International Intraductal Papillary Mucinous Neoplasms Registry: Long-Term Results Based on the New Guidelines.

OBJECTIVE: The aim of this study was to analyze the outcomes of a long-term intraductal papillary mucinous neoplasm (IPMN) registry and evaluate new guidelines. METHODS: A prospectively maintained IPMN registry involving 6 centers in Europe and the United States was used to collect the data. Patients with more than 1-year follow-up and no malignancy diagnosed within the first 3 months of surveillance were included. RESULTS: From 1999 to 2014, 620 patients were included. The median follow-up time was 3 years. Thirty-seven (6%) patients developed malignancy with a median time from IPMN diagnosis to malignancy of 10.3 months. The 1-, 5-, and 10-year actuarial rates of disease-free survival were 97%, 93%, and 92% respectively. Four hundred thirty-one patients met criteria for low-risk branch duct IPMN consisting of cyst size less than 3 cm, with no solid component or main duct dilation. Eight malignancies were diagnosed in this subgroup, all of them within the first 5 years. From this subcohort, 112 patients had a follow-up time of more than 5 years, and no malignancy was diagnosed. CONCLUSIONS: In IPMN lesions with low-risk features at baseline, the risk of progression to malignancy after the first 5 years of follow-up was minimal. Furthermore, the main cyst characteristics remained unchanged during their surveillance.

Diagnostic Accuracy of Endoscopic Ultrasound-Guided Fine-Needle Aspiration Cytology, Carcinoembryonic Antigen, and Amylase in Intraductal Papillary Mucinous Neoplasm.

OBJECTIVES: The aim of this study was to determine the accuracy of cytology, carcinoembryonic antigen (CEA), and amylase levels in the preoperative diagnosis of intraductal papillary mucinous neoplasms (IPMNs). METHODS: An international registry was started in 2005 and included patients with clinically suspected IPMNs. Those who underwent surgery and had preoperative endoscopic ultrasonography fine-needle aspiration were selected for the study. RESULTS: One hundred eighty patients were included. Cytological analysis for neoplastic cells in IPMNs showed high specificity (87.8%) but low sensitivity (39.4%). The median CEA level was 525.5 ng/mL (n = 78) in IPMNs versus 9.7 ng/mL in nonmucinous cysts (n = 6), showing an area under the receiver operating characteristic curve (AUC) of 0.87. The optimal cutoff CEA value for distinguishing IPMN from nonmucinous cysts was 129 ng/mL. At this level, the sensitivity was 76.9%, and specificity was 83.3%, yielding a positive predictive value of 95.9% and a negative predictive value of 41.9%. Carcinoembryonic antigen was a poor predictor of neoplasia in IPMNs (AUC = 0.55). Amylase did not distinguish IPMNs from mucinous cystadenomas (MCAs) (median, 3759 U/L [n = 28 IPMNs] and 497 U/L [n = 3 MCAs], AUC = 0.65). CONCLUSIONS: Cytology has a limited role because of its lack of sensitivity. Carcinoembryonic antigen modestly differentiated between mucinous and nonmucinous lesions. Amylase did not distinguish IPMNs versus MCAs.

Risk factors for malignant progression of intraductal papillary mucinous neoplasms.

BACKGROUND: Intraductal papillary mucinous neoplasms of the pancreas are increasingly diagnosed. Due to their malignant potential, greater understanding of their nature is required. AIMS: Define risk factors for malignancy in intraductal papillary mucinous neoplasms. METHODS: An international, multicentre study was performed in Europe and the United States. Clinical databases were reviewed for patients with intraductal papillary mucinous neoplasms diagnosis. RESULTS: Of 1126 patients, 84 were diagnosed with invasive carcinoma/high-grade dysplasia and were compared to the rest of the cohort. Multivariate logistic analysis showed a statistically significant association between cancer/high-grade dysplasia and the variables smoking history (OR 1.9, 95% CI [1.1-3.1]), body mass index (OR 1.1, 95% CI [1-1.1]), symptoms (OR 3.4, 95% CI [1.9-6]), jaundice (OR 0.1, 95% CI [0-0.3]), and steatorrhea (OR 0.3, 95% CI [0.1-0.8]). Univariate analysis showed no association between malignancy and the cyst number/location (p=0.3 and p=0.5, respectively) although a strong association was shown for cyst size (p<0.001). The presence and size of nodules (p<0.01) and main duct involvement (p<0.001) were also strongly related with malignancy. CONCLUSION: The presence of jaundice and steatorrhea, smoking, high body mass index, and imaging features such as cyst size, main duct involvement, and the presence and size of mural nodules are associated with high-grade neoplasia in intraductal papillary mucinous neoplasms.

Neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1, and carbohydrate antigen 19-9 in pancreatic juice: pathobiologic implications in diagnosing benign and malignant disease of the pancreas.

OBJECTIVE: Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1 (MIC-1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients with symptoms suggestive of pancreatic diseases. METHODS: A total of 105 chronic pancreatitis (CP), pancreatic cancer (PC), and nonpancreatic nonhealthy (patients with symptoms mimicking pancreatic disease but found to be free of any pancreatic disease) patients underwent endoscopic pancreatic juice collection after secretin stimulation. Neutrophil gelatinase-associated lipocalin and MIC-1 levels were measured by enzyme-linked immunosorbent assay, whereas CA19-9 was measured by radioimmunoassay. RESULTS: Neutrophil gelatinase-associated lipocalin, MIC-1, and CA19-9 were significantly elevated in the pancreatic juice of patients with CP and patients with PC as compared with nonpancreatic nonhealthy controls (P ≤ 0.034). Neutrophil gelatinase-associated lipocalin seemed most promising in differentiating diseased versus nondiseased pancreata (areas under the curve, 0.88-0.91), whereas MIC-1 was found to be higher in patients with PC than in patients with CP (P = 0.043). Interestingly, MIC-1 levels in diabetic patients with PC were higher than in nondiabetic patients with PC (P = 0.030) and diabetic patients with CP (P = 0.087). Carbohydrate antigen 19-9 showed the least ability to distinguish patient groups (areas under the curve, 0.61-0.76). CONCLUSIONS: Pancreatic juice neutrophil gelatinase-associated lipocalin shows potential utility in establishing pancreatic etiology in the context of nonspecific symptoms, whereas MIC-1 may aid in differentiating PC from CP.