Biliary Tract Surgery
0039-6109/90 $0.00
+ .20
Congenital Biliary Tract Disease F. M. Karrer, MD, * Roberta J. Hall, MD, * Barbara A. Stewart, MD, t and John R. Lilly, MD+
Biliary tract surgery in the pediatric patient is largely confined to operations for congenital malformations of the extrahepatic bile ducts. In the infant age group, biliary atresia is the predominant surgical lesion. Spontaneous perforation of the common bile duct, although rare, is actually the second most common cause of surgical jaundice in infancy. Later in childhood, choledochal cyst is encountered most commonly. Other malformations of the pediatric biliary tract are seen so infrequently as to be a negligible consideration in pediatric surgical practice.
BILIARY ATRESIA Historical Perspective In the earliest description of biliary atresia, in 1892, 15 John Thomson correctly characterized the disease as a progressive inflammatory lesion of the bile ducts. Ladd" is credited with the first successful operation for "correctable" biliary atresia. Because only a minority of patients have a correctable variant, biliary atresia remained a lethal disease in most affected infants despite his success. In 1959, Kasai and Suzuki? devised an operation for all types of biliary atresia. This approach was based on the finding that microscopic biliary structures are present in the fibrotic bile ducts at the From the Departments of Surgery, The Children's Hospital and University of Colorado School of Medicine, Denver, Colorado
*Assistant Professor t Research Fellow :j:Professor and Chief, Pediatric Surgery This work was supported by Grant RR-00069 from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health and The Pediatric Liver Center, University of Colorado Health Sciences Center, Denver, Colorado.
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porta hepatis. These minute ducts communicate with the intrahepatic biliary tree early in the course but later become obliterated. The rationale for the operation was that biliary atresia is a dynamic disease process rather than a static phenomenon and, therefore, that operative correction must be carried out early (before 3 months of age). Incidence and Etiology The incidence of biliary atresia is between 1:10,000 and 1:25,000. There does not seem to be a racial or genetic predilection, but there is a female predominance of 1.4:1. 4 Concurrent with the development of the hepatobiliary system, the formation of the inferior vena cava and portal vein occurs; the rotation of the midgut begins, and the spleen is being formed. About 10% to 15% of patients with biliary atresia have associated anomalies of the polysplenia syndrome such as polysplenia, absent inferior vena cava, preduodenal portal vein, and malrotation. This association suggests an early embryologic insult. However, the obliterative process in the bile ducts in biliary atresia is not localized (as in most congenital atresias) but rather involves a progressive panductular obliterative cholangiopathy. This situation suggests an acquired disease later in gestation or in the perinatal period. The pathogenesis of biliary atresia remains an enigma. Pathology Biliary atresia is a dynamic, progressive panductular obliterative process, which, untreated, results in complete obliteration of the extrahepatic biliary tree. Kasai, by systematic dissection and detailed observation of the entire extrahepatic bile ducts of 116 patients with biliary atresia, demonstrated the existence of tiny biliary structures in the tissue at the porta hepatis." Early in the course of the disease, the intrahepatic ducts are patent, although nondilated, from the intralobular ductules to the porta hepatis, where there is an arborization into the fibrous cone. The size of these minute strictures is quite variable and is correlated with the age of the infant and with bile excretion after hepatic portoenterostomy. These structures are present in most affected infants under 2 months old but gradually disappear over the next few months and by 4 months are completely replaced by fibrous tissue. The degree of involvement of the extrahepatic biliary ducts also is variable (Fig. 1). Although most commonly, the entire extrahepatic system is involved in the obliterative process (Fig. IB), some infants have sparing of the distal ducts (i.e., retained patency of the gallbladder, cystic duct, and common bile duct; Fig. LC). This group, representing 10% to 15% of patients, can have biliary continuity re-established by anastomosis of the gallbladder to the transected liver hilum. A third group has proximal "patency," with dilated pseudocyst-like structures at the liver hilum (Fig. lA). These cystic structures either do not communicate with the intrahepatic ducts at all or communicate only via minute biliary radicles. They usually have no epithelial lining but rather are composed of dense fibrous tissue. Microscopic evaluation of the liver reveals cholestasis with pigment within biliary canaliculi and in the intralobular bile ducts. Bile duct
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Figure 1. The three variants of biliary atresia. a, "Correctable" atresia. Proximal patency is often misleading, because the hilar bile pseudocysts are lined only by granulation tissue and covered by fibrous tissue. b, Biliary atresia, noncorrectable; the most common type. The entire extrahepatic ductal system is obliterated. c, As in the noncorrectable type, the proximal ducts are obliterated in this type, but patency of the gallbladder, cystic duct, and common bile duct is preserved. In all types, intrahepatic ducts are hypoplastic.
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YEARS Figure 4. Comparison of the Kaplan-Meier survival curves for children over and under 66 days old (mean age at time of Kasai's operation in our series) at operation (P < 0.05). (From Stewart BA, Hall RJ, Karrer FM, et al: Long-term survival after Kasai's operation for biliary atresia. Pediatr Surg Int 5:87-90, 1990; with permission.)
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immunosuppression-free survival of a significant number of children after Kasai's operation (28% in our Denver series). 10 Even when it is not curative, the Kasai operation extends survival in the majority of patients, allowing children to grow, thus increasing the chances that a suitable donor organ can be located and reducing transplant morbidity and mortality rates. Liver transplantation should be restricted to children who do not drain bile after Kasai's operation and who have late progression of liver disease despite relief of biliary obstruction.
