- Email: [email protected]
Choledochal cysts in Omani children: A case series
Arab Journal of Gastroenterology 13 (2012) 89–92
Contents lists available at SciVerse ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Gastroenterology in Arab Countries
Choledochal cysts in Omani children: A case series Siham Al-Sinani a,⇑, Khalid Al Naamani b, Wafa Lutfi a, Aisha Al Hajri a a b
Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman Department of Internal Medicine, Armed Forces Hospital, Muscat, Oman
a r t i c l e
i n f o
Article history: Received 26 June 2011 Accepted 8 March 2012
a b s t r a c t Background and study aims: Choledochal cysts (CCs) are rare congenital anomalies of the biliary tract with a low incidence in the western countries and a higher incidence in the eastern part of the world. CCs have female to male preponderance. CCs type distribution is known in certain parts of the world but very little is published about the common types of CCs and gender distribution in the Arab countries. We aim to describe the CC types and gender distribution in Omani children in one centre. Patients and methods: A retrospective review of all children diagnosed to have choledochal cysts over a 2 year period at a tertiary hospital in Oman. Results: We diagnosed six children with CCs. The type distribution of CCs and gender preponderance in Omani children are not similar to what is described internationally. Type IV A was the most common type (50%) and less of type I (16.7%), unlike worldwide distribution. Female to male preponderance described in the literature is not seen in our case series. Fifty percent of our patients were boys. In this case series, we compare our results to the described case reports of CCs from Arab countries and Africa and bring up the difference. Conclusions: We demonstrate the unusual types of CCs and gender distribution in Omani children compared to the literature. To our best knowledge, this is the first case series of CCs in Omani children and the largest reported study in the literature in the Arab countries so far. Ó 2012 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Choledochal cysts (CCs) are rare congenital anomalies of the biliary tract. Incidence of CCs is 1 in 15,000 in Western countries [1,2] and 1 in 1000 in Japan [3]. There is female:male preponderance, commonly reported as 4:1 or 3:1 [3]. Distribution of different types of CCs is: type I is 50–80%, type II is 2%, type III is 1.4–4.5%, type IV is 15–35% and type V is 20% [4]. Aetiology, pathophysiology, natural course and optimal treatment of CCs still remain under debate [4]. Todani and coworkers expanded and modified the classification system in 1977 [5]. Fig. 1 shows the different types of CCs. There are many theories proposed to clarify the aetiology of CCs. They are purely congenital in some references [6]. Others suggest that abnormal pancreaticobiliary duct junction (APBDJ) causes CCs [7]. Davenport et al. observed that the neonatal CCs had fewer neurons and ganglions causing distal obstruction similar to Hirschsprung disease [8]. Ohkawa et al. discovered that an increased neonatal tendency for round dilation is due to APBDJ [9]. Others suggest that all adult cysts are acquired due to distal obstruction with long narrow stenosis leading to round lesions and short and wide stenosis leading to fusiform lesions [10,11]. The classic triad ⇑ Corresponding author. Address: Pediatric Gastroenterology and Hepatology, Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman. E-mail address: [email protected] (S. Al-Sinani).
of abdominal pain, jaundice and right upper abdominal mass described in most adult patients occurs in only 5–10% of paediatric patients [12,13]. In paediatric studies, most children with CCs presented with abdominal pain (76–91%) followed by jaundice (27– 57%). A retrospective study by Hung et al., described a difference in presentation between infants (<1 year of age) with CC compared to older children (1–18 years of age) with CC. In this study, older children presented with abdominal pain (82%) when compared to the infant age group (0%), whereas all infants presented with jaundice and pale stools (100%) when compared to the older children group (35%) [14]. Presentation with cholangitis or pancreatitis was less reported [13]. CCs in newborns and infants should be differentiated from biliary atresia (BA) with cystic dilatation. Jaundice with acholic stools and a small cyst size (<8 mm in diameter) in this age group suggest the possibility of a BA with cystic dilatation [14]. Determination of biliary amylase, which is normal in CCs, may help in this differentiation [14]. Diagnosis of CCs is based on the hepatobiliary imaging. CCs are mostly detected by abdominal ultrasound (US) or CT scan with US sensitivity ranging from 70% to 97% [12,15]. Magnetic resonance cholangiopancreatography (MRCP) is the best method for noninvasive imaging of CCs [16]. Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) provide a more accurate anatomy. CCs can cause morbidity and mortality from recurrent cholangitis, pancreatitis, sepsis, liver abscesses, and
1687-1979/$ - see front matter Ó 2012 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajg.2012.03.005
90
S. Al-Sinani et al. / Arab Journal of Gastroenterology 13 (2012) 89–92
Fig. 1. Choledochal cysts classification. (A) Type-I A cystic dilation of the extrahepatic duct. (B) Type-I B focal segmental dilation of the extrahepatic duct. (C) Type-I C fusiform dilation of the entire extrahepatic bile duct. (D) Type-II simple diverticula of the common bile duct. (E) Type-III cyst/choledochocele distal intramural dilation of the common bile duct within the duodenal wall. (F) Type-IV A combined intrahepatic and extrahepatic duct dilation. (G) Type-IV B multiple extrahepatic bile duct dilations. (H) Type-V/ Caroli disease multiple intrahepatic bile duct dilation.
