Al-Rashdan et al. attempt to critically evaluate this confusing maze of data and ask whether cyst fluid analysis really addresses this unmet clinical quandary of how to appropriately select patients with pancreatic cysts for surgery (4). They focus on the challenge to distinguish between mucinous subtypes by evaluating cyst fluid CEA and amylase. In the 10 year study period, they identified 134 patients with pancreatic cysts who underwent surgical resection. Of these patients,

82 underwent a preoperative EUS. Sixty-six of the 82 were mucinous cysts (14 MCN, 52 Inhibitors,research,lifescience,medical IPMN). Of these 66, 25 had preceding FNA and cyst fluid analysis performed (9 MCN, 11 SB-IPMN and 5 main duct IPMN). The median and mean CEA were not statistically different between the 9 MCN and all 16 IPMN (p=0.19), as well as, MCN and SB-IPMN (p=0.34). The median and mean Inhibitors,research,lifescience,medical amylase were not statistically different between the MCN and all IPMN (p=0.64) and MCN and SB-IPMN (p=0.92). Of note, no data was provided regarding cross-sectional

imaging or EUS findings. Their data is similar to other studies that have found limitations in the accuracy of cyst fluid CEA and amylase—as well as its selective utilization Inhibitors,research,lifescience,medical in practice. In a cohort of 33 mucinous cystadenomas and 235 IPMN patients (5), Slozek et al. showed that neither CEA nor amylase was unable to distinguish between mucinous cystadenomas and IPMN (p=0.26 and 0.23 respectively). However, for this study, how many of the pathologic diagnoses were confirmed by surgical pathology or how the definition of mucinous cystadenoma was made was not provided. Inhibitors,research,lifescience,medical Curiously, cyst fluid CA19-9 was noted to distinguish mucinous cystadenomas and IPMN (p=0.003)

(5). The elevated CA19-9 raises the possibility of a different biomarker to distinguish between types of mucinous cysts. Another study of 14 MCN and 52 IPMN cases confirmed by surgical pathology reported median CEA of 2844 ng/ml (range 1-14,500) in MCN and 574 ng/ml (0-38,500) in IPMN (5). While statistical analysis of this difference was not reported, the whatever overlap between Inhibitors,research,lifescience,medical CEA concentrations is readily apparent. Most recently, in a study of 126 patients, Park et al. reported overlapping median values cyst fluid CEA between MCN and IPMN (428ng/ml [5 HT Receptor inhibitor interquartile range IQR: 44-7870] and 414ng/ml [IQR 102-1223]), again without statistical analysis (7). Median values (and IQR) for cyst fluid amylase overlapped as well for MCN and IPMN (6800 IU/L [IQR 70-25,295] and 5090 IU/L [IQR 1119-38,290], respectively) (7). The data from Al-Rashdan et al. adds to the growing body of evidence that cyst fluid analysis (CEA and amylase) alone is disappointing in its ability to distinguish between the mucinous lesions, MCN and IPMN. However, the question is we would ever look at cyst fluid analysis alone to make our clinical decisions? The answer is probably not.