Molecular analysis of EUS-acquired pancreatic cyst fluid for KRAS and GNAS mutations for diagnosis of intraductal papillary mucinous neoplasia and mucinous cystic lesions: a systematic review and meta-analysis

Background and Aims: Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic performance of KRAS and GNAS mutations in EUS-acquired pancreatic cyst fluid for diagnosis of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic lesions (MCLs). Methods: Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute the pooled sensitivity and specificity and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI). Results: Six studies (785 lesions) were included. For IPMNs and MCLs, KRAS + GNAS (combination) had significantly higher diagnostic accuracy than KRAS alone and GNAS alone (all P < .001). The pooled sensitivity, specificity, and diagnostic accuracy of KRAS + GNAS mutations for diagnosis of IPMNs were 94% (95% CI, 72-99; I² = 86.74%), 91% (95% CI, 72-98; I² = 89.83), and 97% (95% CI, 95-98), respectively, with each significantly higher compared with carcinoembryonic antigen (CEA) alone (all P < .001). For diagnosis of MCLs, KRAS + GNAS had a similar sensitivity and specificity compared with CEA alone; however, diagnostic accuracy was significantly improved (97% [95% CI, 95-98] vs 89% [95% CI, 86-91]; P < .001). Conclusions: Molecular analysis for KRAS + GNAS mutations in EUS-acquired pancreatic cyst fluid has high sensitivity and specificity with significantly improved diagnostic accuracy for diagnosis of IPMNs and MCLs when compared with CEA alone.