Pancreatic Cyst Fluid Research Articles

Optimizing the multimodal approach to pancreatic cyst fluid diagnosis

The objective of this study was to develop a triage algorithm to optimize diagnostic yield from cytology, carcinoembryonic antigen (CEA), and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) testing on different components of a single pancreatic cyst fluid specimen. The authors also sought to determine whether cell block supernatant was suitable for CEA and KRAS testing. Fifty-four pancreatic cysts were triaged according to a volume-dependent protocol to generate fluid (neat and supernatant) and cell block specimens for cytology, comparative CEA, and KRAS testing. Follow-up histology, diagnostic cytology, or a combined clinicopathologic interpretation was recorded as the final diagnosis. There were 26 mucinous cystic lesions and 28 nonmucinous cystic lesions with volumes ranging from 0.3 mL to 55 mL. Testing different components of the specimens (cell block, neat, and/or supernatant) enabled all laboratory investigations to be performed on 50 of 54 cyst fluids (92.6%). Interpretive concordance was observed in 17 of 17 cases (100%) and in 35 of 40 cases (87.5%) that had multiple components tested for CEA and KRAS mutations, respectively. An elevated CEA level (>192 ng/mL) was the most sensitive test for the detection of a mucinous cystic lesion (62.5%) versus KRAS mutation (56%) and "positive" cytology (61.5%). KRAS mutations were identified in 2 of 25 mucinous cystic lesions (8%) in which cytology and CEA levels were not contributory. A volume-based protocol using different components of the specimen was able to optimize diagnostic yield in pancreatic cyst fluids. KRAS mutation testing increased diagnostic yield when combined with cytology and CEA analysis. The current results demonstrated that supernatant is comparable to neat fluid and cell block material for CEA and KRAS testing.

Pancreatic cyst fluid triage

The realization that all neoplastic mucinous cysts have malignant potential has led to intensive evaluation of patients with both symptomatic and asymptomatic pancreatic cysts to determine the nature of the cyst and the possible need for resection. Currently, imaging and cyst fluid analyses offer the best means of accurately assessing pancreatic cysts preoperatively.

Advances in the diagnosis of cystic neoplasms of the pancreas

Management of pancreatic cystic neoplasms is challenging due to limitations of current diagnostic tests. There is considerable interest in developing an accurate and cost-effective diagnostic test (or panel of tests) to differentiate cyst types and to identify those which would benefit most from surgical resection. Current multidetector computed tomography scans may have improved accuracy to distinguish between mucinous and nonmucinous cysts. Attempts to generate quantitative criteria from cross-sectional imaging to differentiate cyst types have yielded mixed results. DNA mutations and microRNA show promise in the ability to distinguish between mucinous and nonmucinous cysts. Cyst fluid mucin glycoproteins and cytokines may identify those cysts with high malignant potential. Proteomic analysis may yield other biomarker candidates. Analysis of DNA mutations and proteins within pancreatic cyst fluid have identified potential biomarkers to aid with the management of patients with pancreatic cystic neoplasms.

MiRNA Biomarkers in Cyst Fluid Augment the Diagnosis and Management of Pancreatic Cysts

The diagnosis of pancreatic cystic lesions has increased dramatically. Most are benign, whereas some, such as intraductal papillary mucinous neoplasms (IPMN), represent precursors of pancreatic adenocarcinoma. Therapeutic stratification of IPMNs is challenging without precise information on dysplasia grade and presence of invasion. We assessed the diagnostic benefit of using miRNAs as biomarkers in pancreatic cyst fluid, focusing on IPMNs because of their frequency and malignant potential. RNA was extracted from 55 microdissected formalin-fixed, paraffin-embedded (FFPE) IPMN specimens, and 65 cyst fluid specimens aspirated following surgical resection. Expression of 750 miRNAs was evaluated with TaqMan miRNA Arrays using 22 FFPE and 15 cyst fluid specimens. Differential expression of selected miRNA candidates was validated in 33 FFPE and 50 cyst fluid specimens using TaqMan miRNA Assays. We identified 26 and 37 candidate miRNAs that distinguish low-grade from high-grade IPMNs using FFPE and cyst fluid specimens, respectively. A subset of 18 miRNAs, selected from FFPE and cyst fluid data, separated high-grade IPMNs from low-grade IPMNs, serous cystadenomas (SCA) and uncommon cysts, such as solid pseudopapillary neoplasms (SPN) and cystic pancreatic neuroendocrine tumors (PanNET). A logistic regression model using nine miRNAs allowed prediction of cyst pathology implying resection (high-grade IPMNs, PanNETs, and SPNs) versus conservative management (low-grade IPMNs, SCAs), with a sensitivity of 89%, a specificity of 100%, and area under the curve of 1. We found candidate miRNAs that helped identify patients with high-grade IPMN and exclude nonmucinous cysts. These classifiers will require validation in a prospective setting to ultimately confirm their clinical usefulness.

