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Surgery for biliary tract problems in children
Symposium: surgery & orthopaedics
Surgery for biliary tract problems in children
Although the disease spectrum that causes neonatal conjugated hyperbilirubinaemia varies considerably in different parts of the world, in most surgical series biliary atresia constitutes more than one-third of cases. Other causes include choledochal cyst, spontaneous perforation of the common bile duct and more rarely gallstones or inspissated bile.2 Most of these causes cannot be differentiated on clinical grounds.3
Alastair JW Millar Khalid Sharif
Biliary atresia Pathogenesis Biliary atresia is often described as an obliterative sclerosing cholangitis; the disease process not only affects the extrahepatic biliary system, but also the liver to involve bile ductules within the substance of the liver as well as the liver parenchyma. This destructive process may start in foetal life, around the time of birth or in early postnatal life. In most cases the infants are jaundiced from birth with the unconjugated physiological hyperbilirubinaemia overlapping the development of cholestasis in time sequence. Minor fluctuations in the levels of hyperbilirubinaemia are common. There is inflammation and degeneration of the ducts, which progresses to fibrosis and usually complete obliteration of the lumen. All the extrahepatic biliary structures may be involved, but occasionally segmental involvement is apparent with only the common bile ducts affected; or on the other hand the gall bladder and common bile duct may be free of disease and the proximal hepatic ducts are principally affected. A cystic variety of biliary atresia is also seen in around 5% of cases, where cysts at the porta hepatis can be identified and may even contain bile but there are no macroscopic connections to the intrahepatic bile ducts.4 Although the time of onset of this obliterative process is variable, in nearly all patients the intrahepatic bile ducts extending to the porta hepatis remain patent until some weeks after birth, but later succumb to the same obliterative process as the extrahepatic biliary system. While cholestasis is prominent, there is an accompanying inflammation and bile duct proliferation within the liver, which can rapidly progress to portal fibrosis and cirrhosis with ensuing portal hypertension. Thus, there are three major patterns of disease classified into: • type 1 – atresia confined to the common bile duct • type 2 – atresia of the common hepatic duct with residual patency of the right and left hepatic ducts • type 3 – atresia of the whole of the extrahepatic duct system. Around 90% are type 3, 8% type 1 and 2% type 2.
Abstract Jaundice in the neonate is common and when not associated with symptoms or signs of systemic illness may at first be regarded with some complacency by both mother and health professional alike. When the cholestatic nature of the jaundice becomes apparent, a cause must be identified, if possible within 2 weeks of onset. Biliary atresia, choledochal cyst, inspissated bile syndrome and spontaneous perforation of the bile duct are the most frequent surgical causes. An investigation protocol includes stool observation, ultrasound scanning, biochemical liver function tests, a screen for infective and metabolic causes, a radioisotope excretion scan (hydroxyiminodiacetic acid HIDA scan) and, if necessary, operative cholangiogram and liver biopsy. Surgical management, if performed timeously, may prevent progression of parenchymal disease and in many cases can be curative. Delayed diagnosis leads to inevitable progression of liver damage with a poor long-term outlook. Cholelithiasis is being seen more frequently both in the infant and older child. Surgical intervention is required for symptomatic disease and for stones in the common bile duct. Tumours of the bile ducts are rare but are most likely to be malignant and should be referred to specialist centres for management.
Keywords biliary atresia; biliary disorders; children; choledochal cyst; inspissated bile syndrome; neonatal jaundice; spontaneous perforation of bile duct
Introduction Jaundice in the newborn period is common and usually a benign manifestation of normal physiological events. If this persists beyond the age of 2 weeks, it takes on an altogether different mantle with potentially more sinister implications. However, a sense of complacency appears fixed in the minds of mothers and also many health professionals, particularly if the baby is breastfed and appears to be thriving.1 Even pale stools and dark urine are seemingly ignored as warning signs of cholestasis. Steps towards making a definite diagnosis may still be hesitant and incomplete.
Aetiology The aetiology of biliary atresia is unknown. In some, it may be a developmental anomaly although meconium is of normal colour in nearly all cases indicating at least initial patency of the biliary tree, but there is a higher incidence of associated cardiovascular, gastrointestinal and genitourinary anomaly (10–20%) – for example, situs inversus, polysplenia, absent inferior vena cava, malrotation and preduodenal portal vein.5 In around 10% of cases, abnormalities of the biliary tree can be identified on antenatal ultrasound. Although theories of ischaemia, immunemediated mechanisms and even pancreatic juice reflux have been proposed, the most attractive is that of a perinatal viral infection. Reovirus 3 and rotavirus infection in newborn mice have been shown to produce a very similar lesion. Antibody
Alastair JW Millar MBChB FRCS(Eng) FRACS FCS(SA) DCH is C.F.M. Saint Professor of Paediatric Surgery in the Department of Pediatric Surgery, Red Cross War Memorial Children’s Hospital and University of Cape Town, Cape Town, South Africa. Khalid Sharif MBBS FRCS(Ire) FRCS(Paed Surg) (Eng) is Consultant Hepatobiliary and Transplant Surgeon, Birmingham Children’s Hospital, Birmingham, UK.
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Symposium: surgery & orthopaedics
studies of mothers and infants are, however, equivocal.6–8 A long common pancreatico-biliary channel has been demonstrated in up to 60% of cases of biliary atresia and in over 80% of cases of choledochal cyst.9
to define best practice. Current overall long-term outcome is that approximately 30–40% will survive more than 10 years with their native liver intact although most will have evidence of cirrhosis.16–18
Management Untreated, the unfortunate infant will become increasingly jaundiced, with progression of hepatosplenomegaly, portal hypertension and ascites. The effect of a failing liver with malabsorption takes its toll. Emaciation, growth retardation, rickets, ascites and the effects of hypersplenism become evident. Severe pruritis leads to constant scratching. Death secondary to systemic or respiratory infection, alimentary tact bleeding or finally liver failure usually occurs by the age of 2 years.
Overall outcome There is considerable evidence that overall outcome is greatly improved with centre case load experience of greater than five cases per year along with better communication between major centres and the more peripheral units. During late childhood and early adolescence, portal hypertension may become evident with the development of oesophageal varices, but bleeding can be satisfactorily managed by injection sclerotherapy or variceal banding. There is a tendency to spontaneous disappearance of the varices in those that survive into adulthood. Of the remaining, 60–70%, approximately half will have failed to sustain bile drainage and will require early referral for liver transplantation. Another 30% will have a partially successful Kasai operation or will have had repeated episodes of cholangitis and although growth will be satisfactory, they may develop evidence of progressive liver disease during the childhood years.
