1.Objective Differential Characteristics of Cystic Biliary Atresia and Choledochal Cysts in Neonates and Young Infants: Sonographic Findings
Lu-Yao Zhou, Bu-Yun Guan, Le Li, Zuo-Feng Xu, Chang-Ping Dai, Wei Wang, Hui-Min Xia, and Xiao-Yan Xie. JUM June 1, 2012 vol. 31 no. 6 833-841
Objectives— To prospectively evaluate the objective differential characteristics between cystic biliary atresia and choledochal cysts on sonography among neonates and young infants.Methods— Twenty-three patients who had sonographic findings of a portal cyst and a final diagnosis were included. Their final diagnoses were cystic biliary atresia in 12 patients and choledochal cysts in 11. All of them underwent detailed sonographic scanning. Data for cystic biliary atresia and choledochal cyst groups were compared by the χ2 test for categorical variables and an unpaired t test for continuous variables.
Results— The triangular cord sign was detected in 11 patients in the atresia group but in none in the cyst group (P < .001). Nine of 11 patients in the cyst group had dilatation of intrahepatic bile ducts, whereas none in the atresia group had that feature (P < .001). Sonography also showed sludge deposits in the cysts in 6 of 11 patients in the cyst group, whereas none in the atresia group had sludge deposits (P = .005). The mean width and length of the cysts in the cyst group were significantly larger than those in the atresia group (P< .05 for both). The mean hepatic artery diameter was significantly larger in the atresia group than in the cyst group (P < .001). The difference in gallbladder abnormalities between the atresia (n = 11) and cyst (n = 0) groups was also significant (P < .001). When all specific sonographic features were used, all patients were correctly classified into the atresia and cyst groups.Conclusions— The triangular cord sign, intrahepatic bile duct dilatation, and echoic cysts might be regarded as objective sonographic features for differentiating cystic biliary atresia and choledochal cysts. Other sonographic features might be very supportive.
Biliary atresia is a destructive inflammatory obliterative cholangiopathy of neonates and infants that affects varying lengths of both intrahepatic and extrahepatic bile ducts.1 It is an uncommon disorder with a prevalence of about 1 per 5000 in East Asian countries.2 No analogous pathologic process exists in older children or adults. Cystic biliary atresia is a subtype of biliary atresia with portal cysts; it has an occurrence rate of 8% to 11%3–5 among patients with biliary atresia. Because of its specific appearance, cystic biliary atresia is the only type of biliary atresia that can be detected antenatally with sonography.6 A choledochal cyst in a neonate or young infant is another uncommon entity with an appearance similar to that of cystic biliary atresia on medical imaging. Both are well-known causes of jaundice in neonates and young infants,5 with a cyst at the porta hepatis.However, cystic biliary atresia and choledochal cysts are two entities with dramatically different management approaches and prognoses.3,7 Patients with cystic biliary atresia can have a better prognosis with timely and early portoenterostomy.8,9 If they are left untreated, progressive liver cirrhosis leads to death by 2 years of age. Some patients with cystic biliary atresia do not have jaundice relief even after early portoenterostomy. On the other hand, a choledochal cyst is a curable choledochal malformation that can have an excellent prognosis with resection of the cyst and hepaticojejunostomy.5,6 In addition, although there is an opinion that a surgical delay might increase the risk of liver fibrosis in patients with choledochal cysts,3 the optimal time for surgery of choledochal cysts has not been decided yet. Hence, it is very important to differentiate cystic biliary atresia from a choledochal cyst when a portal cyst is found in a neonate or young infant.
Sonography usually is recommended as the initial tool for evaluating a neonate with jaundice. Some literature has reported that sonography can play an important role in differentiating cystic biliary atresia from a choledochal cyst by characterizing the appearance of the cyst and gallbladder.5,10,11 However, the published literature is sparse, with small sample sizes. Furthermore, the sonographic technique for diagnosis of biliary atresia is still progressing. New sonographic features have been identified, such as the triangular cord sign and hepatic subcapsular flow, which are very effective in identifying biliary atresia. If sonographic features such as those could also be observed in patients with cystic biliary atresia, then there might be new differential characteristics between cystic iliary atresia and choledochal cysts on sonography.
This study aimed to review the clinical and sonographic features of jaundiced neonates and infants younger than 6 months with a final diagnosis of cystic biliary atresia or a choledochal cyst and to assess the differential characteristics between them.