A comparative analysis of K-ras mutation and carcinoembryonic antigen in pancreatic cyst fluid

Background/aimsAnalysis of cystic fluid may be useful in distinguishing between benign and malignant cysts which has significant impact on their management. The aim of our study was to assess the diagnostic utility of carcinoembryonic antigen (CEA) and K-ras gene mutation in pancreatic cysts fluid. MethodsThe study included 56 patients with pancreatic cystic fluid collected for analysis. The cysts were classified as benign (simple cysts, pseudocysts, serous cystadenoma) - 39 patients or premalignant/malignant (mucinous cystadenoma, IPMN, cystadenocarcinoma) - 17 patients. The patients history, CEA fluid concentrations and presence of K-ras mutation were analyzed. ResultsCEA were higher in patients with malignant cysts (mean levels 238 ± 12.5 ng/ml; range 32.8–4985 ng/ml) compared to benign lesions (mean levels 34.5 ± 3.7 ng/ml; range 3.9–693 ng/ml; p < 0.001). K-ras mutation correctly classified 11 of 17 patients with premalignant/malignant lesions. It was also detected in 1 patient with final diagnosis of benign cyst (the sensitivity 64.7% and the specificity 97.4%; p < 0.01). If CEA and molecular analysis were combined in that cysts with either CEA level>45 ng/ml or presence of K-ras mutation, than 16 of 17 premalignant/malignant cysts were correctly identified (94.1%). ConclusionMolecular analysis of pancreatic cyst fluid adds diagnostic value to the preoperative diagnosis and should be considered when cyst cytologic examination is negative for malignancy.

Glycomic and Proteomic Profiling of Pancreatic Cyst Fluids Identifies Hyperfucosylated Lactosamines on the N-linked Glycans of Overexpressed Glycoproteins

Pancreatic cancer is now the fourth leading cause of cancer deaths in the United States, and it is associated with an alarmingly low 5-year survival rate of 5%. However, a patient's prognosis is considerably improved when the malignant lesions are identified at an early stage of the disease and removed by surgical resection. Unfortunately, the absence of a practical screening strategy and clinical diagnostic test for identifying premalignant lesions within the pancreas often prevents early detection of pancreatic cancer. To aid in the development of a molecular screening system for early detection of the disease, we have performed glycomic and glycoproteomic profiling experiments on 21 pancreatic cyst fluid samples, including fluids from mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, two types of mucinous cysts that are considered high risk to undergo malignant transformation. A total of 80 asparagine-linked (N-linked) glycans, including high mannose and complex structures, were identified. Of special interest was a series of complex N-linked glycans containing two to six fucose residues, located predominantly as substituents on β-lactosamine extensions. Following the observation of these "hyperfucosylated" glycans, bottom-up proteomics experiments utilizing a label-free quantitative approach were applied to the investigation of two sets of tryptically digested proteins derived from the cyst fluids: 1) all soluble proteins in the raw samples and 2) a subproteome of the soluble cyst fluid proteins that were selectively enriched for fucosylation through the use of surface-immobilized Aleuria aurantia lectin. A comparative analysis of these two proteomic data sets identified glycoproteins that were significantly enriched by lectin affinity. Several candidate glycoproteins that appear hyperfucosylated were identified, including triacylglycerol lipase and pancreatic α-amylase, which were 20- and 22-fold more abundant, respectively, following A. aurantia lectin enrichment.