Surgical strategy In the 1950s, Kasai from Sendai, Japan developed a procedure whereby all the diseased extrahepatic bile duct remnants and fibrous tissue were excised from the porta hepatis above and behind the bifurcation of the portal vein; flush with, but not into the liver substance.10 The area thus exposed drained bile through residual and regenerating ductular structures into the alimentary tract by anastomosing a Roux-en-Y loop of jejunum around this area. What was an incurable condition with an inevitably fatal outcome had now become at least manageable. Although for many years the operation fell into disrepute, this was partly because of a misunderstanding of some technical aspects of the procedure.
Liver transplant Biliary atresia is the most frequent indication for liver transplantation in infancy and childhood.19,20 Liver transplantation has been accepted as a complementary procedure with the Kasai portoenterostomy for the treatment of children with biliary atresia, who have developed end-stage liver disease. Although liver transplantation remains a formidable surgical procedure, current greater than 95% 1-year and greater than 85% 5-year survival figures are being reported from the best centres. Certainly a good quality of life is obtained in most children, although life-long immunosuppressive therapy and close medical and surgical supervision is required. The world’s longest survivor to date remains well nearly 40 years after transplant. With the passing of years, techniques will improve and management of infection and control of rejection by new and more effective drugs will make the option of transplantation even more attractive.
‘What are the prognostic indicators and factors?’ Delay in operation is the single most important prognostic factor.11 Currently, in those infants operated on before 60 days of age, one can expect that 90% will drain bile, and greater than 70% will lose their jaundice.12 However, those operated on after 13 weeks of age only have around a 20% chance of sustained bile drainage with loss of jaundice, and irreversible cirrhosis is already established in most. Recent attempts at laparoscopic Kasai portoenterostomy have not found wide support.13 The size of the microscopic ductules in the fibrotic mass that has been cut away is also a good indicator of whether success can be expected; ducts of size greater than 150 microns in diameter being almost always associated with bile drainage. Unfortunately, bile drainage per se does not equate with cure, as there may be ongoing intrahepatic cholestasis and fibrosis. Postoperative management is most important. A contaminated drainage system predisposes to recurrent episodes of bacterial cholangitis. These attacks are most frequent and severe in the first 6 months after operation and are heralded by fever, ileus, change in stool colour and rise in serum bilirubin levels. Each attack should be energetically treated with the appropriate antibiotic (Escherichia coli and Klebsiella being the organisms most frequently cultured). Repeated episodes of cholangitis are usually associated with subsequent more rapid deterioration of liver function and progressive cirrhosis. Choleretics, in the form of phenobarbitone, cholestyramine, ursodeoxycholic acid and corticosteroids, are given in an attempt to improve bile flow.14,15 The efficacy of these choleretics is not yet fully proven but steroids may also reduce scar tissue formation. Dose of corticosteroid, time of starting treatment, and duration have been variable and prospective trials are in progress
PAEDIATRICS AND CHILD HEALTH 18:6
Conclusion Although biliary atresia remains a very serious disease of infancy, one can truly say that in the new millennium the overall outcome should be excellent. In fact, with correctly timed surgical management – both portoenterostomy and liver transplantation – one can expect a nearly 90% long-term survival. Early referral; and management by multidisciplinary specialist paediatric hepatology units is, however, crucial for optimal outcome.
Choledochal cysts Choledochal cyst is a rare cystic dilatation of the bile duct system. It is seen more frequently in females and in oriental races. More than half present in the first decade of life.21,22 Clinical The classical triad of pain, right upper quadrant mass and jaundice occurs in less than 40%. Cholestasis, recurrent pain with or without jaundice, fever, pancreatitis and acute abdominal emergency are other presentations. 279
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Symposium: surgery & orthopaedics
ultrasound early surgical intervention with a Kasai portoenterostomy is indicated. Choledochocoeles are probably a different entity and require endoscopic or open sphincterotomy or cyst duodenostomy.
Pathology Five patterns of dilatation are apparent and have been classified as: • type I – cystic dilation of the common bile duct (saccular or fusiform) 80% • type II – an extrahepatic supraduodenal diverticulum of the bile duct: • type III – choledochocele, a cyst of the intramural duodenal bile duct. • type IV – fusiform intrahepatic and extrahepatic cysts • type V – multiple intrahepatic cysts (Caroli’s disease).
Spontaneous common bile duct perforation Spontaneous perforation of the common bile duct is a rare condition where rupture usually occurs at the junction with the cystic duct, possibly due to a developmental weakness.28 Clinical Typically an uncomplicated perinatal course is interrupted by onset of mild cholestatic jaundice, irritability, abdominal distension and vomiting. Infection with septicaemia may result in sudden clinical deterioration. Examination reveals evidence of ascites without peritonism. Green staining of the scrotum as bile stained fluid extends along the patent process vaginalis may be present in male infants. Apart from the mild cholestatic jaundice, liver function tests are usually surprisingly normal, although the serum alkaline phosphatase and gamma glutamyl transferase levels are mildly raised. Ultrasound is usually diagnostic along with biochemical analysis of the ascites.
Aetiology and pathogenesis The cause is thought in most cases to be due to an anomaly where the pancreatic duct joins the distal common bile duct (CBD) above the sphincter of Oddi.23,24 This leads to a positive pressure differential of pancreatic exocrine secretion over bile secretion with reflux of pancreatic juice into the CBD due to a degree of distal obstruction. This results in damage to duct epithelium and wall. The gall bladder is often of normal size but may be enlarged with a tortuous cystic duct. The wall of the duct is thickened and replaced by fibrous tissue without an epithelial lining. Diagnosis Antenatal diagnosis is being documented with increasing frequency. Most have a normal liver initially but cirrhosis may develop quickly. Ultrasound will identify the cyst but magnetic resonance cholangiography can now very nicely delineate the detail of the intrahepatic and extrahepatic biliary system. Pancreatitis, cholelithiasis and infection can supervene and it would be wise not to delay surgery even when liver function tests are normal.
