either choledocholithiasis or cholangitis.15,116 CT scan is better at determining the level of biliary tract obstruction and has a 94% accuracy in diagnosing choledocholithiasis in the setting of suspected bile duct calculi.18 MRCP has sensitivities and specificities approaching ERCP in the diagnosis of bile duct stones and is useful in delineating biliary anatomy. However, its use in the setting of acute cholangitis is limited. ERCP is highly accurate in revealing the cause of biliary obstruction and at the same time allows for therapeutic intervention to occur at the same session.116 Nonetheless, given the well-defined life-threatening complications associated with ERCP and the availability of other noninvasive imaging techniques, ERCP should not be used solely as a diagnostic tool in the setting of acute cholangitis.116

Treatment

Patients with cholangitis can become extremely ill in a short period of time, and rapid initiation of treatment can be lifesaving. Supportive measures are begun without delay and include fluid resuscitation, correction of electrolyte deficits and coagulopathy, and administration of analgesics.118 Empirical broad-spectrum antibiotics are started while blood cultures, and when available, bile cultures are sent. Aminoglycosides and ampicillin are associated with gram-negative resistance and nephrotoxicity and are no longer felt to be the ideal regimen. Newer effective therapies include combinations of extended-spectrum cephalosporins, metronidazole, and ampicillin; fluoroquinolones as single-agent or in combination with metronidazole; and ureidopenicillins alone or with metronidazole.116 Anaerobic coverage is felt to be more important in the elderly and those with biliary manipulations. Antibiotics usually are given for 7–10 days, even if biliary decompression has been accomplished during the interim. A retrospective study by van Lent and colleagues evaluated whether continuation of antibiotics is needed after biliary drainage is achieved and signs of inflammation have subsided.117 Eighty patients who were treated successfully for cholangitis with ERCP were included in the study and followed for 6 months. Forty-one patients received antibiotics for 3 days or less, 19 patients for 4–5 days, and 20 patients for more than 5 days. The three groups were well matched, and the rate of recurrent cholangitis (24%) was not different for the three groups. The authors felt that a 3-day duration of antibiotic therapy may be sufficient in treating cholangitis when adequate drainage has been achieved and fever is abating.

Drainage of the biliary tree is the mainstay of therapy for patients with acute cholangitis.117 However, the timing and route of biliary decompression vary depending on the response of antibiotics, the cause of the obstruction, and the presence of morbidities.118 Biliary sepsis will resolve in most patients with conservative therapy, allowing time for a detailed delineation of the biliary anatomy by noninvasive imaging (CT scan or MRI) in order to determine the cause and level of obstruction. However, urgent decompression is needed in the 10–15% of patients who fail to respond within 24 hours to supportive measures and antibiotic therapy.117 When biliary decompression is not achieved, liver abscesses are inevitable.117 Mortality approaches 100% in patients who are not subjected to drainage interventions after failing conservative therapy.119

The methods of relieving biliary tract obstruction include endoscopic, percutaneous transhepatic, and surgical drainage techniques. With a success rate of 90–98%, ERCP with bile duct clearance is superior to the other methods and is the modality of choice for decompressing the biliary tree during acute cholangitis, particularly if caused by choledocholithiasis.116,118 In a study of 83 patients with acute cholangitis randomized to undergo either endoscopic or surgical decompression, the mortality was 10% in the endoscopic arm versus 30% in the surgical group.116 Meanwhile, in an evaluation of 65 patients undergoing endoscopic drainage versus 40 patients receiving traditional surgery for acute cholangitis, 5 operated patients and no individuals subjected to endoscopy died.120 In comparison with percutaneous drainage, ERCP also has been shown to have lower morbidity, shorter hospitalization, and higher definitive success rates.116 Sugiyama and colleagues found that in elderly patients (age 80 or older) with acute cholangitis, endoscopic drainage had lower morbidity (16.7%) and mortality (5.6%) than surgical (87.5 and 25%, respectively) or percutaneous drainage (36.4 and 9.1%, respectively).121

Various endoscopic treatment options are available from the placement of nasobiliary catheters or biliary stents to sphincterotomy and stone extraction. In patients who have responded to antibiotic therapy, sphincterotomy with bile duct clearance is preferred, whereas drainage catheters are used in those with ongoing sepsis and multiple large stones.118 In critically ill patients or in those with coagulopathy, concerns about bleeding and increased procedure times are associated with endoscopic sphincterotomy.

