Nonmucinous Cysts Research Articles

Does pancreas cyst size correlate with the risk for malignancy?

Context: Some studies have suggested that small pancreas cysts can be observed. Large cysts or those with increasing size may require intervention. Mucin-producing or malignant cysts have been suspected by increased cyst flid viscosity, elevated flid CEA level, imaging features, and cytopathology.Objective: The purpose of this analysis is to determine the actual correlation of pancreas cyst size and the presence of malignant or premalignant features.Design: Retrospective study of all consecutive pancreatic cysts that were referred for analysis by endoscopic ultrasound (EUS) over an 18 month period at a single center academic tertiary referral institution.Patients or Participants: A total of 65 cysts in 65 patients were examined (36 men, 29 women, mean age of 56.8 and 59.3 years, respectively).Main outcome measures: The diagnostic predictability of pancreas cyst size alone to identify mucin producing or malignant cysts and all nonmucinous cysts based on cytopathology.Results: The mean 2D size of malignant or mucinous cysts was 9.88cm2. The mean 2D size of all nonmucinous cysts was 16.4cm2 but was not statistically signifiant (p=0.15). Pseudocysts tended to be larger and had a mean size of 22.5cm2 and was statistically different in size from the malignant or mucinous cysts (p=0.044) as well as mean size of serous cysts (7.51cm2, p=0.023). The difference in size between mucinous and serous cysts also was not statistically signifiant (p= 0.62).Conclusions: Pseudocysts have a larger mean size than malignant or mucinous cysts as well as serous cysts. However, the parameter of cysts size alone does not aid in differentiating mucinous and nonmucinous cysts. Cyst flid analysis is essential to determine the type of cyst and optimal management.

Differentiation of mucinous from non-mucinous pancreatic cyst fluid using dual-stained, 1 dimensional polyacrylamide gel electrophoresis.

BackgroundPancreatic cysts are being increasingly identified in patients. Mucinous cysts have malignant potential whereas non-mucinous cysts do not. Distinguishing potentially malignant cysts from harmless ones by the characterization of cyst fluid contents remains a difficult problem. This study was undertaken to determine whether cyst fluid mucin glycoprotein analysis could differentiate mucinous from non-mucinous pancreatic cysts.MethodsCyst fluid from 28 patients who underwent resection of a pancreatic cyst was used for the study. In each case the type of cyst was histologically identified. One dimensional SDS polyacrylamide gel electrophoresis (1D-SDS PAGE) was performed on cyst fluid samples. For the detection of the separated proteins, we employed a novel dual staining technique. The gel was first stained with periodic acid Schiff (PAS), a mucin histochemical stain followed by a secondary protein staining with Simply Blue Safestain (Invitrogen).ResultsVisual scoring (based on the presence of mucins) gave a sensitivity of 95%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 88% for prediction of mucinous histology.ConclusionsOne dimensional SDS polyacrylamide gel electrophoresis of pancreatic cyst fluid, followed by mucin (PAS) and protein (Simply Blue Safestain) staining, provides a means of concentrating and visualizing mucins, which allows the accurate differentiation of mucinous from non-mucinous histology in pancreatic cysts.

Clinical Utility of Intracystic Glucose Levels in Differentiating Mucinous From Non-mucinous Pancreatic Cysts

