http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–6 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.979148
ORIGINAL ARTICLE
Evaluation and screening ultrasonic signs in the diagnosis of fetal biliary cystic malformation Xiang Cong1, Xiubin Sun2, and Shaoping Liu1 J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/13/15 For personal use only.
1
Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, P.R. China and 2Department of Statistics, Public Health School of Shandong University, Jinan, P.R. China Abstract
Keywords
Objective: To evaluate and screen for fetal biliary cystic malformation (BCM) associatedultrasonic key signs or sign-combinations. Methods: Thirty cases of fetal abdominal cysts were investigated, followed up and divided into BCM and non-BCM groups. Expression rates of seven fetal BCM-associated ultrasonic signs in the two groups (A: the cyst was located in the right upper quadrant of the abdomen, B: located beneath the porta hepatis, C: having no septum, D: not the gallbladder, E: connected to the gallbladder, F: connected to the hepatic ducts, G: its inferior portion ended in the epigastric region, anterior to the spinal column) were compared. The diagnostic efficacy of single signs and sign-combinations was evaluated by diagnostic test. Results: The expressions of Sign A and Sign D had no statistically significant differences between the two groups. Single sign of B, F and G had diagnostic efficacy. The diagnostic index of B reached 1.8571. The diagnostic index of the sign-combinations B and D, F or G, and E or F or G reached 2.0000. Conclusion: When the fetal cyst was located beneath the porta hepatis and was not the gallbladder, BCM could be diagnosed. Sign G might be another significant ultrasonic sign in BCM prenatal diagnosis.
Biliary cystic malformation, choledochal cyst, cystic biliary atresia, diagnostic test, prenatal diagnosis
Introduction Biliary cystic malformation (BCM) was first described by Casaccia et al. [1] to characterize cyst-like developmental disorders of the biliary tree, including two categories: choledochal cyst (CC) and cystic biliary atresia (CBA). It is usually difficult to differentiate between them, so that the two entities are generally termed as BCM [1–3]. Fetal BCM may always be diagnosed as origin-uncertain abdominal cysts, duodenal atresia, hepatic cyst, ovarian cyst, mesenteric cyst, renal abnormalities, normal gallbladder or situs inversus [1,4,5]. In Redkar’s study, the accuracy of prenatal diagnosis of BCM was only 7.7% [4]. On ultrasound (US), fetal BCM has been described as: anechoic cysts located in the right upper quadrant of the abdomen, sub-hepatic or in the region of porta hepatis, with no septum, and connected to the gallbladder or hepatic ducts [1,6,7], etc. Though the latter two are always considered as the decisive signs in prenatal diagnosis [7], but they could not be prenatally observed in all BCM cases in our experience. Address for correspondence: Shaoping Liu, Department of Ultrasound, Qilu Hospital of Shandong University, Wenhuaxi Road No. 107, Jinan, Shan Dong Province, China. Tel: 0086-531-82166100. E-mail: [email protected]
History Received 24 August 2014 Revised 14 October 2014 Accepted 17 October 2014 Published online 13 November 2014
Additionally, we found that the inferior portion of BCM cysts always ended in the epigastric region, anterior to the spinal column. It was helpful in differentiating the BCM from other fetal abdominal cysts, and might be another characteristic US sign in BCM prenatal diagnosis. All these facts aroused our attention. Too many US signs and complicated diagnostic criteria may confuse the inexperienced sonographer. This study was aimed to evaluate and screen for fetal BCM-associated US key signs or sign-combinations through statistical diagnostic tests, in order to simplify the prenatal diagnostic ideas.
Methods Patients From May 2009 through November 2013, enrolled in this study were patients who visited the US Department of Qilu Hospital of Shandong University with suspected BCM or intra-abdominal cysts that needed to be differentiated from BCM. These patients were chosen based on the following criteria in terms of intra-abdominal cysts: located in the epigastric or right upper quadrants, close to the inferior border of the liver, and without marked peristalsis. During the research, 30 patients with intra-abdominal cystic disease were
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enrolled and followed up. Based on the final diagnoses, they were divided into two groups: the BCM and the non-BCM (NBCM) group. Sixteen of them were BCM (5 male, 11 female). Mean gestational age at the initial US diagnosis was 29.6 (range, 19 to 38) weeks. Nine (2 male, 7 female) were born live. The follow-up period varied from 6 to 35 months. Eight cases underwent laparotomy at a median age of 3 months (range, 1 to 12 months), of which seven cases were confirmed to be CC (type I-a in 5, type I-b in 1 and type IV in 1), and one case of type III CBA underwent Kasai portoenterostomy at 1 month. One case of CC had non-surgical observation until the followup ended at 6 months old without any symptoms, and CC-Ia was diagnosed based on the ultrasonic follow-up. Seven cases underwent labor induction during mid pregnancy (at 22 to 27 gestational weeks). The prenatal US showed that the intraabdominal cysts were connected to the biliary ducts. Four of them performed MRI before induction, three performed autopsy, and they were all diagnosed as CC. Fourteen cases were NBCM cysts (8 male, 6 female). Mean gestational age at initial diagnosis was 28.5 (range, 20 to 39) weeks. Eleven cases had conservative US follow-up observations without any clinical symptoms (big gallbladder in 2, left-sided gallbladder in 2, right adrenal hematoma in 2, and hepatic cyst close to the inferior border or hepatic hilum in 5). The cystic lesions resolved spontaneously in two adrenal hematomas (disappeared by 3 months and 6 months of age) and one hepatic cyst (was proved disappeared at 24 months old). Two cases of mesenteric cysts were excised by surgery at the age of 3 months and 6 months. The case with immature adrenal teratoma underwent induction at 35 weeks of gestation and was confirmed by pathological results.
Instruments and methods Instruments GE 730 Expert (US) or Philips IU 22 (NL) Color Doppler US diagnostic apparatus was used with a probe frequency of 3.5– 5.0 MHz in prenatal diagnosis, and with a probe frequency of 8.0 to 10.0 MHz in neonatal abdominal examination. US scanning of BCM-associated US signs Routine prenatal US imaging was performed and focused on the following BCM-associated US signs in the subjects – A: the intra-abdominal cyst was located in the right upper quadrant of the abdominal cavity, B: the cyst was located beneath the porta hepatis (tightly attached to the junction of left and right branches of hepatic portal veins), C: the cyst had no septum, D: the cyst was not the gallbladder, E: the cyst was connected to the gallbladder, F: the cyst was connected to the hepatic ducts, G: the inferior portion of cyst ended in the epigastric region, anterior to the spinal column. The schematic diagrams of Signs A–D were shown in Figure 1, Sign E and F in Figure 2, and Sign G in Figure 3. A transverse plane parallel scanning was conducted in each case. It started from the porta hepatis, then down to the lower end of the cyst (the site of lower end was concerned) (Figure 3a–d).