Materials and MethodsA study evaluating the value of sonography for biliary atresia screening among neonates with pathologic jaundice was initiated in July 2009. The study was approved by our Institutional Clinical Research Ethics Committee, and informed parental consent was obtained for every case. Between July 2009 and March, 2011, 263 neonates and infants younger than 6 months who had pathologic jaundice prospectively underwent sonographic screening to rule out biliary atresia. Twenty-six of them showed portal cysts on sonography. Of these, 2 patients who were suspected of having cystic biliary atresia and 1 patient who was suspected of having a choledochal cyst did not undergo surgery in our hospital and were lost to follow-up. As a result, 23 patients who had sonographic findings of a portal cyst and a final diagnosis were included.
One pediatric radiologist with 3 years of experience in pediatric sonography performed all sonographic examinations. Sonography was performed with an SSA-660A scanner (Toshiba Medical Systems Co, Ltd, Tokyo, Japan) incorporating a 3.5-MHz curvilinear transducer and a 12-MHz linear array transducer and an EUB-7000HV scanner (Hitachi Medical Corporation, Tokyo, Japan) incorporating a 2- to 5-MHz curvilinear transducer and a 6- to 13-MHz linear array transducer. Immediately after detailed scanning, the diagnosis of cystic biliary atresia or a choledochal cyst was made by the pediatric radiologist, who was blinded to the clinical findings for every patient. The patients were not fed for at least 4 hours before the sonographic examinations. During the examinations, the patients were allowed to feed to keep quiet. The presence and thickness of a triangular cord in the porta hepatis and the diameters of the portal vein and hepatic artery were recorded in each case. A triangular cord was defined as a thickness of the echogenic anterior wall of the right portal vein just proximal to the right portal vein bifurcation site of greater than 4 mm.12 The diameter of the hepatic artery was measured at the level of the right proximal hepatic artery running parallel to the right portal vein.13 The maximum width and length of the gallbladder and the cyst were also measured. The presence or absence of dilatation of the intrahepatic bile ducts, the presence or absence of sludge in the cyst, a communication between the gallbladder and the cyst, hepatomegaly, splenomegaly, ascites, and the echogenicity of liver parenchyma were noted during the examinations. The liver was considered enlarged if the right lobe extended below the right kidney. Splenomegaly was defined as a spleen of greater than 6 cm.14
The gallbladder was classified as normal, atretic, or irregularly elongated. A normal gallbladder was defined as one that was 15 mm or greater in length and globular or ovoid without wall abnormalities. An atretic gallbladder was defined as one that was less than 15 mm in maximum length. An irregularly elongated gallbladder was defined as one that was 15 mm or greater in length and had an abnormal wall with an irregularly compromised lumen. An atretic or irregularly elongated gallbladder was regarded as an abnormal gallbladder.
Patients with an abnormal gallbladder or the presence of the triangular cord sign on sonography were considered to have cystic biliary atresia. Those with a normal gallbladder and absence of the triangular cord sign were considered to have choledochal cysts. Dilatation of the intrahepatic bile duct and sludge in a large cyst were supportive features of choledochal cysts. Dilatation of the hepatic artery and a small cyst without sludge were supportive features of cystic biliary atresia.
Cystic biliary atresia was confirmed by surgical cholangiography and pathologic examination in 11 patients and with liver biopsy in 1. Choledochal cysts were confirmed by surgery in 11 patients. Eleven patients with cystic biliary atresia underwent excision of the extrahepatic bile duct, including the cyst, and Roux-en-Y portoenterostomy. The other patient who did not have surgery because he was older than 4 months was confirmed to have biliary atresia by liver biopsy. All 11 patients with choledochal cysts underwent cyst excision and hepaticojejunostomy or choledochojejunostomy.
The sonographic findings were analyzed with a focus on the presence or absence of a triangular cord, the size of the cyst, the presence or absence of sludge in the cyst, dilatation of the intrahepatic bile ducts and hepatic artery, portal vein diameters, and the sizes and morphologic characteristics of the gallbladder, spleen, and liver. Cyst sizes in cystic biliary atresia between those with a communication between the gallbladder and the cyst and those without were compared. Clinical data such as age, sex, and serum bilirubin level were also recorded and analyzed. Statistical analysis of the two groups was performed with the χ2 test and Fisher exact test for counting data and a t test for measurement data. P < .05 was considered statistically significant. The sensitivity, specificity, and positive and negative predictive values for gallbladder size, gallbladder abnormalities, the triangular cord sign, and sludge in the cyst for predicting cystic biliary atresia were calculated.