CHOLEDOCHAL CYST
Choledochal cyst is a congenital malformation of the pancreaticobiliary system manifested primarily by common bile duct dilation, usually cystic. The estimated incidence ranges from 1 in 13, 000 to one in 2 million live births. There is a 3:1 female predominance, and a strong but unexplained predilection for Asians. Classification
Choledochal cysts were originally classified into three categories: type I, cystic dilatation of the common bile duct, the usual form; type II, diverticulum of the common bile duct; and type III, choledochocele (cystic dilation of the terminal common bile duct at the duodenum). Recently, the classification was expanded by adding type IV-A, multiple cysts of the intrahepatic and extrahepatic ducts; type IV-B, multiple cysts of the extrahepatic ducts only; and type V, single or multiple intrahepatic bile duct cysts with normal extrahepatic anatomy (Caroli's disease). Pathology
During the past two decades, an increasing incidence of coexisting pancreaticobiliary lesions has been noted in patients with choledochal cyst, indicating that the lesion is not a single anomaly but rather a conglomerate of developmental faults of the pancreaticobiliary system. Specifically, intrahepatic biliary cysts are found in about one third of afflicted patients. Second, most patients have a long "common channel" (i,e., the distance from the junction of the pancreatic duct and common bile duct to the ampulla is elongated). Third, many patients have a partial obstruction of the terminal common bile duct. Fourth, histologically, the bile duct wall is markedly thickened by fibrous connective tissue, the muscle layer is absent, and the mucosa is flattened, dysplastic, and ulcerated. The only common denominator in choledochal cyst has been a cystic lesion of the common bile duct. The criterion appears arbitrary. The sporadic and inconsistent pattern of associated ductal malformations suggests that, in some cases, the cystic component also may be absent or negligible. We have designated cases having all components of a choledochal cyst except a cyst as a forme fruste choledochal cyst" (Fig. 5). The treatment is identical to that of true choledochal cysts, that is, excision of the common bile duct and choledochoenterostomy.
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Figure 5. Operative cholangiogram in a patient with forme fruste choledochal cyst. Note the stenotic left major hepatic duct (straight arrow) and the long common channel with proximal junction of pancreatic and common bile duct (curved arrow). Operative treatment was by total excision of the extrahepatic bile ducts and Roux-en- Y choledochojejunostomy. (From Lilly JR, Stellin GP, Karrer FM: Forme fruste choledochal cyst. J Pediatr Surg 20:449, 1985.)
Etiology A congenital etiology is supported by reports of antenatal diagnosis, a pediatric predominance, and a characteristic association with other biliary malformations. Originally, the malformation was thought to be secondary to an unequal cellular proliferation of the common bile duct during fetal development. Next, a common channel etiology was advanced, in which an aberrant, proximally located pancreaticobiliary junction was thought to result in pancreatic reflux with subsequent duct wall destruction and dilation. Recently, a biliary autonomic dysfunction has been incriminated; that is, ganglion cells were noted to be decreased in the terminal common bile duct, causing a partial obstruction that might lead to proximal cyst formation.
Symptoms Forty to sixty per cent of patients with choledochal cysts present before 10 years of age. The classic triad of abdominal pain, jaundice, and an abdominal mass is seen in only one third of patients. Instead, patients present with a variety of symptoms, most of which are secondary to partial biliary obstruction with consequent cholangitis or pancreatitis. Infrequently, choledochal cysts rupture, leading to acute bile peritonitis. Finally, infants with choledochal cyst often present with asymptomatic jaundice secondary to total biliary obstruction.
Diagnosis Serologic studies of liver function are frequently abnormal but are nondiagnostic. Abdominal ultrasound will demonstrate the choledochal cyst. A hepatobiliary isotope scan outlines the cyst and may delineate intrahepatic cystic disease, partial biliary obstruction, or both. Computed tomography also may reveal any intrahepatic disease and defines the relation of the cyst to the other portal structures. Endoscopic retrograde cholangiopancreatog-
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raphy (ERCP) and transhepatic cholangiography (PTC) (Fig. 6) are helpful preoperative radiologic examinations. Both provide more precise anatomic detail than does ultrasound, radionuclide studies, or CT, permitting multiple views and providing better-quality images than will be obtained with intraoperative cholangiography. The ERCP examination requires a skilled endoscopist, however, and usually is not feasible in infants or younger children. The PTC study may be difficult in patients with nondilated intrahepatic bile ducts. Treatment and Prognosis Until recently, internal drainage by cyst enterostomy (choledochocystduodenostomy, choledochocystjejunostomy) was the accepted surgical treatment of choledochal cyst. However, postoperative morbidity proved to be unacceptably high. Recurrent cholangitis, cholelithiasis, failure of cyst decompression, pancreatitis, or anastomotic stricture led to a 50% reoperative rate. The fundamental cause for this high complication rate was that cyst enterostomy employed diseased biliary tissue for anastomosis. Also of concern was the malignant potential of the cyst, which would not be abolished by internal drainage. Biliary carcinomas develop in 2.5% to 4.7% of patients with choledochal cysts (20 times the rate in the normal population), and approximately half of the reported patients developed the malignancy after internal drainage procedures. 16 Consequently, the surgical procedure of choice is total excision of the choledochal cyst. The cyst may be externally mobilized prior to excision; but, particularly when pericystic inflammation has distorted the portal anatomy, we prefer an internal approach, which avoids damage to neighboring vascular, biliary, and pancreatic structures. In this technique, the cyst is opened and its wall arbitrarily separated into an internal and external wall (Fig. 7). The inner cystic wall is stripped out. The stripping dissection extends proximally to the junction of the normal hepatic duct, where it is
Figure 6. Transhepatic cholangiogram in a patient with a choledochal cyst, demonstrating cystic disease of both the right and left major intrahepatic ducts. Note that the peripheral intrahepatic ducts are normal in caliber, proving that the proximal dilations are true congenital cysts.
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BACK WALL
Figure 7. Artist's depiction of the operative technique employed in Denver for excision of choledochal cyst. The cyst has been opened; dissection is begun in the back wall to separate it arbitrarily into two layers (see text for details). (From Lilly JR: Total excision of choledochal cyst. Surg Gynecol Obstet 146:254, 1978; with permission.)