J Matern Fetal Neonatal Med, Early Online: 1–6
Collation and record of US single signs’ and signcombinations’ expression The expression of US single signs and sign-combinations in both groups were collated and recorded as ‘‘+’’ or ‘‘’’ (case information was collected from the latest prenatal US results in our department). Sign-combinations were obtained by randomized pairwise combination (two signs were logically combined with ‘‘and’’ and ‘‘or’’) and the combination of signs with highest specificity (logically combined with ‘‘or’’). For example, sign-combination ‘‘A and B (+)’’ means that both Sign ‘‘A’’ and Sign ‘‘B’’ were expressed in one case. Sign-combination ‘‘A or B (+)’’ means that Sign ‘‘A’’ or Sign ‘‘B’’, any one or both of them were expressed in one case. Statistics SPSS17.0 statistical software (Chicago, IL) was applied in the statistical treatment. Qualitative data indicated in cases, comparison of Fisher’s exact probability of rate. p50.05 was a statistical difference. A statistical diagnostic test was used to calculate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic index of each sign or sign-combination in the differentiation of fetal BCM from NBCM. The diagnostic index was the reference to screen for the most valuable signs and sign-combinations. When it was greater than 1.7000, it was usually considered to have diagnostic efficiency, and its theoretical maximum was 2.0000. The results are listed in Tables 1 and 2.
Results The differences of BCM-associated US signs expressed in BCM and NBCM groups Comparison results of the single sign expression rate between the BCM and NBCM groups are shown in Table 1. Signs ‘‘A’’ and ‘‘D’’ had no statistical difference between the two groups. There were statistical differences (p50.05) in the other five signs between the two groups. The statistical diagnostic test results of BCM-associated US signs and sign-combinations Forty-nine groups of single sign and randomized pairwise of two signs were subjected to statistical diagnostic test analysis. The results showed that in this series, Sign ‘‘G’’ had a diagnostic specificity of up to 1.0000 as did Signs ‘‘E’’ and ‘‘F’’. The combination of those three signs (‘‘E or F or G’’) was also tested. Twenty single signs and sign-combinations had diagnostic efficacy (with the diagnostic index 41.7000) and are shown in Table 2. Single signs The value of the diagnostic index was in the following order: B4G4F4E4C4D4A (Table 2). Signs ‘‘B’’, ‘‘G’’ and ‘‘F’’ had diagnostic efficacy. Sign ‘‘B’’ had the highest diagnostic index of up to 1.8571. The new Sign ‘‘G’’ that we proposed had a diagnostic index of up to 1.8125, with the same diagnostic specificity as Signs ‘‘E’’ and ‘‘F’’, and a higher sensitivity (0.8125). ‘‘E’’ and ‘‘F’’ the acknowledged decisive Signs, had lower sensitivity (0.3750 and 0.7500).
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DOI: 10.3109/14767058.2014.979148
Prenatal ultrasonic diagnosis
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Figure 1. Schematic diagram of BCM-associated US signs A, B, C and D. BCM: biliary cystic malformation, US: ultrasonic, C: cyst, GB: gallbladder, UV: umbilical vein, ST: stomach, RT/LT: right/left, RPV/LPV right/left portal vein, PH: porta hepatis. (a) This is one case of the hepatic cyst diagnosed at 31 gestational weeks (GWs). The cyst lay in right upper quadrant of fetal abdomen (Sign A+), without septum (Sign C+), and not the GB (Sign D+). (b) This is one case of CC diagnosed at 27 GWs. The sub-hepatic cyst was located nearly centrally (A), with no septum (C+), and was not a GB itself (D+). (c) This is one case of CC-Ia diagnosed at 36 GWs. The cyst was located beneath the porta hepatis (tightly attach to the junction of left and right branches of the hepatic portal vein, B+), with no septum (C+), and was not a GB itself (D+). (d) This is one case of right adrenal hematoma diagnosed at 27 GWs. The cyst lie under the porta hepatis but was not attached to it tightly (Sign B), and with septum (Sign C).
Figure 2. The schematic diagram of BCM-associated US signs E and F. BCM: biliary cystic malformation, US: ultrasonic, C: cyst, GB: gallbladder, CD: cystic duct, ST: stomach, GBN: gallbladder neck, HD: hepatic duct, UV: umbilical vein, LPV left portal vein. (a) This is one case of CC-Ia diagnosed at 29 gestational weeks (GWs). The cyst was connected to the gallbladder (E+). (b) This is one case of CC-Ia diagnosed at 25 GWs. The cyst was connected to the hepatic ducts (F+), but the dilated cystic duct was not visualized (E). (c–d) Two cases of CC-Ia diagnosed at 37 GWs and 24 GWs. The cysts were connected to the hepatic ducts (F+).
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J Matern Fetal Neonatal Med, Early Online: 1–6
Figure 3. The schematic diagrams of transversal parallel scanning procedure and recognizing of Sign G in the case of CC, left-sited GB and ADH. CC: choledochal cyst, GB: gallbladder, ADH: adrenal hematoma, C: cyst, ST: stomach, LPV/RPV left/right portal vein, LHD: left hepatic duct, SP: spleen, UV: umbilical vein, SPI: spine, LK/RK: left/right kidney, AO: aorta, IVC: inferior vena cava, H: heart, BL: bladder, R-ADR: right-adrenal region. (a–d) A continuous scanning was conducted in one case of CC-Ia diagnosed at 35 gestational weeks (GWs). (a) The US scan started in an oblique coronal plane crossed the porta hepatis. Color Doppler Flow Imaging help to confirm the relationship between the porta hepatis and the cyst. (b) Then adjusted the probe angle perpendicular to the surface. In this figure, the left hepatic duct and the cyst were shown. (c) The probe was moved downward in parallel crossed the plane of spleen. (d) The probe was continued moved downward in parallel crossed the plane of kidneys (not arrive umbilicus). The inferior portion of the cyst ended anterior to the spinal column (G+). (e) One case of left-sided GB diagnosed at 39 GWs. An oblique coronal plane show the longitudinal axis of the ‘‘cyst’’, its upper top was located under the left liver lobe, and its lower end terminate at the anterior ridge of right liver lobe (G). (f) One case of right adrenal hematoma diagnosed at 28 GWs. A para-midline sagittal plane showed the lower end of the cyst located superior to the right kidney (G).
