Fluorescence in situ hybridization for diagnosis of cholangiocarcinoma in primary sclerosing cholangitis: a systematic review and meta-analysis

Background: Patients with primary sclerosing cholangitis (PSC) are at risk of developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) may aid diagnosis of CCA. Objective: To determine the diagnostic utility of FISH for CCA detection in patients with PSC. Design: Meta-analysis. Setting: Tertiary-care medical center. Patients: Patients in studies where histopathologic correlation of CCA was available; 2 x 2 contingency data were constructed. Intervention: Database search and review of study findings. Main Outcome Measurements: Sensitivity, specificity, likelihood ratio, and pooled diagnostic odds ratio. Results: The search yielded 8 studies, involving 828 patients who could be included in our meta-analysis. The pooled sensitivity and specificity of FISH for diagnosis of CCA in patients with PSC were 68% (95% confidence interval [CI], 61%-74%) and 70% (95% CI, 66%-73%), respectively. The pooled positive likelihood ratio was 2.69 (95% CI, 1.84-3.97), and the negative likelihood ratio was 0.47 (95% CI, 0.39-0.58). The pooled diagnostic odds ratio was 7.24 (95% CI, 3.93-13.36). For FISH polysomy (6 studies, n = 690), the pooled sensitivity and specificity of FISH were 51% (95% CI, 43%-59%) and 93% (95% CI, 91%-95%), respectively. The heterogeneity indices of I-2 measure of inconsistency was 45.9%. Visual inspection of the funnel plot showed low potential for publication bias. Limitations: Inclusion of low-quality studies. Conclusion: Our study suggests that FISH polysomy is highly specific; however, limited sensitivity of FISH highlights that better markers are required for early detection of CCA in PSC.