Published online February 1, 2006
PEDIATRICS
Vol. 117
No. 3
March 2006, pp.
e596-e600
(doi:10.1542/10.1542/peds.2005-1411)
Prenatal Diagnosis of Familial Type I Choledochal Cyst
Matthew S. Clifton, MDa,
Ruth B. Goldstein, MDb,
Anne Slavotinek, PhDd,
Mary E. Norton, MDc,
Hanmin Lee, MDa,
Jody Farrell, RN, MSNa and
Kerilyn K. Nobuhara, MDa
a Surgery
b Radiology
c Obstetrics/Gynecology
d Pediatrics, University of California, San Francisco, California
 |
ABSTRACT
|
|---|
Familial choledochal cysts are extremely rare. High-resolution
ultrasound now allows for the antenatal diagnosis of these anomalies.
After delivery, elective surgical resection should be planned;
however, increases in size, deterioration of liver function,
and ascending cholangitis frequently force early intervention.
We report an unusual occurrence of siblings with type I choledochal
cysts and review the existing literature on cause, genetics,
classification, diagnosis, and management of this disease.
Key Words: congenital abnormalities • liver disease • prenatal diagnosis
Abbreviations: PBM, pancreaticobiliary maljunction • PKD, polycystic kidney disease
Familial choledochal cysts are extremely rare. High-resolution ultrasound now allows for the antenatal diagnosis of these anomalies. After delivery, elective surgical resection should be planned; however, increases in size, deterioration of liver function, and ascending cholangitis frequently force early intervention. We report an unusual occurrence of siblings with type I choledochal cysts and review the existing literature on cause, genetics, classification, diagnosis, and management of this disease.
|
CASE REPORTS
|
|---|
A 28-year-old gravida 5 para 3–4 aborta 1 woman was referred
to our institution for prenatal evaluation of a fetal abdominal
mass that initially was detected on a 24-week sonogram at another
hospital. On our detailed obstetric 31-week sonogram, the mass
measured 2.6
x 2.1 cm on an axial image of the abdomen and was
located to the right of midline (Fig
1A). A small gallbladder
with irregular margins was also identified (Fig
1B), and the
stomach and the duodenum seemed normal. Of note, the mother
had 1 previous child who received a diagnosis at 8 years of
age of a choledochal cyst, raising the clinical suspicion of
a similar entity in this fetus (see "Family History"). The case
was discussed at length with the Fetal Treatment Center team;
given the size of the cyst and family history, the decision
was made for monthly sonographic surveillance and postnatal
intervention as appropriate. Follow-up sonogram at 36 weeks
demonstrated a slight increase in size at 3.2
x 1.9 cm but no
overall change in appearance of the cystic mass. The female
infant was born at 38 weeks' gestation, weighing 4125 g, via
spontaneous vaginal delivery. The infant tolerated ad libitum
feedings and passed normal stools. A postnatal abdominal sonogram
revealed a normal liver and contracted gallbladder (Fig
2A)
with an enlarged, bilobed structure in the position of the common
bile duct (Fig
2B), which communicated with the gallbladder
via the cystic duct (Fig
2C). The intrahepatic ducts were normal.
These findings were consistent with the diagnosis of choledochal
cyst, and the absence of intrahepatic ductal dilation excluded
Caroli's disease. Serial evaluation revealed initial total and
direct bilirubin levels of 7.7 and 2.2 mg/dL on day-of-life
1 and increased steadily to 11.8 and 4.3 mg/dL, respectively,
by the third day of life (reference range: 0.3–1.3 and
0.1–0.3 mg/dL, respectively). Aspartate aminotransferase
was slightly elevated on the third day of life at 57 U/L (reference
range: 16–41 U/L), whereas alanine aminotransferase was
normal at 24 U/L (reference range: 11–59 U/L).
-Glutamyl
transferase was elevated at 173 U/L (reference range: 5–39
U/L). Of note, the family history is significant for a 10-year-old
sibling who underwent resection of a type I choledochal cyst
at 8 years of age (case report 2). On physical examination,
the right upper quadrant was firm but nontender and was otherwise
unremarkable.