Sign-combinations Sixteen double-sign-combinations and one triple-sign-combination that had been tested had diagnostic efficacy. Signcombinations ‘‘E or F’’, ‘‘E or G’’, ‘‘B and D’’, ‘‘F or G’’ and ‘‘E or F or G’’ had a diagnostic index higher than 1.9000, and the latter three were up to 2.0000 (Table 2). The relationship between the expression of Signs ‘‘E’’, ‘‘F’’ and ‘‘G’’ and the classification of BCM Nine cases were born alive and classified after surgery and US scan (Table 3). Only three CCs showed the dilated cystic ducts (Sign E) prenatally. The relationship between the cyst and the gallbladder were clarified in four more CCs after birth
except the case of CC-Ib and type III CBA (which was proved an atrophic gallbladder after surgery). Six cases expressed Sign F prenatally were classified as CC-Ia, type III CBA and CC-IV after surgery. In two case of CC-Ia, Sign F was expressed after birth. Sign G was commonly expressed in this series, except two cases (including one CC-Ia which had larger cyst exceeding the horizontal line crossing the umbilicus and the type III CBA with a smaller cyst). Both Sign ‘‘F’’ and ‘‘G’’ occurred in the case of CC-IV and CC-Ia.
Discussion Both CC and biliary atresia (BA) are congenital developmental disorders of the biliary duct. The incidences of neonatal
Prenatal ultrasonic diagnosis
DOI: 10.3109/14767058.2014.979148
Table 1. The difference of US signs expressed in BCM and NBCM cases.
Table 3. Signs E, F and G expression and the classification of BCM in live-born cases.
Groups US signs A B C D
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E F G
E
Results of expression
BCM
NBCM
p value
+ + + + + + +
14 2 16 0 16 0 16 0 6 10 12 4 13 3
13 1 2 12 9 5 12 2 0 14 0 14 0 14
1.0000 0.0000 0.0140 0.2092
G
Signs and sign-combinations Sensitivity Specificity 0.0714 0.8571 0.3571 0.1429 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 0.8571 0.8571 0.8571 0.8571 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 0.8571
1 2 3 4 5 6 7 8 9
+ + +
+ + + + + + +
+ + + + + +
+ + + + + + + +
+ + + + + + +
CC-IV CC-Ia CC-Ia CC-Ia CC-Ia CC-Ib CC-Ia CBA-III CC-Ia
0.0185 0.0000 0.0000
Table 2. Diagnostic test results of single signs and sign-combinations of BCM-associated US signs in BCM and NBCM cases.
0.8750 1.0000 1.0000 1.0000 0.3750 0.7500 0.8125 1.0000 1.0000 1.0000 0.9375 0.9375 1.0000 1.0000 1.0000 1.0000 0.8125 0.8125 0.8125 0.8125 0.7500 0.7500 0.7500 0.8750
F
Case No. Prenatal Postnatal Prenatal Postnatal Prenatal Classification
US: ultrasound, BCM: biliary cystic malformations, NBCM: non-biliary cystic malformations. US signs: A: the intra-abdominal cyst was located in the right upper quadrant of the abdominal cavity, B: the cyst was located at the porta hepatis, C: the cyst had no septum, D: the cyst was not the gallbladder, E: the cyst was connected to the gallbladder, F: the cyst was connected to the hepatic ducts, G: the inferior portion of cyst ended in the epigastric region, anterior to the spinal column.
A B C D E F G B and D F or G E or F or G E or F E or G A and C B or E B or F B or G A and G B and G C and G D and G B and F C and F D and F A and B
5
+LR
LR
Diagnostic index
0.9423 7.0000 1.5556 1.1667 . . . . . . . . 7.0000 7.0000 7.0000 7.0000 . . . . . . . 6.1250
1.7500 0.0000 0.0000 0.0000 0.6250 0.2500 0.1875 0.0000 0.0000 0.0000 0.0625 0.0625 0.0000 0.0000 0.0000 0.0000 0.1875 0.1875 0.1875 0.1875 0.2500 0.2500 0.2500 0.1458
0.9464 1.8571 1.3571 1.1429 1.3750 1.7500 1.8125 2.0000 2.0000 2.0000 1.9375 1.9375 1.8571 1.8571 1.8571 1.8571 1.8125 1.8125 1.8125 1.8125 1.7500 1.7500 1.7500 1.7321
BCM: biliary cystic malformation, +LR: positive likelihood ratio, LR: negative likelihood ratio. US signs are the same as given for Table 1. Data of sign-combinations without diagnostic efficacy (diagnostic index 51.7000) are not shown.
CC and BA are 1/13 000 and 1/8000–1/14 000, respectively [8–10]. They are more prevalent among Asian populations with a reported incidence of 1 in 1000 [11], and with a male and female ratio of 1:4 [3]. The etiologies of CC and BA are
BCM: biliary cystic malformation. E: the cyst was connected to the gallbladder, F: the cyst was connected to the hepatic ducts, G: the inferior portion of cyst ended in the epigastric region, anterior to the spinal column.
