Prolonged Neonatal Jaundice in Cystic Fibrosis

Four patients with cystic fibrosis developed prolonged obstructive jaundice starting in the newborn period. Obstructive biliary cirrhosis was shown post mortem in one of them who died at 5 months from pneumonia, while another dying at 8 years had an histologically normal liver at necropsy. The two survivors were jaundiced for 6 months and 5 weeks respectively, before making a clinical recovery, and in both liver biopsy at the height of the jaundice showed bile stasis.Meconium ileus was present in half of all recorded cases of cystic fibrosis with prolonged neonatal jaundice. Jaundice is probably due to extrahepatic biliary obstruction from bile of increased density, with secondary intrahepatic bile stasis.     

Neonatal gallbladder enlargement and alpha 1-antitrypsin deficiency

Patients with clinical signs of alpha 1-antitrypsin deficiency in the neonatal period usually present with prolonged obstructive jaundice. We report a patient with alpha 1-antitrypsin deficiency who presented with gallbladder enlargement in the neonatal period. This gallbladder enlargement may be due to cystic duct hypoplasia or atresia, which has been reported in association with alpha 1-antitrypsin deficiency. The diagnosis of alpha 1-antitrypsin deficiency should be considered in neonates with gallbladder enlargement and prolonged obstructive jaundice.     

Neonatal cholestasis as the presenting feature in cystic fibrosis

Between 1960 and 1994 cystic fibrosis was found in nine out of 1474 infants investigated for neonatal cholestasis. Four had delay in passing meconium. In all patients cholestatic jaundice was present during the first 48 hours and in three patients cholestasis was complete, mimicking biliary atresia. Serum cholesterol concentrations were normal in all but two children. Sweat chloride was repeatedly above 95 mmol/l in all instances. Three children had another condition enhancing the risk of cholestasis (alpha1-antitrypsin deficiency, hypopituitarism, perinatal asphyxia, and total parenteral nutrition). Liver histology displayed portal fibrosis and inflammation with bile duct proliferation; mucous plugs in bile ducts were observed in only one patient. Only one child died from cirrhosis. These results indicate that cystic fibrosis is not a major cause of neonatal cholestasis. However early signs of intestinal obstruction and low concentrations of serum cholesterol may indicate cystic fibrosis, regardless of liver histology. Neonatal cholestasis has no prognostic value concerning evolution to cirrhosis.     

Neonatal cholestasis as the presenting feature in cystic fibrosis.

Between 1960 and 1994 cystic fibrosis was found in nine out of 1474 infants investigated for neonatal cholestasis. Four had delay in passing meconium. In all patients cholestatic jaundice was present during the first 48 hours and in three patients cholestasis was complete, mimicking biliary atresia. Serum cholesterol concentrations were normal in all but two children. Sweat chloride was repeatedly above 95 mmol/l in all instances. Three children had another condition enhancing the risk of cholestasis (alpha1-antitrypsin deficiency, hypopituitarism, perinatal asphyxia, and total parenteral nutrition). Liver histology displayed portal fibrosis and inflammation with bile duct proliferation; mucous plugs in bile ducts were observed in only one patient. Only one child died from cirrhosis. These results indicate that cystic fibrosis is not a major cause of neonatal cholestasis. However early signs of intestinal obstruction and low concentrations of serum cholesterol may indicate cystic fibrosis, regardless of liver histology. Neonatal cholestasis has no prognostic value concerning evolution to cirrhosis.     

Granular cell tumor of the biliary system

Granular cell tumors (GCT) are rare benign neoplasms of Schwann cell origin which have been found in virtually every location in the body. Their location in the biliary system is unusual, and typically occurs in black females during the fourth decade of life. Forty-eight cases have been reported since 1952. We present two patients treated for obstructive jaundice caused by GCT of the extrahepatic biliary tree. The literature on biliary GCT is reviewed and their management is outlined. Local excision with Roux-y-hepaticojejunostomy was performed in one patient with GCT obstructing the common bile duct at the level of the cystic duct. Pancreaticoduodenectomy was performed on one patient for GCT of the common bile duct involving the ampulla and adjacent pancreas. GCT of the extrahepatic biliary system are rare but should be considered in black females who present with obstructive jaundice in the fourth decade of life. Local excision with cholecystectomy and reconstruction of the biliary remnant is indicated. Primary biliary anastomosis is desired but choledochojejunostomy or hepaticojejunostomy may be necessary. Rarely, pancreaticoduodenectomy may be indicated in GCT of the distal common bile duct. © 1994 Wiley-Liss, Inc.     

