Chapter 50. Choledochal Cyst and Benign Biliary Strictures

Benign conditions of the intra- or extrahepatic bile ducts can range from focal or diffuse dilations (choledochal cyst) to obstructive strictures of the biliary tree. Historically, choledochal cyst disease was considered a disease of childhood but is increasingly being recognized in adults. In the United States, benign biliary strictures most commonly occur as a result of injury after cholecystectomy but also occur in a number of diverse inflammatory conditions affecting the biliary tree. Both conditions represent significant clinical challenges where proper evaluation and management are paramount to prevent serious clinical sequelae.

Choledochal cysts are focal or diffuse dilations of the biliary tree and, aside from biliary atresia, are the most common congenital abnormality of the biliary tree. Choledochal cysts can occur as single or multiple cysts throughout the extra- or intrahepatic bile ducts. The cysts can predispose patients to recurrent cholangitis or pancreatitis, choledocholithiasis, secondary biliary cirrhosis, biliary stricture, and malignancy.

The incidence of choledochal cysts varies significantly throughout the world. Choledochal cysts appear to be most common in Asian countries with an estimated incidence of 1 in 13,000 and have been reported to be as high as 1 in 1000, in reports from Japan. In Western countries, choledochal cysts occur much less frequently, with reported rates that vary from 1 in 150,000 to 1 in 2 million live births.1 Biliary cysts are four times more common in women compared with men. Approximately 60% of patients with choledochal cysts present during their first decade of life and 25% present in adults.2 There are a few case reports of choledochal cysts occurring within families but generally do not have a recognized hereditary pattern.

Classification

The anatomy of choledochal cyst disease was first described by Vater in 1723 and in 1959 Alonso-Lej categorized three types of choledochal cysts.3 The classification system was revised by Todani and colleagues in 1977 to the five cyst categories4 that are in use today (Table 50-1). A similar classification has been proposed based on bile duct cholangiographic appearance.5 A further Todani classification reflects the presence or absence of pancreaticobiliary maljunction; however, this revision has not widely been accepted.6

Traditionally, the classic type and most common choledochal cyst is type I disease: (A) cystic (Fig. 50-1A), (B) saccular, or (C) fusiform dilation of the extrahepatic biliary tree. Type II cysts are simple diverticula of the common bile duct, which are usually extrahepatic, supraduodenal, and saccular (Fig. 50-1B). A rare combination of type I cystic dilation and type II diverticulum was reported in a few cases representing a mixed type. Type III cysts, also known as choledochocele, is a cystic dilation of one segment of the bile duct (Fig. 50-1C). Manning and colleagues7 described two anatomic variations of intraduodenal choledochocele. The most frequent variety is with the common bile duct and main pancreatic duct entering into the choledochocele separately. The second variety of intraduodenal choledochocele is essentially a diverticulum off the common bile duct at the level of the ampulla of Vater, with the pancreatic duct entering the end of the common bile duct in the usual location. Multiple dilations of the intra- and extrahepatic biliary tree are known as type IV cysts divided into types IVa and IVb. Type IVa represents fusiform extra- and intrahepatic cysts (Fig. 50-1D). Type IVb consists of multiple extrahepatic cysts (Fig. 50-1E). Type V cyst, Caroli's disease, is confined to the entire liver or a solitary lobe, usually on the left (Fig. 50-1F).2,3 This disease may be associated with periportal fibrosis and cirrhosis leading to subsequent hepatosplenomegaly and portal hypertension.

While Todani's 1977 schema is the most widely accepted classification, it is not without controversy. Some have argued that the term “choledochal cyst” should refer to only type I and IV cysts (which comprise over 90% of biliary cysts).8 This proposal is based on current understanding of pathogenesis, treatment, malignancy risk, and natural history, which vary substantially with types I and IV cysts versus types II, III, or V cysts. A recent paper from Indiana University questioned whether choledochoceles were truly choledochal cysts. They reviewed 146 patients with choledochal cysts and identified 28 patients with choledochoceles. They concluded that classifications of choledochal cysts should not include choledochoceles because they differ from choledochal cysts regarding age, gender, presentation, pancreatic ductal anatomy, and their management.9

Pathogenesis

The cause of choledochal cysts is unknown. While there have been reports of acquired cysts in the literature, most are congenital in nature. There may be multiple mechanisms involved in the creation of biliary cysts, and several theories have been proposed.

The high incidence of biliary cysts in Asia suggests a role for either genetic or environmental factors. The first theory pertains primarily to the pathogenesis of Caroli disease and is related to a defect in maturation with ductal plate malformation. This defect can be either sporadic or inherited, with both autosomal-recessive and, rarely, autosomal-dominant inheritance patterns seen in families. Ductal plates describe the development of intrahepatic liver progenitor cells that are in contact with the mesenchyme of the portal vein and are then remodeled into mature ducts. Defective bile duct plate remodeling during embryogenesis results in inflammation and ulceration of biliary epithelium into larger bile ducts. These ducts then become segmentally dilated in a focal, lobar, or multilobar distribution.10

The second theory for the etiology of choledochal cyst formation is that bile duct obstruction or distention in the prenatal or neonatal periods may contribute to biliary cyst formation. The obstruction may be secondary to a stricture, web, or sphincter of Oddi dysfunction. With distal biliary obstruction there is pancreatic juice reflux into the biliary tree, resulting in chronic inflammation and increased bile duct pressure leading to dilation.11 In animal models, bile duct ligation in neonates leads to cyst formation; in contrast, bile duct ligation in adult animals results in gallbladder distention.12 In addition, there are case reports of a congenital web at the lower end of the common bile duct and antenatal choledochal cyst with distal common bile duct formation.13

The most common proposed theory for choledochal cyst formation is related to pancreaticobiliary maljunction.14 Pancreaticobiliary maljunction is defined as an extramural junction of the pancreatic and biliary ducts in the duodenum beyond the intramural sphincter function and is characterized by a long common channel. On average, patients with this anomaly have a common channel that is 1.86 cm compared with 0.46 cm in patients with a normal junction.15 In the literature, pancreaticobiliary maljunction has been reported in 57–96% of patients with choledochal cyst disease (Fig. 50-2).16 Pancreaticobiliary maljunction is also thought to be a significant risk factor for the development of cholangiocarcinoma in the biliary cyst,17 as well as the development of gallbladder cancer. Several investigators have speculated on the embryologic etiology of pancreaticobiliary maljunction, hypothesizing that the development of pancreaticobiliary maljunction is a result of an arrest in the migration of the choledochopancreatic junction into the duodenal wall.18

Because of the long common channel, patients with pancreaticobiliary maljunction may have increased reflux of pancreatic juice into the biliary tree, because the ductal junction lies outside the sphincter of Oddi and cannot prevent the mixing of bile and pancreatic juices.19 The mixed juices then have the potential of stagnating in the ducts or gallbladder, resulting in a cycle of inflammation, activation of proteolytic enzymes, theoretical biliary epithelial damage, alterations in bile composition, and ductal distention. It is thought that a combination of these factors contributes to the development of malignancy within the choledochal cyst or gallbladder. Elevated sphincters of Oddi pressures have also been documented in patients with pancreaticobiliary maljunction, resulting in more reflux.20,21

On pathology, choledochal cysts have variable microscopic features, with appearance ranging from normal bile duct mucosa to carcinoma. In children, the classic histologic appearance is a thick and dense fibrotic cyst wall with evidence of acute or chronic inflammation. In adults, common findings are inflammation, erosions, sparseness of mucin glands, and metaplasia.1,22 Type III cysts are most often lined by duodenal mucosa, although they sometimes are lined by bile duct epithelium.22 When malignancy is present, it is most commonly found along the posterior cyst wall.23

Presentation

Choledochal cyst disease can present with a vast spectrum of symptoms. The classic triad of presentation of a choledochal cyst is a female child with jaundice, abdominal pain, and right upper quadrant abdominal mass. This triad is found in only a minority of children at the time of presentation. Infants commonly present with elevated conjugated bilirubin (80%), failure to thrive, or an abdominal mass (30%). An abdominal mass becomes less common with increasing age and is rarely appreciated in adults. In adults, abdominal pain and recurrent cholangitis are the most common presentations.24 The abdominal pain usually mimics that of calculous cholecystitis and many patients do have gallstones either in the cyst or in the gallbladder. Almost 38% of adult patients have had a cholecystectomy before the diagnosis of a choledochal cyst because of right upper quadrant pain, which was attributed to gallbladder disease.25 Intermittent jaundice and recurrent cholangitis are also common, as is pancreatitis (30%), especially in patients with a type III cyst (choledochocele).1,9,26 Rarely, choledochal cysts will present as intraperitoneal rupture or bleeding due to erosion into adjacent vessels.

Diagnosis

The diagnosis of a choledochal cyst requires a high level of suspicion. Unless choledochal cyst is considered in the differential diagnosis in patients with ductal dilation, type I cysts may go undiagnosed. Patients with biliary obstruction, either acutely or chronically, may also have biliary dilation that can mimic a type I cyst. In contrast to a type I cyst, an obstructing lesion will often cause elevated alkaline phosphatase and bilirubin, as well as improvement in biliary dilation after appropriate treatment. The presence of pancreaticobiliary maljunction in uncertain cases can also be helpful in making the diagnosis of a type I cyst versus a biliary obstruction.

Ultrasonography is the most common first-line imaging tool and was used in 93% of the pediatric population and 72% of the adult patients in The Johns Hopkins series.25 While ultrasound is the standard for antenatal and childhood diagnosis, computed tomography (CT) scan may be more appropriate in adult patients, in whom the differential diagnosis is broader. Important considerations on CT scan (Fig.50-3) include assessing the hepatobiliary and pancreatic anatomy, with evaluation for possible biliary malignancy, metastatic disease, and vascular encasement.

Ultimately, when choledochal cyst disease is suspected on imaging, visualization of the pancreatic, intrahepatic, and extrahepatic ductal anatomy is required. Magnetic resonance cholangiopancreatography (MRCP) has become the noninvasive procedure of choice for the diagnosis of choledochal cyst. As quality of MRCP has improved, many surgeons now consider MRCP the only imaging technique needed for diagnosis and operative planning. Park and colleagues27 retrospectively reviewed 72 adult patients who underwent both MRCP and endoscopic retrograde cholangiopancreatography (ERCP) and found that when compared with ERCP, MRCP was accurate 100% of the time with types IVb and V cysts.

Cholangiography has been considered the gold standard for diagnosis of choledochal cysts but now is necessary as primarily a therapeutic procedure to place stents to relieve jaundice or cholangitis or to obtain brushings for cytology. Cholangiography can demonstrate areas of cystic dilation, the presence of stones, and exclude complete obstruction of the bile duct (Fig. 50-4). It is also effective in demonstrating the presence of pancreaticobiliary maljunction. Percutaneous transhepatic cholangiography (PTC) or ERCP is typically performed on adults and larger children. In small children, ERCP is not the ideal tool because it involves the use of general anesthesia can lead to pancreatitis and may not define the very proximal biliary anatomy, which tends to be abnormal. Therefore, in children intraoperative cholangiography may be used. The use of MRCP in children is increasing as experience with MRCP grows, and its technological accuracy may rival that of endoscopic evaluation. However, patients with type I or type IV cysts that extend to the hepatic bifurcation, PTC allows for excellent imaging of the entire biliary system and the placement of one or two transhepatic biliary catheters that may be helpful to facilitate complete resection and biliary reconstruction (Fig 50-5). To decrease the high risk of pancreatitis in patients with pancreaticobiliary maljunction and a long channel, it is important to avoid placing the stent through the ampulla while performing PTC.