Introduction: To determine the utility of intracystic glucose levels in differentiating mucinous from nonmucinous pancreatic cysts. Compare the sensitivity and specificity of intracystic glucose versus carcinoembrogenic antigen (CEA) levels in differentiating mucinous from non-mucinous pancreatic cysts. Methods: A total of 17 subjects were included in the analysis. Average age was 66±14 years and 65% were female. Subjects were considered to have mucinous pancreatic cysts based on incidental finding of cyst(s) on MRI, ductal communication suggestive of IPMN, absence of prior history of pancreatitis, EUS features, and cyst fluid analysis and CEA levels. All patients with pseudocysts had documented prior episode of pancreatitis within past 6 months with imaging (CT/MRI) demonstrating new onset pancreatic cystic lesion. These patients had corroborating cyst fluid analysis and CEA levels. In addition, sensitivity and specificity of glucose levels of 2 mg/dL or less, glucose levels of 21 mg/dL or less, and CEA >184 ng/mL were estimated. Results: Intracyst glucose levels ranged from <2 to 121 mg/dL with a mean of 23.5±33.4 mg/dL; 53% had glucose levels ≥2 mg/dL. Patients with non mucinous cysts (pseudocysts) had higher levels of intracystic glucose. Differentiation of mucinous from non-mucinous pancreatic cysts based on intracyst glucose levels was found to be excellent with an AUC of 0.87 (95% CI 0.66, 1.0). Differentiation based on CEA levels was not as good (AUC 0.70; 95% CI 0.45, 0.96) and was not found to be significantly better than flipping a coin. A cutoff of 21 mg/dL or less would provide 100% sensitivity and 83% specificity (Table 1). CEA ≥184 ng/mL on the other had has a sensitivity of only 36% and a specificity of 100%. Using a combination of glucose ≤21 or CEA ≥184 does not improve diagnosis (100% sensitivity and 83% specificity as well).Table 1: Validity of CEA Intracystic Glucose Levels for Differentiating Mucinous From Nonmucinous CystsConclusion: Non-mucinous pancreatic cysts tend to have higher intracystic glucose level. High intracystic glucose level (>21 ng/mL) appears to have a high sensitivity and specificity in differentiating mucinous from non-mucinous pancreatic cysts. This simple, inexpensive test can aid in the evaluation of pancreatic cystic lesions which often pose a diagnostic conundrum.

Evaluating the Revised International Consensus Guidelines for Management of Pancreatic Cysts

Introduction: The aim of this study is to compare the recently proposed 2012 International Consensus Guidelines (Fukuoka criteria) for the management of pancreatic cysts with the previous 2006 guidelines (Sendai criteria). Methods: A 5-year retrospective chart review between August 2007 and August 2012 was performed on patients who underwent surgery after meeting Sendai critera for a pancreatic cyst at a single tertiary academic center. Relevant clinical variables, cyst characteristics, and pathology results were collected to determine the presence of any high-risk stigmata, worrisome features, or alarming EUS findings. Results: Of the 125 eligible patients, 14 patients were excluded from the final analysis because of inadequate data. Among the remaining 111 patients, 14 patients had either adenocarcinoma (N=6) or high-grade dysplastic mucinous lesions (N=8). Using Fukuoka criteria, all of these lesions would have met criteria for surgical resection. Fewer surgeries would have been performed (N=51; 46%) compared to the Sendai criteria, of which 22 (20%) were found to be non-mucinous cysts. Seven MCNs, 3 mixed IPMNs, and 1 cystic neuroendocrine tumor would have been followed rather than resected. Conclusion: Application of the Fukuoka criteria to previously positive Sendai criteria cases results significantly in fewer surgeries without missing cases involving adenocarcinoma or high-grade dysplasia.Table 1

Abstract 1861: S100P is a potential biomarker in distinguishing mucinous from non-mucinous pancreatic cysts and predicting invasive adenocarcinoma