Management Management involves a careful surgical exploration. Pseudocystic containment of bile around the perforation may be confusing. In most, provided distal patency of the biliary system can be confirmed with operative cholangiogram, all that is required is to adequately drain the area of perforation. When there is any evidence of distal common bile duct obstruction, which can be demonstrated by intra-operative cholangiogram, cholecystectomy and hepaticojejunostorny enteric drainage is indicated.29
Treatment Surgical technique involves an operative cholangiogram, cyst excision and hepaticojejunostomy.25 Usually one can find a relatively avascular plane of dissection outside the cyst but beneath the overlying peritoneum. The distal orifice is usually excentrically placed antero-medially. When the cyst is too large to obtain a meaningful cholangiogram, cholecystoscopy helps to identify proximal and distal duct structures and any evidence of stones or sludge. Care should be taken not to damage the main pancreatic duct at surgery. Cyst excision should extend proximally to the right and left hepatic duct confluence with extension and opening of the left hepatic duct to obtain a wide anastomosis for adequate drainage into the bowel.26 A long (40 cm) Roux-en-Y hepaticojejunostomy is the preferred method of enteric bile drainage and has excellent long-term outcome. Late sequalae of carcinoma and retention of secretions usually relate to inadequate cyst excision.27 If cholangitis occurs anastomotic stenosis must be suspected.
Inspissated bile syndrome and cholelithiasis First described by Ladd in the 1930s, the incidence inspissated bile syndrome peaked in the 1950s because of the prevalence of untreated rhesus disease of the newborn resulting in haemolysis and sludge in the bile ducts.30 Cholelithiasis is being increasingly recognised as an entity in the neonate and infant, particularly those who have survived neonatal intensive care with illnesses associated with prematurity including necrotising enterocolitis and feeding intolerance. Any condition requiring parenteral nutrition may lead to cholestasis, gall bladder sludge and gallstones. Other contributing factors in infants include: decreased bile acid output; shortened erythrocytic lifespan; phototherapy for physiologic jaundice; furosemside therapy; and maternal narcotic addiction. There is a bimodal age incidence with a second peak in late childhood and adolescence. Although in infancy sex incidence is equal, there is an increasing female preponderance with age. While biliary sludge is composed of mainly mucin, calcium bilirubinate and cholesterol, the usual mixed cholesterol stones predominate in adolescent girls.
Choledochal cyst with cirrhosis Rarely choledochal cysts present at birth in association with established cirrhosis. The aetiology is speculative but this should be regarded as ‘cystic’ biliary atresia, with a poorer long-term outcome expected. Histologically the cyst wall is made up of fibrous tissue with a chronic inflammatory reaction. The epithelial lining is wholly or partially absent. If noted on antenatal
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Diagnosis Clinical symptoms and signs may vary from severe colic, those associated with acute cholecystitis, pancreatitis, cholangitis with common duct stones, to mild fatty food intolerance. 280
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Gallbladder ultrasound is very effective in evaluating the presence of stones or sludge. Thickness of the gallbladder wall, size of CBD and other pancreatico-biliary pathology can also be identified. The patient can be further investigated with liver function tests and magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography (ERCP). Radioisotope scanning with 99mTc-iminoacetic acid derivatives showing non-function is usually diagnostic of acute cholecystitis.
s urgical excision and radiotherapy has improved a previous dismal prognosis.36
Summary Early diagnosis of cholestatic jaundice in the neonate and infant and referral to a specialised unit is an absolute requirement if the results of surgery for biliary atresia are to be improved. Other causes of surgical jaundice are rare but timely surgical intervention can usually be curative. Roux-en-Y hepaticojejunostomy with a greater than 35 cm drainage loop provides excellent bilioenteric drainage. Cholelithiasis is being increasingly recognised and symptomatic stones are treated by laparoscopic cholecystectomy with minimal morbidity. ◆
Management Spontaneous resolution of non-calcified sludge or stones has been documented in neonates but calcified stones are unlikely to resolve spontaneously. Ursodeoxycholic acid (20 mg/kg/day) therapy may be useful where there is bile inspissation rather than formed stones.31 Operative cholangiogram with a flush of the biliary system may be sufficient for inspissated bile. Cholecystectomy is required for symptomatic and calcified stones. Increasingly laparoscopic cholecystectomy is being performed even in infants. Gallstones from haemolytic disease are frequent but predominantly occur in older children. There is some debate as to whether cholecystectomy is required rather than cholecystostomy and removal of the stones at the time of splenectomy, as theoretically the haemolytic diathesis is reduced.32 However, in practice most require cholecystectomy. Suspected common bile duct stones should be searched for and removed. Retained stones can be extracted via ERCP.33 Biliary dyskinesia, defined as symptomatic biliary colic without cholelithiasisis is being increasingly identified as a cause for abdominal pain in children. Diagnosis is suggested if the emptying fraction of the gall bladder after a fatty meal, as seen on hepatobiliary radioisotope scan or ultrasound is less than 35%. One should, however, be cautious in proceeding to cholecystectomy as in one recent series at 2-year follow-up of two similar symptom groups, one having had a cholecystectomy, outcomes were the same.34
References 1 Mieli-Vergani G, Howard ER, Portman B, et al. Late referral for biliary atresia – missed opportunities for effective surgery. Lancet 1989; 1: 421–3. 2 Grosfeld JL, Rescorla FJ, Skinner MA, et al. The spectrum of biliary tract disorders in infants and children. Experience with 300 cases. Arch Surg 1994; 129: 513–8 (discussion 518–20). 3 Valman HB. The first year of life: Jaundice in the newborn. BMJ 1989; 299: 1272–4. 4 Mackenzie TC, Howell LJ, Flake AW, et al. The management of prenatally diagnosed choledochal cysts. J Pediatr Surg 2001; 36(8): 1241–3. 5 Davenport M, Savage M, Mowat AP, et al. Biliary atresia splenic malformation syndrome: an etiologic and prognostic subgroup. Surgery 1993; 113(6): 662–8. 6 Phillips PA, Keast D, Papadimitriou JM, et al. Chronic obstructive jaundice induced by Reovirus type 3 in weanling mice. Pathology 1969; 1(3): 193–203. 7 Riepenhoff-Talty M, Schaekel K, Clark HF, et al. Group A rotaviruses produce extrahepatic biliary obstruction in orally inoculated newborn mice. Pediatr Res 1993; 33(4 Pt 1): 394–9. 8 Brown WR, Sokol RJ, Levin MJ, et al. Lack of correlation between infection with reovirus 3 and extrahepatic biliary atresia or neonatal hepatitis. J Pediatr 1988; 113(4): 670–6. 9 Chiba T, Ohi R, Mochizuki I. Cholangiographic study of the pancreaticobiliary ductal junction in biliary atresia. J Pediatr Surg 1990; 25(6): 609–12. 10 Kasai M, Suzuki S. A new operation for “non-correctable” biliary atresia with hepatic portoenterostomy. Shujyutsu 1959; 13: 733–739. 11 Tagge DU, Tagge EP, Drongowski RA, et al. A long-term experience with biliary atresia. Reassessment of prognostic factors. Ann Surg 1991; 214(5): 590–8. 12 Karrer FM, Price MR, Bensard DD, et al. Long-term results with the Kasai operation for biliary atresia. Arch Surg 1996; 131(5): 493–6. 13 Aspelund G, Ling SC, Ng V, et al. A role for laparoscopic approach in the treatment of biliary atresia and choledochal cysts. J Pediatr Surg 2007; 42(5): 869–72. 14 Kobayashi H, Yamataka A, Koga H, et al. Optimum prednisolone usage in patients with biliary atresia postportoenterostomy. J Pediatr Surg 2005; 40(2): 327–30.
