The role of K-ras gene mutation analysis in EUS-guided FNA cytology specimens for the differential diagnosis of pancreatic solid masses: a meta-analysis of prospective studies.

Background: Differential diagnosis of pancreatic solid masses with EUS-guided FNA (EUS-FNA) is still challenging in about 15% of cases. Mutation of the K-ras gene is present in over 75% of pancreatic adenocarcinomas (PADC).

Objective: To assess the accuracy of K-ras gene mutation analysis for diagnosing PADC.

Design: We systematically searched the electronic databases for relevant studies published. Data from selected studies underwent meta-analysis by use of a bivariate model providing a pooled value for sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve.

Setting: Meta-analysis of 8 prospective studies.

Patients: Total of 931 patients undergoing EUS-FNA for diagnosis of pancreatic solid masses.

Intervention: K-ras mutation analysis.

Main Outcome Measurements: Diagnostic accuracy of K-ras mutation analysis and of combined diagnostic strategy by using EUS-FNA and K-ras mutation analysis in the diagnosis of PADC.

Results: The pooled sensitivity of EUS-FNA for the differential diagnosis of PADC was 80.6%, and the specificity was 97%. Estimated sensitivity and specificity were 76.8% and 93.3% for K-ras gene analysis, respectively, and 88.7% and 92% for combined EUS-FNA plus K-ras mutation analysis. Overall, K-ras mutation testing applied to cases that were inconclusive by EUS-FNA reduced the false-negative rate by 55.6%, with a false-positive rate of 10.7%. Not repeating EUS-FNA in cases in which mutation testing of the K-ras gene is inconclusive would reduce the repeat-biopsy rate from 12.5% to 6.8%.

Limitations: Small number of studies and between-study heterogeneity.

Conclusion: K-ras mutation analysis can be useful in the diagnostic work-up of pancreatic masses, in particular when tissue obtained by EUS-FNA is insufficient, and the diagnosis inconclusive.