View larger version (112K):
[in this window]
[in a new window]
|
FIGURE 1 A, Level II antenatal ultrasound of case report 1. Transverse image demonstrating cystic structure (*) located posteriorly in subhepatic space, adjacent to inferior vena cava (arrow). B, Transverse image showing small gallbladder with irregular wall thickening (arrow).
|
|
View larger version (84K):
[in this window]
[in a new window]
|
FIGURE 2 A, Abdominal ultrasound of case report 1. Transverse cross-sectional view demonstrating decompressed gallbladder (GB) with irregular wall thickening and no intrahepatic biliary ductal dilation. CC, choledochal cyst. B, Transverse cross-sectional view caudal to A demonstrating CC. C, Transverse cross-sectional view demonstrating junction of cystic duct (CD) with choledochal cyst (CC).
|
|
The infant was taken to the operating room on the sixth day
of life because of worsening liver function tests. At laparotomy,
an intraoperative cholangiogram was performed revealing a Todani
type I choledochal cyst (Fig
3). Resection of the choledochal
cyst and cholecystectomy were performed, followed by roux-en-Y
hepaticojejunostomy. Postoperatively, the serum direct bilirubin
continued a steady decline to 2.7 mg/dL on the day of discharge
(postoperative day 8). Pathology was consistent with choledochal
cyst. At the 6-month follow-up, the infant is healthy with normal
expected growth and complete resolution of the hyperbilirubinemia.
View larger version (90K):
[in this window]
[in a new window]
|
FIGURE 3 Intraoperative cholangiogram. Contrast fills the fusiform, bilobed CC and refluxes up into the common hepatic duct (CHD). The CD is also visible (arrow).
|
|
|
FAMILY HISTORY
|
|---|
Two years before the presentation of our patient, her 8-year-old
brother presented to a community hospital with a 1-day history
of epigastric abdominal pain, nausea, and vomiting. He experienced
1 similar episode 2 weeks earlier, which was self-limited. Evaluation
revealed an elevated serum amylase and lipase. Work-up included
an abdominal sonogram, which revealed a cyst extending from
the common bile duct to the common hepatic duct and a normal-appearing
gallbladder. Computed tomography scan of the abdomen revealed
a 4.5-
x 6.5-cm cyst extending from the porta hepatis to the
head of the pancreas, in communication with the common hepatic
duct. He was treated with bowel rest for 24 hours, with resolution
of the abdominal pain, and subsequently was transferred to our
institution. On examination, there was no evidence of scleral
icterus or jaundice and no palpable abdominal mass. Laboratory
values revealed a bilirubin of 0.9 mg/dL, alkaline phosphatase
of 272 U/L (reference range: 60–321 U/L), and amylase
of 74 U/L (decreased from 237 U/L at the time of initial presentation;
reference range: 23–134 U/L).
The patient was taken to the operating room for a laparoscopic excision of a Todani type I choledochal cyst with roux-en-Y hepaticojejunostomy reconstruction. His postoperative recovery was uneventful, and he was discharged from the hospital on postoperative day 8, tolerating a regular diet with minimal incisional pain. Pathology was consistent with a choledochal cyst and normal gallbladder without evidence of lithiasis.
Our case report patient had 2 unaffected siblings in addition to the brother with a choledochal cyst. Maternal and paternal ethnicity was Mexican, and consanguinity was denied.
|
INCIDENCE
|
|---|
Choledochal cysts are exceedingly rare in the general population,
and reports of familial occurrence are scarce. Choledochal cysts
occur more commonly in female than male individuals (with a
ratio of 3–4:1), and the incidence in Western nations
(Europe and North and South America) is 1 in 100000 to 150000
live births.
1 Although classically considered a disease of infancy,
an increased number of patients are now being discovered in
adulthood.
2 Familial case reports of congenital choledochal
cysts are extremely rare, with only 6 such reports in the literature.
