Imaging in Pediatric Obstructive Jaundice.

Cholestatic jaundice characterized by elevated conjugated bilirubin can be due to multitude of factors in neonates and childhood. Extrahepatic biliary atresia (EHBA), choledochal cyst, neonatal hepatitis, cytomegalovirus (CMV), and biliary plug are some of the common causes in neonate and early infancy. Causes in late infancy and childhood comprises viral hepatitis, choledochal cyst, cholelithiasis, worm infestation, and biliary compression secondary to extrinsic causes (node, collection, tumor). Some serious disorders like biliary atresia must be considered with the emphasis on early diagnosis of treatable causes. In the modern era, with multiple diagnostic modalities available including high-resolution ultrasonography, magnetic resonance imaging (MRI), CT scan, and nuclear imaging [hepatobiliary iminodiacetic acid (HIDA) scan], rapid diagnosis can be made in many surgically treatable cases. The authors will discuss the imaging modality available with advantages, disadvantages, and common indications of each modality, and overview of obstructive jaundice discussing the wide spectrum of causes in neonates and late childhood. Combining available knowledge with careful and meticulous search can help narrow down the diagnosis and initiate prompt treatment.

Ultrasound shear wave elastography: does it add value to gray-scale ultrasound imaging in differentiating biliary atresia from other causes of neonatal jaundice?

BACKGROUND: Neonatal/infantile jaundice is relatively common, and most cases resolve spontaneously. However, in the setting of unresolved neonatal cholestasis, a prompt and accurate assessment for biliary atresia is vital to prevent poor outcomes. OBJECTIVE: To determine whether shear wave elastography (SWE) alone or combined with gray-scale imaging improves the diagnostic performance of US in discriminating biliary atresia from other causes of neonatal jaundice over that of gray-scale imaging alone. MATERIALS AND METHODS: Infants referred for cholestatic jaundice were assessed with SWE and gray-scale US. On gray-scale US, two radiology readers assessed liver heterogeneity, presence of the triangular cord sign, hepatic artery size, presence/absence of common bile duct and gallbladder, and gallbladder shape; associated interobserver correlation coefficients (ICC) were calculated. SWE speeds were performed on a Siemens S3000 using 6C2 and 9 L4 transducers with both point and two-dimensional (2-D) SWE US. Both univariable and multivariable analyses were performed, as were receiver operating characteristic curves (ROC) and statistical significance tests (chi-squared, analysis of variance, t-test and Wilcoxon rank sum) when appropriate. RESULTS: There were 212 infants with biliary atresia and 106 without biliary atresia. The median shear wave speed (SWS) for biliary atresia cases was significantly higher (P<0.001) than for non-biliary-atresia cases for all acquisition modes. For reference, the median L9 point SWS was 2.1 m/s (interquartile range [IQR] 1.7-2.4 m/s) in infants with biliary atresia and 1.5 m/s (IQR 1.3-1.9 m/s) in infants without biliary atresia (P<0.001). All gray-scale US findings were significantly different between biliary-atresia and non-biliary-atresia cohorts (P<0.001), intraclass correlation coefficient (ICC) range 0.7-1.0. Triangular cord sign was most predictive of biliary atresia independent of other gray-scale findings or SWS - 96% specific and 88% sensitive. Multistep univariable/multivariable analysis of both gray-scale findings and SWE resulted in three groups being predictive of biliary atresia likelihood. Abnormal common bile duct/gallbladder and enlarged hepatic artery were highly predictive of biliary atresia independent of SWS (100% for girls and 95-100% for boys). Presence of both the common bile duct and the gallbladder along with a normal hepatic artery usually excluded biliary atresia independent of SWS. Other gray-scale combinations were equivocal, and including SWE improved discrimination between biliary-atresia and non-biliary-atresia cases. CONCLUSION: Shear wave elastography independent of gray-scale US significantly differentiated biliary-atresia from non-biliary-atresia cases. However, gray-scale findings were more predictive of biliary atresia than elastography. SWE was useful for differentiating biliary-atresia from non-biliary-atresia cases in the setting of equivocal gray-scale findings.