unknown. Abnormalities in embryonic development and viral infection are thought to be the common causes of both diseases. Additionally, Babbitt’s [12] theory of abnormal pancreaticobiliary duct junction has gained much popularity in CC etiology. Also, neonatal hepatitis is considered related to isolated BA [13]. CBA is a special variant of BA, accounting for 10% of BA [13]. CC and CBA often share similar US and clinical presentations, which makes it difficult to differentiate them prenatally. In Redkar’s study [4], the BCM cysts (n ¼ 13) were diagnosed as intra-abdominal cysts (n ¼ 7), duodenal atresia (n ¼ 3), ovary cyst (n ¼ 1) and hepatic cyst (n ¼ 1). All the 16 BCM cases admitted to our hospital were transferred from other hospitals, and only four of them were diagnosed as CC initially. One was suspected as duodenal atresia, and the other 11 were diagnosed as intra-abdominal cysts of unknown origin. The origins of BCM cysts are difficult to identify, probably because they are relatively uncommon and have multiple US signs or it is difficult for ultrasonographists to master diagnostic techniques. Statistical diagnostic text was applied in this study. Improvement of the prenatal detection rate of these disorders will be clinically significant for patient education in follow-up strategies, for the timing of postnatal surgery, and the improvement of prognosis. Expressions of Signs ‘‘A’’ and ‘‘D’’ were common in both the BCM and NBCM groups. The remarkably low specificities accounted for their having no statistical difference between the two groups (Table 1). Statistical diagnostic tests showed that the Sign ‘‘B’’, ‘‘F’’ and ‘‘G’’ were of higher diagnostic efficacy among single signs (Table 2). The locations of BCM cysts were always delineated as in the region of the portal hepatis [1,14–16]. In our study, all BCM cysts were located beneath the porta hepatis as Sign B (Figures 1c, 2d and 3a) described. This sign was proved the highest diagnostic index in BCM differentiating diagnosis. It did not appear in cases other than the two big gallbladders misdiagnosed as CC in primary hospitals. Compared to Signs ‘‘E’’ and ‘‘F’’ (the decisive signs for BCM prenatal diagnosis, shown in Figure 2), Sign G (Figure 3) showed the same diagnostic specificity with higher sensitivity. The adjacent anatomical location of BCM cysts
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and the pancreas is easily identified after birth. But fetal pancreatic tissue often shows an inconspicuous contour. This may partially account for the difficulty in BCM prenatal diagnosis. In some type of BCM cysts, the lesion often involves the entire common bile duct (such as type I, IV CC and type-I CBA) [8,17]. Sign G was the US sign most closely associated with the lower part of common bile duct, and thus had a relatively high specificity for prenatal diagnosis of BCM. Type I CC and type I CBA were relatively common in prenatal diagnosed cases [2,4,14]. So it could be considered as an effective new diagnostic sign for fetal BCM. None of the single signs was sufficient to prenatally screen all the BCM cysts when used alone. Diagnostic test results derived from those cases showed that the combination of single signs improved the diagnostic efficacies of fetal BCM. The diagnostic index of the signcombination of ‘‘B and D’’ was up to 2.0000. This could be interpreted as: if the cyst was located at the porta hepatis and the possibility of the cyst being the gallbladder was ruled out, a diagnosis of BCM could be made. The sign-combinations of ‘‘E’’, ‘‘F’’, ‘‘G’’ (‘‘E or F or G’’, ‘‘F or G’’) with the highest specificity raised the diagnostic index to 2.0000. This could be interpreted as follows: if prenatal US showed that an intraabdominal cyst was connected to the gallbladder or to the hepatic ducts or its lower portion terminated in the epigastric region anterior to the spine, and any of the above three criteria was met, then a diagnosis of BCM could be made. The E, F and G are all US signs related to the expansion scope of fetal extrahepatic ducts. But our data did not show their close relationship between the signs expression and the classification (Table 3). The dilated cystic duct and hepatic duct may occur after birth. Simultaneous expression of Sign ‘‘F’’ and ‘‘G’’ prenatally occurred in type I-a, IV CC cases, indicated the whole extrahepatic ducts dilation. One of the followed-up cases was type III CBA with nonvisualized gallbladder prenatally. It suggested that CBA should be suspected if prenatal US showed BCM cyst accompanied with non-visualization or aplasia of gallbladder as reported [1–3,16,18]. The over-fitting result (the diagnostic index was up to 2.0000) of sign-combinations in the diagnostic test may be due to the limited number of samples and not all types of CC and CBA were included in this study. According to the analysis, the above results are consistent with the anatomical features and the logic of prenatal diagnosis for such types of cysts. Its significance is that it could be an easier and definite diagnostic protocol for prenatal BCM screening. However, the practical application effects need to be tested by more samples in a future multi-center study.
Conclusion After statistical analysis and comparison, a simplified diagnostic idea about BCM prenatal diagnosis could be suggested here that when the cyst is found located beneath the portahepatis; firstly, the possibility of GB should be excluded, and after that the BCM could be diagnosed. Signs ‘‘E’’ and ‘‘F’’ were considered as decisive signs in prenatal diagnosis of BCM, but may not be expressed in all cases. Another new sign ‘‘G’’ (the inferior portion of cyst ended in the epigastric
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region, anterior to the spinal column) was significant, and might help to confirm the cyst’s biliary origin.
Acknowledgements We thank M.D. Yi Zhang, Ning Zhong, Jian Wang, Pengfei Zhang, Guowei Tao, Zhe Ma and all our colleagues for their sincere help in preparing this manuscript. Thanks to Dr Edward C. Mignot, Shandong University, for linguistic advice. We also like to extend our appreciation to Mrs Xinmei Pang for invaluable assistance in document retrieval.
Declaration of interest This work was supported by the Science and Technology Research Project (2013) of Shandong Province Population and Family Planning Commission. The authors report no conflicts of interest.