cholangiocarcinoma if left untreated [14]. Treatment involves the management of complications, definitive surgical treatment, and long-term follow-up. CCs are premalignant lesions. The estimated frequency of hepatobiliary malignancy in adult patients with CCs is 10–30% [17]. Most patients with cholangiocarcinoma are adults as the risk increases with age [18]. Hepatobiliary malignancy is described in children with CCs [19]. It is described in all types of CCs but most commonly with type I and type IV cysts. Most malignancies occur in the cystic lesions, but are reported in the noncystic part after cyst excision [15]. Periodic screening for cholangiocarcinoma is recommended. Cholangiocarcinoma carries a poor prognosis with 2-year survival of less than 5% [19]. ERCP based intervention in children with CCs complicated by pancreatitis, cholangitis and obstructive jaundice was reported to be successful till definitive surgery was performed [20]. Treatment of CCs is surgical excision with cholecystectomy and Roux-en-Y hepaticojejunostomy (HJ) when possible. Recently, a large retrospective study showed that the laparoscopic Roux-en-Y HJ is safe and effective for CCs in children with comparable or even superior intermediate-term results to those of open HJ [21]. Lately, robotic surgical resection of CCs with HJ has been reported to be safe and effective in children [22]. With the involvement of intrahepatic and extrahepatic sites, complete excision may not be feasible. The outcome of cyst excision and HJ in children is good [23,14]. Hepatic transplantation is the definitive therapy for those who have diffuse disease, hepatic cirrhosis, or malignancy.
Case reports Case 1: A 12 year old girl presented with right upper quadrant abdominal pain, fever and vomiting of few days duration. On examination, she was febrile and not jaundiced. She had tender right upper abdominal quadrant. There was no hepatosplenomegaly (HSM). Her blood investigations are shown in Table 1. Abdominal US showed a cystic lesion with intraluminal echogenic foci.
MRCP showed focal cystic dilatation of the common bile duct (CC type I). Patient was treated with antibiotics and underwent cyst excision and HJ. Histology ruled out cholangiocarcinoma. Patient is well on follow up visits. Case 2: A 4 month old boy presented with a history of jaundice since the age of 40 days. He had a history of poor feeding, pale stools and dark urine. On examination, the child was jaundiced and small for age with no dysmorphic features. Abdomen was soft and not distended with firm HSM. His blood investigations are shown in Table 1. Abdominal US showed a cyst at porta hepatis with no intrahepatic bile duct dilatation. Gallbladder was contracted. MRCP was suggestive of type II CC. Liver biopsy showed features compatible with extrahepatic biliary obstruction, signs of acute cholangitis and cirrhosis. Patient was diagnosed to have biliary atresia with type II CC and liver cirrhosis and managed accordingly. Liver transplantation was advised. Patient passed away at another hospital at the age of 13 months while awaiting liver transplantation because of end stage liver disease with sepsis. Case 3: A 7 day old girl was seen for antenatal findings of hepatic cyst. She had normal birth weight. She was well apart from mild jaundice. Stools and urine colour were normal. Systemic examination was normal apart from mild jaundice. Her blood investigations are shown in Table 1. Abdominal US showed a well defined cystic lesion in the right lobe with two branching out pouchings with normal gallbladder consistent with the unilobar type V CC. MRCP was planned but the patient was lost to follow up. Case 4: A 12 month old boy was seen for evaluation of HSM. He had dysmorphic features (frontal bossing, deeply seated eyes, nystagmus, low set ears, small triangular face, short limbs, single palmar crease bilaterally and widely spaced 1st and 2nd toes), developmental delay, severe failure to thrive and hypotonia. His stools were normally coloured with no jaundice. He had HSM with no ascites. His blood investigations are shown in Table 1. His renal function showed elevated urea and creatinine. Abdominal US showed dilatation of intra-hepatic biliary tracts and enlarged coarse liver. Gallbladder was normal. He had bilateral renal cysts
91
S. Al-Sinani et al. / Arab Journal of Gastroenterology 13 (2012) 89–92 Table 1 Patients’ demographics, blood investigations, CCs types, management and outcome. Item (reference range)
Case-1
Case-2
Case-3
Case-4
Case-5
Case-6
Gender Age Dysmorphism or anomalies
Female 12 years No
Male 4 months No
Female 7 days No
Male 7 days Left PUJ obstruction Left polydactyl
Female 14 years No
AST IU/L (0–32) ALT U/L (0–31) ALP U/L (<281) GGT U/L (<203) T bili (0–17)/D bili (0–4) lmol/L INR (0.8–1.11) PT seconds (9–12.8) Albumin g/L (38–54) CCs type Intervention
N 192 N 60 N
127 748 421 393 367/113
44 364 390 178 N
Male 12 months Facial dysmorphism Bilateral renal cysts DD 52 N 302 170 N
N N N 749 N
110 100 530 NA 220/200
N N N Type I HJ
1.17 14.5 N Type II Liver transplantation advised
Well
Chronic liver disease cirrhosis passed away at age of 13 months
N N N Type IV A Close follow up symptomatic management Chronic renal failure normal liver function
N N N Type IV A Close follow up symptomatic management Normal liver function well
1.44 16 32 Type IV A HJ
Outcome
N N 33 Type V Lost to follow up Lost to follow up
Post operative HJ leak
Abbreviations: DD, developmental delay; PUJ, pelviureteric junction; AST, asparate aminotransferase; IU/L, international units/liter; ALT, alanine aminotransferase; U/L, units/ liter; ALP, alkaline phosphatase; GGT, gammaglutamyl transferase; N, normal; NA, not available; T bili, total bilirubin; D bili, direct bilirubin; lmol/L: micromol/L; PT, prothrombin time; g/L, gram/liter; CCs, choledochal cysts; HJ, hepaticojejunostomy.
