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Congenital choledochal malformation: search for a marker of epithelial instability.

Abstract：

PURPOSE: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). CONCLUSION: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.

journal_name

J Pediatr Surg

journal_title

Journal of pediatric surgery

authors

La Pergola E,Zen Y,Davenport M

doi

10.1016/j.jpedsurg.2016.03.012

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

1445-9

issue

eissn

0022-3468

issn

1531-5037

pii

S0022-3468(16)30005-7

journal_volume

pub_type

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Congenital choledochal malformation: search for a marker of epithelial instability.