Hypoplasia of Extrahepatic Biliary Tree and Intrahepatic Cholangiolopathy in Cystic Fibrosis Imperfectly Mimic Biliary Atresia in 4 Infants With Cystic Fibrosis and Kasai Portoenterostomy.

Four male infants with cystic fibrosis and prolonged neonatal jaundice underwent Kasai procedure to relieve biliary obstruction due to apparent biliary atresia. The excised remnants had viscid mucus accumulation in hypoplastic gallbladders and distended peribiliary glands. Main hepatic ducts were narrow and/or malformed. Microscopic differences between the gallbladder and extrahepatic bile ducts in cystic fibrosis and sporadic biliary atresia were unequivocal, despite some histologic overlap; no erosive or fibro-obliterative lesions typical of biliary atresia were seen. Common in liver, biopsies were small duct cholangiopathy with intense focal cholangiolitis and massive accumulation of ceroid pigment within damaged cholangiocytes, and in portal macrophages, portal fibrosis, and unequivocal features of large duct obstruction were inconspicuous compared with biliary atresia. Plugs of bile in small ducts tended to be pale and strongly periodic acid-Schiff-reactive in cystic fibrosis. Distinguishing the liver lesion from that of biliary atresia is challenging but possible. Liver biopsies from 2 additional infants with cystic fibrosis and prolonged jaundice that spontaneously resolved showed a similar small duct cholangiopathy. Small gallbladders and extrahepatic ducts challenge surgical judgment as findings in liver biopsies challenge the pathologist. The decision to perform a Kasai procedure is reasonable when mimicry of biliary atresia is grossly complete. We hypothesize that a disorder of bile volume/flow during development and/or early infancy linked to the CFTR mutation alone or in combination with the stresses of neonatal intensive care causes destructive cholangiolitis and intrahepatic reduction of bile flow with secondary hypoplasia of extrahepatic biliary structures.

Neonatal Jaundice.

Hyperbilirubinemia is a common occurrence in neonates; it may be physiological or pathological. Conjugated hyperbilirubinemia may result from medical or surgical causes, and can result in irreversible liver damage if untreated. The aim of imaging is the timely diagnosis of surgical conditions like biliary atresia and choledochal cysts. Abdominal ultrasound is the first line imaging modality, and Magnetic resonance cholangiopancreatography (MRCP) also has a role, especially in pre-operative assessment of choledochal cysts (CDCs). For biliary atresia, the triangular cord sign and gallbladder abnormalities are the two most useful ultrasound features, with a combined sensitivity of 95%. Liver biopsy has an important role in pre-operative evaluation; however, the gold standard for diagnosis of biliary atresia remains an intra-operative cholangiogram. Choledochal cysts are classified into types according to the number, location, extent and morphology of the areas of cystic dilatation. They are often associated with an abnormal pancreaticobiliary junction, which is best assessed on MRCP. Caroli's disease or type 5 CDC comprises of multiple intrahepatic cysts. CDCs, though benign, require surgery as they may be associated with complications like cholelithiasis, cholangitis and development of malignancy. Severe unconjugated hyperbilirubinemia puts neonates at high risk of developing bilirubin induced brain injury, which may be acute or chronic. Magnetic resonance imaging of the brain is the preferred modality for evaluation, and shows characteristic involvement of the globus pallidi, subthalamic nuclei and cerebellum - in acute cases, these areas show T1 hyperintensity, while chronic cases typically show hyperintensity on T2 weighted images.

Current management of biliary atresia based on 35 years of experience at a single center.

OBJECTIVE: The prognosis of patients with biliary atresia undergoing Kasai portoenterostomy is related to the timing of the diagnosis and the indication for the procedure. The purpose of the present study is to present a practical flowchart based on 257 children who underwent Kasai portoenterostomy. METHODS: We conducted a retrospective cohort study of patients who underwent Kasai portoenterostomy between 1981 and 2016. RESULTS: During the first period (1981 to 2009), 230 infants were treated, and the median age at the time of surgery was 84 days; jaundice was resolved in 77 patients (33.5%). During the second period, from 2010 to 2016, a new diagnostic approach was adopted to shorten the wait time for portoenterostomy; an ultrasonography examination suggestive of the disease was followed by primary surgical exploration of the biliary tract without complementary examination or liver biopsy. Once the diagnosis of biliary atresia was confirmed, a portoenterostomy was performed during the same surgery. During this period, 27 infants underwent operations; the median age at the time of surgery was 66 days (p<0.001), and jaundice was resolved in 15 patients (55.6% - p=0.021), with a survival rate of the native liver of 66.7%. CONCLUSION: Primary surgical exploration of the biliary tract without previous biopsy was effective at improving the prognostic indicators of patients with biliary atresia undergoing Kasai portoenterostomy.