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transected, and distally to the pancreatic duct, where it is suture ligated proximal to the entrance of the pancreatic duct (Fig. 8). The inner cyst wall is resected, leaving the thin outer wall in place over the portal vein and hepatic artery. The gallbladder is always removed. Biliary reconstruction is by Roux-en-Y intestinal anastomosis to the end of the opened common hepatic duct. Some surgeons employ a valved jejunal interposition to prevent cholangitis, but cholangitis is unusual after a properly performed excisional operation in our experience. Leaving a
Figure 8. Distal intraoperative cholangiogram in a patient with choledochal cyst. The cyst has been resected; the pancreatic duct entrance was not seen during resection, so the cholangiogram was done to identify its junction (white arrow) before completing the distal resection. Black arrows outline the remainder of the pancreatic duct. (From Lilly JR, Starzl TE: Liver, gallbladder and extrahepatic bile ducts. In Welch KJ (ed): Complications of Pediatric Surgery, Prevention and Management. Philadelphia, WB Saunders, 1982, chapter 19.)
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proximal cyst cuff equal to the diameter of the jejunum to facilitate anastomosis also has been recommended. However, the diseased cyst remnant could cause late anastomotic stricture or be the site for malignant growth. Therefore, a deliberate effort should be made to remove all diseased bile duct tissue before biliary reconstruction. If the coexisting biliary malformations are at the hepatic hilum (Fig. 9A), the involved duct sometimes can be laid open longitudinally (Fig. 9B); the opened major duct is then incorporated into the biliointestinal anastomosis (Fig. 9C).9 Intrahepatic cystic involvement confined to one hepatic lobe has occasionally been treated by lobectomy. The risk of malignancy in the intrahepatic cysts is about the same as in choledochal cysts. Currently, choledochal cyst excision has a low surgical mortality rate. The morbidity rate is less than 10% and is secondary to cholangitis, anastomotic stricture, and pancreatic duct injury. The former two complications may be unavoidable in the presence of intrahepatic disease. The latter may be eliminated by compulsive identification of the pancreatic duct before cyst transection either by direct vision or by operative cholangiography (see Fig. 8). The prognosis of choledochal cyst is excellent if the diagnosis is made before irreversible liver damage occurs provided all diseased ductal tissue is accessible to excision.
IDIOPATHIC PERFORATION OF THE COMMON BILE DUCT
Although relatively rare, spontaneous perforation of the common bile duct is second only to biliary atresia as a cause of surgical jaundice in the infant. Choledochal cyst, a more common malformation, usually presents later in childhood. The cause of the perforation is not known, but its characteristic location at the junction of the cystic and common bile ducts indicts a congenital fault. The coincidental findings of biliary sludge (or even stones) and a diminution of caliber of the distal common bile duct are most likely a consequence, not the cause, of the perforation. Typically, the afflicted infant has an insidious onset of ascites, sometimes manifested by development of inguinal or umbilical hernia.:" Lowgrade jaundice and clay-colored stools occur. Because the ductal perforation usually is tiny, bile extravasation is slow, allowing its encapsulation and the development of a pseudocyst (Fig. 10). Diagnosis is made by sonographic demonstration of the pseudocyst and confirmed by hepatobiliary isotope scans, which show biliary extravasation. Misinterpretation of the lesion as a choledocal cyst, with treatment by cyst enterostomy, has proved to be disastrous. 13 Treatment is surgical. An intraoperative cholangiogram via the gallbladder often demonstrates the biliary pseudocyst and always the extravasation of contrast at the site of perforation (Fig. 11). Inflammation is intense in the portal triad. Extensive dissection or attempts to repair the perforation are not only dangerous but unnecessary. In most cases, simple peritoneal drainage of the perforation site is all that is required. Even in those unusual instances in which the intraoperative cholangiogram demonstrates complete biliary obstruction, simple peritoneal drainage and biliary decompression
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B
c Figure 9. Technique in coexisting cystic disease of the left major hepatic duct. A, Anatomy. In this circumstance, excision of the choledochal cyst is done at the liver hilum, and the incision is extended (B) into the intrahepatic cyst. C, The choledochoenterostomy incorporates the filleted left major hepatic duct. (From Lilly JR: Surgery of coexisting biliary malformations in choledochal cyst. J Pediatr Surg 14:643, 1979.)
via the tube cholecystostomy often suffice. Decompression frequently results in complete resolution of obstruction and, if not, permits quiescence of inflammation and safer subsequent operation (ampullary dilatation, choledochoenterostomy). We advocate retention of the tube cholecystostomy for postoperative cholangiography; peritoneal drains should not be removed until complete healing of the ductal perforation is demonstrated, usually 2 to 3 weeks after the operation. 12
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Figure 10. Artist's depiction of spontaneous perforation of the common bile duct. The perforation generally is small; bile escapes so slowly that a pseudocyst is formed. Misinterpretation of the pseudocyst as a choledochal cyst with treatment by cyst enterostomy has proved to be disastrous. Simple peritoneal drainage suffices in most cases.
The prognosis is excellent except in those infants who, because of either delay in diagnosis or operative procrastination, develop infected ascites. In these cases, sepsis and death are unusually rapid. In the majority of infants, however, the surgical course of spontaneous perforation of the common bile duct is bland, and hepatobiliary sequelae are absent.