with chronic renal failure. MRCP showed dilated left and right intrahepatic duct, and dilated CBD consistent with type IV A CC. He was managed symptomatically with plans to initiate dialysis. Case 5: A 7 day old boy with antenatal diagnosis of left pelviureteric junction obstruction was referred for evaluation of the incidental findings of liver cysts on postnatal abdominal US. He was otherwise well, not jaundiced, and had normal stool and urine colour. Examination revealed left hand polydactyly. There was no HSM. His blood investigations are shown in Table 1. Abdominal US showed dilated bilobar intrahepatic bile ducts. Gallbladder was normal. MRCP showed gross dilatation of the left and right main hepatic ducts with mildly dilated common hepatic duct consistent with type IV A CC. Patient was being managed conservatively with close follow up. Case 6: A 14 year old girl presented with long standing history of jaundice and abdominal pain with worsening of symptoms few months prior to the presentation. On examination, she was small for age, afebrile, and jaundiced. She had tender right upper abdominal quadrant with palpable mass. Her blood investigations are shown in Table 1. US showed a large choledochal cyst. ERCP showed fusiform cystic dilatation of the intra and extrahepatic biliary ducts with normal GB and pancreatic divisum suggestive of CC type IV A with pancreatic divisum. Discussion Not much is described about the prevalence, types and presentation of CCs in the Arab, Middle Eastern and African children. One of the earliest studies is by Ogunbiyi et al. [24]. He described two cases of CCs in female Saudi paediatric patients seen over a period of 5 years. Both presented with recurrent abdominal pain with no palpable abdominal mass or jaundice. Both patients had type I CC and the presence of stones in the cyst in one patient. Intraoperative cholangiography demonstrated anomalous junction of the pancreatic duct with CBD. Both patients underwent cyst excision. In 2001, Saeed and Amin [25] undertook a retrospective study of 8 patients (seven females, one male; aged between 2 days and 7 years) in Bahrain during a seven-year study period. Patients presented with abdominal pain, abdominal mass, fever, vomiting, and jaundice. Antenatal US was unable to identify the cysts in any of these patients. Postnatal US and MRCP diagnosed the condition. Types
of CCs in this group of patients were not clear from the available abstract. In 2004, Naga and Suleiman [26], from Egypt conducted a retrospective analysis of 13 patients with CCs seen between 1987 and 1998. Two out of 13 patients were children (both girls aged 6 and 12 years). The first child presented with recurrent cholangitis and the other presented with variceal bleeding. Both children had bilobar type V CCs. At least one of them was managed with a biliary stent and followed for 4 years with a good outcome during the follow up period. The management and outcome of the other child was not clear from the study. In 2005, Akinyinka et al. [27] reported 3 cases of CCs over an 18 year period in Nigeria. All were females aged between less than a month and 13 months. All presented with abdominal swelling with or without jaundice or acholic stools. All patients were diagnosed with US antenatally and postnatally. Two of the patients were operated and both made full recovery. The third patient died secondary to end stage liver disease. Once again, it is not clear from the abstract what were the CCs types in this abstract. Over a period of 2 years (January 2009–2011), we diagnosed six children with CCs ranging between the age of 7 days to 14 years. The presentation was variable as demonstrated in each case description. We diagnosed a relatively higher number of cases over a short period in one centre compared to the reported studies from Arabic, Middle Eastern and African populations. The types of CCs in Omani children seem to be of the uncommon type when compared to the literature. Three of 6 children had type IV A (50%), one had type I (16.7%), one had type II (16.7%) and one had unilobar type V CC (16.7%). This clearly demonstrates the differences in CCs type distribution in Omani children with type IV A being the most common type and less of type I, which is the commonest type worldwide. Two of the three patients with type IV A CC had some dysmorphic features and renal disease, which could be possibly related to the coexistence of a genetic disorder. Female to male preponderance described in the literature is not seen in our case series. Fifty percent of our patients were boys. To our best knowledge, this is the first case series report of CCs in Oman. Although the number of patients does not allow us to draw a definitive conclusion, it shows a relatively higher number of cases over a short period in one centre compared to the reported studies from Arabic, Middle Eastern and African populations. It also demonstrates the unusual types of CCs and gender distribution in
92
S. Al-Sinani et al. / Arab Journal of Gastroenterology 13 (2012) 89–92
Omani children compared to the literature. This could be possibly related to the coexistence of a genetic disorder illustrated by the presence of dysmorphism and renal disease in two out of three patients with type IV A CC. Type IV A seen in 3 out of 6 patients (50%) compared to other CC types, increases the challenges of treating such patients with diffuse disease and increases the demands for liver transplantation as a therapeutic intervention in such cases. Drawback of this study is the small number of patients and short duration of the study. We suggest larger studies to be undertaken in order to come up with incidence in this population. The aetiology, possible genetic associations, incidence and outcome of CCs in Omani children will need to be studied further in a larger scale. Conflicts of interest The authors declared that there was no conflict of interest. Ethical approval As per College of Medicine, SQU ethical approval committee. Available upon request. References [1] Howard ER. Choledochal cysts. In: Howard ER, editor. Surgery of liver disease in children. Oxford: Butterworth-Heinemann; 1991. p. 78–90. [2] Gigot JF, Nagorney DM, Farnell MB, Moir C, Ilstrup D. Bile duct cysts: a changing spectrum of presentation. J Hepatobiliary Pancreat Surg 1996;3: 405–11. [3] O’Neill Jr JA. Choledochal cyst. Curr Probl Surg 1992;29:361–410. [4] Singham J, Yoshida EM, Scudamore CH. Choledochal cysts: part 1 of 3: classification and pathogenesis. Can J Surg 2009;52(5):434–40. [5] Todani T, Watanabe Y, Narusue M, Tabuchi K, Okajima K. Congenital bile duct cysts: classification, operative procedures, and review of thirty-seven cases including cancer arising from choledochal cyst. Am J Surg 1977;134(2):263–9. [6] Cheng SP, Yang TL, Jeng KS, Liu CL, Lee JJ, Liu TP. Choledochal cyst in adults: aetiological considerations to intrahepatic involvement. ANZ J Surg 2004; 74(11):964–7. [7] Babbitt DP. Congenital choledochal cysts: new etiological concept based on anomalous relationships of the common bile duct and pancreatic bulb. Ann Radiol (Paris) 1969;12(3):231–40. [8] Davenport M, Basu R. Under pressure: choledochal malformation manometry. J Pediatr Surg 2005;40(2):331–5.