The role of ultrasound in the investigation of neonatal jaundice.

Infants with persistent conjugated jaundice, lasting longer than 14 days of age in a term infant and 21 days in a preterm infant, should be referred to a national paediatric liver unit for investigation of the cause. This paper reviews the ultrasound findings in such cases with a particular emphasis upon the diagnosis of biliary atresia.

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.

Clinical Assessment of Differential Diagnostic Methods in Infants with Cholestasis due to Biliary Atresia or Non-Biliary Atresia.

The different methods in differentiating biliary atresia (BA) from non-BA-related cholestasis were evaluated in order to provide a practical basis for a rapid, early and accurate differential diagnosis of the diseases. 396 infants with cholestatic jaundice were studied prospectively during the period of May 2007 to June 2011. The liver function in all subjects was tested. All cases underwent abdominal ultrasonography and duodenal fluid examination. Most cases were subjected to hepatobiliary scintigraphy, magnetic resonance cholangiopancreatography (MRCP) and a percutaneous liver biopsy. The diagnosis of BA was finally made by cholangiography or histopathologic examination. The accuracy, sensitivity, specificity and predictive values of these various methods were compared. 178 patients (108 males and 70 females with a mean age of 58±30 days) were diagnosed as having BA. 218 patients (136 males and 82 females with a mean age of 61 ±24 days) were diagnosed as having non-BA etiologies of cholestasis jaundice during the follow-up period in which jaundice faded after treatment with medical therapy. For diagnosis of BA, clinical evaluation, hepatomegaly, stool color, serum gamma-glutamyltranspeptidase (GGT), duodenal juice color, bile acid in duodenal juice, ultrasonography (gallbladder), ultrasonography (griangular cord or strip-apparent hyperechoic foci), hepatobiliary scintigraphy, MRCP, liver biopsy had an accuracy of 76.0%, 51.8%, 84.3%, 70.0%, 92.4%, 98.0%, 90.4%, 67.2%, 85.3%, 83.2% and 96.6%, a sensitivity of 83.1%, 87.6%, 96.1%, 73.7%, 90.4%, 100%, 92.7%, 27.5%, 100%, 89.0% and 97.4%, a specificity of 70.2%, 77.5%, 74.8%, 67.0%, 94.0%, 96.3%, 88.5%, 99.5%, 73.3%, 75.4% and 94.3%, a positive predictive value of 69.0%, 72.6%, 75.7%, 64.6%, 92.5%, 95.7%, 86.8%, 98.0%, 75.4%, 82.6% and 98.0%, and a negative predictive value of 83.6%, 8.5%, 95.9%, 75.7%, 92.3%, 100%, 84.2%, 93.7%, 100%, 84.0% and 92.6%, respectively. It was concluded that all the differential diagnosis methods are useful. The test for duodenal drainage and elements is fast and accurate. It is helpful in the differential diagnosis of BA and non-BA etiologies of cholestasis. It shows good practical value clinically.

Ultrasonography evaluation of infants with Alagille syndrome: In comparison with biliary atresia and neonatal hepatitis.

OBJECTIVE: To evaluate the ultrasonography (US) features of Alagille syndrome (ALGS), as compared with biliary atresia (BA) or neonatal hepatitis (NH). METHODS: Our study included 23 ALGS, 75 BA and 70 NH patients. The initial US images were retrospectively reviewed for gallbladder (GB) morphology with systemic classification, GB length and luminal area, presence of triangular-cord (TC) sign and hypertrophied hepatic-artery. The presence of anomalies associated with ALGS was evaluated. The diagnostic values of each finding and their combinations were evaluated. RESULTS: Both ALGS (57%) and BA (79%) were more frequently associated with abnormal GB shapes than NH (19%, all P<0.001). The short and small GBs were more frequently observed in ALGS and BA than in NH (all P<0.001). None in the ALGS and NH showed TC sign, while 41% in the BA did (all P<0.001). Hypertrophied hepatic-artery was noted less frequently in both ALGS (13%) and NH (14%) than in BA (83%, all P<0.001). The combination of US criteria with associated anomalies increased the positive-predictive-value for ALGS. CONCLUSION: Abnormal shaped GB with absence of the TC sign and hypertrophied hepatic-artery and presence of associated anomalies can be a differential point of ALGS.

