Benign conditions of the intrahepatic or extrahepatic bile ducts can range from focal or diffuse dilatations (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 dilatations of the biliary tree, and aside from biliary atresia, they are the most common congenital abnormality of the biliary tree. Choledochal cysts can occur as single or multiple cysts throughout the extrahepatic 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 13,500; the incidence has been reported to be as high as 1 in 1000 in studies 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 4 times more common in women compared with men. Approximately 80% of choledochal cysts are diagnosed in children, and 20% of cases present in adults.² There are a few case reports of choledochal cysts occurring within families, but generally, they 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 3 types of choledochal cysts.³ The classification system was revised by Todani and colleagues in 1977 to the 5 cyst categories⁴ that are in use today (Table 64-1). A similar classification has been proposed based on bile duct cholangiographic appearance.^5,6

Traditionally, the classic and most common choledochal cyst is type I disease: (A) cystic (Fig. 64-1A), (B) saccular, or (C) fusiform dilatation of the extrahepatic biliary tree. Type II cysts are simple diverticula of the common bile duct, which are usually extrahepatic, supraduodenal, and saccular (Fig. 64-1B). A rare combination of type I cystic dilatation and type II diverticulum was reported in a few cases representing a mixed type. A type III cyst, also known as choledochocele, is a focal cystic dilatation of the most distal segment of the bile duct (Fig. 64-1C). Manning and colleagues⁷ described 2 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 dilatations of the intrahepatic and extrahepatic biliary tree are known as type IV cysts divided into type IVa and type IVb. Type IVa represents fusiform extrahepatic and intrahepatic cysts (Fig. 64-1D). Type IVb consists of multiple extrahepatic cysts (Fig. 64-1E). Type V cyst, Caroli disease, is confined to the entire liver or a solitary lobe, usually on the left (Fig. 64-1F).^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 compose 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 type I and IV cysts versus type II, III, or V cysts. A review 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 with respect to age, sex, presentation, pancreatic ductal anatomy, and 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 dilatation.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 90% of patients with choledochal cyst disease (Fig. 64-2).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, since 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 sphincter 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.

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.²³ 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.²⁴ Intermittent jaundice and recurrent cholangitis are also common, as is pancreatitis (30%), especially in patients with a type III cyst (choledochocele).^1,9,25 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 dilatation 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.²⁴ 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. 64-3) 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 colleagues²⁶ 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 type IVB and V cysts.

Cholangiography had previously been considered the gold standard for diagnosis of choledochal cysts but now only 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 dilatation and the presence of stones and exclude complete obstruction of the bile duct (Fig. 64-4). 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. In patients with type I or type IV cysts that extend to the hepatic bifurcation, PTC allows for the placement of 1 or 2 transhepatic biliary catheters, which may be helpful to facilitate complete resection and biliary reconstruction (Fig. 64-5). 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. Adenocarcinoma comprises 73% to 84% of malignancy associated with choledochal cysts, and additional histologic subtypes include anaplastic carcinoma (10%), undifferentiated cancer (5%-7%), squamous cell carcinoma (5%), and other types such as bile duct sarcoma.²⁷ The incidence of cholangiocarcinoma with biliary cysts varies with patient age and cyst type. The lifetime risk of associated cholangiocarcinoma is 6% to 30% in several studies, and importantly, the rate of malignancy increases with age. Patients discovered in their 20s have only a 2.3% risk of concomitant malignancy, but this risk increases to 14.6% for patients with choledochal cysts discovered in their 30s and 40s.^8,22,27-29 In older untreated patients, the reported incidence of cholangiocarcinoma is as high as 75%.²⁸ In a review examining the occurrence of malignancy in 5780 patients with choledochal cyst, the overall incidence of biliary tract cancer was 7.5%. The incidence in children (age 0-18 years) was low (0.4%), with increased rates in those older than 18 years (11%). The incidence steadily increased with age up to 38% in patients older than 60 years. Among patients who develop malignancy, 70% arise as cholangiocarcinoma within the cyst wall and approximately 24% arise as gallbladder cancer.³⁰ Type I and IV cysts have a higher risk of cancer, whereas cancer is rare in type II and III cysts. In type IIIcysts, cancer risk may be limited to those choledochoceles lined by biliary and not duodenal epithelium. Caroli disease also carries a risk (approximately 7%) of cholangiocarcinoma. Most patients with Caroli disease, however, will present first with compromised liver function or cholangitis before developing malignancy.