Biliary tract dilatation and abnormal choledocho-pancreatic ductal junction in children

Nine children aged between 2 months and 11 years, who had congenital dilatation of extrahepatic biliary tract, with or without intrahepatic dilatation, are presented. The radiological studies performed in eight patients demonstrated abnormal choledochopancreatico ductal junction. Thus, a long common channel is formed out of the duodenal wall, leading to a continuous reflux of pancreatic juice into the biliary system, chronic inflammation of biliary tract wall, fibrosis of muscular layer and finally different types of dilatations. The main clinical findings were upper abdominal pain, vomiting, or obstructive jaundice. In only one child the dilatation was cystic type and the clinical manifestation was palpable abdominal mass. In eight patients the initial diagnosis of biliary tract dilatation was made through abdominal ultrasound and in one case by direct visualization through emergent exploratory laparotomy. The final confirmation of the presence of long common channel was made by preoperative endoscopic retrograde cholangiopancreatography or intraoperative cholangiogram. The radiologic investigation was not performed in only one case due to bad clinical conditions. The surgical treatment indicated to all cases was Roux- en- Y hepatic- jejunostomy. The late follow up demonstrated that all patients are well and assymptomatic.     

Association of serum interleukin-8 levels with the degree of fibrosis in infants with chronic liver disease

OBJECTIVE: Biliary atresia is a neonatal obstructive cholangiopathy characterized by a destructive, obliterative process affecting both the intrahepatic and extrahepatic ducts of the biliary tree that uniquely presents in the first months of life. The consequence of progressive inflammatory and sclerotic reaction is the development of obstructive jaundice. To determine the proinflammatory cytokine profile in children with biliary atresia, we measured circulating levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and IL-8. METHODS: Twelve children, five males and seven females, with biliary atresia were studied. In addition, four patients with progressive familial intrahepatic cholestasis and three with Alagille syndrome were also included. Five patients with neonatal hepatitis were studied as controls of a liver disease without portal fibrosis. Serum concentration of total and conjugated bilirubin, gamma-glutamyl transferase and glutamic-pyruvic transaminase were measured by routine methods in all patients at time of sampling for the study. The degree of fibrosis in liver biopsies was scored using the histologic activity index. RESULTS: In our study IL-8 was detectable in 11 of 12 patients with biliary atresia with a median level of 262 pg/ml and a highly statistically significant difference (P < 0.0001) from controls. In patients with progressive familial intrahepatic cholestasis or with Alagille syndrome serum IL-8 levels were similarly elevated. In patients with neonatal hepatitis, IL-8 levels were marginally increased. Serum IL-8 levels were significantly correlated (Rs = 0.725, P < 0.0001) with the histologic activity index. CONCLUSIONS: Although further studies are needed to determine the role of IL-8 in portal inflammation, our results suggest that increased production of IL-8 may be a mechanism leading to the progressive portal inflammation and fibrosis in patients with chronic liver disease.     

Pancreatic Hormone Changes in Infantile Obstructive jaundice

Metabolic disturbances of pancreatic hormones in obstructive jaundice in infancy were evaluated experimentally and clinically. In our experimental study, using young rats, the level of plasma insulin (IRI) gradually increased after ligation of the common bile duct. These levels were a little lower than those in the non-treated controls. The level of plasma glucagon (IRG) incerased remarkably 4 weeks after ligation of the common bile duct. Clinically, there were no significant differnces in the levels of IRI and IRG among normal controls and cases of neonatal hepatitis and congenital biliary atresia (CBA). In CBA patients, these levels can be correlated with the progression of hepatic fibrosis; an increase in IRG and a decrease in teh IRI/IRG mol ratio was noticed in patients with grade III of hepatic fibrosis. These indicate that, in obstructive jaundice in infancy, the more severe the hepatic damage due to obstructive jaundice, the higher the level of plasma glucagon concentration will rise.     