Neonatal Jaundice Detection System.

Neonatal jaundice is a common condition that occurs in newborn infants in the first week of life. Today, techniques used for detection are required blood samples and other clinical testing with special equipment. The aim of this study is creating a non-invasive system to control and to detect the jaundice periodically and helping doctors for early diagnosis. In this work, first, a patient group which is consisted from jaundiced babies and a control group which is consisted from healthy babies are prepared, then between 24 and 48 h after birth, 40 jaundiced and 40 healthy newborns are chosen. Second, advanced image processing techniques are used on the images which are taken with a standard smartphone and the color calibration card. Segmentation, pixel similarity and white balancing methods are used as image processing techniques and RGB values and pixels' important information are obtained exactly. Third, during feature extraction stage, with using colormap transformations and feature calculation, comparisons are done in RGB plane between color change values and the 8-color calibration card which is specially designed. Finally, in the bilirubin level estimation stage, kNN and SVR machine learning regressions are used on the dataset which are obtained from feature extraction. At the end of the process, when the control group is based on for comparisons, jaundice is succesfully detected for 40 jaundiced infants and the success rate is 85 %. Obtained bilirubin estimation results are consisted with bilirubin results which are obtained from the standard blood test and the compliance rate is 85 %.

The value of radionuclide hepatobiliary scintigraphy in combination with determination of bilirubin from duodenal drainage in differential diagnosis of infantile persistent jaundice.

The aim of this study was to investigate the value of technetium etifenin injection (99mTc-EHIDA) hepatobiliary scintigraphy in combination with determination of bilirubin from duodenal drainage in differential diagnosis between infantile hepatitis syndrome and biliary atresia. 99mTc-EHIDA hepatobiliary scintigraphy in combination with duodenal fluid examination was used for evaluation in 84 infants with persistent infantile jaundice. For diagnosing biliary atresia, the sensitivity and specificity of scintigraphy were 100% and 74.5%, respectively; the sensitivity and specificity of scintigraphy in combination with duodenal fluid examination were 100% and 100%, respectively. In conclusion, hepatobiliary scintigraphy, which is a noninvasive, safe, valuable examination method, in combination with examination of duodenal fluid, is of value for the differential diagnosis between infantile hepatitis syndrome and biliary atresia.

Predictive value of bile duct dimensions measured by ultrasound in neonates presenting with cholestasis.

OBJECTIVES: : The significance of extrahepatic bile duct dilatation on ultrasound examination in jaundiced infants is often uncertain. We wished to clarify the diagnostic and prognostic significance of the present finding in neonatal conjugated hyperbilirubinaemia. PATIENTS AND METHODS: : We retrospectively enrolled all of the infants younger than 3 months with extrahepatic biliary dilatation > or =1.2 mm (nonfasting ultrasound) who presented during the study period. We reviewed clinical, radiological, and laboratory data to determine mode of presentation, diagnosis, interventions, and long-term outcome. RESULTS: Seventy-six infants (41 male) were identified, all of whom were referred with conjugated hyperbilirubinaemia. Median gestational age was 39 weeks (range 24-42 weeks). Inspissated bile was the most common diagnostic category, whereas congenital choledochal malformation was the diagnosis made in 13% infants. Dilatation was an incidental finding in 9% of the infants. Seventeen percent of infants had required either surgical or radiological intervention by the time of follow-up. Overall, 41% infants had spontaneous resolution of bile duct dilatation, including 8% who had "grown into" an unchanged duct size rather than involution of dilatation. The median size of bile duct at presentation for those who required intervention was 4.7 versus 2 mm for the remainder (P < 0.001). Of those who resolved spontaneously, the median size of duct at presentation was 1.8 mm. CONCLUSIONS: : Bile duct dilatation <3 mm (nonfasting ultrasound) with neonatal cholestasis is unlikely to be of significance whereas >4 mm is likely to be associated with choledochal malformation or need for intervention. The intermediate group is likely to be associated with inspissated bile syndrome following resolution of which innocent biliary dilatation may persist.