References 1. Casaccia G, Bilancioni E, Nahom A, et al. Cystic anomalies of biliary tree in the fetus: is it possible to make a more specific prenatal diagnosis? J Pediatr Surg 2002;37:1191–4. 2. Saito T, Horie H, Yoshida H, et al. The perinatal transition of the hepatobiliary cyst size provides information about the condition of bile flow in biliary cystic malformation cases. J Pediatr Surg 2006; 41:1397–402. 3. Zhang Y, Meng H, Ouyang Y, et al. Value of prenatal ultrusonography in diagnosis of fetal biliary cystic malformation. Chin J Ultrasonogr 2010;19:427–30. 4. Redkar R, Davenport M, Howard ER. Antenatal diagnosis of congenital anomalies of the biliary tract. J Pediatr Surg 1998;33: 700–4. 5. McEwing R, Hayward C, Furness M. Foetal cystic abdomina masses. Australas Radiol 2003;47:101–10. 6. Diao M, Li L, Cheng W. Timing of surgery for prenatally diagnosed asymptomatic choledochal cysts: a prospective randomized study. J Pediatr Surg 2012;47:506–12. 7. Gallivan EK, Crombleholme TM, D’Alton ME. Early prenatal diagnosis of choledochal cyst. Prenat Diagn 1996;16:934–7. 8. Tongprasert F, Traisrisilp K, Tongsong T. Prenatal diagnosis of choledochal cyst: a case report. J Clin Ultrasound 2012;40:48–50. 9. Clifton MS, Goldstein RB, Slavotinek A, et al. Prenatal diagnosis of familial type I choledochal cyst. Pediatrics 2006;117:e596–600. 10. Burc L, Vuillard E, Guibourdenche J, et al. Prenatal diagnosis and follow up of biliary atresia. BJOG 2001;108:1108–10. 11. Singham J, Yoshida EM, Scudamore CH. Choledochal cysts: part 1 of 3: classification and pathogenesis. Can J Surg 2009;52:434–40. 12. Babbitt DP, Starshak RJ, Clemett AR. Choledochal cyst: a concept of etiology. Am J Roentgenol Radium Ther Nucl Med 1973;119: 57–62. 13. Petersen C, Davenport M. Aetiology of biliary atresia: what is actually known? Orphanet J Rare Dis 2013;8:128. 14. Tsuchida Y, Kawarasaki H, Iwanaka T, et al. Antenatal diagnosis of biliary atresia (type I cyst) at 19 weeks’ gestation: differential diagnosis and etiologic implications. J Pediatr Surg 1995;30:697–9. 15. Iwai N, Deguchi E, Sasaki Y, et al. Antenatal diagnosis of biliary atresia (noncorrectable cyst type): a case report. Eur J Pediatr Surg 1999;9:340–2. 16. Nori M, Venkateshwarlu J, Vijaysekhar, et al. Extrahepatic biliary atresia with choledochal cyst: prenatal MRI predicted and post natally confirmed: a case report. Indian J Radiol Imaging 2013;23: 238–42. 17. Hinds R, Davenport M, Mieli-Vergani G, et al. Antenatal presentation of biliary atresia. J Pediatr 2004;144:43–6. 18. Boughanim M, Benachi A, Dreux S, et al. Nonvisualization of the fetal gallbladder by second-trimester ultrasound scan: strategy of clinical management based on four examples. Prenat Diagn 2008; 28:46–8.
ORIGINAL ARTICLE
Evaluation and screening ultrasonic signs in the diagnosis of fetal biliary cystic malformation Xiang Cong1, Xiubin Sun2, and Shaoping Liu1 J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Nyu Medical Center on 05/13/15 For personal use only.
1
Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, P.R. China and 2Department of Statistics, Public Health School of Shandong University, Jinan, P.R. China Abstract
Keywords
Objective: To evaluate and screen for fetal biliary cystic malformation (BCM) associatedultrasonic key signs or sign-combinations. Methods: Thirty cases of fetal abdominal cysts were investigated, followed up and divided into BCM and non-BCM groups. Expression rates of seven fetal BCM-associated ultrasonic signs in the two groups (A: the cyst was located in the right upper quadrant of the abdomen, B: located beneath the porta hepatis, C: having no septum, D: not the gallbladder, E: connected to the gallbladder, F: connected to the hepatic ducts, G: its inferior portion ended in the epigastric region, anterior to the spinal column) were compared. The diagnostic efficacy of single signs and sign-combinations was evaluated by diagnostic test. Results: The expressions of Sign A and Sign D had no statistically significant differences between the two groups. Single sign of B, F and G had diagnostic efficacy. The diagnostic index of B reached 1.8571. The diagnostic index of the sign-combinations B and D, F or G, and E or F or G reached 2.0000. Conclusion: When the fetal cyst was located beneath the porta hepatis and was not the gallbladder, BCM could be diagnosed. Sign G might be another significant ultrasonic sign in BCM prenatal diagnosis.
Biliary cystic malformation, choledochal cyst, cystic biliary atresia, diagnostic test, prenatal diagnosis
Introduction Biliary cystic malformation (BCM) was first described by Casaccia et al. [1] to characterize cyst-like developmental disorders of the biliary tree, including two categories: choledochal cyst (CC) and cystic biliary atresia (CBA). It is usually difficult to differentiate between them, so that the two entities are generally termed as BCM [1–3]. Fetal BCM may always be diagnosed as origin-uncertain abdominal cysts, duodenal atresia, hepatic cyst, ovarian cyst, mesenteric cyst, renal abnormalities, normal gallbladder or situs inversus [1,4,5]. In Redkar’s study, the accuracy of prenatal diagnosis of BCM was only 7.7% [4]. On ultrasound (US), fetal BCM has been described as: anechoic cysts located in the right upper quadrant of the abdomen, sub-hepatic or in the region of porta hepatis, with no septum, and connected to the gallbladder or hepatic ducts [1,6,7], etc. Though the latter two are always considered as the decisive signs in prenatal diagnosis [7], but they could not be prenatally observed in all BCM cases in our experience. Address for correspondence: Shaoping Liu, Department of Ultrasound, Qilu Hospital of Shandong University, Wenhuaxi Road No. 107, Jinan, Shan Dong Province, China. Tel: 0086-531-82166100. E-mail: [email protected]
History Received 24 August 2014 Revised 14 October 2014 Accepted 17 October 2014 Published online 13 November 2014
Additionally, we found that the inferior portion of BCM cysts always ended in the epigastric region, anterior to the spinal column. It was helpful in differentiating the BCM from other fetal abdominal cysts, and might be another characteristic US sign in BCM prenatal diagnosis. All these facts aroused our attention. Too many US signs and complicated diagnostic criteria may confuse the inexperienced sonographer. This study was aimed to evaluate and screen for fetal BCM-associated US key signs or sign-combinations through statistical diagnostic tests, in order to simplify the prenatal diagnostic ideas.
Methods Patients From May 2009 through November 2013, enrolled in this study were patients who visited the US Department of Qilu Hospital of Shandong University with suspected BCM or intra-abdominal cysts that needed to be differentiated from BCM. These patients were chosen based on the following criteria in terms of intra-abdominal cysts: located in the epigastric or right upper quadrants, close to the inferior border of the liver, and without marked peristalsis. During the research, 30 patients with intra-abdominal cystic disease were
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enrolled and followed up. Based on the final diagnoses, they were divided into two groups: the BCM and the non-BCM (NBCM) group. Sixteen of them were BCM (5 male, 11 female). Mean gestational age at the initial US diagnosis was 29.6 (range, 19 to 38) weeks. Nine (2 male, 7 female) were born live. The follow-up period varied from 6 to 35 months. Eight cases underwent laparotomy at a median age of 3 months (range, 1 to 12 months), of which seven cases were confirmed to be CC (type I-a in 5, type I-b in 1 and type IV in 1), and one case of type III CBA underwent Kasai portoenterostomy at 1 month. One case of CC had non-surgical observation until the followup ended at 6 months old without any symptoms, and CC-Ia was diagnosed based on the ultrasonic follow-up. Seven cases underwent labor induction during mid pregnancy (at 22 to 27 gestational weeks). The prenatal US showed that the intraabdominal cysts were connected to the biliary ducts. Four of them performed MRI before induction, three performed autopsy, and they were all diagnosed as CC. Fourteen cases were NBCM cysts (8 male, 6 female). Mean gestational age at initial diagnosis was 28.5 (range, 20 to 39) weeks. Eleven cases had conservative US follow-up observations without any clinical symptoms (big gallbladder in 2, left-sided gallbladder in 2, right adrenal hematoma in 2, and hepatic cyst close to the inferior border or hepatic hilum in 5). The cystic lesions resolved spontaneously in two adrenal hematomas (disappeared by 3 months and 6 months of age) and one hepatic cyst (was proved disappeared at 24 months old). Two cases of mesenteric cysts were excised by surgery at the age of 3 months and 6 months. The case with immature adrenal teratoma underwent induction at 35 weeks of gestation and was confirmed by pathological results.