3 Choledochal cysts occur most commonly in patients of Asian descent,
with more than two thirds of the reported cases occurring in
Japanese patients.
3 There is no evidence of increased incidence
in the Hispanic population.
|
CAUSE
|
|---|
The cause of choledochal cysts remains uncertain, although several
theories exist. Pancreaticobiliary maljunction (PBM), a condition
whereby the pancreatic duct joins the common bile duct 1 to
2 cm proximal to the sphincter of Oddi,
4 creates an anomalously
long common channel (>15 mm in length). This anatomic variation
allows pancreatic secretions to reflux into the biliary ductal
system and may lead to increased ductal pressure and subsequent
dilation.
5 Evidence in favor of this theory points to the high
rate of PBM in Japanese patients with choledochal cyst disease.
However, PBM alone cannot explain the predominance in female
individuals or those of Asian ancestry,
1 and the presence of
a long common channel does not guarantee development of a choledochal
cyst. In addition, choledochal cysts occur in the absence of
PBM. Other theories suggest an acquired ductal cause, such as
a web, stricture, or dysfunction at the sphincter of Oddi as
a source of disease.
6 Familial cases point to a possible inherited/genetic
component predisposing to formation of choledochal cysts.
|
CLASSIFICATION
|
|---|
The initial attempt at classification of congenital choledochal
cysts, wherein 3 distinct types were described, was undertaken
by Alonso-Lej et al
7 in 1959. Although the use of the word "cyst"
is a misnomer, it has continued to be used to this day. Later,
in 1977, Todani et al
8 further subdivided the classification
while also adding types IV and V. Most recently, Visser et al
6 proposed abandoning the numbering system in favor of a simplified
nomenclature. The Todani classification system is based solely
on morphologic/gross appearance. In reality, types I and IV
represent a continuum of disease and possess similar risk profiles
for malignant degeneration. Choledochal cyst is a term reserved
for previously described types I and IV cysts, because the intrahepatic
ducts are never entirely normal in this setting. Choledochal
diverticulum describes the previous Todani type II: a diverticulum
of the common bile duct, sometimes resembling a duplicated gall
bladder. Choledochocele is considered a variant of duodenal
duplication, manifested by dilation of the intraduodenal common
bile duct, and is a distinct entity.
Caroli's disease, previously type V choledochal cyst, is an autosomal recessive inherited condition characterized by cystic dilation of intrahepatic bile ducts. It has been linked to various chromosomal abnormalities, including an unbalanced translocation between chromosomes 3 and 8.9 Although possessing some radiologic similarities to choledochal cyst, it is also a distinct entity.6 The individual classification schemes are detailed in Table 1.
|
GENETICS
|
|---|
It remains unclear as to whether a genetic predisposition to
choledochal cysts and Caroli's disease exists. Familial case
reports of congenital choledochal cysts have been described
but are limited to 4 cases of mother-daughter transmission,
1 case of father-daughter transmission, 2 affected sisters,
and 2 affected pairs of brother and sister.
10 In twin studies,
a high incidence of concordance for a phenotypic feature between
monozygous twins can be indicative of a significant genetic
contribution to the cause. Only 1 of 8 pairs of reported monozygous
twins has been concordant for a choledochal cyst,
3,7 and there
is 1 report of a twin pair with Caroli's disease.
11 The evidence
for a genetic contribution to the cause of choledochal cysts
therefore is tempered by a lack of concordance in twin pairs
and few Mendelian pedigrees, making a complex pattern of inheritance
or a multifactorial cause most likely for the majority of families.
No loci have been mapped for choledochal cysts, and there are
no known biochemical or chromosome markers for this anomaly.