99mTc sestamibi imaging - can it be a useful substitute for hepatobiliary scintigraphy in infantile jaundice?

AIM: Hepatobiliary scintigraphy is an integral part in the diagnostic work-up of the neonatal cholestasis syndrome. However, less than optimal specificity is its major disadvantage. Differentiation between biliary atresia and neonatal hepatitis is nearly impossible in some cases with poor hepatocellular function. 99mTc sestamibi (MIBI) is a cationic lipophilic agent which is a substrate of P-glycoprotein. This glycoprotein is normally expressed in biliary canalicular surfaces of hepatocytes. This property provides a hepatic excretory mechanism which is different from bilirubin excretion. In this study we evaluated the value of 99mTc MIBI in differential diagnosis of neonatal cholestasis. PATIENTS, METHODS: 20 infants with a mean age of 2.41 months (range, 0.1-5 months) were included in the study. Ten infants turned out to have extrahepatic biliary atresia and the other ten had neonatal hepatitis. Hepatobiliary (with 99mTc BrIDA) and 99mTc MIBI scintigraphy were performed for all the patients. RESULTS: 99mTc MIBI scintigraphy has shown bowel activity in all patients, including the patients with biliary atresia. Hepatobiliary scintigraphy revealed bowel activity only in five patients with neonatal hepatitis. CONCLUSION: Bowel visualization with 99mTc MIBI may be seen in patients with biliary atresia and 99mTc MIBI has limited value in differential diagnosis of neonatal cholestasis.

Bilirubin levels predict renal cortical changes in jaundiced neonates with urinary tract infection.

BACKGROUND: This study was undertaken to determine the incidence of urinary tract infection (UTI) and the frequency of anatomical abnormalities in newborns with unexplained jaundice and to find out if there is any correlation between bilirubin level and renal damage. METHODS: We studied 462 full-term neonates for UTI. They were aged 3-25 days, with either high (>10 mg/dL) or prolonged (>10 days) hyperbilirubinemia, with or without manifestations such as fever, vomiting, diarrhea, poor feeding, lethargy, and irritability. Neonates positive for UTI were further investigated with ultrasound, cystourethrography, and acute phase renal scintigraphy with technetium-99m dimercaptosuccinate acid (DMSA). RESULTS: Thirty neonates (6.5%) were found to have UTI. Twenty-eight of them had indirect hyperbilirubinemia and two had direct hyperbilirubinemia, with total bilirubin levels of 11.8-20.1 mg/dL. None of the neonates was found to have jaundice because of other reasons such as infection. Vesicoureteral reflux was found in 5 neonates and one of them was combined with hydronephrosis. Renal scintigraphy with technetium-99m DMSA showed renal cortex changes in 14 (46.7%) of the 30 neonates with UTI. These 14 neonates also had increased levels of bilirubin in comparison to those with normal findings of DMSA. CONCLUSIONS: The incidence of UTI in uncomplicated neonatal jaundice is relatively high. Anatomical abnormalities of the urinary tract are not rare in infected children. Increased bilirubin levels are related to pathological findings in renal scintigraphy.

Neonatal sludge: a finding of congenital hypothyroidism.