Instruments and methods Instruments GE 730 Expert (US) or Philips IU 22 (NL) Color Doppler US diagnostic apparatus was used with a probe frequency of 3.5– 5.0 MHz in prenatal diagnosis, and with a probe frequency of 8.0 to 10.0 MHz in neonatal abdominal examination. US scanning of BCM-associated US signs Routine prenatal US imaging was performed and focused on the following BCM-associated US signs in the subjects – A: the intra-abdominal cyst was located in the right upper quadrant of the abdominal cavity, B: the cyst was located beneath the porta hepatis (tightly attached to the junction of left and right branches of hepatic portal veins), C: the cyst had no septum, D: the cyst was not the gallbladder, E: the cyst was connected to the gallbladder, F: the cyst was connected to the hepatic ducts, G: the inferior portion of cyst ended in the epigastric region, anterior to the spinal column. The schematic diagrams of Signs A–D were shown in Figure 1, Sign E and F in Figure 2, and Sign G in Figure 3. A transverse plane parallel scanning was conducted in each case. It started from the porta hepatis, then down to the lower end of the cyst (the site of lower end was concerned) (Figure 3a–d).
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Collation and record of US single signs’ and signcombinations’ expression The expression of US single signs and sign-combinations in both groups were collated and recorded as ‘‘+’’ or ‘‘’’ (case information was collected from the latest prenatal US results in our department). Sign-combinations were obtained by randomized pairwise combination (two signs were logically combined with ‘‘and’’ and ‘‘or’’) and the combination of signs with highest specificity (logically combined with ‘‘or’’). For example, sign-combination ‘‘A and B (+)’’ means that both Sign ‘‘A’’ and Sign ‘‘B’’ were expressed in one case. Sign-combination ‘‘A or B (+)’’ means that Sign ‘‘A’’ or Sign ‘‘B’’, any one or both of them were expressed in one case. Statistics SPSS17.0 statistical software (Chicago, IL) was applied in the statistical treatment. Qualitative data indicated in cases, comparison of Fisher’s exact probability of rate. p50.05 was a statistical difference. A statistical diagnostic test was used to calculate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic index of each sign or sign-combination in the differentiation of fetal BCM from NBCM. The diagnostic index was the reference to screen for the most valuable signs and sign-combinations. When it was greater than 1.7000, it was usually considered to have diagnostic efficiency, and its theoretical maximum was 2.0000. The results are listed in Tables 1 and 2.
Results The differences of BCM-associated US signs expressed in BCM and NBCM groups Comparison results of the single sign expression rate between the BCM and NBCM groups are shown in Table 1. Signs ‘‘A’’ and ‘‘D’’ had no statistical difference between the two groups. There were statistical differences (p50.05) in the other five signs between the two groups. The statistical diagnostic test results of BCM-associated US signs and sign-combinations Forty-nine groups of single sign and randomized pairwise of two signs were subjected to statistical diagnostic test analysis. The results showed that in this series, Sign ‘‘G’’ had a diagnostic specificity of up to 1.0000 as did Signs ‘‘E’’ and ‘‘F’’. The combination of those three signs (‘‘E or F or G’’) was also tested. Twenty single signs and sign-combinations had diagnostic efficacy (with the diagnostic index 41.7000) and are shown in Table 2. Single signs The value of the diagnostic index was in the following order: B4G4F4E4C4D4A (Table 2). Signs ‘‘B’’, ‘‘G’’ and ‘‘F’’ had diagnostic efficacy. Sign ‘‘B’’ had the highest diagnostic index of up to 1.8571. The new Sign ‘‘G’’ that we proposed had a diagnostic index of up to 1.8125, with the same diagnostic specificity as Signs ‘‘E’’ and ‘‘F’’, and a higher sensitivity (0.8125). ‘‘E’’ and ‘‘F’’ the acknowledged decisive Signs, had lower sensitivity (0.3750 and 0.7500).
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DOI: 10.3109/14767058.2014.979148
Prenatal ultrasonic diagnosis
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Figure 1. Schematic diagram of BCM-associated US signs A, B, C and D. BCM: biliary cystic malformation, US: ultrasonic, C: cyst, GB: gallbladder, UV: umbilical vein, ST: stomach, RT/LT: right/left, RPV/LPV right/left portal vein, PH: porta hepatis. (a) This is one case of the hepatic cyst diagnosed at 31 gestational weeks (GWs). The cyst lay in right upper quadrant of fetal abdomen (Sign A+), without septum (Sign C+), and not the GB (Sign D+). (b) This is one case of CC diagnosed at 27 GWs. The sub-hepatic cyst was located nearly centrally (A), with no septum (C+), and was not a GB itself (D+). (c) This is one case of CC-Ia diagnosed at 36 GWs. The cyst was located beneath the porta hepatis (tightly attach to the junction of left and right branches of the hepatic portal vein, B+), with no septum (C+), and was not a GB itself (D+). (d) This is one case of right adrenal hematoma diagnosed at 27 GWs. The cyst lie under the porta hepatis but was not attached to it tightly (Sign B), and with septum (Sign C).