Final diagnoses were cystic biliary atresia in 12 patients and choledochal cysts in 11. The ages of patients with cystic biliary atresia and choledochal cysts at the time of presentation ranged from 23 to 150 (mean ± SD, 76.4 ± 41.1) and 10 to 120 (60.9 ± 36.4) days, respectively. There were 6 boys and 6 girls in the atresia group and 4 boys and 7 girls in the cyst group. There were no significant differences in age (P = .351) and sex (P = .68) between the atresia and cyst groups.The total bilirubin levels in the atresia and cyst groups ranged from 123.2 to 308.0 (208.4 ± 57.4) and 44.9 to 269.4 (150.6 ± 79.7) mmol/L, respectively (P = .113). The direct bilirubin levels in the atresia cyst groups ranged from 93.6 to 226.5 (161.0 ± 39.6) and 34.2 to 190.9 (112.3 ± 56.9) mmol/L (P = .062).
There were significant differences in the frequency of several sonographic features between the atresia and cyst groups (Table 1). The triangular cord sign was detected in 11 patients (91.7%) in the atresia group (Figure 1) but in none in the cyst group (P < .001). Intrahepatic bile duct dilatation was detected in 9 of 11 patients (81.8%) in the cyst group, whereas none had that feature in the atresia group (P < .001).
Comparison of Sonographic Features Between Cystic Biliary Atresia and Choledochal Cysts in Neonates and Young Infants
Sonography showed a cystic structure in the porta hepatis in all patients in both groups. The sizes (maximum width × maximum length) of the cysts on sonography ranged from 4 × 3 to 47 × 24 mm in the atresia group (n = 12) and 20 × 7 to 130 × 80 mm in the cyst group (n = 11). Specifically, it was observed that 1 patient with later-stage biliary atresia had 4 cysts (Figure 2) in the porta hepatis, with diameters ranging from 7 to 10 mm; only the largest cyst was taken into account. The mean width and length of the cysts in the cyst group (62.2 ± 39.9 and 41.1 ± 30.7 mm, respectively) were significantly larger than those in the atresia group (16.2 ± 13.2 and 8.9 ± 6.5 mm; P = .002; P = .001). However, the width to length ratios between the two groups were not significantly different (0.64 ± 0.22 versus 0.63 ± 0.20; P = .934). Sludge deposits in cysts were found in 6 of 11 patients (54.5%) in the cyst group (Figure 3), whereas none in the cystic atresia group had sludge deposits (P = .005).On sonography, the mean hepatic artery diameter in the atresia group was significantly larger than that in the cyst group (2.4 ± 0.4 versus 1.7 ± 0.2 mm; P < .001), whereas no significant difference was found for the portal vein diameter between the two groups (4.1 ± 0.8 versus 3.8 ± 0.6 mm; P = .373).
Cystic biliary atresia in a 51-day-old girl. A, Cyst (cursors) at the porta hepatis with a size of 46.6 × 23.5 mm. B, Irregularly elongated gallbladder (cursors) with a length of 42.5 mm and a width of 7.8 mm. C, Triangular cord sign (arrows) at the anterior wall of the right portal vein with a thickness of 7.0 mm. D, Enlarged hepatic artery (cursors) with a diameter of 2.4 mm. CY indicates cyst.
Later-stage cystic biliary atresia in a 123-day-old boy. A, Four cysts (arrows) at the porta hepatis with diameters ranging from 7 to 10 mm. Arrowheads indicate an atretic gallbladder with a length of 9 mm. B, Triangular cord sign (arrows) at the anterior wall of the right portal vein with a thickness of 8.0 mm. C, High-frequency image showing fluids around the liver (arrows) and a coarse liver echo texture. D, Color Doppler image showing reopening of the umbilical vein (arrow).
In the atresia group, sonography showed atretic gallbladders in 2 patients (16.7%), irregularly elongated gallbladders (Figure 1) in 9 (75%), and a relatively normal gallbladder in 1 (8.3%). In the cyst group, all 11 patients (100%) were observed to have normal gallbladders. The morphologic characteristics of the gallbladders between the two groups were significantly different (P < .001). Two patients in the atresia group had gallbladder lengths of less than 15 mm, whereas all patients in the cyst group had gallbladder lengths of greater than 15 mm. However, the mean gallbladder length and the gallbladder width to length ratio were not significantly different in the atresia group (26.4 ± 11.9 and 0.25 ± 0.10 mm) compared with the cyst group (32.7 ± 10.2 and 0.27 ± 0.07 mm; P = .189; P= .476). On the contrary, the mean gallbladder width in the atresia group (5.6 ± 2.0 mm) was significantly smaller than that in the cyst group (8.5 ± 2.5 mm; P = .005).Sensitivity, specificity, and positive and negative predictive values for gallbladder size, gallbladder abnormalities, the triangular cord sign, and sludge in the cyst for predicting cystic biliary atresia are shown in Table 2. When all specific sonographic features were taken into account, all patients were correctly classified into the atresia and cyst groups, for an overall accuracy rate of 100%.