Management

Once the diagnosis of choledochal cyst is made and the patient's biliary anatomy is delineated through preoperative imaging, several important clinical considerations must be taken into account. If a patient presents with pancreatitis or cholangitis, these problems must be treated supportively prior to considering definitive operative management of the biliary cyst. Because of the extensive sludge or stones that may be present within choledochal cysts and the high incidence of pancreaticobiliary maljunction, these patients are at especially high risk for pancreatitis. Furthermore, there is a risk of pancreatitis during ERCP with ampullary stent placement.

Another important clinical consideration in patients with choledochal cysts is the presence of malignancy. The most common malignancy associated with choledochal cyst disease is cholangiocarcinoma, although other malignant neoplasms have been reported, including gallbladder cancer, adenocarcinoma, and bile duct sarcoma. The incidence of cholangiocarcinoma with biliary cysts varies with patient age and cyst type. The lifetime risk of associated cholangiocarcinoma is as high as 26% in some studies, and, importantly, the rate of malignancy increases with age. Patients discovered in their twenties have only a 2.3% risk of concomitant malignancy, but it increases to 14.6% for patients with choledochal cysts discovered in their thirties and forties.8,12,22,28 In older untreated patients, the reported incidence of cholangiocarcinoma is as high as 75%.29 Types I and IV have a higher risk of cancer, while cancer is rare in types II and III cysts. In type III cysts, cancer risk may be limited to those choledochoceles lined by biliary and not duodenal epithelium.

Historically, choledochal cyst presenting in childhood were often treated with a cyst-enteric bypass leaving the cyst in situ. These patients remain at risk for the development of cancer within the retained cyst.29 Caroli's disease also carries a risk (about 7%) of cholangiocarcinoma. Most patients with Caroli's disease, however, will present first with compromised liver function or cholangitis before developing malignancy. The Johns Hopkins series had 92 choledochal cyst patients with 8 of them being diagnosed with cancer at the time of surgery or in follow-up. Every cyst type except types II and III was involved with cancer. None of the patients who had a complete cyst excision developed cancer after a mean of 10 years of follow-up. However, this population was still at a greater risk of malignancy than the general population.25 Malignancy may develop with incompletely resected cysts, at the anastomotic site, or in residual cyst left within the pancreas.29

Speculated etiological factors in carcinogenesis associated with biliary cysts include bile stasis, reflux of pancreatic juice mixed with bile, superinfection, or inflammation.29,30 Cholangiocarcinoma in choledochal cysts is strongly linked to patients with pancreaticobiliary maljunction.17 There is strong pathologic evidence of a hyperplasia-dysplasia-carcinoma sequence of carcinogenesis in patients with pancreaticobiliary maljunction. While the exact pathways have yet to be elucidated, cells with hyperplasia in patients with pancreaticobiliary maljunction have elevated expression of cellular proliferation markers, including cyclooxygenase-2 and vascular epithelial growth factor.31 On a molecular level, hyperplastic cells also have a high incidence of K-ras mutations (13–63%)32,33 while dysplastic cells frequently have microsatellite instability (60%)34 and cancerous lesions often have over expression of cyclin D135 and p53 mutations.36 Prophylactic cholecystectomy is also advised in all patients with either pancreaticobiliary maljunction or choledochal cyst.

In addition to the continued risk of cancer after excision, the most frequent long-term complication after biliary reconstruction is postoperative biliary stricture at the site of the anastomosis (~25%).37 Therefore, long-term follow-up should include surveying patients for the development of an anastomotic stricture. Significant elevations in serum alkaline phosphatase levels merit further investigation and treatment to prevent long-term complications from postoperative biliary strictures.

Unfortunately, current methods for screening for malignancy within a choledochal cyst have not proved effective, and therefore expectant management cannot be advised for most patients. Intraductal ultrasound and cytologic brushings of the cyst wall show promise for potentially detecting malignancy. Patients with choledochal cysts who are poor candidates or who refuse biliary reconstructive surgery may be candidates for lesser interventions to treat symptoms caused by gallstones or sludge, such as cholecystectomy or endoscopic treatment.

Operative Management

Historically, choledochal cysts were managed with biliary-enteric drainage via cyst-enterostomy. Recognition of an increased risk of bile duct and gallbladder cancer at an average of 10 years29 after enteric drainage has changed the recommended management to complete cyst excision. The current treatment of choice is surgical excision, as it is well documented to lead to a decrease in the rate of malignancy from 16 to less than 1%.25,29 The main goal of management is therefore to prevent malignant degeneration of the cyst via surgical excision. In newly diagnosed adult patients with biliary cysts, the possibility of an existing cancer needs to be considered.

The operative management of choledochal cysts should first consist of careful exploration of the patient. Upon entry to the abdomen via a midline incision, the initial step should be searching for possible metastatic disease. Once metastatic disease has been excluded, management of the choledochal cyst consists of cholecystectomy and complete cyst excision. If possible, excision should include all remnants of the cyst. Because of the extensive fibrosis that may be present, complete excision of the cyst can be technically challenging. Following cholecystectomy and choledochal cyst excision, the bile duct is reconstructed. Standard methods to reconnect the bile duct include hepaticojejunostomy or hepaticoduodenostomy, although Roux-en-Y hepaticojejunostomy is by far the most commonly used technique.

Enteric interposition grafts have been proposed as an option because of theoretical restoration of physiologic bile flow. Both jejunal interposition grafts and appendiceal interposition grafts between the duodenum and bile duct have been reported in the pediatric surgery literature. The value of these techniques, however, has been questioned because of graft dysfunction from stenosis and kinking.38

Successful resection and biliary reconstruction with types I and II choledochal cysts has also been reported using laparoscopic techniques, particularly in children.39 A recent review of 35 adult patients with choledochal cysts that were resected laparoscopically was done, which showed a 0% mortality, 8.5% conversion rate, and 14.8% morbidity rate. Thus, showing that laparoscopic surgery for choledochal cysts was feasible, safe, and even advantageous.40 While the choice of performing these procedures via an open or laparoscopic approach should be a matter of preference and technical ability for the surgeon, it is important that the procedure not be compromised by the use of laparoscopy.

Type I Cysts.

The surgical approach recommended for type I is complete cyst excision with Roux-en-Y hepaticojejunostomy reconstruction. The technical aspects of this operation involve mobilization of the hepatic flexure and wide Kocher's maneuver to expose the distal portion of the cyst that lies posterior to the duodenal wall (Fig. 50-6A). After the cyst has been exposed, the gallbladder, which usually arises from the midportion of the choledochal cyst, should be dissected away from the hepatic bed (Fig. 50-6B). The procedure then focuses on the distal portion of the choledochal cyst (Fig. 50-6C). Type IB (fusiform) cysts are particularly prone to extend distally within the common bile duct as it enters the dorsal aspect of the pancreas. The goal is then to excise the intrapancreatic portion of the cyst without injuring the pancreatic duct or the long common channel. Resection of the pancreatic head can usually be avoided unless there is documented malignancy. The distal portion of the cyst is encircled and transected as it enters into the pancreas and then reflected cephalad (Fig. 50-6D). This allows posterior dissection and identification of the portal vein and hepatic artery. The dissection may be facilitated by the presence of a preoperatively placed transhepatic stent. The dissection is continued until the most proximal portion of the duct at the hilum. The cyst is then resected at the hepatic duct confluence or more proximally if the cyst extends into the individual hepatic ducts (Fig. 50-6E). The excised cyst should be examined grossly for malignancy, and then the specimen should be sent for frozen section. If malignancy is present at the surgical margins, the resection may be extended either proximally or distally with the possibility of a pancreaticoduodenectomy to obtain negative margin and adequate lymph node dissection.

Reconstruction of the biliary tree is typically preformed with a Roux-en-Y hepaticojejunostomy at the bifurcation with a single anastomosis or multiple individual anastomoses with each of the hepatic ducts (Fig. 50-6F). A suitable segment of intestine is mobilized with a Roux-en-Y jejunal limb, approximately 60 cm in length, and the anastomosis is created with a standard retrocolic end-to-side Roux-en-Y hepaticojejunostomy, using a single layer of absorbable suture (Fig. 50-6G and 50-6H).

Type II Cysts.

The recommended procedure for type II choledochal cysts is complete cyst excision. After the cyst has been exposed, the common bile duct wall defect should be closed transversely with or without a T-tube. A transverse closure helps minimize potential narrowing or stricturing of the common bile duct. These patients should also undergo a cholecystectomy at the time of cyst excision. Recently, resection of type II cysts has been completed successfully via a laparoscopic approach.

Type III Cysts.

Because these cysts are unusual and have an overall lower rate of malignant transformation, reports of surgical excision of choledochoceles are uncommon. Primary management of choledochoceles is by ERCP with endoscopic unroofing of the choledochocele and sphincterotomy of the common bile duct.9,41 Surgical management is much less common in patients with choledochoceles compared to patients with other choledochal cysts. Surgical intervention for choledochoceles is needed for patients where sphincterotomy is very difficult or there is concern for malignancy, although very uncommon.

The surgical approach for choledochoceles involves complete excision of the cyst and is approached via transverse duodenotomy in the second or third portion of the duodenum. Before the duodenotomy, cholecystectomy is performed and then the ampulla can be localized by passing a biliary Fogarty catheter into the duodenum via the transected cystic duct. The anatomy can also be better defined via extensive Kocher's maneuver and intraoperative ultrasound. The common bile duct and pancreatic duct must be identified to prevent injury to the pancreatic duct. After the duodenotomy, the pancreatic duct should be intubated with a small Silastic tube so that the intraduodenal biliary cyst can be excised. The cyst is excised and a sphincterotomy can be done by suturing the duodenal mucosa to the bile duct mucosa and pancreatic duct mucosa individually using interrupted absorbable sutures. A piece of 5 or 8F plastic tubing can be placed into the pancreatic duct and secured with a single absorbable suture as a temporary stent to prevent acute pancreatitis. Finally the duodenotomy is closed in a transverse fashion. It is highly unlikely that a Whipple procedure is required and should be considered only if malignancy is suspected.

Type IV Cysts.

Types IVa and IVb cysts are managed similarly to type I cysts regarding cholecystectomy, extrahepatic cyst excision, and biliary enteric anastomosis. However, the procedures are technically more challenging, and complete removal is not always possible for type IV cysts because of multiple extrahepatic cysts and intrahepatic cysts. Furthermore, these patients will most likely need reconstruction proximal to the bifurcation and involve anastomosing individual hepatic ducts. If one lobe of the liver predominantly involves the intrahepatic cyst, hepatic lobectomy should be recommended. In many situations, bilobar cyst disease remains leaving this area at risk for malignancy. The long-term management in this situation is controversial. Intrahepatic disease in type IVa disease and Caroli's disease are prone to secondary biliary cirrhosis, hepatic atrophy, and portal hypertension. If the liver parenchyma is not cirrhotic and there is no evidence of intrahepatic duct malignancy, the hepatic parenchyma should be preserved, even in the setting of stones or strictures. If cirrhosis is unilateral or segmental, resection of the involved parenchyma is necessary. Transhepatic biliary stents may be especially helpful for managing patients with type IV cysts, particularly those with type IVa cysts that extend into the intrahepatic ducts. The stents allow for proper decompression alleviating chronic inflammation and may prevent or facilitate the management of long-term complications of biliary stasis, stones, cholangitis, cirrhosis, and be used for surveillance for malignant transformation.

Oncological principles should be followed in cases in which malignancy is involved. If no metastatic disease is present and the vascular supply to the uninvolved hepatic parenchyma can be preserved, resection of the involved bile ducts and adjacent parenchyma and lymph node dissection is indicated. In rare cases, extensive resections involving combined hepatic and pancreatic resection may be necessary. In cases in which metastatic disease is present, palliative stenting of the bile ducts is indicated.