Current management of biliary atresia based on 35 years of experience at a single center

OBJECTIVE: The prognosis of patients with biliary atresia undergoing Kasai portoenterostomy is related to the timing of the diagnosis and the indication for the procedure. The purpose of the present study is to present a practical flowchart based on 257 children who underwent Kasai portoenterostomy. METHODS: We conducted a retrospective cohort study of patients who underwent Kasai portoenterostomy between 1981 and 2016. RESULTS: During the first period (1981 to 2009), 230 infants were treated, and the median age at the time of surgery was 84 days; jaundice was resolved in 77 patients (33.5%). During the second period, from 2010 to 2016, a new diagnostic approach was adopted to shorten the wait time for portoenterostomy; an ultrasonography examination suggestive of the disease was followed by primary surgical exploration of the biliary tract without complementary examination or liver biopsy. Once the diagnosis of biliary atresia was confirmed, a portoenterostomy was performed during the same surgery. During this period, 27 infants underwent operations; the median age at the time of surgery was 66 days (p<0.001), and jaundice was resolved in 15 patients (55.6% - p=0.021), with a survival rate of the native liver of 66.7%. CONCLUSION: Primary surgical exploration of the biliary tract without previous biopsy was effective at improving the prognostic indicators of patients with biliary atresia undergoing Kasai portoenterostomy.

Stool color card screening for biliary atresia.

INTRODUCTION: Biliary atresia is a major cause of extrahepatic obstructive jaundice in neonates. Early Kasai operation is the gold standard of treatment. In this study, we evaluated the effectiveness of stool color card screening by using claims data from the National Health Insurance Research Database. METHODS: This was a retrospective cohort study. Data from medical charts of all inpatients who were diagnosed with biliary atresia from 1996 to 2008 were collected from Taiwan's National Health Insurance Research Database. Patients who received a Kasai operation or liver transplant were identified by the Operation code. The patients' gender, age at admission, and type of operation were collected and analyzed. RESULTS: From 1996 to 2008, the overall incidence of biliary atresia was 1.48 per 10,000 live births. The median age at first admission for patients with suspected biliary atresia decreased after the implementation of stool color card screening (47 vs 43 days). The proportion of very late referral decreased from 9.5% to 4.9%. The median age of Kasai operation advanced from 51 to 48 days. The proportions of Kasai operation within 60 days of age were 68.9% before and 73.6% after screening program. CONCLUSION: Stool color card screening seemed to increase parents' and physicians' awareness of biliary atresia. It also was associated with a decline in the proportion of late referral. Thus, screening might be especially effective in areas with high a proportion of late referral. Improvements in the speed of workup and the operation room should be the focus of education and training in the future.

Thirty-four years' experience with biliary atresia in Denmark: a single center study.

BACKGROUND: Biliary atresia (BA) is a rare disease in Denmark (population ∼ 5.5 million) and there has been some controversy on how smaller countries should manage such conditions to obtain the best possible outcomes. The aim of this study was to evaluate the efficacy of primary surgery (i. e., Kasai portoenterostomy [KP]) over a prolonged period of time, during which one center has become the primary referral unit for the entire country. METHODS: A retrospective cohort study was carried out. RESULTS: During the period 1976-2010, 89 infants were referred to Rigshospitalet, Copenhagen. The median age at KP was 59 days, with 11 (12%) older than 100 days. Overall, 47 (53%) resolved their jaundice and achieved normal bilirubin levels within 6 months of KP. There was a significant increase in resolution of jaundice over time (X2=8.8; p=0.03) with a rate of 79% in the latest period. Overall, 52 are still alive (58%); 37 (39%) with their native liver at a median age of 6.8 years (2 months - 34 years), and 15 (18%) are alive following LT with a median age of 12 years (33 months - 23 years). The 5- and 10-year native liver survival rates are 44 and 37%, respectively. CONCLUSION: The overall results of this series reinforce our impression that even (or perhaps especially) in a small country, the same principles of concentrating patients and expertise will lead to better results.

Biliary atresia associated with choledochal cyst.

Choledochal cyst and biliary atresia are rare but important causes of neonatal jaundice. Both present with jaundice and acholic stool in neonatal period. Treatment and prognosis of both entities are very different. We are presenting a case in which choledochal cyst co-existed with biliary atresia; the antenatal diagnosis was that of choledochal cyst. Patient had cyst excision with hepatojejnostomy, but ultimately required portoenterostomy because of associated biliary atresia. We conclude that choledochal cyst and biliary atresia are two entities with similar antenatal and postnatal presentation; they should be differentiated as management and prognosis are different.

Obstructive jaundice in neonates.