Abstract Introduction. Our previous publications demonstrated that S100P was a highly sensitive biomarker in identifying pancreatic mucinous neoplasms (PMNs) and invasive ductal adenocarcinomas (ADCs) on both cytological and surgical specimens. When working on pancreatic cystic lesions, there are two important undertakings: 1) distinguishing mucinous neoplasms from non-mucinous cysts and 2) predicting the presence of invasive adenocarcinomas. In this study, we investigated the potential utility of S100P for these purposes. Design. Thirty pancreatic cystic fluid samples obtained by EUS-FNA biopsy were retrieved from Geisinger Biospecimen Bank. Diagnosis was based on definitive cytological diagnosis in all cases and additional surgical pathology confirmation in 11 cases. These 30 samples included 7 benign cysts in Group 1, 14 PMNs in Group 2, and 9 ADCs in Group 3. The S100P protein level of each sample was quantitatively measured by enzyme-linked immunoassay (ELISA) (CircuLex S100P ELISA kit, MBL International Corporation) according to the vendor's protocol. Results. The results are summarized in Table 1. Marked elevation of S100P was seen in 6 of 9 ADCs (2129.81 + 1834.34 ng/ml), in contrast to the moderate increase in Group 2 (666.67 + 1439.91 ng/ml) and the minimal increase in Group 1 (22.27 + 18.62 ng/ml). Using 50 ng/ml as a cutoff value to differentiate a PMN/ADC (Group 2 and Group 3) from a benign cyst (Group 1), the sensitivity, specificity, positive predictive value and negative predictive value for identifying a PMN/ADC were 60.9%, 100%, 100%, and 43.8%, respectively. Conclusion. These preliminary data suggest that S100P is a useful biomarker in identifying invasive adenocarcinomas and in distinguishing mucinous neoplasms from non-mucinous cysts. Caution should be taken since some ADCs may show only mildly increased S100P levels, similar to some PMNs and non-mucinous cysts. Additional study in a large series of cases is needed to substantiate the current findings. Table 1.Summary of S100P protein level (ng/ml) in 30 pancreatic cysts by ELISACase #Benign CystsMucinous NeoplasmsAdenocarcinomas12.515.4812.6722.596.6413.2135.0410.8544.07428.0918.371849.20530.6219.802162.98643.2929.402831.67743.75120.483076.958137.954441.439158.684736.0810221.7711285.6012290.78133385.19144628.37 Citation Format: Wenyi Mi, David L. Diehl, Jianhi Shi, Joseph Blansfield, Marie Hunsinger, Wannian Yang, Fan Lin. S100P is a potential biomarker in distinguishing mucinous from non-mucinous pancreatic cysts and predicting invasive adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1861. doi:10.1158/1538-7445.AM2014-1861

The role of cytopathology and cyst fluid analysis in the preoperative diagnosis and management of pancreatic cysts >3 cm.

Pancreatic cyst size >3 cm is a worrisome rather than high-risk feature for malignancy based on the 2012 International Guidelines for the management of mucinous cysts. The value of cytology in preoperative evaluation and surgical triage is unclear. All pancreatic cysts >3 cm resected over a 7-year period were evaluated for clinical, radiologic, and pathologic information. Performance of cytology for the detection of malignancy and surgical triage compared with imaging was assessed. There were 93 histologically confirmed cysts, 52 of which were mucinous and 41 of which were nonmucinous. Of these, 37% were malignant, including 16 nonmucinous malignancies and 18 mucinous cysts (12 with invasive carcinoma, 6 with high-grade dysplasia). Thirty-nine cysts (41% malignant, 59% benign) were not subject to endoscopic ultrasound-fine needle aspiration (EUS-FNA) prior to resection (average size, 6.0 cm). Fifty-four were evaluated by EUS-FNA, with 35 available for review (average size, 5.4 cm). Cytology/cyst fluid analysis had the highest specificity (88.9%) compared with imaging, whereas magnetic resonance imaging (MRI) showed the highest sensitivity (100%). MRI had the highest predictive value for mucinous (100%) versus nonmucinous cysts (100%). MRI and EUS were able to predict malignancy from the presence of high-risk imaging features in all cases. Some benign cases also showed high-risk imaging features on MRI (28.6%), computed tomography (32.3%), and EUS (45.8%). Cytology correctly classified 5 of 6 benign cysts with high-risk imaging as benign. Preoperative evaluation of pancreatic cysts >3 cm is warranted, as many are nonmucinous cysts and not high-grade. Cytology is more specific than imaging for the detection of malignancy in cysts >3 cm.