Figure 2. The schematic diagram of BCM-associated US signs E and F. BCM: biliary cystic malformation, US: ultrasonic, C: cyst, GB: gallbladder, CD: cystic duct, ST: stomach, GBN: gallbladder neck, HD: hepatic duct, UV: umbilical vein, LPV left portal vein. (a) This is one case of CC-Ia diagnosed at 29 gestational weeks (GWs). The cyst was connected to the gallbladder (E+). (b) This is one case of CC-Ia diagnosed at 25 GWs. The cyst was connected to the hepatic ducts (F+), but the dilated cystic duct was not visualized (E). (c–d) Two cases of CC-Ia diagnosed at 37 GWs and 24 GWs. The cysts were connected to the hepatic ducts (F+).
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Figure 3. The schematic diagrams of transversal parallel scanning procedure and recognizing of Sign G in the case of CC, left-sited GB and ADH. CC: choledochal cyst, GB: gallbladder, ADH: adrenal hematoma, C: cyst, ST: stomach, LPV/RPV left/right portal vein, LHD: left hepatic duct, SP: spleen, UV: umbilical vein, SPI: spine, LK/RK: left/right kidney, AO: aorta, IVC: inferior vena cava, H: heart, BL: bladder, R-ADR: right-adrenal region. (a–d) A continuous scanning was conducted in one case of CC-Ia diagnosed at 35 gestational weeks (GWs). (a) The US scan started in an oblique coronal plane crossed the porta hepatis. Color Doppler Flow Imaging help to confirm the relationship between the porta hepatis and the cyst. (b) Then adjusted the probe angle perpendicular to the surface. In this figure, the left hepatic duct and the cyst were shown. (c) The probe was moved downward in parallel crossed the plane of spleen. (d) The probe was continued moved downward in parallel crossed the plane of kidneys (not arrive umbilicus). The inferior portion of the cyst ended anterior to the spinal column (G+). (e) One case of left-sided GB diagnosed at 39 GWs. An oblique coronal plane show the longitudinal axis of the ‘‘cyst’’, its upper top was located under the left liver lobe, and its lower end terminate at the anterior ridge of right liver lobe (G). (f) One case of right adrenal hematoma diagnosed at 28 GWs. A para-midline sagittal plane showed the lower end of the cyst located superior to the right kidney (G).
Sign-combinations Sixteen double-sign-combinations and one triple-sign-combination that had been tested had diagnostic efficacy. Signcombinations ‘‘E or F’’, ‘‘E or G’’, ‘‘B and D’’, ‘‘F or G’’ and ‘‘E or F or G’’ had a diagnostic index higher than 1.9000, and the latter three were up to 2.0000 (Table 2). The relationship between the expression of Signs ‘‘E’’, ‘‘F’’ and ‘‘G’’ and the classification of BCM Nine cases were born alive and classified after surgery and US scan (Table 3). Only three CCs showed the dilated cystic ducts (Sign E) prenatally. The relationship between the cyst and the gallbladder were clarified in four more CCs after birth
except the case of CC-Ib and type III CBA (which was proved an atrophic gallbladder after surgery). Six cases expressed Sign F prenatally were classified as CC-Ia, type III CBA and CC-IV after surgery. In two case of CC-Ia, Sign F was expressed after birth. Sign G was commonly expressed in this series, except two cases (including one CC-Ia which had larger cyst exceeding the horizontal line crossing the umbilicus and the type III CBA with a smaller cyst). Both Sign ‘‘F’’ and ‘‘G’’ occurred in the case of CC-IV and CC-Ia.
Discussion Both CC and biliary atresia (BA) are congenital developmental disorders of the biliary duct. The incidences of neonatal
Prenatal ultrasonic diagnosis
DOI: 10.3109/14767058.2014.979148
Table 1. The difference of US signs expressed in BCM and NBCM cases.
Table 3. Signs E, F and G expression and the classification of BCM in live-born cases.
Groups US signs A B C D
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E F G
E
Results of expression
BCM
NBCM
p value
+ + + + + + +
14 2 16 0 16 0 16 0 6 10 12 4 13 3
13 1 2 12 9 5 12 2 0 14 0 14 0 14
1.0000 0.0000 0.0140 0.2092
G
Signs and sign-combinations Sensitivity Specificity 0.0714 0.8571 0.3571 0.1429 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 0.8571 0.8571 0.8571 0.8571 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 1.0000 0.8571
1 2 3 4 5 6 7 8 9
+ + +
+ + + + + + +
+ + + + + +
+ + + + + + + +
+ + + + + + +
CC-IV CC-Ia CC-Ia CC-Ia CC-Ia CC-Ib CC-Ia CBA-III CC-Ia
0.0185 0.0000 0.0000
Table 2. Diagnostic test results of single signs and sign-combinations of BCM-associated US signs in BCM and NBCM cases.
0.8750 1.0000 1.0000 1.0000 0.3750 0.7500 0.8125 1.0000 1.0000 1.0000 0.9375 0.9375 1.0000 1.0000 1.0000 1.0000 0.8125 0.8125 0.8125 0.8125 0.7500 0.7500 0.7500 0.8750
F
Case No. Prenatal Postnatal Prenatal Postnatal Prenatal Classification
US: ultrasound, BCM: biliary cystic malformations, NBCM: non-biliary cystic malformations. US signs: A: the intra-abdominal cyst was located in the right upper quadrant of the abdominal cavity, B: the cyst was located at the porta hepatis, C: the cyst had no septum, D: the cyst was not the gallbladder, E: the cyst was connected to the gallbladder, F: the cyst was connected to the hepatic ducts, G: the inferior portion of cyst ended in the epigastric region, anterior to the spinal column.
A B C D E F G B and D F or G E or F or G E or F E or G A and C B or E B or F B or G A and G B and G C and G D and G B and F C and F D and F A and B
5
+LR
LR
Diagnostic index
0.9423 7.0000 1.5556 1.1667 . . . . . . . . 7.0000 7.0000 7.0000 7.0000 . . . . . . . 6.1250
1.7500 0.0000 0.0000 0.0000 0.6250 0.2500 0.1875 0.0000 0.0000 0.0000 0.0625 0.0625 0.0000 0.0000 0.0000 0.0000 0.1875 0.1875 0.1875 0.1875 0.2500 0.2500 0.2500 0.1458
0.9464 1.8571 1.3571 1.1429 1.3750 1.7500 1.8125 2.0000 2.0000 2.0000 1.9375 1.9375 1.8571 1.8571 1.8571 1.8571 1.8125 1.8125 1.8125 1.8125 1.7500 1.7500 1.7500 1.7321
BCM: biliary cystic malformation, +LR: positive likelihood ratio, LR: negative likelihood ratio. US signs are the same as given for Table 1. Data of sign-combinations without diagnostic efficacy (diagnostic index 51.7000) are not shown.