Inflammatory protein profiling of pancreatic cyst fluid using EUS-FNA in tandem with cytokine microarray differentiates between branch duct IPMN and inflammatory cysts

BackgroundDiagnosis of pancreatic cystic neoplasms remains problematic. We hypothesize that inflammatory mediator proteins in pancreatic cyst fluid can differentiate branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) and pancreatic inflammatory cysts. We aim to 1) detect inflammatory mediator proteins (IMPs) using a multiplexed IMP-targeted microarray in pancreatic cyst fluid obtained during endoscopic ultrasound fine needle aspiration (EUS-FNA) and 2) compare IMP profiles in pancreatic cyst fluid from BD-IPMNs and inflammatory cysts. Pancreatic cyst fluid from ten patients (5 BD-IPMN and 5 inflammatory cysts) was obtained by EUS-FNA and analyzed directly with a multiplexed microarray assay to determine concentrations of 89 IMPs. Statistical analysis was performed using non-parametric methods. ResultsEighty-three of the 89 assayed IMPs were detected in at least one of the 10 patient samples. Seven IMPs were detected in BD-IPMN but not inflammatory cysts, while eleven IMPs were identified in inflammatory cysts but not BD-IPMN. Notably, granulocyte–macrophage colony-stimulating factor (GM-CSF) expression was present in all five inflammatory cyst samples. Hepatocyte growth factor (HGF) was present in significantly higher concentrations in inflammatory cysts compared to BD-IPMN. ConclusionOur exploratory analysis reveals that GM-CSF and HGF in EUS-FNA-collected pancreatic cyst fluid can distinguish between BD-IPMN and inflammatory cyst. Coupling microarray molecular techniques to EUS-FNA may represent a major step forward to our understanding complex pancreatic disease.

Mo1212 Correlation of GNAS Mutation With Diagnostic Information in Pancreatic Cyst Fluids

Background Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are associated with substantially increased risk of malignant transformation when compared to other types of pancreatic lesions such as serous cystadenoma (SCA) and mucinous cystadenoma (MCA). A recent study suggests that detection of a mutation in codon 201 of GNAS in pancreatic cyst fluid DNA may be able to distinguish IPMN from other lesions of the pancreas, including both MCA and SCA [1]. This study found the detection of a GNAS mutation to be 100% specific, and the presence of either a GNAS or KRAS mutation to be 96% sensitive for IPMN. We examined the diagnostic significance of GNAS mutations in a cohort of pancreatic cyst fluid specimens and correlated the results with the associated diagnostic information. Methods 200 residual pancreatic cyst fluid DNA specimens from 198 distinct patients were retrieved from specimen archives and tested. These specimens were chosen so that there was an equal mix of KRAS mutated and wildtype results, and a range of CEA results above and below 192 ng/mL. DNA was amplified with primers targeting the codon 201 region, and sequenced using capillary electrophoresis and Sanger sequencing. The clonality of the mutation was identified as the ratio of mutant to wildtype, with a limit of detection of 10%. IPMN was determined to be present if there was duct dilation or connectivity to the duct system together with observation of mucinous characteristics of the fluid (e.g. gross mucin, mucin stain, elevated CEA, etc.). Results GNAS mutations were found in 50/200 (25%) specimens. A significant association between the presence of KRAS mutation and GNAS mutation was found, with more GNAS mutations present among KRAS-mutated than KRASwildtype cysts (odds ratio=4, p=7.0e-5). There was no significant difference in mean CEA values between according to GNAS mutation status. Two small ( CAT) that has not been previously reported in IPMN; this mutation was present in only that one specimen. In 20/50 (40%) of GNAS mutated-specimens neither duct dilation nor cyst communication with the duct system was observed. Conclusions Based on the present evaluation, GNAS is found to be mutated in a significant number of cases lacking the classic features of IPMNs. Further work is needed to better understand the role of GNAS in discriminating IPMNs from other cystic neoplasms of the pancreas and in evaluating the malignant potential of either; additional surgical outcomes would be valuable for this assessment. 1. Sci. Transl. Med. 3, 92ra66 (2011).

Mo1213 Differentiation Between Chronic Pancreatitis and Pancreatic Cancer by Using Metabolomic Analysis