Benign bile duct strictures These are generally rare but may complicate trauma, surgery, radiotherapy for malignant disease or bile duct perforation. An idiopathic variety exists that differs from sclerosing cholangitis as they tend to be single and are associated with fibrosis of the bile duct wall and loss of epithelium.35
Bile duct tumours These rare tumours present with painless obstructive jaundice in most instances. Diagnosis depends on imaging and biopsy. Malignancy in the form of rhabdomyosarcoma is seen more frequently than benign ‘unusual’ lesions such as inflammatory pseudotumour and granular cell tumour. Although only around 100 cases of rhabdomyosarcoma have been reported it is a well-defined entity with mean age at presentation in the 4th year. More than a third of the tumours have spread either locally or distally by the time of presentation with jaundice, fever and a mass. Tumours may be polypoid with grape-like projections within the bile duct and are typically embryonal with botryoid features on histology. Aggressive treatment with a combination of chemotherapy,
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15 Meyers RL, Book LS, O’Gorman MA, et al. High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia. J Pediatr Surg 2003; 38(3): 406–11. 16 Ohi R, Nio M, Chiba T, et al. Long-term follow-up after surgery for patients with biliary atresia. J Pediatr Surg 1990; 25(4): 442–5. 17 Laurent J, Gauthier F, Bernard O, et al. Long-term outcome after surgery for biliary atresia. Study of 40 patients surviving for more than 10 years. Gastroenterology 1990; 99(6): 1793–7. 18 Hadzic N, Davenport M, Tizzard S, et al. Long-term survival following Kasai portoenterostomy: is chronic liver disease inevitable? J Pediatr Gastroenterol Nutr 2003; 37(4): 430–3. 19 Starzl TE, Demetris AJ, Van Thiel D. Liver transplantation (1). N Engl J Med 1989; 321(15): 1014–22. 20 Starzl TE, Demetris AJ, Van Thiel D. Liver transplantation (2). N Engl J Med 1989; 321(16): 1092–9. 21 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 1977; 134(2): 263–9. 22 Stringer MD, Choledochal cysts In: Howard ER, Stringer MD, Colombani PM, eds. Surgery of liver, bile-ducts and pancreas in children, 2nd Edn. London: Arnold, 2002, p. 149–68. 23 Miyano T, Suruga K, Suda K. Abnormal choledocho-pancreatico ductal junction related to the etiology of infantile obstructive jaundice diseases. J Pediatr Surg 1979; 14(1): 16–26. 24 Babbitt DP. Congenital choledochal cysts: new etiological concept based on anomalous relationships of the common bile duct and pancreatic bulb. Ann Radiol (Paris) 1969; 12(3): 231–40. 25 Miyano T, Yamataka A, Kato Y, et al. Hepaticoenterostomy after excision of choledochal cyst in children: a 30-year experience with 180 cases. J Pediatr Surg 1996; 31(10): 1417–21. 26 Stringer MD. Wide hilar hepatico-jejunostomy: the optimum method of reconstruction after choledochal cyst excision. Pediatr Surg Int 2007; 23(6): 529–32. 27 Bismuth H, Krissat J. Choledochal cystic malignancies. Ann Oncol 1999; 10(suppl 4): 94–8. 28 Davenport M, Heaton ND, Howard ER. Spontaneous perforation of the bile duct in infants. Br J Surg 1991; 78(9): 1068–70.
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29 Sprigland N, Greco R, Rosenfeld D. Spontaneous biliary perforation: does external drainage constitute adequate therapy? J Pediatr Surg 1996; 31: 782–784. 30 Ladd WE. Congenital obstruction of the bile ducts. Ann Surg 1935; 102: 742–751. 31 Heaton ND, Davenport M, Howard ER. Intraluminal biliary obstruction. Arch Dis Child 1991; 66(12): 1395–8. 32 Newman KD, Powell DM, Holcomb 3rd GW. The management of choledocholithiasis in children in the era of laparoscopic cholecystectomy. J Pediatr Surg 1997; 32(7): 1116–9. 33 Kumar R, Nguyen K, Shun A. Gallstones and common bile duct calculi in infancy and childhood. Aust N Z J Surg 2000; 70(3): 188–91. 34 Scott Nelson R, Kolts R, Park R, et al. A comparison of cholecystectomy and observation in children with biliary dyskinesia. J Pediatr Surg 2006; 41(11): 1894–8. 35 Bowles MJS, Salisbury JR, Howard ER. Localized, benign, nontraumatic strictures of the extrahepatic biliary tree in children. Surgery 2001; 130: 55–9. 36 Spunt SL, Lobe TE, Pappo AS, et al. Aggressive surgery is unwarranted for biliary tract rhabdomyosarcoma. J Pediatr Surg 2000; 35(2): 309–16.
