Congenital choledochal malformation: search for a marker of epithelial instability.
OBJECTIVE
There is a predisposition to the development of malignancy in congenital choledochal malformation (CCM) although the degree of risk is unknown. We investigated the role of CA19-9 in bile and the MIB-1 (Ki-67) epithelial proliferation index as markers of an at risk choledochal epithelium at the time of definitive surgery.


METHODS
Bile collected at surgery was analyzed for levels of amylase (as a surrogate of pancreatic reflux) and CA19-9. Immunohistochemical staining for CA19-9 and MIB-1 index (expressed as %) was performed on resected specimens. Data are quoted as median (IQR) and differences assessed using non-parametric statistics. A P value of 0.05 was regarded as significant.


RESULTS
Our study group consisted of 78 children with CCM (Type 1 fusiform, n=34; Type 1 cystic, n=30 and Type 4, n=14). Median bile CA19-9 was 159,400 (6-1×10(6)) kU/L. There was no correlation with bile amylase (P=0.49) or biliary pressure (P=0.17) but modest correlation with bilirubin (rs=0.24; P=0.02). In contrast, bile amylase was correlated with plasma γ-glutamyl transpeptidase (P=0.02), alkaline phosphatase (P=0.05) and aspartate aminotransferase (P=0.02); and inversely correlated with biliary pressure (rs=-0.38; P<0.0008). Epithelial expression of CA19-9 and MIB-1 was assessed in 43 specimens. CA19-9 was diffusely expressed on all choledochal epithelium. MIB-1 expression was divided into: high expression (>40%) n=3; moderate (20-40%) n=5, low (6-20%) n=7 and very low (≤5%) n=28. There was no correlation with choledochal pressure (P=0.87), CA19-9 (P=0.51) or bile amylase (P=0.55).


CONCLUSIONS
Biliary CA19-9 levels were grossly (and unexpectedly) raised in choledochal malformation and appear to arise from biliary rather than pancreatic epithelium. MIB-1 confirms that a small proportion (19%) has marked epithelial proliferation but no clinical correlates could be identified.
Department of Paediatric Surgery, Kings College Hospital, London, UK (now, Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan).
Enrico
E
La Pergola
Institute of Liver Studies, Kings College Hospital, London, UK (now, Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan).
Yoh
Y
Zen
Department of Paediatric Surgery, Kings College Hospital, London, UK (now, Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan). Electronic address: Markdav2@ntlworld.com.
Mark
M
Davenport
D000293:Adolescent; D001646:Bile / Q000378:metabolism; D018395:CA-19-9 Antigen / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D015529:Choledochal Cyst / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019394:Ki-67 Antigen / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
D018395:CA-19-9 Antigen; D019394:Ki-67 Antigen
Amylase; CA19-9; Choledochal cyst; Congenital choledochal malformation; Intrabiliary pressure; MIB-1