Type V Cysts.

Type V choledochal cyst (Caroli's disease) is a difficult condition to manage, and the specific recommendations are not well defined. Current recommendations are to begin with conservative management treating infectious complications with drainage, stone extraction, antibiotics, and ursodiol. While Caroli's disease may be diffuse and bilobar, it is often confined to a single lobe and typically on the left side. Similar to type IVa cysts, Caroli's disease, if unilateral or segmental involvement with cirrhosis, can be managed by resection of the involved parenchyma, resulting in decreased incidence of recurrent cholangitis, pancreatitis, cholestasis, and the need for invasive procedures. Bilobar Caroli's disease is a challenging problem. The use of ursodiol and antibiotics may improve bile flow and reduce the incidence of biliary stones, sludge, and cholangitis. In the absence of cirrhosis or malignancy, Roux-en-Y hepaticojejunostomy with bilateral transhepatic Silastic stents may be indicated to improve biliary drainage. Following operative management, the stents are left in place for 6–12 months, depending on the extent of intrahepatic stones and strictures. Patients that continue to have recurrent cholangitis or recurrent stones often require indefinite transhepatic stenting. Patients with Caroli's disease and progressive liver disease and cirrhosis should be considered for liver transplantation. The timing for when transplantation should be pursued is still under debate. Because patients with Caroli's disease may also have polycystic kidney disease, combined liver-kidney transplants have had excellent outcomes.

Operative Results

Early postoperative complications include pancreatitis, anastomotic leakage, cholangitis, and wound infection. Most series show morbidity of 9–41% and mortality 0–3.3%.9,25,40 The median length of stay ranges from 7 to 12 days postoperatively, where patients with a laparoscopic approach had a slightly decreased stay but longer operative time. Late postoperative complications include the formation of intrahepatic strictures and stones, anastomotic stricture, malignancy, cirrhosis, and intrahepatic abscess formation.

However, long-term results following resection of a benign choledochal cyst with biliary reconstruction are generally excellent, especially with type I cysts. The rate of biliary stricture had been found be very low. The management of more proximal cysts can be more challenging, particularly in the presence of extensive intrahepatic stone disease and liver damage. Type IVa cyst patients have the greatest risk for intrahepatic calculi and stricture formation secondary to the intrahepatic cystic disease. A series by Tsuchida and associates examined 103 patients with a mean follow-up of 12.5 years. Patients with type IVa disease with dilated intrahepatic ducts developed strictures at a rate 40%, with virtually all developing cholangitis.42 In contrast, management with large-bore Silastic transhepatic stenting results in 90% success without recurrent cholangitis.43 Patients remain at long-term risk for cholangitis, postoperative biliary strictures, intrahepatic stones, pancreatitis, or malignancy.

Summary

Choledochal cyst disease is uncommon. The presentation of the disease is more common in children but has been increasing in the adult population, especially in Western countries. Currently, the diagnosis in adults is based on cross-sectional imaging and cholangiography, primarily CT and MRCP. The consequences of not treating choledochal cyst disease can lead to malignant degeneration. The majority of cases of biliary cysts can be treated effectively with cholecystectomy, cyst excision, and biliary-enteric reconstruction. Long-term follow-up is necessary for surveillance of cancer, cholangitis, intrahepatic stones, and postoperative biliary strictures.

Benign biliary strictures include several diverse clinical entities that share the common characteristic of biliary obstruction. Although advances in medical technology have greatly improved their management, bile duct strictures continue to pose a significant clinical challenge. Many of these strictures result from iatrogenic injuries, often in young patients who are otherwise in good health and expected to live for years. Improper management may result in life-threatening complications, including cholangitis, portal hypertension, biliary cirrhosis, and end-stage liver disease. Proper diagnosis and treatment are essential in preventing these complications.

Benign biliary strictures may affect the intra- or extrahepatic bile ducts or both, and may be solitary or multiple. There are numerous etiologies of benign bile duct strictures (Table 50-2). The vast majority of strictures occur following injury to the bile duct during cholecystectomy; however, other procedures in the upper abdomen may injure the biliary tract, especially procedures involving the liver, pancreas, and stomach/duodenum. Inflammatory conditions such as pancreatitis, gallstone disease, and primary sclerosing cholangitis are also important causes of benign bile duct strictures.

Postoperative Biliary Stricture

The introduction and widespread use of laparoscopic cholecystectomy in the 1990s resulted in a significant increase in the frequency of biliary injuries and associated bile duct strictures. Postoperative bile duct injuries may present early in the postoperative period with biliary leak, or months to years later with jaundice or cholangitis from biliary stricture. Proper management begins with delineation of biliary anatomy followed by repair. Nonoperative balloon dilation via percutaneous transhepatic or endoscopic routes is appropriate in select patients with intact biliary-enteric continuity. Operative repair, however, remains the mainstay of treatment in patients with benign strictures.

Incidence

Most bile duct injuries and strictures occur in patients following abdominal surgery in the right upper quadrant. Cholecystectomy is performed on over 750,000 patients on an annual basis in the United States and accounts for over 90% of postoperative biliary strictures and injuries. Although the exact incidence of injuries is unknown because many cases go unreported, numerous studies have attempted to define the incidence and mechanisms of bile duct injuries associated with cholecystectomy. An incidence of one to three major bile duct injuries per 1000 cases was consistently reported during the era of open cholecystectomy. Roslyn and colleagues demonstrated a 0.2% incidence of major bile duct injuries from a series of over 42,000 open cholecystectomies.44 A literature review by Strasberg and associates45 of over 25,000 open cholecystectomies performed since 1980 revealed a 0.3% incidence of major bile duct injuries. In contrast, in a review of nearly 125,000 laparoscopic cholecystectomies reported in the literature in the years 1991–1993, Strasberg and associates reported an overall incidence of biliary injuries of 0.85% and an incidence of major injuries of 0.52%. Multiple large surveys from numerous centers have estimated the rate of major bile duct injury with laparoscopic cholecystectomy to be 0.4–1.3%.46–49 Therefore it appears that the incidence of bile duct injury associated with laparoscopic cholecystectomy is two to three times greater than that with open cholecystectomy.

In the early 1990s, many authors ascribed the increased incidence of bile duct injuries with laparoscopic cholecystectomy as a “learning curve” associated with the new technique and projected that the rate of injury associated with laparoscopic cholecystectomy would decline with time. Unfortunately, these projections were not correct, and the rate of bile duct injuries appears now to have stabilized at a level still higher than that of the prelaparoscopic era. A report of over 10,000 cases at US military institutions46 and nationwide reviews in New Zealand50 and Italy48 have demonstrated no significant improvement in the incidence of injury as surgeons have passed through the learning curve. It is likely that the technology and technique associated with laparoscopic cholecystectomy will need fundamental enhancements for the current rate of injury to diminish.

Pathogenesis

Several factors are associated with increased risk of bile duct injuries at the time of cholecystectomy. Some of these factors may be pathologic, anatomic variations, and/or technical problems that are unique to the laparoscopic approach. Ultimately, the final common pathway of most injuries is either a technical error or misinterpretation of the anatomy. The “classic” biliary injury during laparoscopic cholecystectomy includes misidentification by the surgeon of the common bile duct as the cystic duct or misidentification of an aberrant right sectoral duct as the cystic duct (Fig. 50-7).

Pathologic Factors.

A number of patient-related factors have been associated with bile duct injury. Patients with acute cholecystitis may have severe inflammation in the porta hepatis and Calot's triangle, which can make a laparoscopic approach difficult. Patients with complicated gallstone disease also have a higher risk of injury than those with chronic cholecystitis, symptomatic cholecystitis, or biliary colic. Fletcher and colleagues47 reported that complex cases, which included patients with acute cholecystitis, cholangitis, and gallstone pancreatitis, are associated with an increased incidence of bile duct injuries (1.7 vs 0.6%) versus other indications for laparoscopic cholecystectomy. These patients are also associated with a higher rate of conversion to open cholecystectomy (29 vs 8%).

Anatomic Variations.

Anatomic variations can also contribute to bile duct injury. A congenitally short cystic duct or a duct that appears shortened by an impacted stone may also lead to misidentification of the common bile duct, resulting in injury or transection. Other high-risk congenital anatomic anomalies include a long common wall between the cystic and common bile duct or the cystic duct inserting into the right hepatic duct. The cystic duct has a very variable pattern ranging from joining the common hepatic duct quite high, almost at the biliary confluence, or running parallel to the common hepatic duct before inserting into the common bile duct almost at the level of the pancreas. The risk of bile duct injury also appears to be increased in patients with obesity, chronic inflammation, excessive fat in the dissection area, inadequate exposure, poor or excessive clip placement, injudicious use of electrocautery, and bleeding into the operative field.

Technical Factors.

Several technical factors associated with laparoscopic cholecystectomy make it prone to bile duct injury. First, standard laparoscopy gives a limited perspective from its end, viewing a two-dimensional picture of the operative field. The classic laparoscopic injury occurs when the cystic duct and the common bile duct are aligned in the same plane, leading to clipping and dividing the common bile duct. Retraction of the gallbladder infundibulum excessively cephalad aligns the cystic and common bile duct, leading to misidentification and injury. As the operative dissection is carried cephalad, the common hepatic duct may also be transected, often without recognition, resulting in a postoperative bile leak. The right hepatic artery may also be injured, creating excessive bleeding. This classic injury is estimated to occur in over 75% of major bile duct injuries referred to major centers. The classic laparoscopic injury is usually also associated with excision of a segment of bile duct, making the proximal extent of the injury high, usually at or near the hepatic duct bifurcation.

There is also a growing understanding of surgeon cognitive factors associated with bile duct injury during laparoscopic cholecystectomy. A report examined 252 laparoscopic cholecystectomy bile duct injuries using the human error factor and cognitive science techniques and found that 97% of injuries were due to a visual perceptual illusion or inadequate visualization.51 In a subsequent study from the same group, one of the main explanations for the surgeon's frequent inability to recognize a bile duct injury associated with laparoscopic cholecystectomy appears to be confirmation bias, which is the propensity to seek clues to confirm a belief and to discount clues that might discount that belief.52 While cognitive factors are important for understanding the psychological issues associated with bile duct injuries, surgeons must continue to have appropriate corrective mechanisms in place to minimize the chance of these injuries, including knowledge of anatomy, typical mechanisms of injury, appropriate level of suspicion, and logic.53

The role of intraoperative cholangiography in preventing bile duct injury remains controversial, with mixed results from reported series. A large series in Australia demonstrated a protective effect,47 whereas a review from the Veteran's Administration Hospitals demonstrated that bile duct injury occurred more commonly in patients undergoing cholangiography (0.7 vs 0.2%).45 Clinical information from patients in the Medicare claims database and surgeon data from the American Medical Association Physician Masterfile were recently used to examine the influence of intraoperative cholangiography on the rate of major bile duct injury, finding the rate of injury to be significantly higher when intraoperative cholangiography was not used.54 In this study, surgeons who routinely performed intraoperative cholangiography had a lower rate of injuries than those who did not, and this lower rate disappeared when intraoperative cholangiography was not used by these surgeons. Whether or not intraoperative cholangiography actually prevents bile duct injury, the procedure can often lead to early recognition of the injury, and therefore potentially minimize the injury and its associated morbidity (Fig. 50-8). The best technical approach in preventing and limiting bile duct injuries, regardless of the use of cholangiography, includes methodical dissection with careful exposure and identification of the structures of the triangle of Calot.44

The operative technique for laparoscopic cholecystectomy, which defines the “critical view of safety,” is a corrective mechanism that helps prevent misidentification and injury to the major bile ducts.55 In this method, the triangle of Calot is cleared of fat and fibrous tissue. Only two structures are connected to the lower end of the gallbladder once this is done; the cystic duct and cystic artery and the lowest part of the gallbladder attachment to the liver have been exposed. Once the critical view is attained, the cystic duct and artery may be clipped and divided, as they have been conclusively identified. Failure to achieve the critical view is an indication for conversion or possible cholangiography.