Practice points • Jaundice in the neonate extending beyond 2 weeks must be fully investigated • A multidisciplinary approach has improved outcome • The spectrum of disorders causing conjugated hyperbilirubinaemia includes biliary atresia, choledochal cyst, spontaneous perforation of the common bile duct and gallstones or inspissated bile • Surgical management performed timeously, may prevent progression of parenchymal disease • Biliary atresia is now a disorder with good long-term outcome if managed appropriately (Kasai portoenterostomy and liver transplantation)
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Surgery for biliary tract problems in children
Although the disease spectrum that causes neonatal conjugated hyperbilirubinaemia varies considerably in different parts of the world, in most surgical series biliary atresia constitutes more than one-third of cases. Other causes include choledochal cyst, spontaneous perforation of the common bile duct and more rarely gallstones or inspissated bile.2 Most of these causes cannot be differentiated on clinical grounds.3
Alastair JW Millar Khalid Sharif
Biliary atresia Pathogenesis Biliary atresia is often described as an obliterative sclerosing cholangitis; the disease process not only affects the extrahepatic biliary system, but also the liver to involve bile ductules within the substance of the liver as well as the liver parenchyma. This destructive process may start in foetal life, around the time of birth or in early postnatal life. In most cases the infants are jaundiced from birth with the unconjugated physiological hyperbilirubinaemia overlapping the development of cholestasis in time sequence. Minor fluctuations in the levels of hyperbilirubinaemia are common. There is inflammation and degeneration of the ducts, which progresses to fibrosis and usually complete obliteration of the lumen. All the extrahepatic biliary structures may be involved, but occasionally segmental involvement is apparent with only the common bile ducts affected; or on the other hand the gall bladder and common bile duct may be free of disease and the proximal hepatic ducts are principally affected. A cystic variety of biliary atresia is also seen in around 5% of cases, where cysts at the porta hepatis can be identified and may even contain bile but there are no macroscopic connections to the intrahepatic bile ducts.4 Although the time of onset of this obliterative process is variable, in nearly all patients the intrahepatic bile ducts extending to the porta hepatis remain patent until some weeks after birth, but later succumb to the same obliterative process as the extrahepatic biliary system. While cholestasis is prominent, there is an accompanying inflammation and bile duct proliferation within the liver, which can rapidly progress to portal fibrosis and cirrhosis with ensuing portal hypertension. Thus, there are three major patterns of disease classified into: • type 1 – atresia confined to the common bile duct • type 2 – atresia of the common hepatic duct with residual patency of the right and left hepatic ducts • type 3 – atresia of the whole of the extrahepatic duct system. Around 90% are type 3, 8% type 1 and 2% type 2.
Abstract Jaundice in the neonate is common and when not associated with symptoms or signs of systemic illness may at first be regarded with some complacency by both mother and health professional alike. When the cholestatic nature of the jaundice becomes apparent, a cause must be identified, if possible within 2 weeks of onset. Biliary atresia, choledochal cyst, inspissated bile syndrome and spontaneous perforation of the bile duct are the most frequent surgical causes. An investigation protocol includes stool observation, ultrasound scanning, biochemical liver function tests, a screen for infective and metabolic causes, a radioisotope excretion scan (hydroxyiminodiacetic acid HIDA scan) and, if necessary, operative cholangiogram and liver biopsy. Surgical management, if performed timeously, may prevent progression of parenchymal disease and in many cases can be curative. Delayed diagnosis leads to inevitable progression of liver damage with a poor long-term outlook. Cholelithiasis is being seen more frequently both in the infant and older child. Surgical intervention is required for symptomatic disease and for stones in the common bile duct. Tumours of the bile ducts are rare but are most likely to be malignant and should be referred to specialist centres for management.
Keywords biliary atresia; biliary disorders; children; choledochal cyst; inspissated bile syndrome; neonatal jaundice; spontaneous perforation of bile duct
Introduction Jaundice in the newborn period is common and usually a benign manifestation of normal physiological events. If this persists beyond the age of 2 weeks, it takes on an altogether different mantle with potentially more sinister implications. However, a sense of complacency appears fixed in the minds of mothers and also many health professionals, particularly if the baby is breastfed and appears to be thriving.1 Even pale stools and dark urine are seemingly ignored as warning signs of cholestasis. Steps towards making a definite diagnosis may still be hesitant and incomplete.
Aetiology The aetiology of biliary atresia is unknown. In some, it may be a developmental anomaly although meconium is of normal colour in nearly all cases indicating at least initial patency of the biliary tree, but there is a higher incidence of associated cardiovascular, gastrointestinal and genitourinary anomaly (10–20%) – for example, situs inversus, polysplenia, absent inferior vena cava, malrotation and preduodenal portal vein.5 In around 10% of cases, abnormalities of the biliary tree can be identified on antenatal ultrasound. Although theories of ischaemia, immunemediated mechanisms and even pancreatic juice reflux have been proposed, the most attractive is that of a perinatal viral infection. Reovirus 3 and rotavirus infection in newborn mice have been shown to produce a very similar lesion. Antibody
Alastair JW Millar MBChB FRCS(Eng) FRACS FCS(SA) DCH is C.F.M. Saint Professor of Paediatric Surgery in the Department of Pediatric Surgery, Red Cross War Memorial Children’s Hospital and University of Cape Town, Cape Town, South Africa. Khalid Sharif MBBS FRCS(Ire) FRCS(Paed Surg) (Eng) is Consultant Hepatobiliary and Transplant Surgeon, Birmingham Children’s Hospital, Birmingham, UK.
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Symposium: surgery & orthopaedics
studies of mothers and infants are, however, equivocal.6–8 A long common pancreatico-biliary channel has been demonstrated in up to 60% of cases of biliary atresia and in over 80% of cases of choledochal cyst.9
to define best practice. Current overall long-term outcome is that approximately 30–40% will survive more than 10 years with their native liver intact although most will have evidence of cirrhosis.16–18
Management Untreated, the unfortunate infant will become increasingly jaundiced, with progression of hepatosplenomegaly, portal hypertension and ascites. The effect of a failing liver with malabsorption takes its toll. Emaciation, growth retardation, rickets, ascites and the effects of hypersplenism become evident. Severe pruritis leads to constant scratching. Death secondary to systemic or respiratory infection, alimentary tact bleeding or finally liver failure usually occurs by the age of 2 years.
Overall outcome There is considerable evidence that overall outcome is greatly improved with centre case load experience of greater than five cases per year along with better communication between major centres and the more peripheral units. During late childhood and early adolescence, portal hypertension may become evident with the development of oesophageal varices, but bleeding can be satisfactorily managed by injection sclerotherapy or variceal banding. There is a tendency to spontaneous disappearance of the varices in those that survive into adulthood. Of the remaining, 60–70%, approximately half will have failed to sustain bile drainage and will require early referral for liver transplantation. Another 30% will have a partially successful Kasai operation or will have had repeated episodes of cholangitis and although growth will be satisfactory, they may develop evidence of progressive liver disease during the childhood years.