The Role of Molecular Testing in the Workup of Pancreatic Cysts

Pancreatic cysts are diverse and common lesions that vary in clinical, radiological, and pathological characteristics and are extremely common, affecting approximately 2.6% of asymptomatic adults while reaching a frequency of more than 8% in people older than 80 years.1 Most cysts are benign, even though many are mucinous.2,3 Because not all mucinous cysts are malignant, recognizing the malignant potential for mucinous cysts is of paramount importance. While recent advancements in imaging provide a valuable aid in the differential diagnosis of mucinous and nonmucinous cysts, significant overlap exists.4–6 Cytological evaluation is the first step in the assessment of the pancreatic cyst fluid; however, it is often hampered by high rates of false-negative and indeterminate diagnoses, due mainly to hypocellular or acellular specimens. Biochemical and molecular analysis of pancreatic cyst fluid can be extremely helpful in the assessment of pancreatic cystic lesions. Recent advancements in the understanding of the molecular mechanisms of pancreatic carcinogenesis may lead to more accurate diagnosis. We present a recent case seen in the authors’ practice that illustrates how integrating molecular testing in routine pancreatic cytology can lead to improvement in the pathologist’s capacity to diagnose pancreatic cystic lesions. We provide a brief review of the added value of an integrated, morphobiologic approach to pancreatic cytology.

Investigating MicroRNA Expression Profiles in Pancreatic Cystic Neoplasms

OBJECTIVES:Current diagnostic tools for pancreatic cysts fail to reliably differentiate mucinous from nonmucinous cysts. Reliable biomarkers are needed. MicroRNAs (miRNA) may offer insights into pancreatic cysts. Our aims were to (1) identify miRNAs that distinguish benign from both premalignant cysts and malignant pancreatic lesions using formalin-fixed, paraffin-embedded (FFPE) pathology specimens; (2) identify miRNAs that distinguish mucinous cystic neoplasm (MCN) from branch duct-intraductal papillary mucinous neoplasm (BD-IPMN).METHODS:A total of 69 FFPE pancreatic specimens were identified: (1) benign (20 serous cystadenoma (SCA)), (2) premalignant (10 MCN, 10 BD-IPMN, 10 main duct IPMN (MD-IPMN)), and (3) malignant (19 pancreatic ductal adenocarcinoma (PDAC)). Total nucleic acid extraction was performed followed by miRNA expression profiling of 378 miRNAs interrogated using TaqMan MicroRNA Arrays Pool A and verification of candidate miRNAs. Bioinformatics was used to generate classifiers.RESULTS:MiRNA profiling of 69 FFPE specimens yielded 35 differentially expressed miRNA candidates. Four different 4-miRNA panels differentiated among the lesions: one panel separated SCA from MCN, BD-IPMN, MD-IPMN, and PDAC with sensitivity 85% (62, 97), specificity 100% (93, 100), a second panel distinguished MCN from SCA, BD-IPMN, MD-IPMN, and PDAC with sensitivity and specificity 100% (100, 100), a third panel differentiated PDAC from IPMN with sensitivity 95% (76, 100) and specificity 85% (72, 96), and the final panel diagnosed MCN from BD-IPMN with sensitivity and specificity approaching 100%.CONCLUSIONS:MiRNA profiling of surgical pathology specimens differentiates serous cystadenoma from both premalignant pancreatic cystic neoplasms and PDAC and MCN from BD-IPMN.

Characterization of Glycoproteins in Pancreatic Cyst Fluid Using a High-Performance Multiple Lectin Affinity Chromatography Platform

Currently, pancreatic cancer is the fourth cause of cancer death. In 2013, it is estimated that ∼38 460 people will die of pancreatic cancer. Early detection of malignant cyst (pancreatic cancer precursor) is necessary to help prevent late diagnosis of the tumor. In this study, we characterized glycoproteins and nonglycoproteins on pooled mucinous (n = 10) and nonmucinous (n = 10) pancreatic cyst fluid to identify "proteins of interest" to differentiate between mucinous cyst from nonmucinous cyst and investigate these proteins as potential biomarker targets. An automated multilectin affinity chromatography (M-LAC) platform was utilized for glycoprotein enrichment followed by nano-LC-MS/MS analysis. Spectral count quantitation allowed for the identification of proteins with significant differential levels in mucinous cysts from nonmucinous cysts of which one protein (periostin) was confirmed via immunoblotting. To exhaustively evaluate differentially expressed proteins, we used a number of proteomic tools including gene ontology classification, pathway and network analysis, Novoseek data mining, and chromosome gene mapping. Utilization of complementary proteomic tools revealed that several of the proteins such as mucin 6 (MUC6), bile salt-activated lipase (CEL), and pyruvate kinase lysozyme M1/M2 with significant differential expression have strong association with pancreatic cancer. Furthermore, chromosome gene mapping demonstrated coexpressions and colocalization of some proteins of interest including 14-3-3 protein epsilon (YWHAE), pigment epithelium derived factor (SERPINF1), and oncogene p53.