Physiologic Factors.

Several physiologic processes have been implicated in the formation of bile duct strictures. Ischemia of the bile duct from excessive periductal dissection may have an important role in the formation of postoperative anastomotic strictures. Studies show that the blood supply to the ducts can be thought of having three elements: afferent arteries, marginal arteries, and the epicholedochal plexus. The afferent arteries are branches of the hepatic arteries or less commonly of the superior mesenteric artery or other upper abdominal arteries. The marginal arteries lie on and run parallel to the long axis of the bile ducts. Anatomically, these are the major arteries of the common bile duct located at the 3- and 9-o'clock positions that can be injured or divided by unnecessary dissection during cholecystectomy, or more commonly the bile duct can be excessively “skeletonized” while performing a bile duct anastomosis.

Fibrosis and scarring can be intense following a bile duct injury. In canine models, bile duct ligation results in an elevation of bile duct pressure that is immediate and sustained and is accompanied by an increased bile duct diameter and formation of high local concentrations of bile salts at the canalicular membrane.56 A month after bile duct ligation, the bile duct wall is thickened, will have reduced mucosal folds, and have loss of surface microvilli with epithelial degeneration. On pathologic staining 2 weeks after ligation, there is evidence of increased synthesis of collagen and proline hydroxylase activation. Recently, an animal model of bile duct injury demonstrated healing in traumatized bile duct tissue to occur in a mode of overhealing, implicating myofibroblasts as the main cause of contracture of scar and stricture of the bile duct.57 Inflammation in the surrounding tissues compounds the problem by encouraging fibrosis, especially when associated with bile leakage.

Injuries and strictures of bile ducts occur less commonly in association with other operative procedures. After cholecystectomy, common bile duct exploration is the next most frequently associated procedure with stricture, typically occurring at the site of choledochotomy or an impacted stone. Procedures requiring biliary-enteric anastomoses may be complicated by postoperative stricture. Typically, these procedures involve choledochoenteric or hepaticoenetric anastomosis in such cases as reconstruction after pancreaticoduodenectomy, bile duct resection for mid–bile duct tumors, and after excision of choledochal cysts. Gastrectomy and hepatic resection are the most common nonbiliary operations associated with postoperative strictures. Injuries associated with gastrectomy typically occur during pyloric and proximal duodenal dissection associated with closure of the duodenal stump or with creating a Billroth I gastroduodenostomy. Injuries during hepatic resection often take place during dissection of the hepatic hilum. Bile duct injury and stricture is also associated with hepatic transplantation, pancreatic procedures, and penetrating or blunt trauma. Finally, the recurrence of stricture after an initial attempt at repair is not uncommon and may occur over a decade following initial repair (Fig. 50-9).58

Classification

Strictures and injuries to the bile duct vary widely in their complexity and nature. The ease of management, operative risk, and outcome of biliary injuries vary considerably depending on the location and the type of injury. Injuries associated with laparoscopic cholecystectomy are often complex, located at or near the level of the hepatic duct bifurcation, and potentially include one or more hepatic duct branches. Minor injuries to the bile duct include lacerations of the bile duct, clip placement on an intact bile duct, injury via electrocautery, or avulsion of the cystic duct.

A number of classification systems or major bile duct strictures have been presented, with the traditional classification being that described by Bismuth (Fig. 50-10), which classifies major injuries based on the level of obstruction of the biliary tree regarding the hepatic duct confluence or the involvement of an aberrant right sectoral hepatic duct with or without a concomitant hepatic duct stricture.59 A drawback of the Bismuth classification system is that patients with limited strictures, isolated right hepatic duct strictures, or cystic duct leaks cannot be classified. The Strasberg classification system has been developed to classify all types of injury and is used extensively in describing bile duct injuries associated with laparoscopic cholecystectomy (Table 50-3).55

Presentation

Most patients with bile duct injuries unfortunately are not recognized at the time of laparoscopic cholecystectomy. After open cholecystectomy, only 10% of injuries are suspected after the first week, but nearly 70% are diagnosed within the first 6 months after operation.58 However, injuries after laparoscopic cholecystectomy are recognized earlier more likely because of heightened awareness and suspicion.

Large series reviews have demonstrated that less than one-third of major bile duct injuries are detected at the time of injury during laparoscopic cholecystectomy.60,61 Possible indications that a bile duct injury had occurred intraoperatively include a persistent and unexpected bile leak, atypical anatomy, or a second bile duct discovered during dissection. Injuries may also be discovered if the removed gallbladder specimen and cystic duct are carefully examined to ensure normal duct anatomy. Intraoperative cholangiography will also diagnose bile duct injuries at the time of cholecystectomy and may minimize injury, allowing early repair (see Fig. 50-8).

The clinical presentation of patients with a bile duct injury in the early postoperative period depends on the type of injury. In most cases the injury is associated with uncontrolled bile leakage into the peritoneal cavity, while in others the duct is completely ligated by clip placement leading to obstructive jaundice usually without cholangitis. Patients with significant bile leaks generally present within the first week after operation with abdominal pain, distention, nausea, vomiting coupled with fever, or other signs of sepsis. Prompt investigation is required if patients have bilious drainage from incision sites or from intraoperatively placed drains. Bile leaks result in either biliary ascites with associated chemical peritonitis if allowed to drain freely into the abdominal cavity or, alternatively, bile can become loculated resulting in biloma (Fig. 50-11) or, if infected, a subhepatic or subdiaphragmatic abscess. In the latter scenario, presentation is more subtle with low-grade fever and localized abdominal pain. Because significant abdominal complaints are uncommon after uncomplicated laparoscopic cholecystectomy, all patients with such symptoms should be appropriately evaluated without delay for possible bile leak to prevent progression to frank sepsis. Failure to recognize a major bile leak or to institute appropriate treatment can result in life-threatening sepsis and the development of multisystem organ failure. In a recent series of 200 major bile duct injuries treated at The Johns Hopkins Hospital, three patients were transferred to this tertiary care center and died of complications of sepsis secondary to delayed or inadequate treatment.62

Bile duct strictures may also present months to years after the original operation. Patients with a slowly evolving stricture may have nonspecific abdominal complaints, jaundice, pruritus, cholangitis, or derangements in liver function tests. In addition, patients with an isolated right sectoral hepatic duct injury may present with a history of unexplained fevers, pain, or generalized malaise. Episodes of cholangitis are typically mild and respond effectively to antibiotics. Less often, patients can present with painless jaundice, which can be confused with a malignant stricture.

The findings on physical examination are usually not specific. Abdominal distention and pain may be seen in patients with bile peritonitis or focal tenderness if the patient presents with a collection or abscess. If the patient has jaundice, there may be multiple excoriations from pruritus. Hepatomegaly may be present in patients with chronic biliary obstruction or possible splenomegaly if there is any portal hypertension from portal venous injury or severe underlying hepatocellular damage.

Diagnosis

Patients presenting with a biliary leak from injury usually present without evidence of biliary obstruction, and bilirubin levels are normal or slightly elevated due to absorption of bile from the peritoneal cavity. Patients with postoperative bile leak or cholangitis will also have an elevated white blood cell count, pyrexia, or occasionally frank sepsis. Patients with postoperative bile duct strictures typically reveal a stereotypical biochemical profile of cholestasis. In particular, liver function tests typically consist of an elevated alkaline phosphatase and normal or slightly elevated liver transaminases (alanine and aspartate aminotransferases). Serum bilirubin levels are usually elevated in the range of 2–6 mg/dL. In rare cases, patients with long-term obstruction will present late in the course of disease with cirrhosis, diminished serum albumin, and abnormal coagulation studies from altered hepatic synthetic function.

Definitive diagnosis for bile duct strictures and injuries requires radiographic imaging. Ultrasound and abdominal CT scan are both helpful in patients who present in the early postoperative period for the detection of bilomas and biliary ascites, as well as bile duct dilation from obstruction. Ultrasound has little value in assessing the extent of a stricture and is unhelpful if the biliary tree is decompressed. Abdominal CT scan is usually the best first-line study often showing a dilated biliary tree or intra-abdominal collections or ascites, which can direct further investigations. The CT should be performed with arterial-phase contrast to evaluate for concomitant vascular injury. Nuclear medicine imaging with technetium-HIDA (hepatobiliary iminodiacetic acid) scanning can demonstrate bile leakage noninvasively but typically does not have the sensitivity to define the specific anatomic site of injury. MRCP has been demonstrated to be an effective noninvasive method for demonstrating biliary leakage or obstruction, as well as precisely defining biliary anatomy and the nature of the injury (Fig. 50-12). Last, sinography, typically performed by injecting water-soluble contrast via operatively placed drains, can define the biliary anatomy and the source of bile leakage.

Cholangiography currently remains the gold standard for evaluating the biliary tree. Endoscopic retrograde cholangiography (ERC) is performed via a distal approach to the biliary tree and is useful only in patients if the native bile duct is intact, such as with partial injuries or after end-to-end repair. ERC is the procedure of choice for patients suspected of cystic duct leaks (Fig. 50-13A) or leaks from peripheral hepatic radicals (ducts of Luschka). In these cases, the biliary leak may be effectively controlled with the use of an endoprosthesis. Most cases of major bile duct injury, however, are associated with complete duct transection, and the cholangiogram via the retrograde endoscopic route will demonstrate a normal distal bile duct terminating in misapplied clip(s) devices (Fig. 50-13B). Therefore, ERC will neither define the site of bile leakage nor the proximal anatomy necessary for reconstruction. In such cases, PTC is necessary to define the proximal biliary anatomy and the site of injury (Fig. 50-14). In addition to delineating the anatomy, a percutaneous biliary drainage catheter should be placed at the time of PTC to decompress the biliary tree, and treat cholangitis and control the biliary leak. Percutaneous biliary drainage catheters will also be useful at the time of operative repair as a guide for dissection and identification of the transected bile duct, which is often retracted high into the liver hilum. Finally, in those cases in which biliary-enteric continuity exists, percutaneous catheters allow access for balloon dilation.

Significant arterial injury associated with major bile duct injury has been increasingly reported in recent years. The “classic” biliary injury during laparoscopic cholecystectomy in which the common bile duct is mistaken for the cystic duct often includes injury to the right hepatic artery as it enters either above or below the hepatic duct. While this injury may cause bleeding at the time of operation, the arterial injury often is unnoticed, usually resulting in arterial occlusion or less commonly a hepatic artery pseudoaneurysm. In a large study by Stewart et al63 on combined right hepatic artery and bile duct injury, there were 7 pseudoaneurysms compared to 77 right hepatic artery occlusions. The incidence of disruption of the right branch of the hepatic artery during major bile duct injury ranges between 12 and 39%.64 However, the presence of an arterial injury does not appear to affect either early or late outcomes.63,65 Because of the recognized association of vascular injuries during laparoscopic bile duct injuries especially if there is a history of excessive bleeding at the time of cholecystectomy, a CT scan with arterial and venous phase contrast or arteriography should be obtained. Some authors believe if arterial injury has occurred, biliary reconstruction should be delayed to decrease the risk of late stricture recurrence.55 In patients presenting in a delayed manner after cholecystectomy, the combination of biliary and vascular injuries often leads to segmental or lobar atrophy, which may suggest a role for hepatic resection rather than reconstruction.