Caroli's disease can occur with both autosomal recessive and autosomal dominant polycystic kidney disease (PKD). A mutation in the PKD1 gene has been identified in a family with Caroli's disease and dominant PKD,12 and 2 mutations were reported in the PKHD1 gene in Caroli's disease with recessive PKD.13 Caroli's disease was present in 1 patient who had familial adenomatous polyposis and a deletion of chromosome 5q.14 Finally, clonal chromosomal aberrations of uncertain significance have also been described in a liver biopsy specimen from a patient with Caroli's disease without PKD.9
|
DIAGNOSIS AND MANAGEMENT
|
|---|
The classic triad of jaundice, right upper quadrant pain, and
a palpable abdominal mass is present in <20% of cases. Most
patients present with abdominal pain, fever, and/or nausea and
vomiting. Laboratory values will reflect a picture that is consistent
with mechanical obstruction of the pancreaticobiliary ductal
system, with elevated bilirubin, alkaline phosphatase,
-glutamyl
transferase, and potential elevation of transaminases (aspartate
aminotransferase and alanine aminotransferase) and serum amylase.
1 Within the past 10 years, routine use of high-resolution prenatal
ultrasound has allowed the antenatal diagnosis of subhepatic
cysts, later confirmed to be choledochal cysts.
15 Fewer than
10 familial cases have been described in the literature,
3 and
this represents only the third report of siblings with choledochal
cyst disease.
The optimal timing of intervention for neonates has not yet been established.10 Although it is universally accepted that complete extrahepatic biliary excision including the gallbladder is the treatment of choice, the timing in the neonate is unclear. It has been suggested that progressive intrahepatic ductal dilation, cyst enlargement, and deterioration of liver function are harbingers of obstruction and/or cholangitis, prompting early surgical intervention.15,16 As a temporizing measure, in the setting of nutritional compromise or acute infection, external drainage procedures can be undertaken as a bridge to definitive excision. The best long-term therapy is resection of the cyst with biliary-enteric reconstruction, most commonly a roux-en-Y hepaticojejunostomy.6,16 New developments in minimally invasive surgery have made these lesions amenable to laparoscopic resection and reconstruction.17
Internal drainage procedures without cyst excision, although commonplace in the past, have shown a predilection for malignancy. The reasons for this are not yet entirely clear, but proposed mechanisms include biliary stasis, biliary lithiasis, superinfection, recurrent cholangitis, pancreatitis, and conversion of bile salts to carcinogenic substances by chronic infections.1,15 Types I and IV cysts carry the highest risk of cancer.18 The majority of cancers that are associated with choledochal cysts are cholangiocarcinoma arising within the cyst; however, there are reports of malignant conversion throughout the biliary tree.19,20 Approximately 10% of choledochal cyst malignancies are gallbladder cancers.21 The high rate of malignant conversion has led to the current recommendation of cyst excision before age 30 in any patient who has previously undergone a drainage procedure.6 Development of cancer after excision occurs in <1% of patients, with most of these cases occurring in the setting of incomplete resection.19
|
ACKNOWLEDGMENTS
|
|---|
We acknowledge the help of Drs. Keith Meredith and Michael Foley
in the clinical follow-up of these patients.
|
FOOTNOTES
|
|---|
Accepted Aug 19, 2005.
Address correspondence to Kerilyn Nobuhara, MD, Department of Surgery, University of California, Box 0570, 513 Parnassus Ave, San Francisco, CA 94143-0570. E-mail: nobuharak{at}surgery.ucsf.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
|
REFERENCES
|
|---|
- Lipsett PA, Pitt HA. Surgical treatment of choledochal cysts.
J Hepatobiliary Pancreat Surg. 2003;10
:352
–359[CrossRef][Medline]
- Lipsett PA, Pitt HA, Colombani PM, Boitnott JK, Cameron J. Choledochal cyst disease: a changing pattern of presentation.
Ann Surg. 1994;220
:644
–652[Web of Science][Medline]
- Iwata F, Uchida A, Miyaki T, et al. Familial occurrence of congenital bile duct cysts.
J Gastroenterol Hepatol. 1998;13
:316
–319[Web of Science][Medline]
- Matsumoto Y, Fujii H, Itakura J. Pancreaticobiliary maljunction: pathophysiological and clinical aspects and the impact on biliary carcinogenesis.