Diagnostic laparoscopy-assisted cholangiography in infants with prolonged jaundice

Cholangiography is often crucial for establishing the definitive cause of neonatal jaundice. We present our protocol for using laparoscopy-assisted cholangiography in infants with prolonged jaundice and discuss its benefits. Firstly, a 5 mm supra-umbilical trocar is introduced to create a port for a 0° laparoscope. A 5 mm trocar is then inserted through a right subcostal incision to allow the liver and gallbladder to be visualized. If the gallbladder is of good size, the fundus is exteriorized through the right subcostal trocar site and a catheter is inserted into the gallbladder for cholangiography. If the gallbladder is atretic, the fundus is not exteriorized and a laparotomy is performed for open intraoperative cholangiography because the lumen of an atretic gallbladder is usually not fully patent and cholangiography through its exteriorized fundus often fails. We reviewed 18 jaundiced infants thought to have biliary atresia (BA) who had laparoscopy-assisted cholangiography. At laparoscopy, four patients had good sized gallbladders and minimal to mild liver fibrosis. They underwent cholangiography via the exteriorized fundus, and BA in two cases and biliary hypoplasia in two cases were identified. The remaining 14 had atretic gallbladders and varying degrees of liver fibrosis. Cholangiography via the exteriorized fundus was performed in one patient, but failed and converted to open cholangiography. Open intraoperative cholangiography identified BA in all 14 cases. All BA cases progressed to Kasai portoenterostomy directly after diagnosis. Laparoscopy is used to determine the type of cholangiography to be performed based on the appearance of the gallbladder and this simple, accurate, and safe protocol allows the anatomical structure of the biliary tree to be obtained accurately with minimal surgical intervention.     

Anterior abdominal wall defects and biliary obstruction

Three infants with anterior abdominal wall defects (gastroschisis and exomphalos) who presented with obstructive jaundice secondary to biliary obstruction, are described. All three infants had abnormal biliary systems, with mechanical distortion of the biliary tree. Biliary obstruction secondary to structural biliary anomalies should be considered in patients with abdominal wall defects and cholestasis, as prolonged unrelieved biliary obstruction may lead to biliary cirrhosis and portal hypertension.     

Value of sonography in prolonged neonatal jaundice. Findings in 13 cases]

BACKGROUND: Different conditions are associated with a prolonged cholestatic jaundice in the neonatal period: viral hepatitis, biliary atresia and choledocal cyst are the most frequent causes. Laboratory findings are necessary, although they do not permit an etiologic diagnosis in all cases. Serial ultrasonographic study could be proposed for the evaluation of biliary excretion before and after feeding, in order to differentiate between these three conditions. PATIENTS AND METHODS: Between February 1993 and January 1997, 13 newborns (seven girls and six boys) aged from 30 to 186 days, presented with jaundice and conjugated hyperbilirubinemia. They were evaluated by laboratory tests; serial ultrasonographic examinations were performed after 4 hours fasting then 1 and 2 hours after meal. RESULTS: The gallbladder (GB) was visualized in nine patients. In five of these patients, it contracted after feeding suggesting the diagnosis of neonatal hepatitis, that was confirmed by the clinical evolution. In three patients, the GB did not change in size and the diagnosis of biliary atresia was surgically proven. In one patient, a choledocal cyst was visualized and confirmed by surgery. The GB was not identified after 4 hours of fasting in four patients; biliary atresia was suspected and confirmed by surgery. CONCLUSION: Serial ultrasound of the GB is an easy and non-invasive method. It was useful in identifying those conditions requiring surgery in eight patients. We recommend its use as the initial method in the evaluation of neonatal jaundice before the other invasive methods.     

External and internal-external biliary drainage in children with malignant obstructive jaundice

Background. Obstructive jaundice is an uncommon but important clinical problem in children with cancer. Percutaneous transhepatic biliary drainage is widely used to relieve malignant biliary obstruction in adults, but its use in children has not been well described.¶Materials and methods. Six patients aged between 1 and 17 years underwent external or internal-external biliary drainage to relieve malignant obstructive jaundice. Biochemical, haematological and microbiological parameters were measured before the procedure and repeated 7–9 days later.¶Results. External or internal-external biliary drainage was technically successful in all patients. No patient developed clinically significant biliary sepsis. Asymptomatic duodenal perforation occurred in one patient with bulky duodenal tumour following conversion from external to internal-external drainage.¶Conclusions. External biliary drainage may be successfully performed in children with malignant obstructive jaundice.     