Surgical strategy In the 1950s, Kasai from Sendai, Japan developed a procedure whereby all the diseased extrahepatic bile duct remnants and fibrous tissue were excised from the porta hepatis above and behind the bifurcation of the portal vein; flush with, but not into the liver substance.10 The area thus exposed drained bile through residual and regenerating ductular structures into the alimentary tract by anastomosing a Roux-en-Y loop of jejunum around this area. What was an incurable condition with an inevitably fatal outcome had now become at least manageable. Although for many years the operation fell into disrepute, this was partly because of a misunderstanding of some technical aspects of the procedure.
Liver transplant Biliary atresia is the most frequent indication for liver transplantation in infancy and childhood.19,20 Liver transplantation has been accepted as a complementary procedure with the Kasai portoenterostomy for the treatment of children with biliary atresia, who have developed end-stage liver disease. Although liver transplantation remains a formidable surgical procedure, current greater than 95% 1-year and greater than 85% 5-year survival figures are being reported from the best centres. Certainly a good quality of life is obtained in most children, although life-long immunosuppressive therapy and close medical and surgical supervision is required. The world’s longest survivor to date remains well nearly 40 years after transplant. With the passing of years, techniques will improve and management of infection and control of rejection by new and more effective drugs will make the option of transplantation even more attractive.
‘What are the prognostic indicators and factors?’ Delay in operation is the single most important prognostic factor.11 Currently, in those infants operated on before 60 days of age, one can expect that 90% will drain bile, and greater than 70% will lose their jaundice.12 However, those operated on after 13 weeks of age only have around a 20% chance of sustained bile drainage with loss of jaundice, and irreversible cirrhosis is already established in most. Recent attempts at laparoscopic Kasai portoenterostomy have not found wide support.13 The size of the microscopic ductules in the fibrotic mass that has been cut away is also a good indicator of whether success can be expected; ducts of size greater than 150 microns in diameter being almost always associated with bile drainage. Unfortunately, bile drainage per se does not equate with cure, as there may be ongoing intrahepatic cholestasis and fibrosis. Postoperative management is most important. A contaminated drainage system predisposes to recurrent episodes of bacterial cholangitis. These attacks are most frequent and severe in the first 6 months after operation and are heralded by fever, ileus, change in stool colour and rise in serum bilirubin levels. Each attack should be energetically treated with the appropriate antibiotic (Escherichia coli and Klebsiella being the organisms most frequently cultured). Repeated episodes of cholangitis are usually associated with subsequent more rapid deterioration of liver function and progressive cirrhosis. Choleretics, in the form of phenobarbitone, cholestyramine, ursodeoxycholic acid and corticosteroids, are given in an attempt to improve bile flow.14,15 The efficacy of these choleretics is not yet fully proven but steroids may also reduce scar tissue formation. Dose of corticosteroid, time of starting treatment, and duration have been variable and prospective trials are in progress
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Conclusion Although biliary atresia remains a very serious disease of infancy, one can truly say that in the new millennium the overall outcome should be excellent. In fact, with correctly timed surgical management – both portoenterostomy and liver transplantation – one can expect a nearly 90% long-term survival. Early referral; and management by multidisciplinary specialist paediatric hepatology units is, however, crucial for optimal outcome.
Choledochal cysts Choledochal cyst is a rare cystic dilatation of the bile duct system. It is seen more frequently in females and in oriental races. More than half present in the first decade of life.21,22 Clinical The classical triad of pain, right upper quadrant mass and jaundice occurs in less than 40%. Cholestasis, recurrent pain with or without jaundice, fever, pancreatitis and acute abdominal emergency are other presentations. 279
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ultrasound early surgical intervention with a Kasai portoenterostomy is indicated. Choledochocoeles are probably a different entity and require endoscopic or open sphincterotomy or cyst duodenostomy.
Pathology Five patterns of dilatation are apparent and have been classified as: • type I – cystic dilation of the common bile duct (saccular or fusiform) 80% • type II – an extrahepatic supraduodenal diverticulum of the bile duct: • type III – choledochocele, a cyst of the intramural duodenal bile duct. • type IV – fusiform intrahepatic and extrahepatic cysts • type V – multiple intrahepatic cysts (Caroli’s disease).
Spontaneous common bile duct perforation Spontaneous perforation of the common bile duct is a rare condition where rupture usually occurs at the junction with the cystic duct, possibly due to a developmental weakness.28 Clinical Typically an uncomplicated perinatal course is interrupted by onset of mild cholestatic jaundice, irritability, abdominal distension and vomiting. Infection with septicaemia may result in sudden clinical deterioration. Examination reveals evidence of ascites without peritonism. Green staining of the scrotum as bile stained fluid extends along the patent process vaginalis may be present in male infants. Apart from the mild cholestatic jaundice, liver function tests are usually surprisingly normal, although the serum alkaline phosphatase and gamma glutamyl transferase levels are mildly raised. Ultrasound is usually diagnostic along with biochemical analysis of the ascites.
Aetiology and pathogenesis The cause is thought in most cases to be due to an anomaly where the pancreatic duct joins the distal common bile duct (CBD) above the sphincter of Oddi.23,24 This leads to a positive pressure differential of pancreatic exocrine secretion over bile secretion with reflux of pancreatic juice into the CBD due to a degree of distal obstruction. This results in damage to duct epithelium and wall. The gall bladder is often of normal size but may be enlarged with a tortuous cystic duct. The wall of the duct is thickened and replaced by fibrous tissue without an epithelial lining. Diagnosis Antenatal diagnosis is being documented with increasing frequency. Most have a normal liver initially but cirrhosis may develop quickly. Ultrasound will identify the cyst but magnetic resonance cholangiography can now very nicely delineate the detail of the intrahepatic and extrahepatic biliary system. Pancreatitis, cholelithiasis and infection can supervene and it would be wise not to delay surgery even when liver function tests are normal.
