Congenital choledochal malformation: search for a marker of epithelial instability

PurposeThere 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.MethodsBile 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.ResultsOur 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 × 106) 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).ConclusionBiliary 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.