Neonatal hepatitis syndrome with paucity of interlobular bile ducts in cystic fibrosis.

A male infant presenting with neonatal hepatitis syndrome, characterized by conjugated hyperbilirubinemia and very mild liver function test abnormalities, at 2 weeks of age was found to have no excretion of radioisotope into the intestinal tract on hepatobiliary scan. Liver biopsy revealed severe interlobular bile duct paucity. Other features of Alagille's syndrome were not present; other conditions frequently associated with interlobular bile duct paucity were also excluded. Subsequently, the infant was found to have cystic fibrosis. Cystic fibrosis is thus another disease that may be associated with paucity of interlobular bile ducts presenting as neonatal hepatitis syndrome, and this represents a different pathogenesis of cholestatic jaundice in neonates with cystic fibrosis besides those previously recognized.     

Cystic Fibrosis Presenting with Neonatal Cholestasis Simulating Biliary Atresia in a Patient with a Novel Mutation

Neonatal cholestasis is a rare presenting feature of cystic fibrosis which usually cannot be differentiated from other types of cholestasis. Herein, the authors report a 63 d-old boy with cystic fibrosis presenting with neonatal cholestasis mimicking biliary atresia. A new mutation in CFTR gene resulting in severe phenotype has been described. The cystic fibrosis patients with c.3871 G?>?T mutation may have acholic gaita mimicking biliary atresia in the absence of insipissated bile with minimal histologic findings in the liver.     

Prenatal ultrasonographic appearance of type IIId (uncorrectable type with cystic dilatation) biliary atresia

Although prenatal ultrasonographic (US) diagnosis has been reported in biliary atresia (BA), most cases are type I (correctable with cystic dilatation). We report three prenatal cases of type IIId BA (uncorrectable with cystic dilatation). Routine fetal US at 22 to 24 weeks of gestation showed two communicating cystic lesions 12 to 16 mm in diameter. On color Doppler US, the lesions were separate from the portal vein or hepatic artery. The size did not change during the prenatal period in any case. Choledochal cyst (CC) was considered the most likely diagnosis, although BA with cystic lesions was also considered. After birth, the patients developed acholic stools and prolonged neonatal jaundice. Hepatobiliary scintigraphy showed negative passage. Duodenal fluid showed a negative or slightly positive Gmelin test. The neonates underwent laparotomy at the age of 36, 46, and 32 days, respectively. Intraoperative cholangiography showed the gallbladder and slightly-dilated common-bile duct without entering the proximal or distal bile ducts in all cases. They were classified as type IIId BA and underwent excision of the cystic lesions and dissection of the portal bile-duct remnants, followed by hepatic portoenterostomy. Case 1 showed persistent jaundice and finally underwent liver transplantation (LTx), case 2 became anicteric. Case 3 remained jaundiced and is to undergo LTx. In conclusion, type IIId BA may be one of the differential diagnoses when a cystic lesion is detected under the hepatic hilum by fetal US. However, prenatal diagnosis of BA is still difficult with respect to differentiation from a CC or type I BA. Early postnatal diagnosis followed by immediate treatment is important, especially in type IIId BA.     

Laparoscopy in diagnosis of prolonged neonatal jaundice

When managing neonatal jaundice, there is no single test or imaging modality that can reliably define biliary atresia and neonatal hepatitis. Early diagnosis is an important step for surgical success in extra hepatic biliary atresia. In many situations, exploratory laparotomy and operative cholangiography may be needed to settle the definitive diagnosis, with the risk of having negative exploration in those high risk patients with medical etiology. The use of laparoscopy may help in avoiding unnecessary exploration for such group of patients and arriving at a definite diagnosis. Six patients with conjugated hyperbilirubinemia were evaluated with a diagnostic laparoscopy, laparoscopic cholangiography and liver biopsy. Three of the six patients were diagnosed to have neonatal hepatitis and so an unnecessary laparotomy was avoided in these cases.     

Management of Neonatal Obstructive Jaundice

A plan of management of neonatal obstructive jaundice is proposed for use in units specializing in the treatment of this difficult condition. Reliance is placed in needle liver biopsy used early (and repeatedly if necessary) to judge the rate of development of fibrosis in the liver and to reach a diagnosis. Blind porto-enterostomy is used in biliary atresia when no patent proximal duct is found. Emotional support of parents through this long illness is important. The procedures described should not be attempted by surgeons less experienced with this disease.     