Preoperative Management

The timing of presentation is often a primary determinant of the preoperative management of a patient with a postoperative bile duct stricture or injury. In the early postoperative period, patients with a bile leak associated with a bile duct injury are often either septic due to intra-abdominal infections or otherwise manifesting a systematic inflammatory response from chemical peritonitis associated with the bile leak. Treatment and control of sepsis may require broad-spectrum parenteral antibiotics, percutaneous biliary drainage, and percutaneous or, rarely, operative drainage of bilomas. Once sepsis is controlled, there is no hurry in proceeding with surgical reconstruction of the bile duct injury. Most biliary fistulae can be controlled with the combination of proximal biliary decompression and external drainage. After early control and clinical improvement, the patient may be discharged home for several weeks to permit return of overall health and for the resolution of inflammation in the periportal region.

It should be stressed that despite the belief of many surgeons that a suspected bile leak warrants urgent reoperation, exploration with an attempt at repair should be avoided early after presentation with a bile leak. In this situation exploration often reveals marked inflammation associated with bile spillage and small, decompressed bile ducts retracted high into the porta hepatis, making recognition of the injury and repair virtually impossible. Instead of proceeding to urgent exploration, a more prudent approach is to define biliary anatomy via preoperative cholangiography and to control the bile leak with percutaneous stents. Early operative intervention to deal with bile collections or ascites is not usually required because the intraperitoneal bile either can be drained percutaneously or is simply absorbed by the peritoneal cavity. Delayed reconstruction, with facilitation by percutaneous biliary catheters, allows for the most favorable operative results especially when concurrent hepatic artery injury is suspected.

Patients who present with a biliary stricture remote from the initial operation usually experience symptoms of cholangitis that necessitate urgent cholangiography and biliary decompression. The choice of technique depends on the nature of any prior repair. If the native bile duct is intact, endoscopic drainage with stent placement can sometimes be achieved. If a prior hepaticojejunostomy has been performed, transhepatic biliary drainage will be necessary for diagnosis. Both parenteral antibiotics and biliary drainage are central to controlling sepsis. Patients who present with jaundice without cholangitis should undergo either ERC or PTC to define the anatomy. As with patients presenting early in the postoperative period, ERC may not completely define the proximal biliary anatomy, making PTC the more favorable procedure. Preoperative biliary decompression in patients presenting with jaundice without cholangitis has not been demonstrated to improve outcome.

Operative Management

Operative repair for postoperative bile duct strictures is aimed at reestablishing a reliable, long-term conduit for bile flow from the biliary tree to the gastrointestinal tract. Complications of an unsuccessful operative procedure include bile leak resulting in fluid collection or abscess, recurrent stricture with stones or sludge and potentially cholangitis, or biliary cirrhosis. To this end, the ideal technical procedure results in a tension-free, mucosa-to-mucosa repair to a segment of uninjured bile duct. Ideally, surgeons should also seek to maintain ductal length by not sacrificing tissue. Options for operative repair may include end-to-end repair, Roux-en-Y hepaticojejunostomy, or choledochoduodenostomy. The optimal operative procedure is contingent upon the timing of presentation, overall clinical status of the patient, and level and type of injury.

Injury Recognized at Initial Operation.

If injury to the bile duct is recognized at the time of initial cholecystectomy, the surgeon should consider his or her ability to technically perform immediate reconstruction and should consider seeking the counsel and assistance of a more experienced surgeon. Studies show that immediate open repair by an experienced surgeon is associated with reduced morbidity, shorter duration of illness, and lower cost.62 Each failed attempt at repair is associated with loss of bile duct length and exacerbation of a difficult situation. If the surgeon is unable to repair the injury and competent help is unavailable, drains should be placed to control any bile leak and the patient referred immediately to a tertiary specialty center.

When the surgeon suspects an injury or variant anatomy, biliary anatomy must be clearly defined using intraoperative cholangiography and/or careful dissection, being cautious to avoid additional injury or devascularizing the bile duct. Conversion from laparoscopic to open cholecystectomy is often necessary to properly identify anatomy and the injury. Segmental or accessory duct injuries where the diameter of the bile duct is less than 3 mm and where the bile duct does not communicate with the major duct system or drain a large segment of hepatic parenchyma on cholangiography may be ligated. Bile ducts that are 4 mm or larger in diameter or when the cholangiogram shows sectoral or lobar drainage, then the ducts must be operatively repaired, as they likely drain multiple hepatic segments or an entire liver lobe.

Immediate intraoperative repair is indicated in most cases for a major injury to the common hepatic or common bile duct. The nature of that repair is determined by the length of separation between opposed residual, viable ends of the injured duct. Partial common duct transections, involving less than 180-degree circumference of the biliary tree, may be closed primarily over a T-tube using interrupted absorbable sutures (Fig. 50-15). Transection of the common duct involving more than 180-degree circumference or complete transactions with an injury less than 1 cm in length can usually be repaired with an end-to-end anastomosis with a T-tube that exits either above or below the anastomosis via a separate choledochotomy. Primary reconstruction of the bile duct, however, should be used very selectively and be avoided when the injury is near the bifurcation or when duct approximation cannot be accomplished without tension. A generous Kocher maneuver should be done to mobilize the duodenum out of the retroperitoneum and should be used to alleviate tension at the repair. In at least one series, a 100% restricture rate following primary end-to-end repair has been reported.66 Other series have shown better results and suggest an advantage that, if a stricture occurs, endoscopic access for balloon dilation remains an option.67

Transections of the bile duct high in the biliary tree or with significant loss of bile duct length cannot be repaired with a primary biliary anastomosis that remains tension-free. These injuries require reconstruction using a biliary-enteric anastomosis typically using Roux-en-Y hepaticojejunostomy to ensure a tension-free repair. In this situation, the distal bile duct should be oversewn, the injured tissue in the proximal end debrided, and then a biliary-enteric end-to-side anastomosis to the Roux-en-Y jejunal limb. Transhepatic Silastic biliary stents should be placed to control potential anastomotic leaks and for postoperative cholangiography. A perianastomotic drain should also be placed in all cases so that any potential postoperative leak is well-controlled.

Injury Recognized in the Immediate Postoperative Period.

Biliary injuries that are not appreciated in the intraoperative period may present in the first few days. The presentation may include bile drainage from the wound, bile peritonitis, or progressive jaundice. The initial management of a patient who presents in the delayed fashion following laparoscopic cholecystectomy depends on the nature of the injury and the mode and timing of presentation. Any elective repair should generally occur only after preoperative clinical optimization of the patient, and exact anatomy of the biliary system has been identified. Those presenting with biliary leak should have the bile leak and sepsis controlled prior to having definitive repair. In this situation, the result of reconstruction is almost always better if the definitive repair is made well after the leak and the consequent intra-abdominal inflammation and sepsis are controlled with percutaneous biliary drainage. Biliary spillage and marked inflammation can obscure fields and can make identification of ducts difficult making urgent early laparotomy prior to biliary decompression problematic. Finally, the patient should be clinically stabilized prior to elective repair to correct fluid and electrolyte balances, anemia, and malnutrition. The repair is ideally performed 6–8 weeks after adequate control of the leak has been attained.

In patients who present with biliary stricture weeks to months after cholecystectomy, identification of the biliary system is also essential. Patients with a stricture and symptoms of cholangitis should be treated with broad-spectrum antibiotics until sepsis is controlled, followed by biliary decompression with transhepatic percutaneous catheter placement.

Definitive Management of Bile Duct Stricture.

The goal of operative management of a bile duct stricture is the establishment of bile flow into the proximal gastrointestinal tract in a manner that prevents sludge, stone formation, cholangitis, restructure, and cirrhosis. The type of repair should be determined by several factors: previous history of attempted repair, location of stricture or injury, surgeon experience, and surgeon preference. Intraoperatively, biliary anatomy must be carefully defined followed by exposure of healthy proximal bile ducts. Care must be taken to avoid excessive dissection and devascularization of tissue. A biliary-enteric anastomosis is performed using a mucosa-to-mucosa technique in a tension-free manner.

The preferred technique, with few exceptions, is a hepatico- or choledochojejunostomy to a Roux-en-Y limb of jejunum. End-to-end anastomosis after excision of the stricture or area of injury is not prudent because of the loss of bile duct length and associated fibrosis. Significant loss of bile duct length is also a strict contraindication to performing choledochoduodenostomy, which is unlikely to be performed in a tension-free fashion and is also associated with duodenal fistula if leak occurs.

The exact details of the reconstruction depend on the particular anatomic features of the stricture. For strictures where there is more than 2 cm of healthy common hepatic duct present (Bismuth I), a simple end-to-side biliary-enteric anastomosis will suffice. For strictures in where there is less than 2 cm of healthy common hepatic duct (Bismuth II) or the stricture involves the bifurcation of the hepatic duct but the left and right still communicate (Bismuth III), it may be necessary to lower the hilar plate and extend the dichotomy along a short length of the left hepatic duct to allow a common biliary-enteric anastomosis. Strictures that completely separate the right and left biliary system (Bismuth IV and V) require separate right and left biliary-enteric anastomosis. When duct length cannot be found outside of the hepatic parenchyma, an intraoperative ultrasound is essential to locate the segments II and III ducts. Often, a wedge of liver may need to be resected until an adequate duct can be found to do a biliary-enteric anastomosis.

The use of percutaneous biliary stents with elective reconstruction of the biliary tree remains a topic of debate for hepatobiliary surgeons. Preoperatively placed stents act as intraoperative aids for defining anatomy, especially if the stricture is located proximally. Stents left in place after reconstruction also allow postoperative cholangiography and control early anastomotic leaks in the immediate postoperative period. Many surgeons also advocate extended postoperative transanastomotic stenting, with the purpose of minimizing fibrosis and risk of late anastomotic stricture. In this setting, follow-up cholangiography will reveal early evidence of anastomotic stricture and provide access for balloon dilation if necessary.

Biliary reconstruction with the technique of hepaticojejunostomy with a Roux-en-Y limb with transhepatic biliary stents is depicted in Fig. 50-16. Dissection of the porta hepatis is performed to clear any adhesions between the duodenum or colonic hepatic flexure to the gallbladder fossa, subhepatic space, or Glisson's capsule. Preoperatively placed percutaneous stents are essential in assisting in dissection and bile duct identification in patients with a high bile duct transection. In patients with an intact but strictured bile duct, the duct is divided at the most distal portion of the stricture, and a segment of the strictured duct should be resected and sent to pathology for frozen section. The distal end of the stricture is then oversewn. The proximal extent of the duct should be debrided for a length not to exceed 5 mm to obtain healthy bile duct circumferentially for use in the anastomosis. Careful limited dissection is important to avoid vascular compromise to the bile duct. Preoperatively placed percutaneous transhepatic catheters, which now protrude from the proximal end, are usually exchanged for soft Silastic stents. Silastic stents range from 12 to 22F in size, with multiple side holes that are generally interspersed along 40% of the length of the catheter. A radiologic guidewire is placed through the percutaneous transhepatic catheter; using the Seldinger technique, a series of progressively larger coudé catheters are passed over the guidewire in order to dilate the system for Silastic stent placement. The Silastic stent is arranged with the side holes extending beyond the anastomosis distally and within the liver parenchyma proximally. The end of the Silastic stent without holes is brought through the hepatic parenchyma and out through the upper anterior abdominal wall. A Roux-en-Y jejunal limb is then created by mobilizing a suitable segment of intestine of approximately 60 cm in length. The anastomosis is then constructed with a standard end-to-side Roux-en-Y hepatico- or choledochojejunostomy, typically using a single layer of 4-0 or 5-0 absorbable sutures.