Role of endoscopic ultrasonography in pancreatic cystic neoplasms: Where do we stand and where will we go?

We increasingly encounter pancreatic cystic neoplasms (PCN) in clinical practice and the differential diagnoses vary widely from benign to malignant. There is no 'one and only' diagnostic procedure for PCN. Multiple modalities including computed tomography, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound (EUS) are widely used, but EUS has the advantage of anatomical proximity to the pancreas and upper gastrointestinal tract. In addition, EUS-guided fine-needle aspiration (EUS-FNA) provides both cytological evaluation and cyst fluid analysis. Although the role of EUS-FNA for PCN is established, the sensitivity of cytology is low and cyst fluid analysis is only useful for differentiation between mucinous and non-mucinous cysts. Recently, novel through-the-needle imaging under EUS-FNA, such as confocal laserendomicroscopy, is expected to attribute to a better diagnostic yield. Moreover, feasibility of cyst ablation has been reported and the role of EUS has expanded from diagnosis to treatment. However, clinical impact of cyst ablation in terms of safety, efficacy and cost-effectiveness should be validated further. In summary, EUS and EUS-guided intervention does and will play a central role in the management of PCN from surveillance to treatment, but many clinical questions remain unanswered, which warrants well-designed prospective clinical trials.

Utility of a Commercial Molecular Panel (REDPATH) in Pancreatic Cyst Fluid Analysis: A Single Center Experience

Background: Promising studies using molecular analysis to characterize pancreatic cysts as benign, pre-malignant, or malignant have led to the development of commercial molecular analysis panels, the role of which remains to be fully elucidated. Objective: To determine the clinical utility of commercial molecular analysis (RedPath) of pancreatic cyst fluid. Methods: Retrospective review of 105 consecutive EUS/FNA patients with pancreatic cysts referred to UC Davis Medical Center was completed. Among this group, 34 cases for which RedPath was obtained were used in the ensuing analysis. A CEA cutoff >192 ng/ml was used to classify cysts as mucinous. RedPath criteria for cyst classification as benign non-mucinous, indolent, or malignant included presence of a K-ras-2 mutation, two or more LOH mutations, or greatly elevated DNA quantity. Concordance was assessed using Cohen Kappa values. Simple probit regression was used to model clinical predictors of concordance. Sensitivity and specificity were determined using clinical consensus diagnosis as reference. Results: Fair agreement was noted between CEA and RedPath analysis (K=0.38). There were 24 concordant cases and 10 discordant cases. REDPATH did not predict more malignant pathology in any of the discordant cases. Regression analysis was used to assess whether clinical predictors such as family history of malignancy, presence of symptoms, diabetes, and cyst size were associated with discordance. No statistical significance was observed among these clinical predictors (p=0.69, p=0.98, p=0.30, p=0.63 respectively). No cases were identified in which RedPath results directly altered follow-up interval or referral to surgery. The results were used as supportive evidence in 62% of patients, to confirm surveillance recommendations. In the remaining 38% of patients, RedPath results were either unavailable or not addressed at follow-up. The sensitivity/specificity/accuracy of RedPath for diagnosing benign nonmucinous cysts was 100%/50%/75% and for benign mucinous cysts was 50%/100%/75%. Conclusion: CEA and RedPath analysis had fair concordance. Among discordant cases, RedPath neither predicted more malignant disease than CEA, nor did it alter follow-up intervals. RedPath was used mainly to corroborate CEA/EUS/cytology-based clinical decision on surveillance intervals. No clinical predictors were associated with discordant CEA and RedPath results. The high sensitivity of RedPath for benign nonmucinous cysts suggests a potential role for this modality as a reliable rule-out test for benign nonmucinous pathology. Further research should focus on cost effectiveness, and defining a specific role for its use in the management of pancreatic cystic neoplasms.