Determination of nasal transepithelial potential difference (DDPTE) in cystic fibrosis. Analysis of a simplified measurement technique]

Measurements of nasal transepithelial potential differences (TEPD) were performed in 77 patients in order to assess a routine simplified method of recording. TEPD assays were performed in 34 patients with cystic fibrosis aged 1 month to 25 years, in 22 children with another chronic respiratory illness and in 21 subjects without any bronchopulmonary impairment. In the cystic fibrosis group TEPD values (mean +/- SD) were significantly higher (-49.077 +/- 9.38 mV) than in patients with chronic respiratory illnesses (-20.590 +/- 5.011 mV) or in subjects without bronchopulmonary impairment (-19.857 +/- 5.033 mV) (p less than 0.0001). Measurements could not be performed in 10 patients due to major nasal inflammation. The excellent specificity (100%) and sensitivity (93%) of the method confirm its diagnostic value. It may be used from the neonatal period and may represent an alternative to the sweat test, especially in dubious cases.     

Rabdomyosarcoma of the biliary tree

Rabdomyosarcoma of the biliary tree is one of the rare causes of biliary tract obstruction in childhood. Nevertheless it is the most common cause of obstructive jaundice due to neoplastic biliary obstruction. We present a two-year-old child with obstructive jaundice secondary to an embryonal rhabdomyosarcoma of the biliary tree. She underwent surgery and, after total excision of the mass, a hepaticojejunostomy and Roux-en-Y anastomosis were performed. She was referred to the Pediatric Oncology Group for follow-up. Rhabdomyosarcoma of the bilary tree, although rare, must be considered in the etiology of obstructive jaundice in children.     

Surgical injury of the biliary tract in children.

A retrospective clinical study was performed to evaluate the etiology, incidence, diagnosis, management and outcome of patients presenting with surgical injury to the biliary tract. 4 boys were treated for operative biliary tract injuries between 1970 and 1997. This number represents less than 0.03% of all patients who underwent laparotomy in our unit during the same period. The mean age of the patients at presentation was 7.5 +/- 3 (range, 4 to 10 years). Accidental ligation of choledochus (n = 2), vascular insult of the biliary tract (n = 1) and formalin toxicity (n = 1) were the causes of injuries. The latter presented with caustic sclerosing cholangitis and biliocutaneous fistula while obstructive cholangitis (n = 2) and jaundice (n = 1) were noted in the remaining patients. The duration between surgical injury and presentation ranged from 6 to 125 days. All patients presented with elevated levels of transaminases, alkaline phosphatase and bilirubin. Ultrasonography, percutaneous transhepatic cholangiography and biliary drainage catheter placement were performed in all patients to visualize the extent of injury and to provide better patient status for operation. Biliary stent application provided temporary relief of obstruction in one patient, but all patients required surgical treatment subsequently. Roux-en-Y hepaticojejunostomy (n = 3), and choledochoduodenostomy (n = 1) were the operative procedures. No complications were encountered in the short and long-term follow-up. Our experience revealed that surgical biliary tract injuries have special features that warrant consideration with respect to prevention and management in children. They may be caused by partial or complete transection, suture ligation, clip application or vascular insult and can be avoided by adequate exposure, accurate gentle dissection, use of hemostatic clips rather than clamps and ties, and the liberal use of operative cholangiography. The presenting clinical picture depends on the cause, extent and duration of the injuries. Preoperative detailed evaluation of the hepatobiliary system by radiological and endoscopic means is mandatory for successful treatment. Percutaneous and/or endoscopic techniques can be employed in selected cases, but if these fail or can not be done, open surgical techniques should be performed without hesitation as delayed treatment results in biliary cirrhosis and hepatic failure. Excision of excessive scar tissue at the biliary tract and portal hilus, constructing the widest possible stoma, obtaining mucosa to mucosa approximation around 360 degrees, enduring a good blood supply to the anastomotic line and avoiding tension on the anastomosis are mainstays of successful surgery. Thus, reconstructive biliary tract surgery should be considered as a specialized procedure and should be performed by skillful and experienced hands.