In comparing nasobiliary catheters with biliary stents for the treatment of acute cholangitis, a randomized study found both to be equally effective, but stents were more comfortable and avoided the risk of accidental removal.116

Percutaneous transhepatic drainage is reserved for patients in whom the papilla is inaccessible or ERCP has failed and for those suspected of hilar cholangiocarcinoma, hepatolithiasis, and intrasegmental cholangitis.116,118 Although successful in 90% of patients with biliary obstruction, percutaneous drainage has higher rates of morbidity (30–80%) and mortality (5–15%) than endoscopic techniques. As with ERCP, coagulopathy must be corrected prior to the procedure.

Used for almost 100 years, open surgery for acute cholangitis is associated with mortality rates of up to 40%.116 Surgery may be limited to choledochotomy, decompression, and T-tube insertion when performed for emergency situations. In patients who have undergone other methods of biliary drainage for the acute situations, surgery offers definitive treatment of the underlying disease and is associated with low mortality when performed electively after the initial treatment.

The need for cholecystectomy after CBD clearance in patients with cholelithiasis has been discussed in the section on choledocholithiasis. To prevent further biliary complications, some have advocated cholecystectomy for patients who are fit after the initial treatment of acute cholangitis. In nonrandomized and retrospective studies, the risk of developing subsequent biliary problems ranges from 4 to 12% in patients with CBD stones.116 In a study by Boerma and colleagues, 47% of patients who were randomized to a wait-and-see approach after common duct clearance developed biliary symptoms compared with only 2% of patients who were allocated to cholecystectomy within 6 weeks of the endoscopic procedure.122 Of the wait-and-see patients, 37% eventually needed cholecystectomy. Targarona and colleagues randomized 98 elderly (mean age 80) patients with biliary symptoms to either open cholecystectomy with operative cholangiography and (if necessary) bile duct exploration (48 patients) or to endoscopic sphincterotomy alone (50 patients).123 There were no significant differences in immediate morbidity (23 and 16%) or mortality (4 and 6%) in the surgery versus endoscopic group. However, at a mean follow-up of 17 months, biliary symptoms recurred in 3 surgical patients, none of whom underwent repeat surgery, and in 10 endoscopic patients, 7 of whom had further biliary surgery. In conclusion, these studies suggest that patients with acute cholangitis should undergo elective cholecystectomy after bile duct clearance if they are able to tolerate an operation. Conversely, in Asian patients in whom bile duct stones may originate from intrahepatic stones, cholecystectomy may not prevent future biliary complications.116

Hepatolithiasis is a primary disease of the biliary ducts and is more refractory to surgical treatment than most other benign diseases of the biliary system.124,125 The disease is defined as stones in ducts proximal to the confluence of the hepatic ducts regardless of the presence of stones within the gallbladder or CBD. The relative incidence in Western countries is approximately 1%, whereas in Taiwan, South Korea, and China it has been reported to be 20, 18, and 40%, respectively.126 Originally felt to be common only in Southeast Asia and referred to as Oriental cholangiohepatitis and Hong Kong disease, the widespread immigration of Asians to the United States has resulted in an increasing number of patients with hepatolithiasis presenting to American surgeons.124,127 Moreover, the North American experience includes a significant number of Caucasians and Latin Americans. This increasing incidence may be attributed to different etiologies such as primary sclerosing cholangitis, choledochal cysts, and iatrogenic biliary strictures.

The pathogenesis of primary hepatic stones was discussed earlier in the section on choledocholithiasis and appears to involve bile infection; biliary stasis; low-protein, low-fat diets and malnutrition; and parasitic infections.1 Brown pigment stones (calcium bilirubinate) are the most common stones and cholesterol stones are the most common of the other forms found. Hepatolithiasis presents with recurrent pyogenic cholangitis and sepsis, complicated by parenchymal infection and liver abscesses, obstructive cholangiopathy, and subsequent parenchymal destruction and atrophy of involved lobe.125,127,128 The natural course of the disease may lead to the development of biliary cirrhosis, portal hypertension, and liver failure and is complicated by cholangiocarcinoma in about 10% of patients.124,125,129

The diagnostic procedures used in establishing the diagnosis of hepatolithiasis include ultrasonography, CT scan, MRI, and direct (either endoscopic or percutaneous) cholangiography.18,125,130,131 Characterizing features include varying combinations of ductal dilatation, intrahepatic and extrahepatic bile duct stones, segmental ductal strictures, and lobar or segmental atrophy. In acute exacerbation, parenchymal or ductal contrast enhancement, abscess formation, or biliary obstruction may be noted.125

The management of hepatolithiasis is difficult and far from satisfactory. The principles of treatment are centered on the decompression of abscesses, removal of stones, dealing with recurrences and anticipating the development of malignancy. More than two-thirds of patients undergo multiple surgical procedures, and 10% ultimately require liver transplantation for liver failure.124 Initial biliary decompression usually can be achieved by endoscopic or percutaneous transhepatic drainage.128 The goal of definitive treatment is complete removal of all bile duct stones and elimination of bile stasis at the sites of intra- or extrahepatic strictures.