INSPISSATED BILE SYNDROME Although not strictly in the purview of congenital biliary tract disease, the inspissated bile syndrome occurs with sufficient frequency to warrant inclusion in a discussion of pediatric obstructive jaundice. In this disease, bile becomes abnormally thick and viscid as a consequence of an underlying disorder such as dehydration, hemolysis, parenteral alimentation, or cystic fibrosis. The resultant biliary sludge may plug the lumen of the common
Figure 11. Operative cholangiogram in an infant with spontaneous perforation of the common bile duct. Straight arrows outline the encapsulated bile leak. The radiologic meniscus (curved arrow) suggesting choledocholithiasis resolved spontaneously after simple peritoneal drainage. (From Lilly JR, Starzl TE: Liver, gallbladder and extrahepatic bile ducts. In Welch KJ (ed): Complications of Pediatric Surgery: Prevention and Management. Philadelphia, WB Saunders, 1982, chapter 19.)
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bile duct, causing obstructive jaundice (Fig. 12). Often, the biliary obturation spontaneously resolves with treatment of the underlying disorder, but occasionally, operative therapy is necessary, particularly if inspissation has progressed to actual stone formation. In most instances, the operation is limited to simple irrigation of the extrahepatic bile ducts via tube cholecystostomy.
MISCELLANEOUS BILIARY TRACT MALFORMATIONS Agenesis, duplication, and congenital diverticulum of the gallbladder are reported sporadically. These malformations usually are asymptomatic. Gallbladder agenesis may be embarrassing in operations done for presumed acute cholecystitis. Occasionally, duplications and diverticulum predispose to stone formation. Agenesis of the extrahepatic bile ducts is also rare and incompatible with survival beyond 1 to 2 years. Duplications of the extrahepatic ducts are oddities that have surgical significance only in instances of extensive liver resection or liver transplantation.
SUMMARY Jaundice in the pediatric patient requires prompt and directed evaluation. This dictum is highlighted in infants with biliary atresia, in whom the progressive sclerosing process results in complete obliteration of patent but microscopic hilar biliary structures by 4 months of age. Kasai's operation, if done before that time, will re-establish bile drainage in 90% of infants. One fourth to one third of patients achieve long-term jaundice-free survival. Complications of cholangitis, portal hypertension, and fat malabsorption are experienced by many patients. In children with early or late operative failure, liver replacement now offers legitimate hope for extended survival. Choledochal cyst is a conglomerate of pancreaticobiliary anomalies consisting of a choledochal cyst, a common-channel-type pancreaticobiliary
Figure 12. Operative cholangiogram showing complete obstruction in an infant with the inspissated bile syndrome. An ABO blood incompatibility resulted in excessive hemolysis with secondary bile sludge in the common bile duct. In this instance, an impacted bilirubin stone had to be removed surgically. (From Lilly JR: Common bile duct calculi in infants and children. J Pediatr Surg 15:577, 1980.)
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junction, intrahepatic cystic disease, and partial obstruction of the distal common bile duct. Many patients have one or more of these malformations. It is now widely accepted that the preferred treatment of choledochal cyst is total excision of the diseased biliary duct with reconstruction by Rouxen-Y choledochojejunostomy. "Internal" excision avoids injury to other structures in the hepatoduodenal ligament, particularly if pericystic inflammation is present. Congenital perforation of the common bile duct responds in most cases to simple peritoneal drainage of the perforation. Retention of the tube cholecystostomy is useful for subsequent cholangiographic follow-up. Tube cholecystostomy may also be useful for irrigation of the biliary tract in infants with inspissated bile syndrome.
REFERENCES 1. Brandt CT, Rothbarth LJ, Kumpe D, et al: Splenic embolization in children: Long-term efficacy. J Pediatr Surg 24:642, 1989 2. Hall JR, Lilly JR, Stiegmann GV: Endoscopic esophageal varix ligation: Technique and preliminary results in children. J Pediatr Surg 23:1222, 1988 3. Karrer FM, Lilly JR: Corticosteroid therapy in biliary atresia. J Pediatr Surg 20:693, 1985 4. Karrer FM, Lilly JR, Stewart BA, et al: The Biliary Atresia Registry 1976-1989. J Pediatr Surg (in press) 5. Kasai M: Treatment of biliary atresia with special reference to hepatic portoenterostomy and its modifications. In Bill A, Kasai M (eds): Biliary Atresia and Choledochal Cyst. Progress in Pediatric Surgery, vol 6. Munich, Urban and Schwarzenburg, 1974, pp 552 6. Kasai M, Mochizuki I, Ohkohchi N, et al: Surgical limitations for biliary atresia: Indication for liver transplantation. J Pediatr Surg 24:851, 1989 7. Kasai M, Suzuki S: A new operation for "non-correctable" biliary atresia: Hepatic portoenterostomy. Shujitsu 13:733, 1959 8. Ladd WE: Congenital atresia and stenosis of the bile ducts. JAMA 91:1082, 1928 9. Lilly JR: Surgery of coexisting biliary malformations in choledochal cyst. J Pediatr Surg 14:643, 1979 10. Lilly JR, Karrer FM, Hall RJ, et al: The surgery of biliary atresia. Ann Surg 210:289, 1989 11. Lilly JR, Stellin GP, Karrer FM: Forme fruste choledochal cyst. J Pediatr Surg 20:449, 1985 12. Lilly JR, Weintraub WH, Altman RP: Spontaneous perforation of the extrahepatic bile ducts and bile peritonitis in infancy. Surgery 75:664, 1974 13. Prevot J, Babut JM: Spontaneous perforations of the biliary tract in infancy. Progr Pediatr Surg 1:187, 1970 14. Sokol RJ: Vitamin E deficiency and neurologic disease. Annu Rev Nutr 8:351, 1988 15. Thomson J: On congenital obliteration of the bile ducts. Edinburgh Med J 37:523, 604, 724, 1892 16. Todani T, Watanabe Y, Narusue M, et al: Congenital bile duct cysts: Classification, operative procedures and review of thirty-seven cases including cancer arising from choledochal cyst. Am J Surg 134:263, 1977
Address reprint requests to John R. Lilly, MD Department of Surgery-B323 The Children's Hospital 1010 East 19th Street Denver, Colorado 80218
0039-6109/90 $0.00
+ .20
Congenital Biliary Tract Disease F. M. Karrer, MD, * Roberta J. Hall, MD, * Barbara A. Stewart, MD, t and John R. Lilly, MD+
Biliary tract surgery in the pediatric patient is largely confined to operations for congenital malformations of the extrahepatic bile ducts. In the infant age group, biliary atresia is the predominant surgical lesion. Spontaneous perforation of the common bile duct, although rare, is actually the second most common cause of surgical jaundice in infancy. Later in childhood, choledochal cyst is encountered most commonly. Other malformations of the pediatric biliary tract are seen so infrequently as to be a negligible consideration in pediatric surgical practice.