The Johns Hopkins series included 92 choledochal cyst patients, with 8 of the patients 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.²⁸ Malignancy may develop with incompletely resected cysts, at the anastomotic site, or in residual cyst left within the pancreas.²⁸

Speculated etiologic 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 whereas dysplastic cells frequently have microsatellite instability (60%)³⁴ and cancerous lesions often have overexpression 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 (approximately 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 for 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 years²⁸ after enteric drainage has changed the recommended management to complete cyst excision. The current treatment of choice is surgical excision, because 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.³⁷

Enteric interposition grafts have been proposed as an option due to 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 type I and type II choledochal cysts have also been reported using laparoscopic techniques, particularly in children. A 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% reoperation rate.³⁹ In another series by Senthilnathan et al,⁴⁰ 110 patients underwent laparoscopic resection and reconstruction of type I or type IVA choledochal cysts. The overall mortality was 1%, reoperative rate was 2%, and morbidity was 10%. Thus, this study demonstrated that laparoscopic surgery for choledochal cysts is 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 of 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 cysts 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 maneuver to expose the distal portion of the cyst that lies posterior to the duodenal wall (Fig. 64-6A). After the cyst has been exposed, the gallbladder, which usually arises from the mid-portion of the choledochal cyst, should be dissected away from the hepatic bed (Fig. 64-6B). The procedure then focuses on the distal portion of the choledochal cyst (Fig. 64-6C). 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. 64-6D). 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. 64-6E). 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. 64-6F). 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. 64-6G,H).

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. Although uncommon, surgical intervention for choledochoceles is needed for patients in whom sphincterotomy is very difficult or there is concern for malignancy.

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. Prior to 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 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 8-Fr 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

Type IVA and IVB cysts are managed similarly to type I cysts with regard to 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 that involves anastomosing individual hepatic ducts. If 1 lobe of the liver is predominantly involving the intrahepatic cyst, then 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 cysts and Caroli 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, then 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; may prevent or facilitate the management of long-term complications, such as biliary stasis, stones, cholangitis, and cirrhosis; and may be used for surveillance for malignant transformation.

Oncologic 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, then resection of the involved bile ducts and adjacent parenchyma and lymph node dissection are 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 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. Although Caroli 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 disease, if unilateral or with segmental involvement with cirrhosis, can be managed by resection of the involved parenchyma, resulting in decreased incidence of recurrent cholangitis, pancreatitis, and cholestasis and decreased need for invasive procedures. Bilobar Caroli 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 to 12 months, depending on the extent of intrahepatic stones and strictures. Patients who continue to have recurrent cholangitis or recurrent stones often require indefinite transhepatic stenting. Patients with Caroli 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. Since patients with Caroli disease may also have polycystic kidney disease, combined liver-kidney transplants have had excellent outcomes. Mabrut and colleagues performed a multicenter study that included 155 patients with type V choledochal cysts from Western surgical centers. Patients underwent either hepatic resection (75%) or liver transplantation (19%) with excellent or good results achieved in 86% of patients. Five-year overall survival was 97% after liver resection and 89% after liver transplant.¹⁰

OPERATIVE RESULTS

Early postoperative complications include pancreatitis, anastomotic leakage, cholangitis, and wound infection. Most series show morbidity rates of 9% to 41% and mortality rates of 0% to 3.3%.^9,24,39 The median length of stay ranges from 7 to 12 days after surgery; patients who undergo a laparoscopic approach have a slightly decreased hospital 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 Cho and ­associates⁴² examined 204 patients with a mean follow-up of 14 years. Patients with type IVA disease with dilated intrahepatic ducts developed strictures at a rate of 24%, with virtually all ­presenting with 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 intrahepatic or extrahepatic bile ducts or both, and may be solitary or multiple. There are numerous etiologies of benign bile duct strictures (Table 64-2). 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 (PSC) 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 dilatation 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 1 to 3 major bile duct injuries per 1000 cases was consistently reported during the era of open cholecystectomy. Roslyn and colleagues⁴⁴ demonstrated a 0.2% incidence of major bile duct injuries from a series of over 42,000 open cholecystectomies. 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 the 1990s, Strasberg and associates⁴⁵ reviewed nearly 125,000 laparoscopic cholecystectomies and reported an overall incidence of biliary injuries of 0.85% and an incidence of major injuries of 0.52%. Recently, multiple large studies from numerous centers have estimated the rate of major bile duct injury with laparoscopic cholecystectomy to be 0.08% to 0.6%.^46-48 A recent 5-year review of the New York State Planning and Research Cooperative System (SPARCS) showed that over 156,000 patients had undergone laparoscopic cholecystectomy and only 149 biliary injuries were identified, indicating a rate of 0.08%.⁴⁶ Therefore, it appears that the incidence of bile duct injury associated with laparoscopic cholecystectomy is now comparable to that with open cholecystectomy. This improvement likely reflects increased experience, improved instrumentation, and movement beyond the “learning curve.” Finally, the effect of new techniques such as single-port laparoscopic cholecystectomy or the value of robotic technology in the safe performance of laparoscopic cholecystectomy is yet to be determined. However, some concern has been expressed related to the learning curve of such procedures when compared with the established laparoscopic procedure.