Background Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are associated with substantially increased risk of malignant transformation when compared to other types of pancreatic lesions such as serous cystadenoma (SCA) and mucinous cystadenoma (MCA). A recent study suggests that detection of a mutation in codon 201 of GNAS in pancreatic cyst fluid DNA may be able to distinguish IPMN from other lesions of the pancreas, including both MCA and SCA [1]. This study found the detection of a GNAS mutation to be 100% specific, and the presence of either a GNAS or KRAS mutation to be 96% sensitive for IPMN. We examined the diagnostic significance of GNAS mutations in a cohort of pancreatic cyst fluid specimens and correlated the results with the associated diagnostic information. Methods 200 residual pancreatic cyst fluid DNA specimens from 198 distinct patients were retrieved from specimen archives and tested. These specimens were chosen so that there was an equal mix of KRAS mutated and wildtype results, and a range of CEA results above and below 192 ng/mL. DNA was amplified with primers targeting the codon 201 region, and sequenced using capillary electrophoresis and Sanger sequencing. The clonality of the mutation was identified as the ratio of mutant to wildtype, with a limit of detection of 10%. IPMN was determined to be present if there was duct dilation or connectivity to the duct system together with observation of mucinous characteristics of the fluid (e.g. gross mucin, mucin stain, elevated CEA, etc.). Results GNAS mutations were found in 50/200 (25%) specimens. A significant association between the presence of KRAS mutation and GNAS mutation was found, with more GNAS mutations present among KRAS-mutated than KRASwildtype cysts (odds ratio=4, p=7.0e-5). There was no significant difference in mean CEA values between according to GNAS mutation status. Two small ( CAT) that has not been previously reported in IPMN; this mutation was present in only that one specimen. In 20/50 (40%) of GNAS mutated-specimens neither duct dilation nor cyst communication with the duct system was observed. Conclusions Based on the present evaluation, GNAS is found to be mutated in a significant number of cases lacking the classic features of IPMNs. Further work is needed to better understand the role of GNAS in discriminating IPMNs from other cystic neoplasms of the pancreas and in evaluating the malignant potential of either; additional surgical outcomes would be valuable for this assessment. 1. Sci. Transl. Med. 3, 92ra66 (2011).

Mo1201 Pancreatic Stellate Cells Express Inducible Nitric Oxide Synthase

BACKGROUND: IPMN is a precursor lesion to pancreatic ductal adenocarcinoma consisting of 4 epithelial subtypes with varying grades of dysplasia. Intestinal type (IPMN-I) often involves the main duct and has a higher risk of developing invasive carcinoma in comparison to gastric type (IPMN-G). Differentiation of high-risk/malignant IPMN from low-risk IPMN and other benign/low-grade cystic pancreatic lesions remains a challenge, especially in the preoperative setting. mAb Das-1 reacts specifically to a colonic epithelial phenotype. It is both sensitive and specific in identifying various pre-malignant and malignant lesions of the upper GI tract including Barrett's esophagus and incomplete gastrointestinal metaplasia associated with gastric cancer. We have previously demonstrated that it specifically detects high risk IPMN tissue histologically. AIM: To assess the ability of mAb Das-1 to identify cyst fluid of IPMN with a high risk of malignant transformation. METHODS: Cyst fluid was aspirated during surgical resection of IPMN (n=10), serous cystadenoma (n=1), and cystic low-grade neuroendocrine tumor (n=1). Cyst fluid was also aspirated during EUS-FNA of pancreatic pseudocysts (n=4). Sandwich ELISA was performed on each sample (utilizing mAb Das-1 IgM & IgG isotypes) and results were confirmed by Western Blot analysis. Statistical significance was calculated by T-test. RESULTS: Pancreatic cyst fluid from all benign/low-grade lesions (n=8) demonstrated very little reactivity with mAb Das-1 (OD 0.137±0.181). Specifically, reactivity was low among cyst fluid collected from low-grade IPMN-G (OD 0.088±0.003, n=2), pseudocyst (n=4) (OD 0.088±0.041), and non-pseudocyst, benign/low-grade lesions (n=4) (OD 0.187±0.251). In comparison, high-risk and malignant IPMN lesions (intermediate-grade IPMN-I & all high-grade/invasive IPMNs n=8) expressed a significantly higher amount of reactivity (OD 0.866±0.151) when compared to low-grade IPMN-G (p<0.001), pseudocyst (p<0.001), and all benign/low-grade lesions (p<0.002). When stratified by subtype, low-grade IPMN-G (n=2, OD 0.088±0.003), IPMN-G with highgrade dysplasia or invasive carcinoma (n=2, OD 0.402±0.313), intermediate-grade IPMN-I (n=2, OD 0.6339±0.100), IPMN-I with high-grade dysplasia or invasive carcinoma (n=3, OD 1.232±0.265) and high-grade Oncocytic IPMN (OD 1.161), demonstrated a progressive increase in reactivity to mAb Das-1 among each subtype. All results obtained by ELISA were confirmed by western blot analysis. CONCLUSION: mAb Das-1 demonstrates significantly higher reactivity in cyst fluid from high-risk and malignant IPMN compared to fluid from low-grade IPMN-G, pancreatic pseudocyts, and other low-grade pancreatic cystic lesions. The expression of this marker in preoperative cyst fluid may be a useful tool to identify high-risk IPMN lesions and stratify surgical management.