[9] Ohkawa H, Sawaguchi S, Yamazaki Y, Ishikawa A, Kikuchi M. Experimental analysis of the ill effect of anomalous pancreaticobiliary ductal union. J Pediatr Surg 1982;17(1):7–13. [10] Todani T, Watanabe Y, Toki A, Morotomi Y. Classification of congenital biliary cystic disease: special reference to type Ic and IVA cysts with primary ductal stricture. J Hepatobiliary Pancreat Surg 2003;10(5):340–4. [11] Craig AG, Chen LD, Saccone GT, Chen J, Padbury RT, Toouli J. Sphincter of Oddi dysfunction associated with choledochal cyst. J Gastroenterol Hepatol 2001;16(2):230–4. [12] Mesleh Marc, Deziel Daniel J. Bile duct cysts. Surg Clin N Am 2008;88: 1369–84. [13] de Vries JS, de Vries S, Aronson DC, Bosman DK, Rauws EA, Bosman A, et al. Choledochal cysts: age of presentation, symptoms, and late complications related to Todani’s classification. J Pediatr Surg 2002;37(11):1568–73. [14] Hung MH, Lin LH, Chen DF, Huang CS. Choledochal cysts in infants and children: experiences over a 20-year period at a single institution. Eur J Pediatr 2011;170(9):1179–85. [15] Sato M, Ishida H, Konno K, Naganuma H, Ishida J, Hirata M, et al. Choledochal cyst due to anomalous pancreatobiliary junction in the adult: sonographic findings. Abdom Imaging 2001;26(4):395–400. [16] Soreide K, Korner H, Havnen J, Soreide JA. Bile duct cysts in adults. Br J Surg 2004;91(12):1538–48. [17] Liu CL, Fan ST, Lo CM, Lam CM, Poon RT, Wong J. Choledochal cysts in adults. Arch Surg 2002;137(4):465–8. [18] Voyles CR, Smadja C, Shands WC, Blumgart LH. Carcinoma in choledochal cycts. Age-related incidence. Arch Surg 1983;118(8):986–8. [19] Rossi RL, Silverman ML, Braasch JW, Munson JL, ReMine SG. Carcinomas arising in cystic conditions of the bile ducts. A clinical and pathologic study. Ann Surg 1987;2005(4):377–84. [20] Houben CH, Chiu PW, Lau J, Lee KH, Ng EK, Tam YH, et al. Preoperative endoscopic retrograde cholangiopancreatographic treatment of complicated choledochal cysts in children: a retrospective case series. Endocscopy 2007; 39(9):836–9. [21] Diao M, Li L, Cheng W. Laparoscopic versus Open Roux-en-Y hepatojejunostomy for children with choledochal cysts: intermediate-term follow-up results. Surg Endosc 2011;25(5):1567–73. [22] Dawrant MJ, Najmaldin AS, Alizai NK. Robot-assisted resection of choledochal cysts and hepaticojejunostomy in children less than 10 kg. J Pediatr Surg 2010; 45(12):2364–8. [23] Miyano T, Yamataka A, Kato Y, Segawa O, Lane G, Takamizawa S, et al. Hepaticoenterostomy after excision of choledochal cyst in children: a 30-year experience with 180 cases. J Pediatr Surg 1996;31(10):1417–21. [24] Ogunbiyi OA, Benjamin B, Patil KK. Choledochal cyst: a report of two cases. Afr J Med Med Sci 1994;23(4):391–5. [25] Saeed AMS, Amin AAM. Initial experience of surgical management of choledochal cysts in Bahrain (abstract). J Bahrain Med Soc 2001;13(1):28–33. [26] Naga MI, Suleiman DN. Endoscopic management of choledochal cyst. Gastrointest Endosc 2004;59(3):427–32. [27] Akinyinka OO, Falade AG, Akinbami FO, Alli T, Atalabi M, Irabor D, et al. Choledochal cysts in African infants: a report of 3 cases and a review of the literature (abstract). Trop Gastroenterol 2005;26(1):34–6.