BILIARY ATRESIA Historical Perspective In the earliest description of biliary atresia, in 1892, 15 John Thomson correctly characterized the disease as a progressive inflammatory lesion of the bile ducts. Ladd" is credited with the first successful operation for "correctable" biliary atresia. Because only a minority of patients have a correctable variant, biliary atresia remained a lethal disease in most affected infants despite his success. In 1959, Kasai and Suzuki? devised an operation for all types of biliary atresia. This approach was based on the finding that microscopic biliary structures are present in the fibrotic bile ducts at the From the Departments of Surgery, The Children's Hospital and University of Colorado School of Medicine, Denver, Colorado
*Assistant Professor t Research Fellow :j:Professor and Chief, Pediatric Surgery This work was supported by Grant RR-00069 from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health and The Pediatric Liver Center, University of Colorado Health Sciences Center, Denver, Colorado.
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porta hepatis. These minute ducts communicate with the intrahepatic biliary tree early in the course but later become obliterated. The rationale for the operation was that biliary atresia is a dynamic disease process rather than a static phenomenon and, therefore, that operative correction must be carried out early (before 3 months of age). Incidence and Etiology The incidence of biliary atresia is between 1:10,000 and 1:25,000. There does not seem to be a racial or genetic predilection, but there is a female predominance of 1.4:1. 4 Concurrent with the development of the hepatobiliary system, the formation of the inferior vena cava and portal vein occurs; the rotation of the midgut begins, and the spleen is being formed. About 10% to 15% of patients with biliary atresia have associated anomalies of the polysplenia syndrome such as polysplenia, absent inferior vena cava, preduodenal portal vein, and malrotation. This association suggests an early embryologic insult. However, the obliterative process in the bile ducts in biliary atresia is not localized (as in most congenital atresias) but rather involves a progressive panductular obliterative cholangiopathy. This situation suggests an acquired disease later in gestation or in the perinatal period. The pathogenesis of biliary atresia remains an enigma. Pathology Biliary atresia is a dynamic, progressive panductular obliterative process, which, untreated, results in complete obliteration of the extrahepatic biliary tree. Kasai, by systematic dissection and detailed observation of the entire extrahepatic bile ducts of 116 patients with biliary atresia, demonstrated the existence of tiny biliary structures in the tissue at the porta hepatis." Early in the course of the disease, the intrahepatic ducts are patent, although nondilated, from the intralobular ductules to the porta hepatis, where there is an arborization into the fibrous cone. The size of these minute strictures is quite variable and is correlated with the age of the infant and with bile excretion after hepatic portoenterostomy. These structures are present in most affected infants under 2 months old but gradually disappear over the next few months and by 4 months are completely replaced by fibrous tissue. The degree of involvement of the extrahepatic biliary ducts also is variable (Fig. 1). Although most commonly, the entire extrahepatic system is involved in the obliterative process (Fig. IB), some infants have sparing of the distal ducts (i.e., retained patency of the gallbladder, cystic duct, and common bile duct; Fig. LC). This group, representing 10% to 15% of patients, can have biliary continuity re-established by anastomosis of the gallbladder to the transected liver hilum. A third group has proximal "patency," with dilated pseudocyst-like structures at the liver hilum (Fig. lA). These cystic structures either do not communicate with the intrahepatic ducts at all or communicate only via minute biliary radicles. They usually have no epithelial lining but rather are composed of dense fibrous tissue. Microscopic evaluation of the liver reveals cholestasis with pigment within biliary canaliculi and in the intralobular bile ducts. Bile duct
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Figure 1. The three variants of biliary atresia. a, "Correctable" atresia. Proximal patency is often misleading, because the hilar bile pseudocysts are lined only by granulation tissue and covered by fibrous tissue. b, Biliary atresia, noncorrectable; the most common type. The entire extrahepatic ductal system is obliterated. c, As in the noncorrectable type, the proximal ducts are obliterated in this type, but patency of the gallbladder, cystic duct, and common bile duct is preserved. In all types, intrahepatic ducts are hypoplastic.
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YEARS Figure 4. Comparison of the Kaplan-Meier survival curves for children over and under 66 days old (mean age at time of Kasai's operation in our series) at operation (P < 0.05). (From Stewart BA, Hall RJ, Karrer FM, et al: Long-term survival after Kasai's operation for biliary atresia. Pediatr Surg Int 5:87-90, 1990; with permission.)
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immunosuppression-free survival of a significant number of children after Kasai's operation (28% in our Denver series). 10 Even when it is not curative, the Kasai operation extends survival in the majority of patients, allowing children to grow, thus increasing the chances that a suitable donor organ can be located and reducing transplant morbidity and mortality rates. Liver transplantation should be restricted to children who do not drain bile after Kasai's operation and who have late progression of liver disease despite relief of biliary obstruction.