Mo1200 Detection of Intraductal Papillary Mucinous Neoplasm (IPMN) With a High Risk of Malignant Transformation From Pancreatic Cyst Fluid Aspirates by the DAS-1 Monoclonal Antibody

Mo1200 Detection of Intraductal Papillary Mucinous Neoplasm (IPMN) With a High Risk of Malignant Transformation From Pancreatic Cyst Fluid Aspirates by the DAS-1 Monoclonal Antibody

Tu1514 Limited Application of New International Consensus Diagnostic Criteria for Autoimmune Pancreatitis in Clinical Practice

G A A b st ra ct s of patients with surgical pathology as the gold standard for outcome. Design: 137 patients underwent diagnostic analysis of EUS aspirated pancreatic cyst fluid. DNA was extracted from cyst fluid with quantity and quality (extent of degradation) measured by optical density and qPCR. Mutational analysis targeted KRAS point mutation and loss of heterogeneity (LOH) mutations of 16 markers at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 18q, 21q, 22q. Molecular findings were integrated with results from EUS, chemistry and cytology. For each marker, presence or absence of mutation and clonality were determined, determined, with high clonality comprising 75% of more of cells affected by LOH and low clonality comprising 50-75% of cells. Interpretation of combined molecular, imaging, and chemistry results were classified and subsequently compared to surgical outcome or followup. Surgical pathology was classified into indolent biological behavior (benign or low grade disease), and aggressive biological behavior (high grade or malignant disease). Results: Surgical pathology was available on 81 of these patients. Outcomes included benign cystic neoplasms with low and high grade dysplasia, malignant ductal disease, endocrine neoplasms and pseudocysts. There were 32 aggressive outcomes and 49 indolent outcomes. Molecular findings, including elevated DNA level, and high numbers and clonality of mutations, correlated strongly with aggressive biological behavior. While KRAS mutation was highly specific for mucinous cyst formation, individual molecular parameters used in isolation showed limited sensitivity for detection of aggressive disease. Combining all molecular parameters together, sensitivity was 94%, and specificity was 100%, with overall accuracy of 97%. Conclusions: The molecular biology of pancreatic cystic disease involves multiple pathways that can each lead to cancer. The majority of pancreatic cysts do not progress to cancer and the diagnosis and biological potential of individual lesions can be effectively characterized by integrating broad panel molecular findings with information from first line testing. The presence or absence of aggressive molecular changes, taken in the context of overall findings provides an effective means to individualize patient management when first line results are unclear.

Abstract 4555: Protein and glycan biomarkers of malignant potential in pancreatic cyst fluid

Abstract The early detection of a portion of pancreatic cancer precursors_cystic neoplasms of the pancreas_is possible through high-resolution abdominal imaging, providing an opportunity to successfully treat these lesions before they become invasive. The increased use of abdominal imaging has led to a higher rate of identifying pancreatic cysts, but currently it is not possible to accurately determine which cysts have high malignant potential and should be removed. Our previous work showed that the glycosylation and abundance of specific proteins in the cyst fluid was significantly different between potentially malignant cysts and benign cysts, providing leads for biomarkers to guide patient management. In this work we tested the hypothesis that a panel of specific protein glycoforms forms an accurate biomarker for pancreatic cysts with high malignant potential. Using antibody-lectin sandwich arrays, screens of nearly 100 different candidate markers and multiple glycoforms of each marker confirmed previous results and also showed that two distinct glycan structures are present on several proteins at high levels in the cyst fluid of cancer precursors (intraductal pancreatic mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN)) but not in benign cysts (serous cystadenomas (SC) and pseudocysts (PC)). The glycans, N-acetyl glucosamine and the blood group H structure, previously have not been recognized as cancer biomarkers. A six-marker panel comprising the measurement of one of these glycans on MUC5AC, MUC16, endorepellin, and fibronectin correctly detected 37 of 39 (95%) potential cancer precursors and 16 of 18 (89%) of the benign cysts. This performance significantly surpasses current diagnostic accuracy. The validation of this biomarker panel could lead to more accurate treatment decisions for patients with potentially malignant cysts while sparing patients with benign cysts from unnecessary procedures. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4555. doi:1538-7445.AM2012-4555

Comparison of Surgical and Endoscopic Sample Collection for Pancreatic Cyst Fluid Biomarker Identification