If the stones and strictures are located in a single segment or lobe of the liver, hepatic resection generally is recommended.124,128,132–135 Interestingly, there appears to be a predisposition for the left lobe of the liver. Resection is particularly important for patients with parenchymal atrophy and stricture of the intrahepatic ducts who may have concomitant cholangiocarcinoma.124 Even with resection, a significant number of patients will have recurrent disease. Kim and colleagues evaluated their experience with hepatectomy in 44 patients with hepatolithiasis by dividing them into two groups, those with intrahepatic biliary stricture and those without it.136 At a median follow-up of 65 months, the incidence of residual or recurrent stones was 36% for those with stricture and 11% for those without. The rate in late cholangitis was higher in the stricture group (54%) versus the no-stricture group (6%), as was the initial failure rate (50 vs 31%, respectively). Intrahepatic stricture recurred in 46% of the stricture group versus none in the no-stricture group, with stricture reoccurrence seen at the primary site in two-thirds. Therefore, the importance of including the strictured duct in the hepatic resection is emphasized by this study.

Nevertheless, the number of patients in whom resection is feasible is limited secondary to the diffuse and multifocal nature of the disease.132 If stones are located predominantly in the extrahepatic ducts or at the primary convergence and there is minimal stenosis of the intrahepatic ducts, it may be possible to use endoscopic treatment. When stones or strictures are located at the secondary convergence or beyond, surgery and percutaneous transhepatic cholangioscopic lithotripsy have a complete stone clearance rate of 84–100% and 72–92%, respectively.124 However, the stone recurrence rate is high, ranging from 33 to 40%. Hepaticojejunostomy has been used in the past to prevent biliary-enteric regurgitation and to decrease stagnation of debris and calculi in the intrahepatic ducts. The use of hepaticojejunostomy is controversial and refuted by others, who claim that increased biliary complications occur in patients with hepaticojejunostomies in the setting of hepatolithiasis.124 However, adding a cutaneous stoma to the Roux limb of the hepaticojejunostomy creates an access point for entering the biliary system for treating future complications.137 A more appealing alternative to a stoma is the creation of a Hutson loop. This entails tacking the jejunal loop of the biliary-enteric anastomosis to the abdominal wall and clearly marking it with staples or a metal ring such that it can be easily accessed by percutaneous means. We believe that this option should be considered in every patient that undergoes surgery.

With the advent of biliary endoscopy and radiological intervention, percutaneous choledochoscopic removal of intrahepatic stones has been well established.138 Stones can be removed via cholangioscopic guidance with basket forceps or lithotripsy, and strictures can be dilated. In a study from Hong Kong, 79 patients with intrahepatic stones underwent percutaneous transhepatic choledochoscopy.138 The success rate was 76.8%, with a complication rate of 21.5%. Cholangitis occurred within 3–5 years in one-third of the patients after the procedure. Another study found that recurrent calculi are more common in the setting of bile duct strictures, and addressing the strictures is mandatory part of treatment.139 Meanwhile, one study of percutaneous transhepatic cholangioscopic lithotripsy reported a biliary clearance rate of 100%, with a mean of two sessions required and a complication rate of 6.7%.132 During the follow-up period of 1–127 months (mean 75 months), one recurrence was noted and treated by repeat choledochoscopy. Others have used percutaneous intracorporeal electrohydrolic lithotripsy for hepatolithiasis. Using this technique, in a series of 53 patients, complete clearance of stones was achieved in 92%, and during a mean follow-up of 5 years, 9% had recurrent symptoms of biliary obstruction.140 Han and colleagues described the use of laparoscopy in the treatment of intrahepatic stones.129 A flexible choledochoscope, inserted through a choledochotomy, was used for stone removal in 12 patients, with a mean operating time of 288 minutes. Remnant stones were found in only one patient and removed by percutaneous choledochoscopy performed through the T-tube site. No cholangitis or recurrent stones were found at follow-up at 10–45 months.

The most recently documented North American experience describes treating 42 patients between 1986 and 2005 at the University of Toronto.133 They operated on 17 patients (46%) for indications of lobar atrophy or stones confined to a single lobe. Patients who underwent an operation were found to have less need for reintervention. The incidence of cholangiocarcinoma was 12%, including patients who were diagnosed at initial presentation.

Although the evolution of this disease is unclear, it will likely continue to challenge us. With lessons learned from more common biliary pathologies and the application of novel technologies, we would anticipate better outcomes for our future patients.