CHOLEDOCHAL CYST
Choledochal cyst is a congenital malformation of the pancreaticobiliary system manifested primarily by common bile duct dilation, usually cystic. The estimated incidence ranges from 1 in 13, 000 to one in 2 million live births. There is a 3:1 female predominance, and a strong but unexplained predilection for Asians. Classification
Choledochal cysts were originally classified into three categories: type I, cystic dilatation of the common bile duct, the usual form; type II, diverticulum of the common bile duct; and type III, choledochocele (cystic dilation of the terminal common bile duct at the duodenum). Recently, the classification was expanded by adding type IV-A, multiple cysts of the intrahepatic and extrahepatic ducts; type IV-B, multiple cysts of the extrahepatic ducts only; and type V, single or multiple intrahepatic bile duct cysts with normal extrahepatic anatomy (Caroli's disease). Pathology
During the past two decades, an increasing incidence of coexisting pancreaticobiliary lesions has been noted in patients with choledochal cyst, indicating that the lesion is not a single anomaly but rather a conglomerate of developmental faults of the pancreaticobiliary system. Specifically, intrahepatic biliary cysts are found in about one third of afflicted patients. Second, most patients have a long "common channel" (i,e., the distance from the junction of the pancreatic duct and common bile duct to the ampulla is elongated). Third, many patients have a partial obstruction of the terminal common bile duct. Fourth, histologically, the bile duct wall is markedly thickened by fibrous connective tissue, the muscle layer is absent, and the mucosa is flattened, dysplastic, and ulcerated. The only common denominator in choledochal cyst has been a cystic lesion of the common bile duct. The criterion appears arbitrary. The sporadic and inconsistent pattern of associated ductal malformations suggests that, in some cases, the cystic component also may be absent or negligible. We have designated cases having all components of a choledochal cyst except a cyst as a forme fruste choledochal cyst" (Fig. 5). The treatment is identical to that of true choledochal cysts, that is, excision of the common bile duct and choledochoenterostomy.
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Figure 5. Operative cholangiogram in a patient with forme fruste choledochal cyst. Note the stenotic left major hepatic duct (straight arrow) and the long common channel with proximal junction of pancreatic and common bile duct (curved arrow). Operative treatment was by total excision of the extrahepatic bile ducts and Roux-en- Y choledochojejunostomy. (From Lilly JR, Stellin GP, Karrer FM: Forme fruste choledochal cyst. J Pediatr Surg 20:449, 1985.)
Etiology A congenital etiology is supported by reports of antenatal diagnosis, a pediatric predominance, and a characteristic association with other biliary malformations. Originally, the malformation was thought to be secondary to an unequal cellular proliferation of the common bile duct during fetal development. Next, a common channel etiology was advanced, in which an aberrant, proximally located pancreaticobiliary junction was thought to result in pancreatic reflux with subsequent duct wall destruction and dilation. Recently, a biliary autonomic dysfunction has been incriminated; that is, ganglion cells were noted to be decreased in the terminal common bile duct, causing a partial obstruction that might lead to proximal cyst formation.
Symptoms Forty to sixty per cent of patients with choledochal cysts present before 10 years of age. The classic triad of abdominal pain, jaundice, and an abdominal mass is seen in only one third of patients. Instead, patients present with a variety of symptoms, most of which are secondary to partial biliary obstruction with consequent cholangitis or pancreatitis. Infrequently, choledochal cysts rupture, leading to acute bile peritonitis. Finally, infants with choledochal cyst often present with asymptomatic jaundice secondary to total biliary obstruction.
Diagnosis Serologic studies of liver function are frequently abnormal but are nondiagnostic. Abdominal ultrasound will demonstrate the choledochal cyst. A hepatobiliary isotope scan outlines the cyst and may delineate intrahepatic cystic disease, partial biliary obstruction, or both. Computed tomography also may reveal any intrahepatic disease and defines the relation of the cyst to the other portal structures. Endoscopic retrograde cholangiopancreatog-
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raphy (ERCP) and transhepatic cholangiography (PTC) (Fig. 6) are helpful preoperative radiologic examinations. Both provide more precise anatomic detail than does ultrasound, radionuclide studies, or CT, permitting multiple views and providing better-quality images than will be obtained with intraoperative cholangiography. The ERCP examination requires a skilled endoscopist, however, and usually is not feasible in infants or younger children. The PTC study may be difficult in patients with nondilated intrahepatic bile ducts. Treatment and Prognosis Until recently, internal drainage by cyst enterostomy (choledochocystduodenostomy, choledochocystjejunostomy) was the accepted surgical treatment of choledochal cyst. However, postoperative morbidity proved to be unacceptably high. Recurrent cholangitis, cholelithiasis, failure of cyst decompression, pancreatitis, or anastomotic stricture led to a 50% reoperative rate. The fundamental cause for this high complication rate was that cyst enterostomy employed diseased biliary tissue for anastomosis. Also of concern was the malignant potential of the cyst, which would not be abolished by internal drainage. Biliary carcinomas develop in 2.5% to 4.7% of patients with choledochal cysts (20 times the rate in the normal population), and approximately half of the reported patients developed the malignancy after internal drainage procedures. 16 Consequently, the surgical procedure of choice is total excision of the choledochal cyst. The cyst may be externally mobilized prior to excision; but, particularly when pericystic inflammation has distorted the portal anatomy, we prefer an internal approach, which avoids damage to neighboring vascular, biliary, and pancreatic structures. In this technique, the cyst is opened and its wall arbitrarily separated into an internal and external wall (Fig. 7). The inner cystic wall is stripped out. The stripping dissection extends proximally to the junction of the normal hepatic duct, where it is
Figure 6. Transhepatic cholangiogram in a patient with a choledochal cyst, demonstrating cystic disease of both the right and left major intrahepatic ducts. Note that the peripheral intrahepatic ducts are normal in caliber, proving that the proximal dilations are true congenital cysts.
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Figure 7. Artist's depiction of the operative technique employed in Denver for excision of choledochal cyst. The cyst has been opened; dissection is begun in the back wall to separate it arbitrarily into two layers (see text for details). (From Lilly JR: Total excision of choledochal cyst. Surg Gynecol Obstet 146:254, 1978; with permission.)