Significant efforts are underway to develop new biomarkers from pancreatic cyst fluid. Previous research has made use of cyst fluid collected from surgically removed cysts, but the clinical implementation of biomarkers would use cyst fluid collected by endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA). The purpose of this study was to investigate the clinical applicability of cyst fluid research obtained using surgical specimens. Matched pairs of operating-room collected (OR) and EUS-FNA samples from 12 patients were evaluated for the levels of three previously described biomarkers, CA 19-9, CEA, and glycan levels detected by wheat germ agglutinin on MUC5AC (MUC5AC-WGA). CA 19-9 and MUC5AC-WGA correlated well between the sample types, although CEA was more variable between the sample types for certain patients. The variability was not due to the time delay between EUS-FNA and OR collection or differences in total protein concentrations but may be caused by contamination of the cyst fluid with blood proteins. The classification of each patient based on thresholds for each marker was perfectly consistent between sample types for CA 19-9 and MUC5AC-WGA and mostly consistent for CEA. Therefore, results obtained using OR-collected pancreatic cyst fluid samples should reliably transfer to the clinical setting using EUS-FNA samples.

Sa1549 Low Volume Pancreatic Cyst Fluid Acquired by Endoscopic Ultrasound (EUS) Guided FNA: Is It Okay to Dilute It for CEA Measurement?

Sa1549 Low Volume Pancreatic Cyst Fluid Acquired by Endoscopic Ultrasound (EUS) Guided FNA: Is It Okay to Dilute It for CEA Measurement?

Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts

BackgroundAccurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts.MethodsA single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.ResultsAmong the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (p = 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%).ConclusionCyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.

Differentiating Branch Duct and Mixed IPMN in Endoscopically Collected Pancreatic Cyst Fluid via Cytokine Analysis

Background. Differentiating branch duct from mixed intraductal papillary mucinous neoplasm (BD-IPMN) is problematic, but clinically important as mixed IPMNs are managed surgically, while some BD-IPMN may be followed. Inflammatory mediator proteins (IMPs) have been implicated in acute and chronic inflammatory and malignant pancreatic diseases. Aim. To compare IMP profile of pancreatic cyst fluid collected endoscopically from BD-IPMN and mixed IPMN. Methods. Pancreatic cyst fluid from ten patients (5 BD-IPMN and 5 mixed IPMN) was collected by endoscopic ultrasound-guided fine needle aspiration or endoscopic retrograde cholangiopancreatography. Concentrations of 89 IMPs in these samples were determined using a multiplexed bead-based microarray protein assay and compared between BD-IPMN and mixed IPMN. Results. Eighty-six of 89 IMPs were detected in at least one of the 10 samples. Fourteen IMPs were detected only in mixed IPMN, while none were only in BD-IPMN. Of these, TGF-β1 was most prevalent, present in 3 of 5 mixed IPMNs. Seventy-two IMPs were detected in both BD-IPMN and mixed IPMNs. Of these, only G-CSF (P < 0.05) was present in higher concentrations in mixed IPMNs. Conclusion. TGF-β1 and G-CSF detected in endoscopically collected pancreatic cyst fluid are potential diagnostic biomarkers capable of distinguishing mixed IPMN from BD-IPMN.

Current status on the diagnosis and management of pancreatic cysts in the Asia–Pacific region: Role of endoscopic ultrasound

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.

Performance Characteristics of Molecular (DNA) Analysis of Pancreatic Cyst Fluid

Performance Characteristics of Molecular (DNA) Analysis of Pancreatic Cyst Fluid

The value of cyst fluid analysis in the pre-operative evaluation of pancreatic cysts.

Like any clinical diagnostic test, analysis of pancreatic cyst fluid should add value in the decision making process of patient management. Pancreatic cysts are a complex group of benign, malignant and premalignant lesions with diverse clinical, radiological and pathological features (1). No longer are the vast majority of pancreatic cysts thought to be pseudocysts, inclusion cysts or benign neoplastic cysts that do not require follow-up. Our knowledge and understanding of neoplastic pancreatic cysts in general and mucinous pancreatic cysts in particular has grown exponentially since the recognition of intraductal papillary mucinous neoplasm (IPMN) as a distinct entity from mucinous cystic neoplasm (MCN) (2). Our realization that all neoplastic mucinous cysts have malignant potential has led to intensive evaluation of patients with both symptomatic and asymptomatic pancreatic cysts to determine the nature of the cyst, and thus the possible need for resection (3).