Co-analysis of pancreatic cyst fluid carcinoembryonic antigen and glucose with novel cut-off levels better distinguishes between mucinous and non-mucinous neoplastic pancreatic cystic lesions

Background Pancreatic cyst fluid analysis plays an important role in distinguishing between mucinous and non-mucinous cyst lesions. We aimed to compare the diagnostic performances of cyst fluid carcinoembryonic antigen (CEA), CA 19-9, and glucose in differentiating mucinous from non-mucinous neoplastic pancreatic cystic lesions (PCLs) and determine the best cut-off levels. Methods Patients’ data were evaluated retrospectively. 102 patients’ PCLs were grouped as non-neoplastic ( n = 25), non-mucinous neoplastic ( n = 20), mucinous neoplastic ( n = 47) and pancreatic adenocarcinomas with cystic degeneration ( n = 10); and CEA, CA 19-9, and glucose levels were compared. Receiver-operating characteristic analysis was performed, and the ideal cut-off values were determined. Results Cyst fluid CEA and CA 19-9, levels were significantly higher ( P < 0.001, P < 0.001, respectively) and glucose levels were significantly lower ( P = 0.001) in mucinous than in non-mucinous neoplastic PCLs. Area under curve with 95% confidence interval of CEA, glucose and CEA and glucose test combination was 0.939 (95% CI = 0.885–0.993, P = 0.001), 0.809 (95% CI = 0.695–0.924, P < 0.001) and 0.937 (95% CI = 0.879–0.995), respectively. CEA cut-offs to rule-in and rule-out mucinous neoplastic were 135.1 ng/mL (sensitivity = 62%, specificity = 94.7%) and 6.12 ng/mL (sensitivity = 94.1%, specificity = 80.4%), respectively. Glucose cut-off of 2.8 mmol/L was chosen both to rule-in and rule-out mucinous neoplastic PCLs (sensitivity = 78%, specificity = 80%). Co-analysis of CEA and glucose to distinguish mucinous from non-mucinous neoplastic PCLs had sensitivity = 87.8%, specificity = 93.3%, and diagnostic accuracy = 89.3%. Conclusions We concluded that co-analysis of cyst fluid CEA (cut-off = 135.1 ng/mL) and glucose (cut-off = 2.8 mmol/L) at novel cut-offs had the best testing performance to rule-in mucinous neoplastic PCLs. To rule-out mucinous PCLs co-analysis of CEA (cut-off = 6.12 ng/mL) and glucose (cut-off = 2.8 mmol/L) added value to prediction.

Micro-RNA Analysis of Pancreatic Cyst Fluid for Diagnosing Malignant Transformation of Intraductal Papillary Mucinous Neoplasm by Comparing Intraductal Papillary Mucinous Adenoma and Carcinoma

Although intraductal papillary mucinous neoplasm (IPMN) is thought to be a precursor lesion of pancreatic cancer, diagnosing malignant transformation of IPMN using non-invasive diagnostic methods is difficult and complicated. Micro-RNAs (miRNAs) are currently recognized as biomarkers and molecular targets of various diseases, including malignancy. In this study, we investigated a potential diagnostic approach using miRNA in pancreatic cyst fluid as a marker for evaluating malignant alternation of IPMN. Cystic fluid was sampled mainly during surgical resection. The collected samples were evaluated by performing comprehensive analysis of miRNA using a highly sensitive DNA chip. miRNA expression was compared between IPM adenoma (IPMA) and IPM carcinoma (IPMC) to evaluate the related biomarkers for malignant transformation of IPMN. miRNA analysis revealed that six miRNAs (miR-711, miR-3679-5p, miR-6126, miR-6780b-5p, miR-6798-5p, and miR-6879-5p) in IPMC were significantly enriched compared to those in IPMA. The difference was validated using quantitative real-time PCR. Cyst fluid miRNA analysis might be useful for diagnosing malignant alteration of IPMN. Further evaluations of diagnostic capability as well as functional analysis using the identified miRNAs are required with larger cohorts to confirm its efficacy.

Management of pancreatic cysts and guidelines: what the gastroenterologist needs to know

The prevalence of pancreatic cysts has increased significantly over the last decade, partly secondary to increased quality and frequency of cross-sectional imaging. While the majority never progress to cancer, a small number will and need to be followed. The management of pancreatic cysts can be both confusing and intimidating due to the multiple guidelines with varying recommendations. Despite the differences in the specifics of the guidelines, they all agree on several high-risk features that should get the attention of any clinician when assessing a pancreatic cyst: presence of a mural nodule or solid component, dilation of the main pancreatic duct (or presence of main duct intraductal papillary mucinous neoplasm), pancreatic cyst size ⩾3–4 cm, or positive cytology on pancreatic cyst fluid aspiration. Other important criteria to consider include rapid cyst growth (⩾5 mm/year), elevated serum carbohydrate antigen 19-9 levels, new-onset diabetes mellitus, or acute pancreatitis thought to be related to the cystic lesion.

Marker Identification of the Grade of Dysplasia of Intraductal Papillary Mucinous Neoplasm in Pancreatic Cyst Fluid by Quantitative Proteomic Profiling

The incidence of patients with pancreatic cystic lesions, particularly intraductal papillary mucinous neoplasm (IPMN), is increasing. Current guidelines, which primarily consider radiological features and laboratory data, have had limited success in predicting malignant IPMN. The lack of a definitive diagnostic method has led to low-risk IPMN patients undergoing unnecessary surgeries. To address this issue, we discovered IPMN marker candidates by analyzing pancreatic cystic fluid by mass spectrometry. A total of 30 cyst fluid samples, comprising IPMN dysplasia and other cystic lesions, were evaluated. Mucus was removed by brief sonication, and the resulting supernatant was subjected to filter-aided sample preparation and high-pH peptide fractionation. Subsequently, the samples were analyzed by LC-MS/MS. Using several bioinformatics tools, such as gene ontology and ingenuity pathway analysis, we detailed IPMNs at the molecular level. Among the 5834 proteins identified in our dataset, 364 proteins were differentially expressed between IPMN dysplasia. The 19 final candidates consistently increased or decreased with greater IPMN malignancy. CD55 was validated in an independent cohort by ELISA, Western blot, and IHC, and the results were consistent with the MS data. In summary, we have determined the characteristics of pancreatic cyst fluid proteins and discovered potential biomarkers for IPMN dysplasia.