Specific Glycoforms of MUC5AC and Endorepellin Accurately Distinguish Mucinous from Nonmucinous Pancreatic Cysts

Specific protein glycoforms may be uniquely informative about the pathological state of a cyst and may serve as accurate biomarkers. Here we tested that hypothesis using antibody-lectin sandwich arrays in broad screens of protein glycoforms and in targeted studies of candidate markers. We profiled 16 different glycoforms of proteins captured by 72 different antibodies in cyst fluid from mucinous and nonmucinous cysts (n = 22), and we then tested a three-marker panel in 22 addition samples and 22 blinded samples. Glycan alterations were not widespread among the proteins and were mainly confined to MUC5AC and endorepellin. Specific glycoforms of these proteins, defined by reactivity with wheat germ agglutinin and a blood group H antibody, were significantly elevated in mucinous cysts, whereas the core protein levels were not significantly elevated. A three-marker panel based on these glycoforms distinguished mucinous from nonmucinous cysts with 93% accuracy (89% sensitivity, 100% specificity) in a prevalidation sample set (n = 44) and with 91% accuracy (87% sensitivity, 100% specificity) in independent, blinded samples (n = 22). Targeted lectin measurements and mass spectrometry analyses indicated that the higher wheat germ agglutinin and blood group H reactivity was due to oligosaccharides terminating in GlcNAc or N-acetyl-lactosamine with occasional α1,2-linked fucose. The results show that MUC5AC and endorepellin glycoforms may be highly specific and sensitive biomarkers for the differentiation of mucinous from nonmucinous pancreatic cysts.

Clinical decision making in the management of pancreatic cystic neoplasms

Pancreatic cystic lesions continue to pose diagnostic and management dilemmas for physicians. This may be related, in part, to the fact that these lesions represent a range of diagnostic possibilities, from inflammatory cysts and nonmucinous cysts to mucinous cysts, which may or may not have foci of invasive malignancy. Adequate characterization of cystic lesions is necessary to help devise a management plan. Moreover, patient-related factors such as comorbid conditions are often essential in deciding whether patients should be managed by a conservative approach of watchful waiting versus surgical resection, if so indicated. This review summarizes the recent advances in the management of pancreatic cystic neoplasms.

Mo1513 A Retrospective Analysis of Serial Fluid Analysis of Pancreatic Cystic Neoplasms Under EUS Surveillance: Is There Any Role in Repeat Cyst Fluid CEA Measurement?

Fluid analysis of pancreatic cystic neoplasms (PCNs) using EUS-fine needle aspiration (EUS-FNA) are routinely performed to differentiate mucinous vs. non-mucinous cysts. Specificity of cytology in the diagnosis of malignant PCNs is high but its sensitivity is low. In cyst fluid analysis, a CEA of >192 ng/mL is one of the standard criteria for diagnosing mucinous cysts, but it is not useful for differentiating malignant lesions. Most PCNs including mucinous cysts undergo interval surveillance, including repeat EUS, but the role and significance of repeat fluid analysis is poorly defined in patients with PCNs under serial EUS.

486 Optical Markers Measured in Duodenal Tissue Can Distinguish Mucinous From Non-Mucinous Pancreatic Cysts

486 Optical Markers Measured in Duodenal Tissue Can Distinguish Mucinous From Non-Mucinous Pancreatic Cysts

Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine

Better pancreatic cyst fluid biomarkers are needed. To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. Retrospective study. Tertiary-care referral center. Two independent cohorts of patients (n= 26 and n= 19) with histologically defined pancreatic cysts. Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P= .002, validation P= .006; and kynurenine first cohort P= .002, validation P= .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. Small sample sizes. Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

Testing cross-species and cross-organ stellate cells as model system for pancreatitis research

s / Pancreatology 13 (2013) e1–e94 e65 and 0.002). Kynurenine level had a diagnostic accuracy of 90% and 95%, respectively, in the two cohorts. Neither could differentiate pre-malignant from malignant cysts. Conclusion: Metabolomic profiling identified glucose and kynurenine to have clinical utility for classification of mucinous and non-mucinous pancreatic cysts. Further evaluation with this approach is warranted.