Langenbecks Arch Surg. 2003;388
:122
–131[Web of Science][Medline]
- Iwai N, Yanagihara J, Tokiwa K, Shimotake T, Nakamura K. Congenital choledochal dilatation with emphasis on pathophysiology of the biliary tract.
Ann Surg. 1992;215
:27
–30[Web of Science][Medline]
- Visser BC, Suh I, Way LW, Kang SM. Congenital choledochal cysts in adults.
Arch Surg. 2004;139
:855
–862[Abstract/Free Full Text]
- Alonso-Lej F, Rever WB Jr, Pessagno DJ. Congenital choledochal cyst, with a report of 2, and an analysis of 94, cases.
Int Abstr Surg. 1959;108
:1
–30
- Todani T, Watanabe Y, Naruse 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
:263
–269[CrossRef][Web of Science][Medline]
- Parada LA, Hallen M, Hagerstrand I, Tranberg K-G, Johansson B. Clonal chromosomal abnormalities in congenital bile duct dilatation (Caroli's disease).
Gut. 1999;45
:780
–782[Abstract/Free Full Text]
- Hamada Y, Tanano A, Sato M, Kato Y, Hioki K. Rapid enlargement of a choledochal cyst: antenatal diagnosis and delayed primary excision.
Pediatr Surg Int. 1998;13
:419
–421[CrossRef][Web of Science][Medline]
- Ribeiro A, Reddy RK, Bernstein D, Jeffers L, Schiff E. Caroli's syndrome in twin sisters.
Am J Gastroenterol. 1996;91
:1024
–1026[Web of Science][Medline]
- Torra R, Badenas C, Darnell A, Bru C, Escorsell A, Estivill X. Autosomal dominant polycystic kidney disease with anticipation and Caroli's disease associated with a PKD1 mutation. Rapid communication.
Kidney Int. 1997;52
:33
–38[Web of Science][Medline]
- Sgro M, Rossetti S, Barozzino T, et al. Caroli's disease: prenatal diagnosis, postnatal outcome and genetic analysis.
Ultrasound Obstet Gynecol. 2004;23
:73
–76[CrossRef][Web of Science][Medline]
- Hodgson SV, Coonar AS, Hanson PJ, et al. Two cases of 5q deletions in patients with familial adenomatous polyposis: possible link with Caroli's disease.
J Med Genet. 1993;30
:369
–375[Abstract/Free Full Text]
- Lugo-Vicente HL. Prenatally diagnosed choledochal cysts: observation or early surgery?
J Pediatr Surg. 1995;30
:1288
–1290[CrossRef][Web of Science][Medline]
- Marchildon MB. Antenatal diagnosis of choledochal cyst: the first four cases.
Pediatr Surg Int. 1988;3
:431
–436
- Lee H, Hirose S, Bratton B, Farmer DL. Initial experience with complex laparoscopic biliary surgery in children: biliary atresia and choledochal cyst.
J Pediatr Surg. 2004;39
:804
–807[CrossRef][Web of Science][Medline]
- Todani T, Tabuchi K, Watanabe Y, Kobayashi T. Carcinoma arising in the wall of congenital bile duct cysts.
Cancer 1979;44
:1134
–1141[CrossRef][Web of Science][Medline]
- Watanabe Y, Toki A, Todani T. Bile duct cancer developed after cyst excision for choledochal cyst.
J Hepatobiliary Pancreat Surg. 1999;6
:207
–212[CrossRef][Medline]
- Wiseman K, Buczkowski AK, Chung SW, Francoeur J, Schaeffer D, Scudamore C. Epidemiology, presentation, diagnosis, and outcomes of choledochal cysts in adults in an urban environment.
Am J Surg. 2005;189
:527
–531[CrossRef][Web of Science][Medline]
- Fieber SS, Nance FC. Choledochal cyst and neoplasm: a comprehensive review of 106 cases and presentation of two original cases.
Am Surg. 1997;63
:982
–987[Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
TOP
ABSTRACT
CASE REPORTS