The causes of jaundice in the first few weeks of life may be categorised into hematologic, enzymatic/metabolic, infectious and obstructive. Obstructive jaundice results from an interruption in the drainage of bile in the biliary system. Surgical causes of jaundice in neonates are biliary atresia, inspissated bile syndrome, intrahepatic hypoplasia, choledochal cyst, Caroli's disease and spontaneous perforation of the bile duct. Pediatricians should be aware of the pernicious consequences of unresolved biliary obstruction and should thus refer neonates or infants with inexplicable jaundice for surgical exploration at an earlier age.

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 degrees 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.

Neonatal surgical jaundice revisited.

Neonatal hyperbilirubinemia is a common problem in newborn nurseries and manifest clinically as jaundice. Nearly 25-50% of all newborns and a much higher percentage of premature babies develop hyperbilirubinemia. This is mostly physiological, but a small percentage of these babies have pathological jaundice, requiring detailed investigations and management. It is also absolutely essential to consider a possibility of extra-hepatic biliary atresia early, during management of a case of neonatal direct hyperbilirubinemia as early surgical intervention results in a better outcome in EHBA. This article aims to describe the diagnostic approach to neonatal hyperbilirubinemia with special emphasis on conditions requiring surgical intervention also it throws light on present status of EHBA in Indian circumstances.

Outcome of liver disease in children with Alagille syndrome: a study of 163 patients.

BACKGROUND AND AIMS: Various opinions have been expressed as to the long term prognosis of liver disease associated with Alagille syndrome (AGS). PATIENTS AND METHODS: We reviewed the outcome of 163 children with AGS and liver involvement, investigated from 1960 to 2000, the end point of the study (median age 10 years (range 2 months to 44 years)) being death, liver transplantation, or the last visit. RESULTS: At the study end point, of the 132 patients who presented with neonatal cholestatic jaundice, 102 remained jaundiced, 112 had poorly controlled pruritus, and 40 had xanthomas; cirrhosis was found in 35/76 livers, varices in 25/71 patients, and liver transplantation had been carried out in 44 patients (33%). Forty eight patients died, 17 related to complications of liver disease. Of 31 patients who did not present with neonatal cholestatic jaundice, five were jaundiced at the study end point, 17 had well controlled pruritus, and none had xanthomas; cirrhosis was found in 6/18 patients, varices in 4/11, and none underwent liver transplantation. Nine patients died, two of liver disease. In the whole series, actuarial survival rates with native liver were 51% and 38% at 10 and 20 years, respectively, and overall survival rates were 68% and 62%, respectively. Neonatal cholestatic jaundice was associated with poorer survival with native liver (p=0.0004). CONCLUSIONS: The prognosis of liver disease in AGS is worse in children who present with neonatal cholestatic jaundice. However, severe liver complications are possible even after late onset of liver disease, demanding follow up throughout life.

[Early diagnosis of neonatal cholestatic jaundice]. / Diagnostic précoce des ictères cholestatiques chez le nouveau-né.

Neonatal cholestasis should be considered in every baby in whom jaundice persists after day 10. Biliary atresia is the main cause of neonatal cholestasis and its prognosis is highly dependent on the early age at which surgery is performed. Finding the cause of cholestasis before day 30 is therefore crucial. This relies, in most instances, on simple clinical, biochemical, radiological and ophthalmologic criteria, the most important of which is a careful study of the degree and duration of stool discoloration.

The jaundiced newborn.

Evaluation of the newborn with hyperbilirubinemia is an important and commonly encountered problem in all clinical pediatric-based practices. Cholestatic jaundice is always pathologic and warrants prompt assessment. The timely evaluation and directed treatment of any jaundiced newborn are essential to prevent serious metabolic consequences and irreversible hepatic damage.

Fate of infants with neonatal hepatitis: pediatric surgeons' dilemma.

Thirty-five cases of neonatal hepatitis (20 males and 15 females) were reviewed, 3 of whom were lost during the follow-up, leaving 32 patients for review. There were 10 late deaths and 22 patients survived, 18 of whom with a normal bilirubin level and 4 with a bilirubin level of greater than 1.0 mg/dL. In the 18, jaundice disappeared between the ages of 4 and 7 months. The current lifestyles of the patients include 4 adults aged 19 to 21 who are either working or at university, while the other 18 children are all making good progress at school. Except for moderate growth retardation in 3 children, all are growing well. In all 10 patients who died, liver failure persisted until the time of death. Three died of other causes and 7 died of neonatal hepatitis itself between 4 months and 7 years of age. Four patients ran a fulminating course resulting in death between the ages of 4 and 12 months. All 7 had growth and developmental retardation. A histological examination showed that in those who died, there was significantly more periportal fibrosis, inflammation in the periportal area, and diffuse giant cell transformation. These results indicate that some infants with neonatal hepatitis have a poor prognosis and, therefore, the identification of such a condition requires a careful, long-term follow-up.