Contents lists available at SciVerse ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Gastroenterology in Arab Countries
Choledochal cysts in Omani children: A case series Siham Al-Sinani a,⇑, Khalid Al Naamani b, Wafa Lutfi a, Aisha Al Hajri a a b
Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman Department of Internal Medicine, Armed Forces Hospital, Muscat, Oman
a r t i c l e
i n f o
Article history: Received 26 June 2011 Accepted 8 March 2012
a b s t r a c t Background and study aims: Choledochal cysts (CCs) are rare congenital anomalies of the biliary tract with a low incidence in the western countries and a higher incidence in the eastern part of the world. CCs have female to male preponderance. CCs type distribution is known in certain parts of the world but very little is published about the common types of CCs and gender distribution in the Arab countries. We aim to describe the CC types and gender distribution in Omani children in one centre. Patients and methods: A retrospective review of all children diagnosed to have choledochal cysts over a 2 year period at a tertiary hospital in Oman. Results: We diagnosed six children with CCs. The type distribution of CCs and gender preponderance in Omani children are not similar to what is described internationally. Type IV A was the most common type (50%) and less of type I (16.7%), unlike worldwide distribution. Female to male preponderance described in the literature is not seen in our case series. Fifty percent of our patients were boys. In this case series, we compare our results to the described case reports of CCs from Arab countries and Africa and bring up the difference. Conclusions: We demonstrate the unusual types of CCs and gender distribution in Omani children compared to the literature. To our best knowledge, this is the first case series of CCs in Omani children and the largest reported study in the literature in the Arab countries so far. Ó 2012 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Choledochal cysts (CCs) are rare congenital anomalies of the biliary tract. Incidence of CCs is 1 in 15,000 in Western countries [1,2] and 1 in 1000 in Japan [3]. There is female:male preponderance, commonly reported as 4:1 or 3:1 [3]. Distribution of different types of CCs is: type I is 50–80%, type II is 2%, type III is 1.4–4.5%, type IV is 15–35% and type V is 20% [4]. Aetiology, pathophysiology, natural course and optimal treatment of CCs still remain under debate [4]. Todani and coworkers expanded and modified the classification system in 1977 [5]. Fig. 1 shows the different types of CCs. There are many theories proposed to clarify the aetiology of CCs. They are purely congenital in some references [6]. Others suggest that abnormal pancreaticobiliary duct junction (APBDJ) causes CCs [7]. Davenport et al. observed that the neonatal CCs had fewer neurons and ganglions causing distal obstruction similar to Hirschsprung disease [8]. Ohkawa et al. discovered that an increased neonatal tendency for round dilation is due to APBDJ [9]. Others suggest that all adult cysts are acquired due to distal obstruction with long narrow stenosis leading to round lesions and short and wide stenosis leading to fusiform lesions [10,11]. The classic triad ⇑ Corresponding author. Address: Pediatric Gastroenterology and Hepatology, Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman. E-mail address: [email protected] (S. Al-Sinani).
of abdominal pain, jaundice and right upper abdominal mass described in most adult patients occurs in only 5–10% of paediatric patients [12,13]. In paediatric studies, most children with CCs presented with abdominal pain (76–91%) followed by jaundice (27– 57%). A retrospective study by Hung et al., described a difference in presentation between infants (<1 year of age) with CC compared to older children (1–18 years of age) with CC. In this study, older children presented with abdominal pain (82%) when compared to the infant age group (0%), whereas all infants presented with jaundice and pale stools (100%) when compared to the older children group (35%) [14]. Presentation with cholangitis or pancreatitis was less reported [13]. CCs in newborns and infants should be differentiated from biliary atresia (BA) with cystic dilatation. Jaundice with acholic stools and a small cyst size (<8 mm in diameter) in this age group suggest the possibility of a BA with cystic dilatation [14]. Determination of biliary amylase, which is normal in CCs, may help in this differentiation [14]. Diagnosis of CCs is based on the hepatobiliary imaging. CCs are mostly detected by abdominal ultrasound (US) or CT scan with US sensitivity ranging from 70% to 97% [12,15]. Magnetic resonance cholangiopancreatography (MRCP) is the best method for noninvasive imaging of CCs [16]. Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) provide a more accurate anatomy. CCs can cause morbidity and mortality from recurrent cholangitis, pancreatitis, sepsis, liver abscesses, and
1687-1979/$ - see front matter Ó 2012 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajg.2012.03.005
90
S. Al-Sinani et al. / Arab Journal of Gastroenterology 13 (2012) 89–92
Fig. 1. Choledochal cysts classification. (A) Type-I A cystic dilation of the extrahepatic duct. (B) Type-I B focal segmental dilation of the extrahepatic duct. (C) Type-I C fusiform dilation of the entire extrahepatic bile duct. (D) Type-II simple diverticula of the common bile duct. (E) Type-III cyst/choledochocele distal intramural dilation of the common bile duct within the duodenal wall. (F) Type-IV A combined intrahepatic and extrahepatic duct dilation. (G) Type-IV B multiple extrahepatic bile duct dilations. (H) Type-V/ Caroli disease multiple intrahepatic bile duct dilation.