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transected, and distally to the pancreatic duct, where it is suture ligated proximal to the entrance of the pancreatic duct (Fig. 8). The inner cyst wall is resected, leaving the thin outer wall in place over the portal vein and hepatic artery. The gallbladder is always removed. Biliary reconstruction is by Roux-en-Y intestinal anastomosis to the end of the opened common hepatic duct. Some surgeons employ a valved jejunal interposition to prevent cholangitis, but cholangitis is unusual after a properly performed excisional operation in our experience. Leaving a
Figure 8. Distal intraoperative cholangiogram in a patient with choledochal cyst. The cyst has been resected; the pancreatic duct entrance was not seen during resection, so the cholangiogram was done to identify its junction (white arrow) before completing the distal resection. Black arrows outline the remainder of the pancreatic duct. (From Lilly JR, Starzl TE: Liver, gallbladder and extrahepatic bile ducts. In Welch KJ (ed): Complications of Pediatric Surgery, Prevention and Management. Philadelphia, WB Saunders, 1982, chapter 19.)
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proximal cyst cuff equal to the diameter of the jejunum to facilitate anastomosis also has been recommended. However, the diseased cyst remnant could cause late anastomotic stricture or be the site for malignant growth. Therefore, a deliberate effort should be made to remove all diseased bile duct tissue before biliary reconstruction. If the coexisting biliary malformations are at the hepatic hilum (Fig. 9A), the involved duct sometimes can be laid open longitudinally (Fig. 9B); the opened major duct is then incorporated into the biliointestinal anastomosis (Fig. 9C).9 Intrahepatic cystic involvement confined to one hepatic lobe has occasionally been treated by lobectomy. The risk of malignancy in the intrahepatic cysts is about the same as in choledochal cysts. Currently, choledochal cyst excision has a low surgical mortality rate. The morbidity rate is less than 10% and is secondary to cholangitis, anastomotic stricture, and pancreatic duct injury. The former two complications may be unavoidable in the presence of intrahepatic disease. The latter may be eliminated by compulsive identification of the pancreatic duct before cyst transection either by direct vision or by operative cholangiography (see Fig. 8). The prognosis of choledochal cyst is excellent if the diagnosis is made before irreversible liver damage occurs provided all diseased ductal tissue is accessible to excision.
IDIOPATHIC PERFORATION OF THE COMMON BILE DUCT
Although relatively rare, spontaneous perforation of the common bile duct is second only to biliary atresia as a cause of surgical jaundice in the infant. Choledochal cyst, a more common malformation, usually presents later in childhood. The cause of the perforation is not known, but its characteristic location at the junction of the cystic and common bile ducts indicts a congenital fault. The coincidental findings of biliary sludge (or even stones) and a diminution of caliber of the distal common bile duct are most likely a consequence, not the cause, of the perforation. Typically, the afflicted infant has an insidious onset of ascites, sometimes manifested by development of inguinal or umbilical hernia.:" Lowgrade jaundice and clay-colored stools occur. Because the ductal perforation usually is tiny, bile extravasation is slow, allowing its encapsulation and the development of a pseudocyst (Fig. 10). Diagnosis is made by sonographic demonstration of the pseudocyst and confirmed by hepatobiliary isotope scans, which show biliary extravasation. Misinterpretation of the lesion as a choledocal cyst, with treatment by cyst enterostomy, has proved to be disastrous. 13 Treatment is surgical. An intraoperative cholangiogram via the gallbladder often demonstrates the biliary pseudocyst and always the extravasation of contrast at the site of perforation (Fig. 11). Inflammation is intense in the portal triad. Extensive dissection or attempts to repair the perforation are not only dangerous but unnecessary. In most cases, simple peritoneal drainage of the perforation site is all that is required. Even in those unusual instances in which the intraoperative cholangiogram demonstrates complete biliary obstruction, simple peritoneal drainage and biliary decompression
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B
c Figure 9. Technique in coexisting cystic disease of the left major hepatic duct. A, Anatomy. In this circumstance, excision of the choledochal cyst is done at the liver hilum, and the incision is extended (B) into the intrahepatic cyst. C, The choledochoenterostomy incorporates the filleted left major hepatic duct. (From Lilly JR: Surgery of coexisting biliary malformations in choledochal cyst. J Pediatr Surg 14:643, 1979.)
via the tube cholecystostomy often suffice. Decompression frequently results in complete resolution of obstruction and, if not, permits quiescence of inflammation and safer subsequent operation (ampullary dilatation, choledochoenterostomy). We advocate retention of the tube cholecystostomy for postoperative cholangiography; peritoneal drains should not be removed until complete healing of the ductal perforation is demonstrated, usually 2 to 3 weeks after the operation. 12
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Figure 10. Artist's depiction of spontaneous perforation of the common bile duct. The perforation generally is small; bile escapes so slowly that a pseudocyst is formed. Misinterpretation of the pseudocyst as a choledochal cyst with treatment by cyst enterostomy has proved to be disastrous. Simple peritoneal drainage suffices in most cases.
The prognosis is excellent except in those infants who, because of either delay in diagnosis or operative procrastination, develop infected ascites. In these cases, sepsis and death are unusually rapid. In the majority of infants, however, the surgical course of spontaneous perforation of the common bile duct is bland, and hepatobiliary sequelae are absent.