Congenital hypothyroidism is one of the most urgent diseases of the neonate. When diagnosed and treated at an early stage, its most important complication, mental retardation, is preventable. The signs of congenital hypothyroidism are nonspecific in neonates. Only 5% of the cases have characteristic clinical findings. One of the most important and earliest signs is prolonged jaundice during the neonatal period. We report herein a case of congenital hypothyroidism, who presented with icterus accompanied with sludge formation into the gallbladder, which disappeared after treatment with L-thyroxine.

[Chemotherapy-induced fetal anemia in maternal acute myelocytic leukemia]. / Chemotherapieinduzierte fetale Anämie bei akuter myeloischer Leukämie der Mutter.

This article discusses the management of a pregnancy of a 32-year-old primigravida with acute myelocytic leukemia treated with induction chemotherapy starting in the 20 + 5 week of gestation. Sonographic monitoring showed evidence of fetal ascites and anemia that could be treated with an intrauterine fetal transfusion. After maternal recovery, a caesarean section was performed in the 27 + 5 week of gestation. We delivered a vivid eutrophic female prematurely. The infant showed persisting signs of myelosuppression. Two further transfusions had to be performed. The present report describes the interdisciplinary therapeutic management when polychemotherapy during pregnancy is necessary for the mother. Cases of acute leukemia in pregnancy are complicated by severe prenatal risks caused by the hematologic illness and by the immediate beginning of chemotherapy. In the third trimester premature delivery is preferable to intrauterine exposition to cytostatic agents. In the second trimester the pregnancy has to be monitored for the typical risks and complications of chemotherapy. Fetal cytotoxic myelosuppression is detectable by prenatal observation so that interventional strategies are feasible.

Hepatobiliary scintigraphy and gamma-GT levels in the differential diagnosis of extrahepatic biliary atresia.

AIM: The aim of this paper is to identify extrahepatic biliary atresia (EHBA) as the cause of cholestasis in neonates with prolonged jaundice and thus accelerate the decision for surgical intervention, which is critical for prognosis. METHODS: We retrospectively studied 21 infants (13 girls, 8 boys) aged 2-16 weeks who have undergone( 99m)Tc-mebrofenin iminodiacetate ((99m)Tc-BrIDA) scintigraphy. They were referred because of direct hyperbilirubinemia and jaundice persisting beyond the 2nd postnatal week. They had received phenobarbitone premedication prior to scintigraphy. Dynamic images for 30 min and then static images (if required) at 1, 2 and 24 h postinjection were acquired. Images were evaluated visually and semiquantitatively, by calculating the liver-to-heart (L/H) ratio. Age, L/H ratios, and serum gamma glutamyl transpeptidase (gamma-GT) levels were compared (Mann-Whitney U test) between infants with EHBA (Group A) and infants without (Group B). The L/H ratios were correlated with age in each group and with gamma-GT in the entire population. RESULTS: A total of 7/21 infants were classified in Group A and 14/21 in Group B. The L/H ratios were significantly lower in Group A. The correlation between L/H ratio and age was negative in EHBA and positive in non-atretic infants. The gamma-GT levels were inversely correlated with the L/H ratios in the entire population, being significantly higher in Group A. CONCLUSION: In long-standing neonatal direct hyperbilirubinemia, (99m)Tc-BrIDA scintigraphy and the L/H ratio index seem to give useful information in the differential diagnosis of EHBA, especially when associated with markedly elevated serum gamma-GT levels.

[The role of hepatobiliary scintigraphy in neonates with persistant jaundice]. / Betydningen af galdevejsskintigrafi hos neonatale med prolongeret ikterus.

Hepatobiliary scintigraphy of infants being examined for persistant neonatal jaundice is best carried out using mebrofenin, a 99m Tc-labeled IDA derivative. This article summarizes the most frequently occurring etiologies of persisting neonatal jaundice and the diagnostic work-up of this condition. Perinatal obliteration of extrahepatic bile ducts requires immediate surgery, whereas other causes of persisting jaundice may be treated medically and/or conservatively.

