O2175: Cholangiocarcinoma Sequence Inferred from Increasing Age at Choledochal Cyst Excision

Background: Choledochal cysts (CDC) typically arise from congenital pancreaticobiliary malunion, promoting admixture of pancreatic and biliary fluids and chronic ductal inflammation. CDC are recognized as an independent risk factor for cholangiocarcinoma (CCA), with synchronous and metachronous malignancy rates reported between 2.5-11% and 0.5-2.5%, respectively. Despite this risk, the age-related pathogenesis of biliary epithelial changes leading to CCA in CDC is poorly characterized. This study aimed to elucidate the longitudinal progression of premalignant biliary changes and CCA incidence in patients having CDC resection and to establish precise criteria for cancer screening of patients without synchronous disease.

Methods: We conducted a retrospective analysis of patients treated for CDC or CCA at a single institution between 1988 and 2023. Utilizing our institutional Research Derivative and Cancer Registry, we examined two groups: 1) patients who underwent CDC resection, monitoring for biliary epithelial changes and CCA, and 2) patients with various sites of CCA, assessing history of CDC resection. We compared patient and disease characteristics across different age groups and performed logistic regression to analyze epithelial transformation over time.

Results: Among 130 total CDC patients (Table), the median age at excision was 12 years, 73% were female, and Asian race was represented 2.5-fold higher than our state census. Biliary obstruction and pancreatitis were the two most common presenting symptoms, and CDC types I and IV predominated. On CDC pathology, 64/114 (56.1%) specimens showed inflammation and fibrosis, and 9/114 (7.9%) showed progressive biliary epithelial transformation: 2 metaplasia, 1 hyperplasia, 3 dysplasia, and 3 CCA (2.6% synchronous). One additional patient had CDC excision at age 6 years and developed CCA at age 37 years (0.8% metachronous). Logistic regression showed increasing age at excision associated with increased odds of epithelial transformation (p=0.038; Figure a). No epithelial transformation was observed in patients aged ≤5 years, but the odds ratio was 6.5 for patients aged 6-17 years, increasing to 15.0 for those aged ≥18 years (p=0.0093). Among 886 total non-ampullary CCA patients, 7 (0.79%) were found to have synchronous CDC during cancer evaluation, while none had remote CDC resection. Median age in years at epithelial transformation increased from premalignant lesions (34 [16-35]), to CCA with CDC (51 [37-78]), to CCA without CDC (65 [56-72]; p< 0.001).

Conclusion: Our study, the most comprehensive to date on biliary epithelial changes in CDC patients, yielded risks of synchronous and metachronous CCA at 2.6% and 0.8%, respectively. These data infer a progressive epithelial transformation to CCA correlating with increasing age at CDC resection. This trend, coupled with an alarming case of metachronous CCA, underscores the need to surveil patients with prior CDC resection at the onset of the 4th decade.