INSPISSATED BILE SYNDROME Although not strictly in the purview of congenital biliary tract disease, the inspissated bile syndrome occurs with sufficient frequency to warrant inclusion in a discussion of pediatric obstructive jaundice. In this disease, bile becomes abnormally thick and viscid as a consequence of an underlying disorder such as dehydration, hemolysis, parenteral alimentation, or cystic fibrosis. The resultant biliary sludge may plug the lumen of the common
Figure 11. Operative cholangiogram in an infant with spontaneous perforation of the common bile duct. Straight arrows outline the encapsulated bile leak. The radiologic meniscus (curved arrow) suggesting choledocholithiasis resolved spontaneously after simple peritoneal drainage. (From Lilly JR, Starzl TE: Liver, gallbladder and extrahepatic bile ducts. In Welch KJ (ed): Complications of Pediatric Surgery: Prevention and Management. Philadelphia, WB Saunders, 1982, chapter 19.)
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bile duct, causing obstructive jaundice (Fig. 12). Often, the biliary obturation spontaneously resolves with treatment of the underlying disorder, but occasionally, operative therapy is necessary, particularly if inspissation has progressed to actual stone formation. In most instances, the operation is limited to simple irrigation of the extrahepatic bile ducts via tube cholecystostomy.
MISCELLANEOUS BILIARY TRACT MALFORMATIONS Agenesis, duplication, and congenital diverticulum of the gallbladder are reported sporadically. These malformations usually are asymptomatic. Gallbladder agenesis may be embarrassing in operations done for presumed acute cholecystitis. Occasionally, duplications and diverticulum predispose to stone formation. Agenesis of the extrahepatic bile ducts is also rare and incompatible with survival beyond 1 to 2 years. Duplications of the extrahepatic ducts are oddities that have surgical significance only in instances of extensive liver resection or liver transplantation.
SUMMARY Jaundice in the pediatric patient requires prompt and directed evaluation. This dictum is highlighted in infants with biliary atresia, in whom the progressive sclerosing process results in complete obliteration of patent but microscopic hilar biliary structures by 4 months of age. Kasai's operation, if done before that time, will re-establish bile drainage in 90% of infants. One fourth to one third of patients achieve long-term jaundice-free survival. Complications of cholangitis, portal hypertension, and fat malabsorption are experienced by many patients. In children with early or late operative failure, liver replacement now offers legitimate hope for extended survival. Choledochal cyst is a conglomerate of pancreaticobiliary anomalies consisting of a choledochal cyst, a common-channel-type pancreaticobiliary
Figure 12. Operative cholangiogram showing complete obstruction in an infant with the inspissated bile syndrome. An ABO blood incompatibility resulted in excessive hemolysis with secondary bile sludge in the common bile duct. In this instance, an impacted bilirubin stone had to be removed surgically. (From Lilly JR: Common bile duct calculi in infants and children. J Pediatr Surg 15:577, 1980.)
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junction, intrahepatic cystic disease, and partial obstruction of the distal common bile duct. Many patients have one or more of these malformations. It is now widely accepted that the preferred treatment of choledochal cyst is total excision of the diseased biliary duct with reconstruction by Rouxen-Y choledochojejunostomy. "Internal" excision avoids injury to other structures in the hepatoduodenal ligament, particularly if pericystic inflammation is present. Congenital perforation of the common bile duct responds in most cases to simple peritoneal drainage of the perforation. Retention of the tube cholecystostomy is useful for subsequent cholangiographic follow-up. Tube cholecystostomy may also be useful for irrigation of the biliary tract in infants with inspissated bile syndrome.
REFERENCES 1. Brandt CT, Rothbarth LJ, Kumpe D, et al: Splenic embolization in children: Long-term efficacy. J Pediatr Surg 24:642, 1989 2. Hall JR, Lilly JR, Stiegmann GV: Endoscopic esophageal varix ligation: Technique and preliminary results in children. J Pediatr Surg 23:1222, 1988 3. Karrer FM, Lilly JR: Corticosteroid therapy in biliary atresia. J Pediatr Surg 20:693, 1985 4. Karrer FM, Lilly JR, Stewart BA, et al: The Biliary Atresia Registry 1976-1989. J Pediatr Surg (in press) 5. Kasai M: Treatment of biliary atresia with special reference to hepatic portoenterostomy and its modifications. In Bill A, Kasai M (eds): Biliary Atresia and Choledochal Cyst. Progress in Pediatric Surgery, vol 6. Munich, Urban and Schwarzenburg, 1974, pp 552 6. Kasai M, Mochizuki I, Ohkohchi N, et al: Surgical limitations for biliary atresia: Indication for liver transplantation. J Pediatr Surg 24:851, 1989 7. Kasai M, Suzuki S: A new operation for "non-correctable" biliary atresia: Hepatic portoenterostomy. Shujitsu 13:733, 1959 8. Ladd WE: Congenital atresia and stenosis of the bile ducts. JAMA 91:1082, 1928 9. Lilly JR: Surgery of coexisting biliary malformations in choledochal cyst. J Pediatr Surg 14:643, 1979 10. Lilly JR, Karrer FM, Hall RJ, et al: The surgery of biliary atresia. Ann Surg 210:289, 1989 11. Lilly JR, Stellin GP, Karrer FM: Forme fruste choledochal cyst. J Pediatr Surg 20:449, 1985 12. Lilly JR, Weintraub WH, Altman RP: Spontaneous perforation of the extrahepatic bile ducts and bile peritonitis in infancy. Surgery 75:664, 1974 13. Prevot J, Babut JM: Spontaneous perforations of the biliary tract in infancy. Progr Pediatr Surg 1:187, 1970 14. Sokol RJ: Vitamin E deficiency and neurologic disease. Annu Rev Nutr 8:351, 1988 15. Thomson J: On congenital obliteration of the bile ducts. Edinburgh Med J 37:523, 604, 724, 1892 16. Todani T, Watanabe Y, Narusue M, et al: Congenital bile duct cysts: Classification, operative procedures and review of thirty-seven cases including cancer arising from choledochal cyst. Am J Surg 134:263, 1977
Address reprint requests to John R. Lilly, MD Department of Surgery-B323 The Children's Hospital 1010 East 19th Street Denver, Colorado 80218
