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Background & Aims: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort., Methods: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features., Results: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs., Conclusions: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Backgrounds & Aims: Most guidelines for management of patients with intraductal papillary mucinous neoplasms (IPMN) vary in proposed surveillance intervals and durations-these are usually determined based on expert opinions rather than substantial evidence. The progression of and optimal surveillance intervals for branch-duct IPMNs (BD-IPMN) has not been widely studied. We evaluated the progression of BD-IPMN under surveillance at a single center, and determined optimal follow-up intervals and duration., Methods: We performed a retrospective analysis of 1369 patients with BD-IPMN seen at Seoul National University Hospital in Korea from January 2001 through December 2016. We included only patients whose imaging studies showed classical features of BD-IPMN, and collected data from each patient over time periods of at least 3 years. We reviewed radiologic and pathologic findings, and performed linear and binary logistic regressions to estimate cyst growth., Results: The median annual growth rate of the cyst was 0.8 mm over a median follow-up time of 61 months. During surveillance, 46 patients (3.4%) underwent surgery because of disease progression after a median follow-up time (in this group) of 62 months. Worrisome features were observed in 209 patients (15.3%) during surveillance, including cyst size of 3 cm or more (n = 109, 8.0%), cyst wall thickening (n = 51, 3.7%), main pancreatic duct dilatation (n = 77, 5.6%), and mural nodule (n = 43, 3.1%). Along with annual rate of cyst growth, incidences of main pancreatic duct dilatation and mural nodules associated with the sizes of cysts at detection (P < .001)., Conclusions: In a retrospective analysis of patients with BD-IPMN followed for more than 5 years, we found most cysts to be indolent, but some rapidly grew and progressed. Surveillance protocols should therefore be individualized based on initial cyst size and rate of growth., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Endoscopic ultrasound (EUS)-guided chemoablation with ethanol lavage followed by infusion of paclitaxel is effective for the treatment of mucinous pancreatic cysts. However, complications arise in 3%-10% of patients, presumably linked to the inflammatory effects of ethanol. We aimed to determine whether alcohol is required for effective pancreatic cyst ablation, if removing alcohol from the ablation process would improve complication rates, and whether a multi-agent chemotherapeutic cocktail could increase the rate of complete cyst resolution compared with findings reported from previous trials using alcohol followed by paclitaxel alone., Methods: Between November 2011 and December 2016, we conducted a single-center, prospective, double-blind trial of 39 patients with mucinous-type pancreatic cysts. Patients were randomly assigned to 1 of 2 groups that underwent EUS-guided pancreatic cyst lavage with either 80% ethanol (control) or normal saline (alcohol-free group). Cysts in both groups were then infused with an admixture of paclitaxel and gemcitabine. Primary outcomes were the rates of complete ablation 12 months after the procedure, and rates of serious and minor adverse events within 30 days of the procedure., Results: At 12 months, 67% of patients who underwent alcohol-free EUS-guided cyst chemoablation had complete ablation of cysts compared with 61% of patients in the control group. Serious adverse events occurred in 6% of patients in the control group vs none of the patients in the alcohol-free group. Minor adverse events occurred in 22% of patients in the control group and none of the patients in the alcohol-free group. The overall rate of complete ablation was 64%., Conclusions: In this prospective, randomized, controlled trial, we found that alcohol is not required for effective EUS-guided pancreatic cyst ablation, and when alcohol is removed from the ablation process, there is a significant reduction in associated adverse events. A multi-agent chemotherapeutic ablation admixture did not appear to significantly improve rates of complete ablation compared with the current standard of alcohol lavage followed by paclitaxel alone. ClinicalTrials.gov ID: NCT01475331., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients., Methods: We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers., Results: We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%., Conclusions: We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs)., Methods: We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion., Results: Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias., Conclusions: Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Endoscopic ultrasonography (EUS)-guided interventions have been used to treat patients with cystic lesions of the pancreas (CLPs). We used EUS to guide injection and lavage of ethanol, followed by injection of paclitaxel, into cysts, and investigated treatment response and predictors., Methods: Fifty-two patients were enrolled in the study using the following inclusion criteria: unilocular or oligolocular cysts, indeterminate cystic lesions that required EUS fine-needle aspiration, and cystic lesions that grew during the observation period. Forty-seven patients were followed up for more than 12 months and their outcomes were analyzed., Results: The mean diameter of the CLPs was 31.8 mm (range, 17-68 mm) and the estimated volume was 14.09 mL (range, 1.16-68.74 mL). Twenty CLPs were oligolocular. The mean level of carcinoembryonic antigen was 463 ng/mL (range, 1-8190 ng/mL). The median follow-up period was 21.7 months. A complete response was observed in 29 patients, a partial response in 6 patients, and persistent cysts in 12 patients. Four of 12 patients with persistent cysts underwent surgery. The histopathologic degree of epithelial ablation varied from 0% to 100%. Based on univariate analysis, EUS diameter and original volume predicted cyst resolution; in multivariate analysis, only original volume predicted resolution. Mild pancreatitis and splenic vein obliteration each occurred in 1 patient., Conclusions: EUS-guided injection and lavage of ethanol, followed by injection of paclitaxel, appears to be a safe method for treating pancreatic cysts; 62% of patients had complete resolution. Small cyst volume predicted complete resolution., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Pancreatic involvement in von Hippel-Lindau (VHL) disease, a genetic disorder with a dominant mode of inheritance affecting various organs, has rarely been studied. We assessed the prevalence, type of lesions, natural history, and impact of pancreatic involvement in patients with VHL., Methods: A total of 158 consecutive patients from 94 families with VHL disease were studied in a prospective French collaborative study. All patients underwent systematic screening for VHL lesions, including computerized tomography (CT) scanning of the pancreas reviewed by an experienced radiologist. Clinical data, investigations, and treatments performed were also reviewed., Results: Pancreatic involvement was observed in 122 patients (77.2%) and included true cysts (91.1%), serous cystadenomas (12.3%), neuroendocrine tumors (12.3%), or combined lesions (11.5%). The pancreas was the only organ affected in 7.6% of patients. Patients with pancreatic lesions had fewer pheochromocytomas than those without (14/122 vs. 16/36; P<0.0001), and patients with neuroendocrine pancreatic tumors had renal involvement less often than those without (8/99 vs. 6/20; P = 0.013). None of the patients with neuroendocrine tumors had symptoms of hormonal hypersecretion. Pancreatic lesions evolved in half of patients but required specific treatment in only 10 (8.2%) when they were symptomatic or for the resection of large neuroendocrine tumors., Conclusions: Pancreatic involvement is seen in most patients with VHL disease. Although symptoms are rare, specific treatment of pancreatic lesions is required in selected patients, mainly those with neuroendocrine tumors.