Diagnosis of Pancreatic Cysts: Endoscopic Ultrasound, Through-the-needle Confocal Laser-induced Endomicroscopy and Cystoscopy Trial (DETECT Study)

Purpose: Probe-based confocal laser-induced endomicroscopy (pCLE) enables in-vivo real time GI tract imaging. A prototype high-resolution CLE probe has been developed (Cellvizio, Mauna Kea Technologies), which inserts into a 19G FNA needle allowing for needle-based CLE (nCLE). The diagnosis of pancreatic cysts, which now depends on morphology, cytology and fluid analysis, is challenging. The combination of direct visualization (cystoscopy) using a through-the-needle fiber optic probe (Spyglass, Boston Scientific) and nCLE under EUS guidance may improve the diagnosis of pancreatic cysts.The aim of this study (NCT#01447238) was to determine the feasibility and safety of EUS-guided dual “through-the-needle” imaging (cystoscopy and nCLE) and to identify specific imaging features which correlate with mucinous vs. non-mucinous cysts. Methods: After EUS examination, the cyst was punctured with a 19G FNA needle (Cook Medical) preloaded with a fiber optic probe. After examination of the cyst wall and contents, the probe was exchanged with nCLE probe and in vivo imaging was performed after IV injection of 2.5 ml fluorescein. Both exams were performed by advancing the probe just beyond the needle tip. Finally, fluid was aspirated and string sign, cytology, CEA and amylase evaluated. Clinical diagnosis was based on surgical pathology or clinical presentation combined with EUS findings, CT/MRI, cytology and fluid analysis (independent blinded review). Results: From October 2010 to May 2012, 30 patients with pancreatic cysts were enrolled (Table 1). Clinical diagnosis was “high certainty” in 18 (IPMN-7, MCN-3, SCN-4, pseudocyst-3, lymphoepithelial cyst-1) and “less certain” in 12 (IPMN-7, SCN-4, retention cyst-1). Needle puncture, probe advancement, and image acquisition was successful in all 30 cases; 29 via single puncture. Two patients developed pancreatitis requiring 4-day hospitalizations. The image quality of cystoscopy and nCLE was good/excellent in 20 (67%) and 27 (90%) cases, respectively. Cystoscopy and nCLE findings of mucinous vs. non-mucinous cysts in cases with high certainty diagnosis (2 surgical, 16 clinical) are shown in Table 2. Mucin on cystoscopy and epithelial structures on nCLE were specific (100%) to mucinous cysts and presence of debris on cystoscopy was specific (100%) to non-mucinous cysts. Sensitivity for mucinous cysts using: cystoscopy (mucin) alone, nCLE (epithelial structures) alone, and cystoscopy + nCLE was 90%, 80%, and 100% respectively.Table 1: Patient characteristics and FNA resultsTable 2: FNA results and image findings on cystoscopy and nCLE in mucinous and non-mucinous lesions and their sensitivity, specificity, PPV and NPV for mucinous cystsConclusion: EUS-FNA with through-the-needle cystoscopy and nCLE for pancreatic cysts appears safe and feasible, and specific features were identified which appear to predict the clinical diagnosis of mucinous vs. non-mucinous cysts. Additional data confirming histologic correlation is needed. Disclosure: Dr. Chang - consultant for Olympus, Wilson Cook. Dr. Samarasena - None. Dr. Nakai - None. Dr. Iwashita - None. Dr. Lee - None. Dr. Park - None.

Commercial Molecular Panels Are of Limited Utility in the Classification of Pancreatic Cystic Lesions