cholangiocarcinoma if left untreated [14]. Treatment involves the management of complications, definitive surgical treatment, and long-term follow-up. CCs are premalignant lesions. The estimated frequency of hepatobiliary malignancy in adult patients with CCs is 10–30% [17]. Most patients with cholangiocarcinoma are adults as the risk increases with age [18]. Hepatobiliary malignancy is described in children with CCs [19]. It is described in all types of CCs but most commonly with type I and type IV cysts. Most malignancies occur in the cystic lesions, but are reported in the noncystic part after cyst excision [15]. Periodic screening for cholangiocarcinoma is recommended. Cholangiocarcinoma carries a poor prognosis with 2-year survival of less than 5% [19]. ERCP based intervention in children with CCs complicated by pancreatitis, cholangitis and obstructive jaundice was reported to be successful till definitive surgery was performed [20]. Treatment of CCs is surgical excision with cholecystectomy and Roux-en-Y hepaticojejunostomy (HJ) when possible. Recently, a large retrospective study showed that the laparoscopic Roux-en-Y HJ is safe and effective for CCs in children with comparable or even superior intermediate-term results to those of open HJ [21]. Lately, robotic surgical resection of CCs with HJ has been reported to be safe and effective in children [22]. With the involvement of intrahepatic and extrahepatic sites, complete excision may not be feasible. The outcome of cyst excision and HJ in children is good [23,14]. Hepatic transplantation is the definitive therapy for those who have diffuse disease, hepatic cirrhosis, or malignancy.
Case reports Case 1: A 12 year old girl presented with right upper quadrant abdominal pain, fever and vomiting of few days duration. On examination, she was febrile and not jaundiced. She had tender right upper abdominal quadrant. There was no hepatosplenomegaly (HSM). Her blood investigations are shown in Table 1. Abdominal US showed a cystic lesion with intraluminal echogenic foci.
MRCP showed focal cystic dilatation of the common bile duct (CC type I). Patient was treated with antibiotics and underwent cyst excision and HJ. Histology ruled out cholangiocarcinoma. Patient is well on follow up visits. Case 2: A 4 month old boy presented with a history of jaundice since the age of 40 days. He had a history of poor feeding, pale stools and dark urine. On examination, the child was jaundiced and small for age with no dysmorphic features. Abdomen was soft and not distended with firm HSM. His blood investigations are shown in Table 1. Abdominal US showed a cyst at porta hepatis with no intrahepatic bile duct dilatation. Gallbladder was contracted. MRCP was suggestive of type II CC. Liver biopsy showed features compatible with extrahepatic biliary obstruction, signs of acute cholangitis and cirrhosis. Patient was diagnosed to have biliary atresia with type II CC and liver cirrhosis and managed accordingly. Liver transplantation was advised. Patient passed away at another hospital at the age of 13 months while awaiting liver transplantation because of end stage liver disease with sepsis. Case 3: A 7 day old girl was seen for antenatal findings of hepatic cyst. She had normal birth weight. She was well apart from mild jaundice. Stools and urine colour were normal. Systemic examination was normal apart from mild jaundice. Her blood investigations are shown in Table 1. Abdominal US showed a well defined cystic lesion in the right lobe with two branching out pouchings with normal gallbladder consistent with the unilobar type V CC. MRCP was planned but the patient was lost to follow up. Case 4: A 12 month old boy was seen for evaluation of HSM. He had dysmorphic features (frontal bossing, deeply seated eyes, nystagmus, low set ears, small triangular face, short limbs, single palmar crease bilaterally and widely spaced 1st and 2nd toes), developmental delay, severe failure to thrive and hypotonia. His stools were normally coloured with no jaundice. He had HSM with no ascites. His blood investigations are shown in Table 1. His renal function showed elevated urea and creatinine. Abdominal US showed dilatation of intra-hepatic biliary tracts and enlarged coarse liver. Gallbladder was normal. He had bilateral renal cysts
91
S. Al-Sinani et al. / Arab Journal of Gastroenterology 13 (2012) 89–92 Table 1 Patients’ demographics, blood investigations, CCs types, management and outcome. Item (reference range)
Case-1
Case-2
Case-3
Case-4
Case-5
Case-6
Gender Age Dysmorphism or anomalies
Female 12 years No
Male 4 months No
Female 7 days No
Male 7 days Left PUJ obstruction Left polydactyl
Female 14 years No
AST IU/L (0–32) ALT U/L (0–31) ALP U/L (<281) GGT U/L (<203) T bili (0–17)/D bili (0–4) lmol/L INR (0.8–1.11) PT seconds (9–12.8) Albumin g/L (38–54) CCs type Intervention
N 192 N 60 N
127 748 421 393 367/113
44 364 390 178 N
Male 12 months Facial dysmorphism Bilateral renal cysts DD 52 N 302 170 N
N N N 749 N
110 100 530 NA 220/200
N N N Type I HJ
1.17 14.5 N Type II Liver transplantation advised
Well
Chronic liver disease cirrhosis passed away at age of 13 months
N N N Type IV A Close follow up symptomatic management Chronic renal failure normal liver function
N N N Type IV A Close follow up symptomatic management Normal liver function well
1.44 16 32 Type IV A HJ
Outcome
N N 33 Type V Lost to follow up Lost to follow up
Post operative HJ leak
Abbreviations: DD, developmental delay; PUJ, pelviureteric junction; AST, asparate aminotransferase; IU/L, international units/liter; ALT, alanine aminotransferase; U/L, units/ liter; ALP, alkaline phosphatase; GGT, gammaglutamyl transferase; N, normal; NA, not available; T bili, total bilirubin; D bili, direct bilirubin; lmol/L: micromol/L; PT, prothrombin time; g/L, gram/liter; CCs, choledochal cysts; HJ, hepaticojejunostomy.