Icterícia: atresia de vias biliares / Jaundice: biliary tract atresia

O presente trabalho tem por objetivo alertar para a importância do diangóstico e tratamento precoce da hiperbilirrubinemia direta, por atresia de vias biliares, devido a sua grande complicaçäo que é a cirrose hepática e conseqüente morte do lactente. O médico dispöe de pouco tempo entre o diagnóstico e o tratamento quando possível, sendo que após 2 a 3 meses, terá danos irreversíveis ao lactente. Quando houver quadro icterico, com acolia fecal, colúria, e predomínio da bilirrubina direta, sempre ter na hipótese diagnóstica a atresia de vias biliares. Por ser uma patologia de baixa incidência, muitas vezes poderá passar desapercebido,levando o lactente a condenaçäo

[Hepatobiliary scintigraphy in the study of neonatal hepatic cholestasis]. / La scintigrafia epato-biliare nello studio della colestasi epatica neonatale.

Severe neonatal cholestasis is a clinical problem requiring a differential diagnosis of intra- (hepatitis) and extrahepatic (biliary atresia) causes, prognosis and therapy being different in the two cases. Eighteen patients of pediatric age underwent US and hepatobiliary scintigraphy. US findings were aspecific in both hepatitis and biliary atresia. In the 11 patients with hepatitis, hepatobiliary scintigraphy after phenobarbital revealed labeled bile in the bowel. Only in 1 patient with cytomegalovirus hepatitis was a scintigraphic pattern similar to that of biliary atresia. On the contrary, no intestinal radioactivity within 24 hours was seen in 6 patients with biliary atresia. A portoenterostomy (Kasai's operation) was performed on 4/6 cases with biliary atresia. These patients were followed with hepatobiliary scintigraphy in order to evaluate anastomotic functionality. In a case of biliary cirrhosis secondary to occlusion, orthotopic liver transplantation was performed whose success was scintigraphically monitored. Our results point to hepatobiliary scintigraphy after phenobarbital as the best noninvasive procedure for both diagnosis and postoperative follow-up of biliary atresia. Labeled bile excretion within 24 hours was rarely found in both atresia and neonatal hepatitis.

[Etiopathogenic study of spontaneous perforation of the biliary tract]. / Estudio etiopatogénico de la perforación espontánea del árbol biliar extrahepático en el neonato. A propósito de tres casos.

Spontaneous perforation of extrahepatic bile duct is a rare entity, but is the second cause of surgical jaundice in the newborn period after biliary atresia. We review the etiological theories and three patients with this anomaly. Centrolobulillar cholestasis was present in all cases. Parietal ischemic necrosis was seen in one case, obstructive lesions (extrahepatic biliary atresia) in two and malformative lesions (choledochal cyst) in the last patient. A developmental error and a small circumscribed area of duct wall weakness have been the most accepted factors involved in its pathogenesis. However we have found histologic and morphologic evidence that ratify the obstructive and vascular lesions as relevant elements in the etiology of the spontaneous perforation of the biliary tract.

Neonatal cholestatic conditions requiring surgical reconstruction.

Obstructive jaundice in infancy and childhood can arise from a variety of causes. Recognition of the importance of persistent jaundice beyond 2 weeks of age in the infant or elevation of the conjugated bilirubin more than 2 mg/dl will allow the timely evaluation of neonates with possible biliary atresia prior to the development of irreversible hepatic damage. Episodes of intermittent jaundice or persistent conjugated hyperbilirubinemia should be investigated at any age to exclude obstructive lesions of the extrahepatic biliary tract. In all cases, a rapid but carefully coordinated evaluation can be undertaken by a pediatric gastroenterology and surgical team, allowing optimum economy of effort and preservation of hepatic function. In nearly all cases with obstructive lesions of the extrahepatic biliary tree, satisfactory hepatic function can be preserved through appropriate surgical intervention. Results with biliary atresia continue to improve but are dependent on early diagnosis and treatment. In cases in which hepatic function deteriorates and hepatic failure becomes inevitable, orthotopic hepatic transplantation can be lifesaving and should be undertaken prior to the onset of irreversible hepatic decompensation. Although the terminology may be somewhat confusing and its etiology uncertain, the entity of choledochal cysts, taken within the context of its modern classification, accurately describes a group of cystic anomalies of the extrahepatic (and intrahepatic) biliary tree, which have many common features. The vast majority can be expeditiously dealt with by surgical excision and hepaticoenteral reconstruction. Two particular associations with choledochal cysts are important to note. When it occurs with infancy, choledochal cysts can be difficult to diagnose, but very important to define and treat expeditiously in order to prevent serious impairment of hepatic function. In all patients, but particularly in adults, the risk of associated carcinoma necessitates extremely careful definition of the biliary tree and urges one to advocate complete excision of the cyst at initial operation.