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. The rate of bile duct injuries appears now to have stabilized or perhaps decreased in the laparoscopic era; however, with newer graduates having less experience with open cholecystectomy, the rate of bile duct injury associated with a difficult cholecystectomy may be on the rise for the open procedure. Similarly, due to their lack of experience, conversion from laparoscopic cholecystectomy to open cholecystectomy may increase the rate of bile duct injuries.⁴⁹ An “extreme” vasculobiliary injury with injury to the hepatic artery and/or portal vein may occur in conversion from laparoscopic to open cholecystectomy in the presence of severe inflammation in and around the gallbladder when a fundus-down cholecystectomy is performed. Severe hemorrhage is common and is caused by dissection behind the cystic plate into the right portal pedicle involving vascular injury to a major hepatic artery and a portal vein. This “extreme” vasculobiliary injury can lead to infarction of the liver or diffuse bile duct infarction requiring possible hepatectomy or need for urgent liver transplantation or leading to death.⁵⁰

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 differ in the open or laparoscopic approach. Ultimately, the final common pathway of most injuries is either a technical error or misinterpretation of the anatomy. The chapter will focus primarily on laparoscopic cholecystectomies because 98% of cholecystectomies are initially started as a laparoscopic procedure. 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. 64-7).

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 the Calot triangle, which can make an operation difficult. Patients also with complicated gallstone disease have a higher risk of injury than patients with chronic cholecystitis, symptomatic cholecystitis, or biliary colic. Tang and Cuschieri⁵¹ reported that complex cases, which included patients with acute cholecystitis, cholangitis, and gallstone pancreatitis, are associated with an increased incidence of bile duct injuries (1.2% vs 0.4%) versus other indications for laparoscopic cholecystectomy. These patients also have a higher rate of conversion to open cholecystectomy (30% vs 3%).

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, to 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 2-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.⁵² 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.⁵³ 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.⁵⁴ 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.⁵⁵

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,⁵⁶ 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 Texas Medicare claims data from 2000 through 2009 was examined, and the rate of injury was found to be higher when intraoperative cholangiography was not used.⁵⁷ In this study, surgeons who routinely performed intraoperative cholangiography had a lower rate of injuries than those who did not; however, when confounders were controlled with instrumental variable analysis, there was no statistically significant association between intraoperative cholangiography and common duct injury. This led to the conclusion that intraoperative cholangiography is not effective as a preventive strategy against common duct injury during cholecystectomy. 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. 64-8).

The use of fluorescent cholangiography has recently been introduced to help determine biliary anatomy. Studies show that the frequency of detection of structures ranged from 72% to 100% for the cystic duct, 33% to 100% for the common hepatic duct, 50% to 100% for the common bile duct, and 25% to 100% for the common duct–common hepatic duct junction.^58,59 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 that defines the “critical view of safety” is a corrective mechanism that helps prevent misidentification and injury of the major bile ducts.⁶⁰ In this method, the triangle of Calot is cleared of fat and fibrous tissue. Only 2 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 is 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. There are studies containing several thousand patients in which the critical view of safety was used for target identification without a biliary injury due to misidentification.⁶¹ The critical view of safety is part of the Culture of Safety in Cholecystectomy (COSIC), and this problem has been addressed by the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) in a novel effort called “Safe Cholecystectomy.”⁶²

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 3 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.⁶³ A month following bile duct ligation, the bile duct wall is thickened, will have reduced mucosal folds, and will 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. 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.⁶⁴ Inflammation in the surrounding tissues compounds the problem by encouraging fibrosis, especially when associated with bile leakage.