with chronic renal failure. MRCP showed dilated left and right intrahepatic duct, and dilated CBD consistent with type IV A CC. He was managed symptomatically with plans to initiate dialysis. Case 5: A 7 day old boy with antenatal diagnosis of left pelviureteric junction obstruction was referred for evaluation of the incidental findings of liver cysts on postnatal abdominal US. He was otherwise well, not jaundiced, and had normal stool and urine colour. Examination revealed left hand polydactyly. There was no HSM. His blood investigations are shown in Table 1. Abdominal US showed dilated bilobar intrahepatic bile ducts. Gallbladder was normal. MRCP showed gross dilatation of the left and right main hepatic ducts with mildly dilated common hepatic duct consistent with type IV A CC. Patient was being managed conservatively with close follow up. Case 6: A 14 year old girl presented with long standing history of jaundice and abdominal pain with worsening of symptoms few months prior to the presentation. On examination, she was small for age, afebrile, and jaundiced. She had tender right upper abdominal quadrant with palpable mass. Her blood investigations are shown in Table 1. US showed a large choledochal cyst. ERCP showed fusiform cystic dilatation of the intra and extrahepatic biliary ducts with normal GB and pancreatic divisum suggestive of CC type IV A with pancreatic divisum. Discussion Not much is described about the prevalence, types and presentation of CCs in the Arab, Middle Eastern and African children. One of the earliest studies is by Ogunbiyi et al. [24]. He described two cases of CCs in female Saudi paediatric patients seen over a period of 5 years. Both presented with recurrent abdominal pain with no palpable abdominal mass or jaundice. Both patients had type I CC and the presence of stones in the cyst in one patient. Intraoperative cholangiography demonstrated anomalous junction of the pancreatic duct with CBD. Both patients underwent cyst excision. In 2001, Saeed and Amin [25] undertook a retrospective study of 8 patients (seven females, one male; aged between 2 days and 7 years) in Bahrain during a seven-year study period. Patients presented with abdominal pain, abdominal mass, fever, vomiting, and jaundice. Antenatal US was unable to identify the cysts in any of these patients. Postnatal US and MRCP diagnosed the condition. Types
of CCs in this group of patients were not clear from the available abstract. In 2004, Naga and Suleiman [26], from Egypt conducted a retrospective analysis of 13 patients with CCs seen between 1987 and 1998. Two out of 13 patients were children (both girls aged 6 and 12 years). The first child presented with recurrent cholangitis and the other presented with variceal bleeding. Both children had bilobar type V CCs. At least one of them was managed with a biliary stent and followed for 4 years with a good outcome during the follow up period. The management and outcome of the other child was not clear from the study. In 2005, Akinyinka et al. [27] reported 3 cases of CCs over an 18 year period in Nigeria. All were females aged between less than a month and 13 months. All presented with abdominal swelling with or without jaundice or acholic stools. All patients were diagnosed with US antenatally and postnatally. Two of the patients were operated and both made full recovery. The third patient died secondary to end stage liver disease. Once again, it is not clear from the abstract what were the CCs types in this abstract. Over a period of 2 years (January 2009–2011), we diagnosed six children with CCs ranging between the age of 7 days to 14 years. The presentation was variable as demonstrated in each case description. We diagnosed a relatively higher number of cases over a short period in one centre compared to the reported studies from Arabic, Middle Eastern and African populations. The types of CCs in Omani children seem to be of the uncommon type when compared to the literature. Three of 6 children had type IV A (50%), one had type I (16.7%), one had type II (16.7%) and one had unilobar type V CC (16.7%). This clearly demonstrates the differences in CCs type distribution in Omani children with type IV A being the most common type and less of type I, which is the commonest type worldwide. Two of the three patients with type IV A CC had some dysmorphic features and renal disease, which could be possibly related to the coexistence of a genetic disorder. Female to male preponderance described in the literature is not seen in our case series. Fifty percent of our patients were boys. To our best knowledge, this is the first case series report of CCs in Oman. Although the number of patients does not allow us to draw a definitive conclusion, it shows a relatively higher number of cases over a short period in one centre compared to the reported studies from Arabic, Middle Eastern and African populations. It also demonstrates the unusual types of CCs and gender distribution in
92
S. Al-Sinani et al. / Arab Journal of Gastroenterology 13 (2012) 89–92
Omani children compared to the literature. This could be possibly related to the coexistence of a genetic disorder illustrated by the presence of dysmorphism and renal disease in two out of three patients with type IV A CC. Type IV A seen in 3 out of 6 patients (50%) compared to other CC types, increases the challenges of treating such patients with diffuse disease and increases the demands for liver transplantation as a therapeutic intervention in such cases. Drawback of this study is the small number of patients and short duration of the study. We suggest larger studies to be undertaken in order to come up with incidence in this population. The aetiology, possible genetic associations, incidence and outcome of CCs in Omani children will need to be studied further in a larger scale. Conflicts of interest The authors declared that there was no conflict of interest. Ethical approval As per College of Medicine, SQU ethical approval committee. Available upon request. References [1] Howard ER. Choledochal cysts. In: Howard ER, editor. Surgery of liver disease in children. Oxford: Butterworth-Heinemann; 1991. p. 78–90. [2] Gigot JF, Nagorney DM, Farnell MB, Moir C, Ilstrup D. Bile duct cysts: a changing spectrum of presentation. J Hepatobiliary Pancreat Surg 1996;3: 405–11. [3] O’Neill Jr JA. Choledochal cyst. Curr Probl Surg 1992;29:361–410. [4] Singham J, Yoshida EM, Scudamore CH. Choledochal cysts: part 1 of 3: classification and pathogenesis. Can J Surg 2009;52(5):434–40. [5] Todani T, Watanabe Y, Narusue M, Tabuchi K, Okajima K. Congenital bile duct cysts: classification, operative procedures, and review of thirty-seven cases including cancer arising from choledochal cyst. Am J Surg 1977;134(2):263–9. [6] Cheng SP, Yang TL, Jeng KS, Liu CL, Lee JJ, Liu TP. Choledochal cyst in adults: aetiological considerations to intrahepatic involvement. ANZ J Surg 2004; 74(11):964–7. [7] Babbitt DP. Congenital choledochal cysts: new etiological concept based on anomalous relationships of the common bile duct and pancreatic bulb. Ann Radiol (Paris) 1969;12(3):231–40. [8] Davenport M, Basu R. Under pressure: choledochal malformation manometry. J Pediatr Surg 2005;40(2):331–5.