Ursodeoxycholic acid-augmented hepatobiliary scintigraphy in the evaluation of neonatal jaundice.

UNLABELLED: Early differentiation of extrahepatic biliary atresia from intrahepatic cholestasis is important. Hepatobiliary scintigraphy is an excellent noninvasive investigation for ruling out extrahepatic biliary atresia. This study aimed at identifying the role of ursodeoxycholic acid (UDCA), a choleretic agent, in conjunction with hepatobiliary scintigraphy in differentiating extrahepatic biliary atresia from neonatal hepatitis. METHODS: Fifty-one infants (42 male, 9 female) aged 0.3-5.5 mo (mean, 2.9 mo) presenting with neonatal jaundice underwent 99mTc-mebrofenin hepatobiliary scintigraphy. For patients who did not show any excretion of tracer into the intestine till 24 h, the study was repeated after oral administration of UDCA (20 mg/kg every 12 h) for 48-72 h. Ultrasonography and, if required, liver biopsy and intraoperative cholangiography were used with clinical data such as stool color and serologic and other etiologic investigations to form a final diagnosis. RESULTS: Of 51 patients, 19 showed biliary excretion in the first study, ruling out extrahepatic biliary atresia. Neonatal hepatitis was the final diagnosis in these. Of the remaining 32 patients, 12 nonexcretors converted to excretors after UDCA treatment, whereas 20 still showed no biliary drainage. Four nonexcretors on scintigraphy had a final diagnosis of neonatal hepatitis with galactosemia; the remaining 16 had extrahepatic biliary atresia. The specificity of hepatobiliary scintigraphy in ruling out extrahepatic biliary atresia improved from 54.3% to 88.6% (P < 0.001) after UDCA treatment. None of the patients experienced any ill effects from UDCA administration. CONCLUSION: Pretreatment with UDCA significantly improves the specificity of hepatobiliary scintigraphy in ruling out extrahepatic biliary atresia as a cause of prolonged neonatal jaundice.

Biliary atresia: making the diagnosis by the gallbladder ghost triad.

OBJECTIVE: To describe the gallbladder ghost triad and evaluate its usefulness in the sonographic diagnosis of extrahepatic biliary atresia (BA). METHODS: From October 1997 to February 2002, 217 fasted infants with cholestatic jaundice aged 2-12 weeks were examined sonographically. We defined the gallbladder ghost triad as gallbladder length <1.9 cm, lack of smooth/complete echogenic mucosal lining with an indistinct wall and irregular/lobular contour, and used it as a criteria for BA. Gallbladder wall thickness, triangular cord, diffuse periportal echogenicity and hepatic artery calibre were also recorded. Diagnosis of BA was confirmed surgically and histologically. RESULTS: Thirty of 31 babies with BA demonstrated the gallbladder ghost triad. No false-positives were recorded. The 31st BA baby showed a normal gallbladder at 6 weeks, but developed the ghost triad at 8 weeks. Gallbladder wall thickening was seen in 46/186 non-BA babies, but not in BA. Triangular cord was observed in 24/31 babies. Twenty-two of 186 non-BA babies and 5/31 BA babies showed diffuse periportal echogenicity. The hepatic artery appeared more prominent in BA. All 31 babies diagnosed sonographically as BA had surgery. Three non-BA babies had "negative" laparotomies showing hypoplastic bile ducts. CONCLUSIONS: The gallbladder ghost triad is a very accurate sign of BA. Indeterminate cases require close follow-up.

Pediatric liver imaging.

The evaluation of hepatic diseases in children is often a multimodality process, requiring multiple imaging tests to determine the cause and extent of an abnormality. Ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) have distinct roles to play in the evaluation of hepatic disease in children. This article addresses the hepatic and biliary lesions that are unique or more common in children and describes their cross-sectional imaging characteristics. In addition, the techniques and protocols for US, CT, and MRI are reviewed.