In the postoperative period, Silastic stents are left to external gravity drainage. A cholangiogram is then performed on postoperative day 4 or 5 (Fig. 50-17). If the biliary tree is adequately decompressed and no leakage is seen, the stents can be internalized and the perianastomotic drain is removed.

The length of postoperative transanastomotic stenting is dependent on the individual patient, the clinical setting, and surgeon preference. Long-term stenting involves fluoroscopic exchange of stents at regular 2- to 3-month intervals. Timing of stent removal can be aided by biliary manometric flow studies that give objective data about the adequacy of the anastomosis, or by passing a clinical trial with the stent placed above the anastomosis.68

An alternative described approach of doing a hepaticojejunostomy involves an anterior longitudinal opening created in the bile duct and a long side-to-side anastomosis performed. Often, this is done to the extrahepatic portion of the left hepatic duct after it is lowered by dividing the hepatic plate (Hepp-Couinaud approach). This approach is particularly suitable for injuries at or just below the bifurcation. Right ducts do not lend themselves to this approach as well, because they have a short extrahepatic length. Sometimes the end of the right duct is used. However, dissection of the left duct provides a guide to the coronal plane in which the intrahepatic right hepatic ducts will be found and may further be exposed by removing liver tissue. During these procedures, exposure can be improved by dividing the bridge of tissue between segments 3 and 4 and opening the gallbladder fossa. Finally, if still more exposure is needed, resecting part of segments 4b and 5 will open the upper porta hepatis. The technique can avoid the need for postoperative stenting.

Nonoperative Therapy.

Nonoperative interventional radiology and endoscopic techniques have also been developed for the management of select patients with bile duct strictures and injuries. The most common nonoperative technique in these patients is interventional radiologic percutaneous stenting and balloon dilation, which may be possible in patients with intact biliary-enteric continuity. With the administration of conscious sedation, the proximal biliary tree is accessed so that the stricture can be traversed using a guidewire under fluoroscopic guidance (Fig. 50-18). Angioplasty-type balloon catheters are used to perform dilation of the stricture to a goal diameter based on the stricture location and the normal bile duct diameter. Following dilation, a transhepatic biliary stent is left in place across the stricture. The stent allows for future cholangiography, repeat dilation, and maintenance of the lumen while the bile duct heals. Complications of balloon dilation occur in up to 20% of patients and include cholangitis, hemobilia, and bile leaks. Percutaneous management will usually require numerous dilations.

Results for the treatment of bile duct strictures using percutaneous balloon dilation are limited. In a retrospective comparison, percutaneous balloon dilation was compared to surgical repair in 43 patients with postoperative bile duct strictures treated between 1979 and 1987.69 Twenty-five patients underwent surgical repair with postoperative stenting and 20 patients had percutaneous balloon dilation with transhepatic stenting (mean: four dilations). Three patients underwent both surgical management and balloon dilation. Successful outcome was achieved in 89 and 52% of surgical and balloon dilation patients, respectively. These results would appear comparable to other series in the prelaparoscopic cholecystectomy era.70–73 However, the follow-up in most studies was less than 3 years, which is insufficient to make a definitive comment regarding long-term efficacy.

A series of 51 patients undergoing percutaneous balloon dilation therapy for bile duct strictures following laparoscopic cholecystectomy was reported by Misra and associates.74 At a median 76-month follow-up, overall success with balloon dilation, defined as stent-free without the need for further intervention, was 58%. With additional stenting and balloon dilation for two patients and surgical reconstruction for the remaining patients, all but one patient (98%) had a successful long-term outcome. These results suggest that in highly selected patients, percutaneous balloon dilation can provide long-term successful results.

Endoscopic balloon dilation has a more limited application, because it is technically possible only in patients with primary bile duct stricture repair or with choledochoduodenal anastomosis. ERC is performed, followed by endoscopic sphincterotomy. Sequential balloon dilation is performed after the stricture is traversed by a guide wire, often with one or more endoprostheses left in place after dilation. Complications associated with stent placement include cholangitis, pancreatitis, stent occlusion, migration, dislodgment, and ductal perforation, and have a reported incidence between 9 and 70%.75–77

Repeat cholangiography, often with repeat dilations, may be performed at regular intervals of every 3–6 months. While most endoscopists advocate regular follow-up and reevaluation of the stricture, the risks of stent occlusion and replacement need to be weighed against the risks and costs of the repeat procedures, and there is still some debate about timing of stent change to avoid occlusion. Bergman and associates demonstrated a 70% reobstruction rate with resultant jaundice or cholangitis when stents were not exchanged at 3-month intervals.77 In contrast, De Masi and colleagues describe and advocate leaving the stents in place until patients were symptomatic.78

In addition, the rate of stent occlusion appears to vary with the type of stent used. While metallic stents provide a longer period of patency than plastic stents for patients with malignant obstruction, the indications for their use in patients with benign strictures are limited. Metallic stents cannot be routinely exchanged or removed, and several studies have demonstrated high reocclusion rates at long-term follow-up.79–81 Newer covered metallic stents may provide a suitable alternative as they can be changed or removed after completion of treatment.82

While there have been no determinative studies for the length of time that stents should remain in place, most studies having excellent results have used larger-bore stents (≥10F) left in place for 2–6 months.76,77,83 Long-term studies reporting the endoscopic treatment of benign bile duct strictures are few. One of the few studies that directly compare endoscopic therapy to surgical reconstruction was done by Davids and colleagues from the Netherlands.75 In 66 patients, endoscopic therapy consisted of dilation and placement of an endoprosthesis, which was exchanged every 3 months. Surgical repair in 35 patients consisted of Roux-en-Y hepaticojejunostomy. Surgery was associated with excellent or good results in 29 patients (82%), with 6 patients (17%) developing a recurrent stricture at mean 40 months from initial surgery. In contrast, endoscopic stenting resulted in 81% with excellent or good outcome and 18% developing restricture at a mean of 3 months after stent removal. Recurrent strictures after stent removal in several other series have been reported to occur at a rate varying from 0 to 20% at median follow-up of 29–108 months.76,77,83

Operative Results

Biliary injury and stricture repair are associated with significant morbidity and mortality. With improved medical technology and experience, the incidence of operative mortality has decreased markedly. A recent series of 200 consecutive patients repaired at The Johns Hopkins Hospital reported a perioperative mortality of only 1.7%.62 Advanced age, comorbid disease, and a history of major biliary tract infection are factors associated with operative mortality. Underlying liver disease is the most important correlated factor for operative mortality and morbidity, with advanced biliary cirrhosis and portal hypertension having mortality rates approaching 30%. Fortunately, in the modern era such advanced disease is uncommon.

A recent analysis of Medicare claims, patients' examined mortality associated with major bile duct injuries over an 8-year period in 791 elderly patients demonstrated a perioperative mortality of 2.7% associated with repair.84 In addition, the study demonstrated an adjusted hazard ratio for death during the follow-up period was significantly higher for patients with a bile duct injury than in patients without a bile duct injury. The hazard increased with advancing age and comorbidities and decreased with experience of the repairing surgeon. The adjusted hazard for death during follow-up was 11% greater if the repairing surgeon was the same as the injuring surgeon. This study gives supportive evidence for improved survival in patients with major bile duct injuries treated by experienced hepatobiliary surgeons at tertiary referral centers.

In most series, postoperative morbidity rates are in the range of 20–40%. Morbidity nonspecific to biliary surgery includes hemorrhage, infection, and risks associated with general anesthesia. Complications specific to biliary repairs include anastomotic leak, cholangitis, and hepatic insufficiency associated with preexisting liver disease. Anastomotic leaks can typically be managed via nonoperative means, especially when transanastomotic stenting has been utilized. Percutaneous transhepatic stenting may also have specific morbidity, including bile leaks from hepatotomy sites, hemobilia, and cholangitis from stent occlusion.

The series reporting the outcomes in 200 patients undergoing surgical reconstruction demonstrated a 43% overall postoperative complication rate.62 The most common complications were wound infection (8%), cholangitis (6%), minor stent-related complications (6%), and intra-abdominal abscess/biloma (3%). Postoperative cholangiography revealed an anastomotic leak in 4.6% of patients and extravasation at the liver dome–stent exit site in 10.3%. These complications were all managed conservatively with either new biliary stent placement or biliary stent exchanges required in 2.3%. Postoperative percutaneous abscess/biloma drainage was required in nine patients (5.1%). No patients required reoperation in the postoperative period. Despite the relatively high morbidity rate, median length of stay was similar to that in other reports (8 ± 4.6 days).

There are mixed results regarding perioperative complications when vascular injury has occurred in association with a bile duct injury.65,85,86 A report from Schmidt and associates87 reported that a repair in the presence of uncontrolled infection, a concurrent hepatic artery injury, and injury level (at or above the bifurcation) were independent predictors of the development of major biliary complications.

The ultimate goal of the repair of a bile duct stricture is a successful repair with no further symptoms, including jaundice, cholangitis, and preserved liver function. Excellent long-term results following operative repair of postoperative bile duct injuries after open cholecystectomy have been reported with approximately 80–90% having a successful outcome (Table 50-4).69,75,88–94 Early reports and observations from the laparoscopic era were less favorable than those previously reported with open cholecystectomy repairs. Stewart and Way66 reviewed 85 patients who had undergone 112 biliary repairs and defined four factors that influenced success or failure of operative repairs after laparoscopic cholecystectomy bile duct injury: (1) performance of preoperative cholangiography, (2) choice of surgical repair, (3) details of surgical repair, and (4) experience of the repairing surgeon. Procedures without preoperative cholangiography were unsuccessful 96% of the time, and those with incomplete cholangiography data had a success rate of only 31%. With complete cholangiography data, the success rate was 84%. All patients with complete transection of the bile duct who underwent primary end-to-end repair over a T-tube had a failed result. In contrast, 63% of Roux-en-Y hepaticojejunostomy repairs were successful. Initial repair by the original laparoscopic surgeon was successful in only 17% of cases. Repeat attempts at repair by the same surgeon were never successful. Finally, those patients whose first repair was by a tertiary care biliary surgeon achieved a 94% success rate.

A series providing long-term results after repair of bile duct injuries and strictures in the 1990s was reported by Lillemoe and associates.94 A total of 156 consecutive patients underwent surgical reconstruction with a mean follow-up period of 57.5 months (range 11–119 months; median 54.7 months). The original operation consisted of laparoscopic cholecystectomy in 118 patients (76%), open cholecystectomy in 27 patients (17%), open cholecystectomy with bile duct exploration in 4 patients (3%), or other abdominal surgery or trauma in 7 patients (4%). Sixty patients (41%) had a previous attempt at repair prior to referral with eight patients (5.5%) having more than one attempt at repair prior to referral. Of the 156 operatively repaired patients, 142 patients had completed treatment at the time of final evaluation with an overall success rate of 91%. Even though they were more likely to have had repair prior to referral and higher and more complex injuries, patients with repair of a stricture or injury associated with laparoscopic cholecystectomy had a better success rate than repair after other operations (94 vs 80%; p < .05). There were 13 failures following surgical reconstruction. Ten had successful results following either surgical revision (one patient) or percutaneous balloon dilation (nine patients), resulting in an overall success rate of 98% including secondary intervention. Only three patients continued to require long-term biliary stents to prevent biliary obstruction symptoms and/or cholangitis. Comparable results have been reported from other high-volume hepatobiliary centers with similar volume of patients in the series.96–99 Outcomes after surgical repair for laparoscopic cholecystectomy injury from other series are outlined in Table 50-5.94,97–100

Effect of Surgical Repair in Quality of Life.