Management Management involves a careful surgical exploration. Pseudocystic containment of bile around the perforation may be confusing. In most, provided distal patency of the biliary system can be confirmed with operative cholangiogram, all that is required is to adequately drain the area of perforation. When there is any evidence of distal common bile duct obstruction, which can be demonstrated by intra-operative cholangiogram, cholecystectomy and hepaticojejunostorny enteric drainage is indicated.29
Treatment Surgical technique involves an operative cholangiogram, cyst excision and hepaticojejunostomy.25 Usually one can find a relatively avascular plane of dissection outside the cyst but beneath the overlying peritoneum. The distal orifice is usually excentrically placed antero-medially. When the cyst is too large to obtain a meaningful cholangiogram, cholecystoscopy helps to identify proximal and distal duct structures and any evidence of stones or sludge. Care should be taken not to damage the main pancreatic duct at surgery. Cyst excision should extend proximally to the right and left hepatic duct confluence with extension and opening of the left hepatic duct to obtain a wide anastomosis for adequate drainage into the bowel.26 A long (40 cm) Roux-en-Y hepaticojejunostomy is the preferred method of enteric bile drainage and has excellent long-term outcome. Late sequalae of carcinoma and retention of secretions usually relate to inadequate cyst excision.27 If cholangitis occurs anastomotic stenosis must be suspected.
Inspissated bile syndrome and cholelithiasis First described by Ladd in the 1930s, the incidence inspissated bile syndrome peaked in the 1950s because of the prevalence of untreated rhesus disease of the newborn resulting in haemolysis and sludge in the bile ducts.30 Cholelithiasis is being increasingly recognised as an entity in the neonate and infant, particularly those who have survived neonatal intensive care with illnesses associated with prematurity including necrotising enterocolitis and feeding intolerance. Any condition requiring parenteral nutrition may lead to cholestasis, gall bladder sludge and gallstones. Other contributing factors in infants include: decreased bile acid output; shortened erythrocytic lifespan; phototherapy for physiologic jaundice; furosemside therapy; and maternal narcotic addiction. There is a bimodal age incidence with a second peak in late childhood and adolescence. Although in infancy sex incidence is equal, there is an increasing female preponderance with age. While biliary sludge is composed of mainly mucin, calcium bilirubinate and cholesterol, the usual mixed cholesterol stones predominate in adolescent girls.
Choledochal cyst with cirrhosis Rarely choledochal cysts present at birth in association with established cirrhosis. The aetiology is speculative but this should be regarded as ‘cystic’ biliary atresia, with a poorer long-term outcome expected. Histologically the cyst wall is made up of fibrous tissue with a chronic inflammatory reaction. The epithelial lining is wholly or partially absent. If noted on antenatal
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Diagnosis Clinical symptoms and signs may vary from severe colic, those associated with acute cholecystitis, pancreatitis, cholangitis with common duct stones, to mild fatty food intolerance. 280
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Gallbladder ultrasound is very effective in evaluating the presence of stones or sludge. Thickness of the gallbladder wall, size of CBD and other pancreatico-biliary pathology can also be identified. The patient can be further investigated with liver function tests and magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography (ERCP). Radioisotope scanning with 99mTc-iminoacetic acid derivatives showing non-function is usually diagnostic of acute cholecystitis.
s urgical excision and radiotherapy has improved a previous dismal prognosis.36
Summary Early diagnosis of cholestatic jaundice in the neonate and infant and referral to a specialised unit is an absolute requirement if the results of surgery for biliary atresia are to be improved. Other causes of surgical jaundice are rare but timely surgical intervention can usually be curative. Roux-en-Y hepaticojejunostomy with a greater than 35 cm drainage loop provides excellent bilioenteric drainage. Cholelithiasis is being increasingly recognised and symptomatic stones are treated by laparoscopic cholecystectomy with minimal morbidity. ◆
Management Spontaneous resolution of non-calcified sludge or stones has been documented in neonates but calcified stones are unlikely to resolve spontaneously. Ursodeoxycholic acid (20 mg/kg/day) therapy may be useful where there is bile inspissation rather than formed stones.31 Operative cholangiogram with a flush of the biliary system may be sufficient for inspissated bile. Cholecystectomy is required for symptomatic and calcified stones. Increasingly laparoscopic cholecystectomy is being performed even in infants. Gallstones from haemolytic disease are frequent but predominantly occur in older children. There is some debate as to whether cholecystectomy is required rather than cholecystostomy and removal of the stones at the time of splenectomy, as theoretically the haemolytic diathesis is reduced.32 However, in practice most require cholecystectomy. Suspected common bile duct stones should be searched for and removed. Retained stones can be extracted via ERCP.33 Biliary dyskinesia, defined as symptomatic biliary colic without cholelithiasisis is being increasingly identified as a cause for abdominal pain in children. Diagnosis is suggested if the emptying fraction of the gall bladder after a fatty meal, as seen on hepatobiliary radioisotope scan or ultrasound is less than 35%. One should, however, be cautious in proceeding to cholecystectomy as in one recent series at 2-year follow-up of two similar symptom groups, one having had a cholecystectomy, outcomes were the same.34
References 1 Mieli-Vergani G, Howard ER, Portman B, et al. Late referral for biliary atresia – missed opportunities for effective surgery. Lancet 1989; 1: 421–3. 2 Grosfeld JL, Rescorla FJ, Skinner MA, et al. The spectrum of biliary tract disorders in infants and children. Experience with 300 cases. Arch Surg 1994; 129: 513–8 (discussion 518–20). 3 Valman HB. The first year of life: Jaundice in the newborn. BMJ 1989; 299: 1272–4. 4 Mackenzie TC, Howell LJ, Flake AW, et al. The management of prenatally diagnosed choledochal cysts. J Pediatr Surg 2001; 36(8): 1241–3. 5 Davenport M, Savage M, Mowat AP, et al. Biliary atresia splenic malformation syndrome: an etiologic and prognostic subgroup. Surgery 1993; 113(6): 662–8. 6 Phillips PA, Keast D, Papadimitriou JM, et al. Chronic obstructive jaundice induced by Reovirus type 3 in weanling mice. Pathology 1969; 1(3): 193–203. 7 Riepenhoff-Talty M, Schaekel K, Clark HF, et al. Group A rotaviruses produce extrahepatic biliary obstruction in orally inoculated newborn mice. Pediatr Res 1993; 33(4 Pt 1): 394–9. 8 Brown WR, Sokol RJ, Levin MJ, et al. Lack of correlation between infection with reovirus 3 and extrahepatic biliary atresia or neonatal hepatitis. J Pediatr 1988; 113(4): 670–6. 9 Chiba T, Ohi R, Mochizuki I. Cholangiographic study of the pancreaticobiliary ductal junction in biliary atresia. J Pediatr Surg 1990; 25(6): 609–12. 10 Kasai M, Suzuki S. A new operation for “non-correctable” biliary atresia with hepatic portoenterostomy. Shujyutsu 1959; 13: 733–739. 11 Tagge DU, Tagge EP, Drongowski RA, et al. A long-term experience with biliary atresia. Reassessment of prognostic factors. Ann Surg 1991; 214(5): 590–8. 12 Karrer FM, Price MR, Bensard DD, et al. Long-term results with the Kasai operation for biliary atresia. Arch Surg 1996; 131(5): 493–6. 13 Aspelund G, Ling SC, Ng V, et al. A role for laparoscopic approach in the treatment of biliary atresia and choledochal cysts. J Pediatr Surg 2007; 42(5): 869–72. 14 Kobayashi H, Yamataka A, Koga H, et al. Optimum prednisolone usage in patients with biliary atresia postportoenterostomy. J Pediatr Surg 2005; 40(2): 327–30.