Six of 12 patients (50%) in the atresia group were observed to have a communication between the gallbladder and portal cyst on sonography, which was later confirmed by intraoperative cholangiography. The cyst sizes were different between those who had a communication between the gallbladder and cyst and those who did not. The length of those with a communication (n = 6) ranged from 11 to 47 (25.5 ± 13.1) mm, whereas the length of those without a communication (n = 6) ranged from 4 to 10 (6.8 ± 2.3) mm (P = .006).Two patients in the atresia group had an abnormal coarse liver echo texture and a reopened umbilical vein (Figure 2) on sonography. One of them also had ascites. All patients in the cyst group had a normal liver echo texture, and no ascites was detected.
Sonography has been considered very helpful in making a preoperative differential diagnosis between cystic biliary atresia and choledochal cysts.5,10,15,16 Patients with larger cysts, dilated intrahepatic ducts, and normal gallbladders are more likely to have choledochal cysts. Inversely, those with smaller cysts, nondilated intrahepatic ducts, and abnormal gallbladders are more likely to have cystic biliary atresia. However, debates still exist as to this point of view. Some authors have reported cystic biliary atresia with large cysts or with dilated intrahepatic ducts.5,9,16 In addition, it is hard to draw a clear line between a large cyst and a small cyst. Some authors proposed that the shape of the cyst might play a role in distinguishing cystic biliary atresia from a choledochal cyst5,10 because the cysts in cystic biliary atresia were more likely to be teardrop shaped, whereas the choledochal cysts were more likely to be fusiform. However, we thought it was a little too subjective to differentiate cystic biliary atresia from choledochal cysts by judging the shape of the cysts. Some more specific and objective sonographic features for differentiating the diagnosis are urgently needed.
The state of the art in diagnosis of biliary atresia by sonography has been updated in recent years. Apart from gallbladder abnormalities, other sonographic features have been identified as useful in identifying biliary atresia, such as the triangular cord sign, dilatation of the hepatic artery, and hepatic subcapsular flow. The triangular cord sign was considered an objective criterion for identifying biliary atresia on sonography.12 Although the sensitivity of this sign for identifying biliary atresia varies, it is widely considered a specific sonographic marker of the disease, with specificity ranging from 96% to 100%.12,17– 20 Enlargement of the hepatic artery in infants with biliary atresia was also reported.13,19,21 With a critical diameter of 1.5 mm, the sensitivity and specificity of an enlarged hepatic artery for identifying biliary atresia were 92% and 87%, respectively.13 Hepatic subcapsular flow, defined as vascular structures contiguous with the liver capsular surface on color Doppler sonograms, was found to have sensitivity of 100% and specificity of 86% for identifying biliary atresia.21 A combination of all of these features could improve the accuracy of sonography for diagnosis of biliary atresia to 98% to 100%.17–19 However, few studies in the literature have assessed the value of these sonographic features for differentiating cystic biliary atresia from choledochal cysts.
Specific Sonographic Features as Predictors of Cystic Biliary Atresia
In this study, we found that the triangular cord sign and a dilated hepatic artery are very useful for differentiating cystic biliary atresia from noncystic biliary atresia. The triangular cord sign was detected in 11 of 12 patients (91.7%) in the atresia group, whereas no patient in the cyst group had this sign. The sensitivity and specificity of the triangular cord sign were 91.7% and 100%, respectively. Although the triangular cord sign was not observed in 5 cases of cystic biliary atresia10 because of the negative effect of the cyst at the porta hepatis, we thought that the triangular cord sign could be detected by an experienced operator performing careful scanning. However, it should be noted that not every case of cystic biliary atresia might show the triangular cord sign. The incidence of the triangular cord sign among patients with cystic biliary atresia needs to be further assessed with more cases. We also showed that the caliber of the hepatic artery is significantly larger in patients with cystic biliary atresia, which is the same as that in patients with isolated biliary atresia. We think that the reason for this finding is the same as for that in isolated biliary atresia, even if the latter is still not known clearly.22 Although there is still no standard critical value for determining a larger hepatic artery from normal, we think that a prominent hepatic artery can be supportive in differentiating cystic biliary atresia from choledochal cysts. Nevertheless, we have to confess that measurement of the hepatic artery in patients with larger cysts at the porta hepatis was very difficult.