The PathfinderTG biomarker panel is useful in the evaluation of pancreatic cysts that have clinical features suspicious for malignancy, but its utility in classifying fine-needle aspiration biopsies from small pancreatic cystic lesions is yet to be proven. We used morphology to classify 20 pancreatic cyst cytology aspirates, all of which met radiographic criteria for close observation. Cases were cytologically classified as consistent with pseudocyst, serous cystadenoma, or mucinous neoplasm with low-grade, intermediate-grade, or high-grade dysplasia and analyzed for carcinoembryonic antigen. Redpath Integrated Pathology Inc. rendered diagnoses of nonmucinous (reactive/indolent or serous) or mucinous (low-risk or at risk) cyst on the basis of results of the PathfinderTG panel (KRAS mutations, DNA content, and loss of heterozygosity at microsatellites linked to tumor suppressor genes). Cytologic and commercial laboratory diagnoses were concordant in only 7 (35%) cases. Seven cysts classified as mucinous with low-grade dysplasia by cytology were interpreted as nonmucinous on the basis of the PathfinderTG panel, 2 of which were resected mucinous cysts. Two pancreatitis-related pseudocysts were misdiagnosed as low-risk mucinous cysts; 1 mucinous cyst with low-grade dysplasia was considered at risk for neoplastic progression using the PathfinderTG panel. Only 1 cyst misclassified as pseudocyst by cytology, but low-risk mucinous cyst by molecular analysis, proved to be a mucinous cystic neoplasm with low-grade dysplasia after surgical resection. We conclude that the PathfinderTG panel may aid the classification of pancreatic lesions, but is often inaccurate and should not replace cytologic evaluation of these lesions.

Diagnostic Performance of Pancreatic Cyst Fluid Carcinoembryonic Antigen (CEA) and Amylase: A Community Hospital Experience

Purpose: EUS/FNA is performed on pancreatic cystic lesions (PCL) when feasible and fluid sent for CEA/amylase. Although the literature has varied CEA cutoff values, many centers use CEA (ng/mL) of <5 for distinguishing non-mucinous cysts from mucinous cysts (MC) and >192 for mucinous cystadenomas (MCA). Amylase of 250 U/L is often used to differentiate pseudocysts (PC) from other cysts. Sensitivities (SN) and specificities (SP) differ between studies. Analyses of PCL in a community/non-academic setting may be an important addition to exiting data. Using our cyst data, our goals were to: (1) analyze the performance of CEA in differentiating MC from non-MC and benign from malignant; (2) test the ability of amylase in differentiating MC from non-MC, benign from malignant, IPMN from MCA, PC from non-PC; (3) calculate SN and SP of commonly used CEA and amylase values. Methods: Retrospective review of PCL which had EUS/FNA for CEA and amylase then confirmation of cyst type via cytology/histopathology. Results: Twenty-three cases met the search criteria between December 2007 and November 2011. Median (IQR, interquartile range) of CEA (ng/mL) in MC and non-MC were 642.50 (68.53-9,278.25) and 10.05 (1.65-22,238), respectively (p=0.19). Median (IQR) of CEA in benign MC and malignant MC were 642.50 (28.38-9,466.75) and 2,283 (284-4,282), respectively (p=1.00). Median (IQR) of amylase (U/L) in MC and non-MC were 283 (131-800) and 800 (411.5-14,579), respectively (p=0.35). Median (IQR) of amylase in benign MC and malignant MC were 541.50 (104.25-800) and 227 (227-227), respectively (p=0.60). Median (IQR) of amylase in IPMN and MCA were 125.50 (24-227) and 800 (207-800), respectively (p=0.11). Median (IQR) of amylase in PC and non-PC were 14,579 (800-28,358) and 314.5 (88.75-800), respectively (p=0.06). None of the differences were statistically significant; small sample size was a limitation. CEA <5 for diagnosis of non-MC had SN of 50% and SP of 94%. CEA >192 for the diagnosis of MCA had SN of 57% (increased to 64% when IPMN included) and SP of 67%. CEA of >800 in distinguishing MCA/MCAC (mucinous cystadenocarcinoma) from SCA (serous cystadenoma)/PC had SN of 46% and SP of 75%. Ability of amylase <250 to distinguish SCA, MCA, and MCAC from PC had SN of 30% and SP of 100%. Amylase in IPMN were low in our data with median (IQR) of 125.5 (24-227), which is contrary to prior reports of much higher IPMN amylase values. Conclusion: In a non-academic setting, commonly used CEA and amylase values for the diagnosis of PCL yielded similar SN and SP (slightly lower in some cases) as those reported in the medical literature. Cyst fluid CEA and amylase analyses pose diagnostic challenges in differentiating PCL. Amylase in IPMNs were lower compared to prior reports.