CC and BA are 1/13 000 and 1/8000–1/14 000, respectively [8–10]. They are more prevalent among Asian populations with a reported incidence of 1 in 1000 [11], and with a male and female ratio of 1:4 [3]. The etiologies of CC and BA are
BCM: biliary cystic malformation. E: the cyst was connected to the gallbladder, F: the cyst was connected to the hepatic ducts, G: the inferior portion of cyst ended in the epigastric region, anterior to the spinal column.
unknown. Abnormalities in embryonic development and viral infection are thought to be the common causes of both diseases. Additionally, Babbitt’s [12] theory of abnormal pancreaticobiliary duct junction has gained much popularity in CC etiology. Also, neonatal hepatitis is considered related to isolated BA [13]. CBA is a special variant of BA, accounting for 10% of BA [13]. CC and CBA often share similar US and clinical presentations, which makes it difficult to differentiate them prenatally. In Redkar’s study [4], the BCM cysts (n ¼ 13) were diagnosed as intra-abdominal cysts (n ¼ 7), duodenal atresia (n ¼ 3), ovary cyst (n ¼ 1) and hepatic cyst (n ¼ 1). All the 16 BCM cases admitted to our hospital were transferred from other hospitals, and only four of them were diagnosed as CC initially. One was suspected as duodenal atresia, and the other 11 were diagnosed as intra-abdominal cysts of unknown origin. The origins of BCM cysts are difficult to identify, probably because they are relatively uncommon and have multiple US signs or it is difficult for ultrasonographists to master diagnostic techniques. Statistical diagnostic text was applied in this study. Improvement of the prenatal detection rate of these disorders will be clinically significant for patient education in follow-up strategies, for the timing of postnatal surgery, and the improvement of prognosis. Expressions of Signs ‘‘A’’ and ‘‘D’’ were common in both the BCM and NBCM groups. The remarkably low specificities accounted for their having no statistical difference between the two groups (Table 1). Statistical diagnostic tests showed that the Sign ‘‘B’’, ‘‘F’’ and ‘‘G’’ were of higher diagnostic efficacy among single signs (Table 2). The locations of BCM cysts were always delineated as in the region of the portal hepatis [1,14–16]. In our study, all BCM cysts were located beneath the porta hepatis as Sign B (Figures 1c, 2d and 3a) described. This sign was proved the highest diagnostic index in BCM differentiating diagnosis. It did not appear in cases other than the two big gallbladders misdiagnosed as CC in primary hospitals. Compared to Signs ‘‘E’’ and ‘‘F’’ (the decisive signs for BCM prenatal diagnosis, shown in Figure 2), Sign G (Figure 3) showed the same diagnostic specificity with higher sensitivity. The adjacent anatomical location of BCM cysts
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and the pancreas is easily identified after birth. But fetal pancreatic tissue often shows an inconspicuous contour. This may partially account for the difficulty in BCM prenatal diagnosis. In some type of BCM cysts, the lesion often involves the entire common bile duct (such as type I, IV CC and type-I CBA) [8,17]. Sign G was the US sign most closely associated with the lower part of common bile duct, and thus had a relatively high specificity for prenatal diagnosis of BCM. Type I CC and type I CBA were relatively common in prenatal diagnosed cases [2,4,14]. So it could be considered as an effective new diagnostic sign for fetal BCM. None of the single signs was sufficient to prenatally screen all the BCM cysts when used alone. Diagnostic test results derived from those cases showed that the combination of single signs improved the diagnostic efficacies of fetal BCM. The diagnostic index of the signcombination of ‘‘B and D’’ was up to 2.0000. This could be interpreted as: if the cyst was located at the porta hepatis and the possibility of the cyst being the gallbladder was ruled out, a diagnosis of BCM could be made. The sign-combinations of ‘‘E’’, ‘‘F’’, ‘‘G’’ (‘‘E or F or G’’, ‘‘F or G’’) with the highest specificity raised the diagnostic index to 2.0000. This could be interpreted as follows: if prenatal US showed that an intraabdominal cyst was connected to the gallbladder or to the hepatic ducts or its lower portion terminated in the epigastric region anterior to the spine, and any of the above three criteria was met, then a diagnosis of BCM could be made. The E, F and G are all US signs related to the expansion scope of fetal extrahepatic ducts. But our data did not show their close relationship between the signs expression and the classification (Table 3). The dilated cystic duct and hepatic duct may occur after birth. Simultaneous expression of Sign ‘‘F’’ and ‘‘G’’ prenatally occurred in type I-a, IV CC cases, indicated the whole extrahepatic ducts dilation. One of the followed-up cases was type III CBA with nonvisualized gallbladder prenatally. It suggested that CBA should be suspected if prenatal US showed BCM cyst accompanied with non-visualization or aplasia of gallbladder as reported [1–3,16,18]. The over-fitting result (the diagnostic index was up to 2.0000) of sign-combinations in the diagnostic test may be due to the limited number of samples and not all types of CC and CBA were included in this study. According to the analysis, the above results are consistent with the anatomical features and the logic of prenatal diagnosis for such types of cysts. Its significance is that it could be an easier and definite diagnostic protocol for prenatal BCM screening. However, the practical application effects need to be tested by more samples in a future multi-center study.
Conclusion After statistical analysis and comparison, a simplified diagnostic idea about BCM prenatal diagnosis could be suggested here that when the cyst is found located beneath the portahepatis; firstly, the possibility of GB should be excluded, and after that the BCM could be diagnosed. Signs ‘‘E’’ and ‘‘F’’ were considered as decisive signs in prenatal diagnosis of BCM, but may not be expressed in all cases. Another new sign ‘‘G’’ (the inferior portion of cyst ended in the epigastric
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region, anterior to the spinal column) was significant, and might help to confirm the cyst’s biliary origin.
Acknowledgements We thank M.D. Yi Zhang, Ning Zhong, Jian Wang, Pengfei Zhang, Guowei Tao, Zhe Ma and all our colleagues for their sincere help in preparing this manuscript. Thanks to Dr Edward C. Mignot, Shandong University, for linguistic advice. We also like to extend our appreciation to Mrs Xinmei Pang for invaluable assistance in document retrieval.
Declaration of interest This work was supported by the Science and Technology Research Project (2013) of Shandong Province Population and Family Planning Commission. The authors report no conflicts of interest.
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