Despite the overall high level of success in the surgical management of laparoscopic cholecystectomy bile duct injuries, there is an impression that patients may have an impaired quality of life even after a successful repair of their bile duct injury. Quality of life after laparoscopic cholecystectomy bile duct injury has been addressed in several recent reports, with differing results.101–104 Two studies using the Short Form 36 (SF-36) Health Survey quality-of-life instrument in patients with laparoscopic cholecystectomy injury found both the physical and mental quality-of-life aspects to be reduced compared to controls at approximately 5-year follow-up.101,104 A study with SF-36 found that patients with laparoscopic bile duct injury and subsequent biliary reconstruction had quality of life similar to matched controls and national norms in all eight quality-of-life areas.103 Melton and associates102 assessed quality of life in 54 patients having undergone successful surgical repair of laparoscopic cholecystectomy bile duct injuries and compared these results to quality-of-life measures in patients after uncomplicated laparoscopic cholecystectomy and in healthy controls using a standard quality-of-life instrument, which was used to assess the physical, psychological, and social domains of health-related quality of life. Patients after surgical repair had overall quality-of-life scores comparable to those of controls. Only in the psychological dimension were patients post–bile duct injury repair found to have significantly worse scores compared to controls. Patients who reported pursuing a lawsuit following their injury (31%) had significantly worse quality-of-life scores in all domains when compared to those who did not entertain legal action (p < .01).

Summary

Postoperative bile duct strictures and major injuries remain a considerable surgical challenge. With proper diagnostic workup, clinical optimization, and definitive treatment, the vast majority of patients can achieve satisfactory outcomes. With success rates of over 90% at long-term follow-up, the gold standard for managing patients with major bile duct injuries and strictures in the current era remains surgical reconstruction. In select patients with biliary-enteric continuity, percutaneous or endoscopic management with balloon dilation may be an appropriate alternative, with success rates of approximately 50% at long-term follow-up.

Biliary strictures may occur in association with a wide range of processes causing fibrosis of the bile ducts. While inflammatory causes of bile duct strictures account only for a minority of biliary strictures in the United States, biliary strictures from these causes are important diagnostic and therapeutic challenges. Strictures from chronic pancreatitis, biliary calculous disease, sphincter of Oddi stenosis, and peptic ulcer disease can usually be managed with choledochoduodenostomy or Roux-en-Y hepaticojejunostomy without long-term stenting. The management of other infrequent causes of benign biliary strictures depends on the etiology, natural history, and severity of disease.

Chronic Pancreatitis

Chronic pancreatitis is an infrequent cause of bile duct stenosis and stricture, accounting for fewer than 10% of benign biliary strictures. While acute pancreatitis is frequently associated with transient partial obstruction of the distal common bile duct from inflammation and edema, chronic pancreatitis can result in distal bile duct obstruction from inflammation and parenchymal fibrosis of the pancreatic gland. Strictures from chronic pancreatitis typically involve the entire intrapancreatic segment of the common bile duct, resulting in proximal dilation of the biliary tree.

Chronic pancreatitis resulting in bile duct stricture is most commonly caused by alcoholism. Strictures more commonly present in patients who have advanced disease with pancreatic calcification, diabetes, or malabsorption at the time of presentation. The exact incidence of common bile duct strictures is not known because cholangiography is not routinely performed in patients with chronic pancreatitis. With a review of several clinical series, common bile duct strictures associated with chronic pancreatitis occur in approximately 5% of patients with estimated ranges varying from 3 to 29% of patients.105,106

Common bile duct strictures due to chronic pancreatitis may have a wide range of clinical presentations. On one end of the spectrum, patients can be asymptomatic with only abnormal liver function tests. Serum alkaline phosphatase, the most sensitive liver function test, is elevated in over 80% of cases. Patients can also present with abdominal pain with or without jaundice. Importantly, abdominal pain from biliary strictures can be difficult to distinguish from pain caused by chronic pancreatitis. Patients with pain from biliary stricture who are not properly diagnosed and treated for their stricture may undergo inappropriate and unsuccessful operative procedures to address pain presumed to be from chronic pancreatitis. Finally, patients who develop jaundice in the setting of chronic pancreatitis may present a diagnostic dilemma, as an underlying periampullary malignancy must also be considered.107

Evaluation of bile duct strictures from chronic pancreatitis is most effectively accomplished with cholangiography. MRCP is the preferred route for noninvasive assessment, with ERCP and PTC both effective at delineating anatomy and allowing decompression of the biliary tree in the setting of cholangitis or severe jaundice. ERCP is the preferred diagnostic procedure because it has the advantage of demonstrating pancreatic ductal anatomy, including possible abnormalities, which are especially useful in surgical management. The most common cholangiographic image in chronic pancreatitis–associated bile duct strictures is a long (usually 2–4 cm), smooth, gradual tapering of the distal common bile duct (Fig. 50-19).

The most common accepted indications for operative management in common bile duct strictures from chronic pancreatitis are cholangitis, jaundice, or significant pain. It remains unclear, however, if biliary decompression in asymptomatic patients with elevated serum alkaline phosphatase is indicated. Many surgeons do advocate biliary bypass in this situation, as early biliary cirrhosis changes may be observed in liver biopsy specimens in patients with long-standing, significant biliary obstruction from chronic pancreatitis.108,109

Biliary bypass with choledochoduodenostomy or Roux-en-Y choledochojejunostomy represents the optimal form of management for bile duct strictures associated with chronic pancreatitis. Potential advantages of choledochoduodenostomy over Roux-en-Y choledochojejunostomy include maintenance of bile flow into the duodenum that may be more physiologic, increased technical ease, and no loss of small bowel length for formation of a Roux-en-Y limb. Operative management with pancreaticoduodenectomy is appropriate in those patients in whom periampullary malignancy cannot be ruled out by imaging studies or clinical course or in those patients with significant pain attributed to proximal pancreatic duct disease. Both long- and short-term outcomes of surgically managed distal bile duct strictures from pancreatitis are usually excellent.100,110

The management of common bile duct strictures from chronic pancreatitis with either transduodenal sphincterotomy or endoscopic sphincterotomy is not recommended owing to the stricture's long length. While long-term follow-up is lacking, several series have reported success in 60% of patients with follow-up at approximately 2 years after endoscopic balloon dilation of distal bile strictures from chronic pancreatitis.111,112 It would appear that in most cases when a benign process can be expected to require years of follow-up, that surgery would be the best form of management.

Gallstone Disease

Long-standing cholelithiasis with recurrent bouts of cholecystitis results in a progressively fibrosed, shrunken gallbladder. Eventually, the gallbladder lumen can lie alongside the common hepatic duct, resulting in inflammation and resultant bile duct stricture. Often referred to as Mirizzi's syndrome, this process is typically subdivided into two categories. Type I Mirizzi's syndrome occurs when the process results in either mechanical compression of the duct or an inflammatory stricture of the common hepatic duct. In contrast, type II consists of erosion of the stone in the duct, resulting in cholecystocholedochal fistula.

Mirizzi's syndrome usually presents as jaundice or recurrent cholangitis. In some long-standing cases, these findings exist in the face of chronic gallbladder symptoms. In cases of Mirizzi's syndrome associated with acute cholecystitis, care must be taken at the time of cholecystectomy to avoid bile duct injury during initial dissection. The presence of Mirizzi's syndrome obliterates the triangle of Calot and makes laparoscopic cholecystectomy particularly difficult and will often require conversion to an open procedure. If Mirizzi's syndrome is considered, intraoperative cholangiography should be performed.

If urgent cholecystectomy is not indicated, ERC or PTC can help to delineate the anatomy. Importantly, Mirizzi's syndrome can be difficult to distinguish from strictures that result from gallbladder cancer or cholangiocarcinoma.113 ERC can also be helpful for obtaining brush biopsies in these patients.

Formal management of strictures from biliary stones varies according to the extent of disease. Patients in whom the bile duct is inflamed and no fistula is present (type I) can often be managed with cholecystectomy. The common hepatic duct almost always returns to normal after the offending stone has been removed by cholecystectomy and the inflammatory process has resolved. Care must be taken, however, during the dissection to avoid creating a defect in the common hepatic duct. Rarely, after the acute episode has resolved, a well-established stricture presents months to years after the acute episode. In such cases, management by Roux-en-Y hepaticojejunostomy is appropriate. If cholecystocholedochal fistula (type II) is present, partial cholecystectomy is recommended and the cuff of remaining gallbladder is used to repair the bile duct over a T-tube.

In addition to Mirizzi's syndrome, calculous disease also rarely results in strictures due to choledocholithiasis. The pathogenesis of strictures from choledocholithiasis is thought to be from epithelial erosion of the distal bile duct from calculous disease, resulting in inflammation with subsequent fibrosis and stricture.

Nearly all stones remain entrapped in the intrapancreatic portion of the common bile duct because of the anatomic tapering of the common bile duct. These trapped stones are often difficult to remove via endoscopic means or via a supraduodenal approach during common bile duct exploration. In fact, common bile duct exploration to retrieve stones with forceps, scoops, and catheters can often result in additional trauma to the friable distal duct from excessive intraoperative manipulation. After stone removal, the distal bile duct should be gently sized with a soft rubber catheter to check for the presence of a stricture. Strictures often may not be recognized until the postoperative period when T-tube cholangiography is performed. When strictures are found postoperatively, stricture repair should be performed after inflammation has resolved, typically after 4–6 weeks. Stricture repair of the distal bile duct is indicated for persistent strictures using either Roux-en-Y choledochojejunostomy or choledochoduodenostomy biliary-enteric anastomosis. A choledochoduodenal anastomosis is preferable in patients with a large, dilated (>2 cm in diameter) proximal duct because of its technical ease and excellent results.

Recurrent Pyogenic Cholangitis and Other Parasitic Disease

Recurrent pyogenic cholangitis, also known as oriental cholangiohepatitis, is endemic is Southeast Asia. Recurrent pyogenic cholangitis occurs infrequently in Western countries but with immigration from Asia is now increasingly encountered. Most cases are due to parasitic infection (Ascaris lumbricoides or Clonorchis sinensis) of the biliary tree. The infection results in biliary stasis, bacterial overgrowth and inflammation, biliary sludge, and brown (calcium bilirubinate) stone formation. Patients will typically have multiple intra- and extrahepatic stones and strictures, as well as recurrent cholangitis. Although strictures can occur throughout the biliary tree, they are most common in the main hepatic ducts, with disease in the left hepatic duct typically more frequent and more severe than the right. Classically, patients are young, thin, of Asian descent, and present with recurrent bouts of cholangitis. Cholangitis can range in severity from subclinical chronic illness to life-threatening acute suppurative cholangitis.

Diagnostic imaging modalities for oriental cholangiohepatitis include ultrasonography, CT scan, MRCP, ERC, and PTC. While ultrasound is poor at showing biliary strictures reliably, ultrasound is effective at demonstrating biliary obstruction, biliary tract stones, pneumobilia from gas-forming organism infection, and liver abscesses. Intrahepatic stones on ultrasound have a characteristic posterior acoustic shadowing. CT scan is useful for delineating hepatic anatomy and parenchymal involvement in more advanced disease, which is helpful for guiding potential liver resection. MRCP should be the first step to noninvasively define the biliary anatomy for the presence of strictures and stones. In addition, ERCP and PTC provide therapeutic biliary decompression in the setting of acute cholangitis (Fig. 50-20).

Long-term management of recurrent pyogenic cholangitis is aimed at treating biliary strictures using improved biliary drainage via biliary reconstruction. Following temporary decompression of the biliary tree with ERCP or PTC for acute cholangitis, patients are allowed a period of several weeks for clinical optimization prior to further management. Attempts at percutaneous or endoscopic manipulations of the biliary tree for stone extraction and biliary stricture dilation may be entertained. These interventions, however, have only temporary short-term benefit, and operative management will eventually need to be considered.