Benign bile duct strictures These are generally rare but may complicate trauma, surgery, radiotherapy for malignant disease or bile duct perforation. An idiopathic variety exists that differs from sclerosing cholangitis as they tend to be single and are associated with fibrosis of the bile duct wall and loss of epithelium.35
Bile duct tumours These rare tumours present with painless obstructive jaundice in most instances. Diagnosis depends on imaging and biopsy. Malignancy in the form of rhabdomyosarcoma is seen more frequently than benign ‘unusual’ lesions such as inflammatory pseudotumour and granular cell tumour. Although only around 100 cases of rhabdomyosarcoma have been reported it is a well-defined entity with mean age at presentation in the 4th year. More than a third of the tumours have spread either locally or distally by the time of presentation with jaundice, fever and a mass. Tumours may be polypoid with grape-like projections within the bile duct and are typically embryonal with botryoid features on histology. Aggressive treatment with a combination of chemotherapy,
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15 Meyers RL, Book LS, O’Gorman MA, et al. High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia. J Pediatr Surg 2003; 38(3): 406–11. 16 Ohi R, Nio M, Chiba T, et al. Long-term follow-up after surgery for patients with biliary atresia. J Pediatr Surg 1990; 25(4): 442–5. 17 Laurent J, Gauthier F, Bernard O, et al. Long-term outcome after surgery for biliary atresia. Study of 40 patients surviving for more than 10 years. Gastroenterology 1990; 99(6): 1793–7. 18 Hadzic N, Davenport M, Tizzard S, et al. Long-term survival following Kasai portoenterostomy: is chronic liver disease inevitable? J Pediatr Gastroenterol Nutr 2003; 37(4): 430–3. 19 Starzl TE, Demetris AJ, Van Thiel D. Liver transplantation (1). N Engl J Med 1989; 321(15): 1014–22. 20 Starzl TE, Demetris AJ, Van Thiel D. Liver transplantation (2). N Engl J Med 1989; 321(16): 1092–9. 21 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 1977; 134(2): 263–9. 22 Stringer MD, Choledochal cysts In: Howard ER, Stringer MD, Colombani PM, eds. Surgery of liver, bile-ducts and pancreas in children, 2nd Edn. London: Arnold, 2002, p. 149–68. 23 Miyano T, Suruga K, Suda K. Abnormal choledocho-pancreatico ductal junction related to the etiology of infantile obstructive jaundice diseases. J Pediatr Surg 1979; 14(1): 16–26. 24 Babbitt DP. Congenital choledochal cysts: new etiological concept based on anomalous relationships of the common bile duct and pancreatic bulb. Ann Radiol (Paris) 1969; 12(3): 231–40. 25 Miyano T, Yamataka A, Kato Y, et al. Hepaticoenterostomy after excision of choledochal cyst in children: a 30-year experience with 180 cases. J Pediatr Surg 1996; 31(10): 1417–21. 26 Stringer MD. Wide hilar hepatico-jejunostomy: the optimum method of reconstruction after choledochal cyst excision. Pediatr Surg Int 2007; 23(6): 529–32. 27 Bismuth H, Krissat J. Choledochal cystic malignancies. Ann Oncol 1999; 10(suppl 4): 94–8. 28 Davenport M, Heaton ND, Howard ER. Spontaneous perforation of the bile duct in infants. Br J Surg 1991; 78(9): 1068–70.
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29 Sprigland N, Greco R, Rosenfeld D. Spontaneous biliary perforation: does external drainage constitute adequate therapy? J Pediatr Surg 1996; 31: 782–784. 30 Ladd WE. Congenital obstruction of the bile ducts. Ann Surg 1935; 102: 742–751. 31 Heaton ND, Davenport M, Howard ER. Intraluminal biliary obstruction. Arch Dis Child 1991; 66(12): 1395–8. 32 Newman KD, Powell DM, Holcomb 3rd GW. The management of choledocholithiasis in children in the era of laparoscopic cholecystectomy. J Pediatr Surg 1997; 32(7): 1116–9. 33 Kumar R, Nguyen K, Shun A. Gallstones and common bile duct calculi in infancy and childhood. Aust N Z J Surg 2000; 70(3): 188–91. 34 Scott Nelson R, Kolts R, Park R, et al. A comparison of cholecystectomy and observation in children with biliary dyskinesia. J Pediatr Surg 2006; 41(11): 1894–8. 35 Bowles MJS, Salisbury JR, Howard ER. Localized, benign, nontraumatic strictures of the extrahepatic biliary tree in children. Surgery 2001; 130: 55–9. 36 Spunt SL, Lobe TE, Pappo AS, et al. Aggressive surgery is unwarranted for biliary tract rhabdomyosarcoma. J Pediatr Surg 2000; 35(2): 309–16.
Practice points • Jaundice in the neonate extending beyond 2 weeks must be fully investigated • A multidisciplinary approach has improved outcome • The spectrum of disorders causing conjugated hyperbilirubinaemia includes biliary atresia, choledochal cyst, spontaneous perforation of the common bile duct and gallstones or inspissated bile • Surgical management performed timeously, may prevent progression of parenchymal disease • Biliary atresia is now a disorder with good long-term outcome if managed appropriately (Kasai portoenterostomy and liver transplantation)
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