[9] Ohkawa H, Sawaguchi S, Yamazaki Y, Ishikawa A, Kikuchi M. Experimental analysis of the ill effect of anomalous pancreaticobiliary ductal union. J Pediatr Surg 1982;17(1):7–13. [10] Todani T, Watanabe Y, Toki A, Morotomi Y. Classification of congenital biliary cystic disease: special reference to type Ic and IVA cysts with primary ductal stricture. J Hepatobiliary Pancreat Surg 2003;10(5):340–4. [11] Craig AG, Chen LD, Saccone GT, Chen J, Padbury RT, Toouli J. Sphincter of Oddi dysfunction associated with choledochal cyst. J Gastroenterol Hepatol 2001;16(2):230–4. [12] Mesleh Marc, Deziel Daniel J. Bile duct cysts. Surg Clin N Am 2008;88: 1369–84. [13] de Vries JS, de Vries S, Aronson DC, Bosman DK, Rauws EA, Bosman A, et al. Choledochal cysts: age of presentation, symptoms, and late complications related to Todani’s classification. J Pediatr Surg 2002;37(11):1568–73. [14] Hung MH, Lin LH, Chen DF, Huang CS. Choledochal cysts in infants and children: experiences over a 20-year period at a single institution. Eur J Pediatr 2011;170(9):1179–85. [15] Sato M, Ishida H, Konno K, Naganuma H, Ishida J, Hirata M, et al. Choledochal cyst due to anomalous pancreatobiliary junction in the adult: sonographic findings. Abdom Imaging 2001;26(4):395–400. [16] Soreide K, Korner H, Havnen J, Soreide JA. Bile duct cysts in adults. Br J Surg 2004;91(12):1538–48. [17] Liu CL, Fan ST, Lo CM, Lam CM, Poon RT, Wong J. Choledochal cysts in adults. Arch Surg 2002;137(4):465–8. [18] Voyles CR, Smadja C, Shands WC, Blumgart LH. Carcinoma in choledochal cycts. Age-related incidence. Arch Surg 1983;118(8):986–8. [19] Rossi RL, Silverman ML, Braasch JW, Munson JL, ReMine SG. Carcinomas arising in cystic conditions of the bile ducts. A clinical and pathologic study. Ann Surg 1987;2005(4):377–84. [20] Houben CH, Chiu PW, Lau J, Lee KH, Ng EK, Tam YH, et al. Preoperative endoscopic retrograde cholangiopancreatographic treatment of complicated choledochal cysts in children: a retrospective case series. Endocscopy 2007; 39(9):836–9. [21] Diao M, Li L, Cheng W. Laparoscopic versus Open Roux-en-Y hepatojejunostomy for children with choledochal cysts: intermediate-term follow-up results. Surg Endosc 2011;25(5):1567–73. [22] Dawrant MJ, Najmaldin AS, Alizai NK. Robot-assisted resection of choledochal cysts and hepaticojejunostomy in children less than 10 kg. J Pediatr Surg 2010; 45(12):2364–8. [23] Miyano T, Yamataka A, Kato Y, Segawa O, Lane G, Takamizawa S, et al. Hepaticoenterostomy after excision of choledochal cyst in children: a 30-year experience with 180 cases. J Pediatr Surg 1996;31(10):1417–21. [24] Ogunbiyi OA, Benjamin B, Patil KK. Choledochal cyst: a report of two cases. Afr J Med Med Sci 1994;23(4):391–5. [25] Saeed AMS, Amin AAM. Initial experience of surgical management of choledochal cysts in Bahrain (abstract). J Bahrain Med Soc 2001;13(1):28–33. [26] Naga MI, Suleiman DN. Endoscopic management of choledochal cyst. Gastrointest Endosc 2004;59(3):427–32. [27] Akinyinka OO, Falade AG, Akinbami FO, Alli T, Atalabi M, Irabor D, et al. Choledochal cysts in African infants: a report of 3 cases and a review of the literature (abstract). Trop Gastroenterol 2005;26(1):34–6.