Choledochal cyst in a 74-day-old boy. A, Cyst at the porta hepatis with a size of 52.1 × 50.0 mm. At the bottom of the cyst, sludge (arrow) without a posterior acoustic shadow is shown. B, Normal gallbladder (cursors) above the cyst with a size of 22.3 × 4.5 mm. C, Dilated intrahepatic bile duct (arrow) with a diameter of 1.7 mm. D, Hepatic artery (arrow) with a diameter of 1.8 mm. CY indicates cyst.
We confirmed that an abnormal gallbladder is very critical for distinguishing between cystic biliary atresia and choledochal cysts on sonography. Although some authors reported that the gallbladder length in biliary atresia is usually smaller than that in nonbiliary atresia,19,20 when it comes to cystic biliary atresia and choledochal cysts, this conclusion might not be applicable.10 In this study, the occurrence of only 2 gallbladders (16.7%) in the cystic biliary atresia group with a length of less than 15 mm was dramatically smaller than that in isolated biliary atresia. Furthermore, the mean gallbladder length in the atresia group was not significantly smaller than that in the cyst group in this study. We think that it is the shape and not the size of the gallbladder that is useful for differentiating cystic from noncystic biliary atresia. As reported in the literature,5,10 the shape of the gallbladder in patients with cystic biliary atresia was much more likely to be irregularly elongated in our study, with a frequency of 75% (9 of 12).The mean cyst size in the atresia group was smaller than that in the cyst group in our study. This result was the same as what most authors have noted.5,10,11 However, a cyst in a patient with cystic biliary atresia with a diameter of 80 mm reported by Caponcelli et al9 is clearly an exception to this outcome. Kim et al5 noted that it is useful to differentiate cystic biliary atresia from a choledochal cyst by the shape of the cyst. However, it is a little too subjective to define the shape as a teardrop, fusiform, or ovoid. In this study, we compared the cyst length to width ratios between the cyst and atresia groups, and the difference was not significant, which we consider a supportive point for our opinion.
In this study, 6 patients (54.5%) with choledochal cysts had sludge deposits, whereas no cyst with sludge was found in the patients with cystic biliary atresia. Similarly, Casaccia et al15 reported that echoic cysts were strongly suggestive of choledochal cysts. This finding could be explained by the pathologic changes that occur in these two entities. A choledochal cyst is an abnormality in which only the distant extrahepatic bile duct might be obstructive, whereas the proximal bile duct is patent. With the bile continuing to be secreted and flowing into the cyst, some components in the bile deposit and become sludge. On the contrary, biliary atresia is usually an entity with obliteration of the hepatic bile duct or the most proximal part of the extrahepatic bile duct.1 Hence, the bile flow cannot reach the cyst, and the fluid in the cyst does not contain the necessary components to form sludge. The white cystic fluid in cystic biliary atresia found during surgery23 might support this explanation. In addition, the reason why the intrahepatic bile ducts of choledochal cysts are more likely to be dilated than those of cystic biliary atresia was also explained. In our study, the incidence of dilated intrahepatic bile ducts in the cyst group was 81.8% (9 of 11), which was comparable to incidence rates of 47.7% to 100% noted by other authors.5,10
In this study, we also noted that one 123-day-old patient with later-stage biliary atresia had multiple cysts at the porta hepatis. We speculated that these might have been secondary intrahepatic biliary cysts caused by the ongoing process of hilar bile duct obstruction. Generally, multiple intrahepatic biliary cysts occur more often in postoperative biliary atresia. However, a few cases of cystic biliary atresia with multiple intrahepatic biliary cysts found before surgery have been reported.24
The main limitation of our study was that we did not correlate the triangular cord sign with the location of the cystic biliary atresia because of a lack of related information. However, we think that there might be a correlation between the presentation of the triangular cord sign and the location of the biliary atresia. Another limitation of our study was that the sample was very small. Large clinical trials are required to further test our findings.
In conclusion, with the use of a combination of all specific sonographic features, all 23 patients in our study were correctly classified as having cystic biliary atresia or choledochal cysts. Although measurements of the cyst size and hepatic artery diameter could be supportive points for differentiating cystic biliary atresia from choledochal cysts, we think that the triangular cord sign, gallbladder abnormalities, intrahepatic bile duct dilatation, and echoic cysts might be more valuable sonographic features for differentiating cystic biliary atresia from choledochal cysts. Furthermore, the triangular cord sign, intrahepatic bile duct dilatation, and echoic cysts might be regarded as objective sonographic features for distinguishing between cystic biliary atresia and choledochal cysts because they can be detected objectively on sonography.© 2012 by the American Institute of Ultrasound in Medicine.