Standard operative management consists of Roux-en-Y hepaticojejunostomy, usually with a transhepatic stent. An attempt at complete clearance of stones from the intrahepatic ducts should be made, including the use of choledochoscopy. The stent is useful for follow-up cholangiography and further stone clearance after the initial procedure. Another option for follow-up management is for the blind end of the Roux-en-Y limb to be sutured to the peritoneal surface of the abdominal wall, along with a radiopaque marker. This creates an enteric portal for future access to the biliary tree and anastomosis. In cases in which disease is confined to one portion of the liver with extensive fibrosis or hepatic abscess, hepatic resection may be considered.

Other causes of biliary strictures from parasites include various forms of echinococcal disease. Biliary strictures from echinococcal infection are primarily related to the compression of bile ducts by a thick-walled cyst. Because of its low rate of morbidity, long-term endoscopic stent therapy has become the initial therapy of choice in patients with biliary stricture from hydatid disease.114,115 Operative therapy should be considered only in cases of failed previous repairs or failed endoscopic therapy. Surgical treatment of echinococcal liver and biliary disease is associated with a high rate of postoperative bile duct stricture, necessitating long-term clinical surveillance.

Sphincter of Oddi Stenosis

Also referred to as papillitis, stenosis of the sphincter of Oddi is a benign intrinsic obstruction of the common bile duct outlet. Papillitis is typically associated with inflammation, fibrosis, or muscular hypertrophy of the sphincter of Oddi. Patients with sphincter of Oddi stenosis are prone to (1) common bile duct obstruction from fibrosis and stenosis of the papilla, (2) recurrent pancreatitis, and (3) recurrent right upper quadrant abdominal pain in the absence of jaundice or pancreatitis. Initial presentation is most often jaundice or cholangitis. Patients can also sometimes present with an impacted stone at the ampulla.

The etiology of papillitis is unknown. Many cases are thought to be caused by trauma from the passage of multiple small stones or sludge from the common bile duct through the ampulla, resulting in inflammation, fibrosis, and stricture formation. There are other patients, however, that have papillary stenosis without gallstones. The cause in these cases is less clear; potential triggers include primary sphincter motility disorders and congenital anomalies.

Management consists of proper diagnostic imaging and therapeutic sphincterotomy. Cholangiography with either MRCP, PTC, or ERCP is the mainstay of diagnostic imaging. Therapeutic sphincterotomy can be performed either endoscopically or operatively in conjunction with cholecystectomy. The procedure of choice in patients with previous cholecystectomy is endoscopic sphincterotomy.

Primary sclerosing cholangitis (PSC) is an idiopathic condition characterized by a progressive, chronic cholestatic process, resulting in diffuse inflammation, sclerosis, and obliteration of the intra- and extrahepatic biliary duct systems and subsequently leading to biliary cirrhosis. The diagnosis of PSC is confirmed by cholangiography, with findings of multiple areas of stricture and dilation.

PSC has a variable course but can progress to biliary obstruction with secondary cirrhosis, portal hypertension with bleeding varices, or hepatic failure. Finally, PSC is a strong risk factor for the development of cholangiocarcinoma. Surgical management for symptomatic disease in patients with primarily extrahepatic and/or hilar disease and with no evidence of cirrhosis includes resection of the hepatic bifurcation with long-term transhepatic stenting. Finally, liver transplantation is the treatment of choice in patients with primarily intrahepatic strictures or advanced cirrhosis.

Pathogenesis

The etiology of PSC remains unknown, and a variety of causal theories have been proposed. Inflammatory bowel disease, particularly ulcerative colitis, is present in 30–90% of patients with PSC in several large population-based studies.116,117 This tight association with inflammatory bowel disease suggests an autoimmune process. However, other mechanisms likely have a role in pathogenesis because only a minority with ulcerative colitis have PSC.116 Although both ulcerative colitis and PSC may occur in the same individual, the two disorders may occur at different times. PSC, for example, may occur years after colectomy for ulcerative colitis. In addition to commonly occurring in patients with ulcerative colitis, PSC can occur with multifocal fibrosclerosis syndromes, including retroperitoneal, mediastinal, and/or periureteral fibrosis, Riedel's thyroiditis, or pseudotumor of the orbit.

Because there is the association between PSC and inflammatory bowel disease, several investigators have speculated that increased bacterial spread into the portal circulation from inflamed large or small intestine may lead to chronic or recurrent cholangitis. In support of this, an animal model of small intestinal bacterial overgrowth has biliary findings similar to PSC.118 Although some studies have documented increased portal bacteremia in patients with PSC, other studies have not confirmed this finding.119,120

Correlating evidence for an immunological cause of PSC includes its association with hypergammaglobulinemia (30%) and an increase in IgM (50%). Patients with PSC can also have autoantibodies, with titers in the range associated with autoimmune hepatitis. In particular, anti–smooth muscle antibodies and antinuclear antibodies are present in approximately 75%.121 Other autoantibodies commonly associated with the disease include cytoplasmic and nuclear antigens to neutrophils (pANCA). The autoantibody pANCA is often found in patients with PSC and no ulcerative colitis but is uncommon in patients with ulcerative colitis alone.122

Several genetic factors appear to give individuals a predisposition to PSC, including increased prevalence of HLA-B8, -DR3, and -Drw52a. The HLA-B8 and HLA-DR3 haplotypes are associated with other autoimmune diseases, including celiac disease, myasthenia gravis, and diabetes mellitus. A specific mutation of MICA (an MHC class I-related molecule) is also strongly associated with PSC patients (58 compared to 22% in controls).123

In contrast to PSC, secondary sclerosing cholangitis has similar clinical characteristics but has identifiable causes. The inciting factors for secondary sclerosing cholangitis include infectious cholangiopathy associated with acquired immunodeficiency syndrome, congenital biliary abnormalities, ischemic cholangiopathy secondary to intrahepatic arterial infusion of 5-fluorouracil, hepatic allograft rejection, graft-versus-host disease in bone marrow transplantation, collagen vascular diseases, histiocytosis X, sarcoidosis, and mast cell cholangiopathy. Patients with diffuse stricturing from 5-fluorouracil are managed by simple discontinuation of infusion, and in some cases percutaneous transhepatic drainage. Surgery should be reserved for patients with persistent evidence of biliary obstruction. The pathogenesis of acquired immunodeficiency syndrome cholangiopathy is believed to be viral and related to cytomegalovirus infection. No experience in the surgical management of this condition has been reported.

Presentation

Primary sclerosing cholangitis is predominantly a disease of young men. Approximately 70% of patients are male, and the average age at the time of diagnosis is 40 years. The typical presentation includes either an asymptomatic individual with abnormal liver function tests or an individual with intermittent jaundice. Other common symptoms may include right upper quadrant pain, weight loss, fever, pruritus, and fatigue. Despite its name, a minority have acute cholangitis, and blood cultures are rarely positive, approximately 10% are very symptomatic at the time of diagnosis; however, asymptomatic patients can have deceptively advanced disease.

Diagnosis

Laboratory tests with PSC typically reveal a cholestatic picture. Patients will have an elevated alkaline phosphatase, and during exacerbations may have elevated bilirubin. Early in the disease course, patients will have a normal albumin. The diagnosis is usually made through cholangiography, usually MRCP or ERCP. The typical study reveals multifocal strictures and dilations, referred to as “beading,” of the intra- and extrahepatic ducts (Fig 50-21). The therapeutic modality of choice for cases requiring intervention is via the endoscopic route. PTC may be difficult because cannulation of nondilated and fibrotic ducts associated with PSC can be technically challenging via this approach. At the time of diagnostic cholangiography, brushings for cytology should be obtained to help distinguish between benign and malignant strictures.

Management

Management of PSC has several important treatment goals, including halting or reversing the disease process, managing disease progression, and symptom control. Unfortunately, there are no effective medical treatments that slow the progression of PSC. Patients should be monitored closely with cholangiography, liver biopsy, and cytologic brushings, to detect disease progression and development of malignancy or biliary cirrhosis.

Most medical therapies are aimed at symptomatic relief or antibiotic treatment in the setting of cholangitis. Immunosuppression with glucocorticoids, methotrexate, azathioprine, 6-mercaptopurine, tacrolimus, or cyclosporine have not demonstrated efficacy for disease progression or survival. The use of ursodeoxycholic acid (UDCA) has demonstrated improvement of liver function tests and symptoms. A prospective, randomized, placebo-controlled trial of UDCA, however, did not demonstrate long-term clinical benefit with UDCA.124 High-dose UDCA in several small pilot studies has demonstrated decreased disease progression and improved survival125,126; larger-scale prospective trials with high-dose UDCA are still ongoing.

A dominant extrahepatic biliary stricture (a high-grade, localized area of narrowing) occurs in approximately 20% of patients with PSC. These patients can be managed potentially with endoscopic therapy using dilation with or without stenting. Cytologic brushings at the time of endoscopy should also be obtained to investigate for cholangiocarcinoma. Several retrospective reports have demonstrated benefit in relieving symptoms and improving liver function tests from endoscopic therapy,127 and possible delay in disease progression.128 The durability, however, of endoscopic therapy appears to be poor, with most patients requiring repeat dilations at regular intervals. Whether patients should undergo stenting at the time of dilation is not clear, with short-term results of stenting similar to those of dilation treatment alone,129 and with no long-term outcomes at present comparing the two techniques.

Operative biliary reconstruction with transhepatic stenting for primarily extrahepatic and/or hilar disease in noncirrhotic patients has been demonstrated to have excellent long-term outcomes.130,131 Ahrendt and associates131 reported 146 patients with PSC managed with either biliary reconstruction or nonoperative biliary dilation. Survival was significantly longer in noncirrhotic patients with PSC managed surgically compared to those managed nonoperatively, and time before requiring liver transplant was significantly longer in the surgically-managed patients (Fig 50-22).

The natural history of PSC is typically progressive. Regardless of therapy, median survival is typically 12 years following diagnosis.132,133 Survival is significantly worse in patients symptomatic at the time of diagnosis.133 The incidence of cholangiocarcinoma of PSC patients at 5 years is 10–15% and at 10 years increases to 30%.

Hepatic transplantation provides excellent results in patients with PSC and end-stage liver disease, with 5-year actuarial survival and graft functioning of 85 and 72%, respectively.134 Liver transplant should be considered in patients with sclerosing cholangitis before the disease is too advanced. Primary indicators for referral for liver transplant include persistently elevated bilirubin or decreased quality of life from disabling fatigue, severe pruritus, muscle wasting, or bacterial cholangitis. Biliary tract surgery before transplant does not affect either short-term outcomes or survival after transplant.

Patients with preoperatively recognized cholangiocarcinoma have a poor prognosis. These patients are not appropriate candidates for transplantation. On the other hand, the presence of a small (<1 cm) cholangiocarcinoma discovered incidentally on pathology at transplant does not appear to portend a poor prognosis.

Patients transplanted for PSC are also at increased risk of postoperative biliary stricture compared to those transplanted for other primary disease processes. Recurrent PSC occurs in approximately 10% of patients following transplant, but with typically a less aggressive course.134

Summary

PSC currently has no proven effective medical treatment. Resection of the hepatic duct bifurcation in conjunction with long-term transhepatic stenting in noncirrhotic patients with primarily extrahepatic and/or hilar disease can delay or even prevent the need for hepatic transplantation. This operation does not influence the outcomes associated with hepatic transplantation. Transplant is recommended in patients with primarily intrahepatic strictures or advanced cirrhosis.