Lead-Time Trajectory of CA19-9 as an Anchor Marker for Pancreatic Cancer Early Detection.

BACKGROUND & AIMS: There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established. METHODS: CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined. RESULTS: In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection. CONCLUSION: CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.

Analysis of T-cell receptor repertoire in peripheral blood of patients with pancreatic cancer and other pancreatic diseases.

Pancreatic cancer (PC) has been the fourth cancer-related death worldwide, diagnosed at an unresectable stage due to its rapid progression and few symptoms of this disease at early stages. The aim of this study was to determine the association between the diversity of T-cell receptor (TCR) repertoire and clinicopathological characteristics of patients with PC and other benign pancreatic diseases. In order to make a comprehensive analysis the TCR repertoire, high-throughput sequencing was used to differentiate complementarity determining region 3 (CDR3) of the TCR ß chain in peripheral blood samples from 3 PC, 3 chronic pancreatitis, 3 pancreatic cystic lesions and 3 pancreatic neuroendocrine tumour patients. We found that there were significant differences related to TCR repertoire between PC and other pancreatic diseases, and PC is a relatively immunosuppressive tumour. Changes of peripheral TCR repertoire may be used to predict the progression of PC and the response to immunotherapy. And there may exist novel-specific antigens in PC patients which could be used to design targeting immunotherapy in the nearly future.

Diagnostic yield of endoscopic ultrasound with fine-needle aspiration in pancreatic cystic lesions. / Rendimiento diagnóstico de la punción mediante ultrasonografía endoscópica de las lesiones quísticas del páncreas.

INTRODUCTION: Despite advances in imaging techniques, in many cases they are insufficient to establish the diagnosis of pancreatic cystic lesions (PCL). There are few publications in our setting that evaluate the combination of several methods obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to evaluate the overall utility of EUS-FNA in the diagnosis of PCL. MATERIAL AND METHODS: Retrospective study based on a database updated prospectively of a cohort of patients referred for EUS-FNA due to PCL detected in an imaging test. The sensitivity, specificity and diagnostic yield of carcinoembryonic antigen (CEA), cytology and viscosity were studied to detect mucinous lesions. RESULTS: From November 2013 to April 2018, 122 EUS were performed for PCL. EUS-FNA was performed in 94/122 (77%) and 21/122 (17.2%) patients were operated on. We included 33/122 patients who had diagnostic confirmation by histology, imaging (serous cyst with typical pattern) or clinical evolution. The study of the ROC curve determined the cutoff point ≥419 ng/ml to differentiate mucinous/non-mucinous cystic lesions. The diagnostic yield of CEA was 87.5% (21/24), cytology 81.8% (27/33) and viscosity 84.4% (27/32). The three parameters in combination obtained the best result (30/33, 90.9%). CONCLUSION: The combination of CEA analysis, cytology and viscosity of pancreatic fluid obtained by EUS-FNA increases the performance in the diagnosis of mucinous pancreatic cystic lesions, with it being greater than 90%.

The Feasibility of Serum Multiple Tumor Markers Test Between Patients with Primary Pancreatic Cancer and Those with Benign Pancreatic Cystic Disease.

BACKGROUND: Although CA 19-9 is the primary marker used in the diagnosis and treatment of pancreatic cancer, other serum tumor markers have also been utilized in the follow-up of pancreatic cancer. We investigated the clinical utility of CYFRA 21-1, AFP, CEA, CA 19-9, CA 125, NSE, and combinations of these markers in patients with pancreatic cancer. METHODS: We enrolled patients with primary pancreatic cancer and benign pancreatic cystic disease (n = 163). We performed sensitivity tests for multiple tumor markers, plotted receiver operating characteristic curves, and conducted multivariate analysis using the Cox proportional hazard method. Survival data were evaluated using Kaplan-Meier analysis of overall survival. RESULTS: Among multiple tumor markers assessed in this study, CA 19-9 showed good diagnostic performance, with an area under the curve of 0.86 ± 0.04 in ROC analysis. Based on two different cutoff values, CYFRA 21-1 (≥ 2.0 and 1.83 ng/mL) had a respective sensitivity of 80.4% and 82.3% and was also more significant than the other tumor markers in a parallel test. There was a weak significant relationship between tumoral fluorodeoxyglucose uptake and CYFRA 21-1 or CA 19-9. Initial CA 125, CYFRA 21-1, and CEA could be utilized to categorize subgroups with different overall survival. In multivariate analyses, CA 125 (HR 18.8, p < 0.001) and CYFRA 21-1 levels (HR 0.962, p = 0.006) demonstrated independent prognostic significance for predicting overall survival. CONCLUSIONS: In addition to CA 19-9, the present study suggested that various tumor markers could be used in the diagnosis and prognosis of pancreatic cancer. Further studies are warranted to confirm the clinical usefulness of diverse biological markers in pancreatic cancer.

Validation of Sendai and Fukuoka consensus guidelines in predicting malignancy in patients with preoperatively diagnosed mucinous pancreatic cystic neoplasms.

BACKGROUND AND OBJECTIVES: The Sendai consensus guidelines (SCG) and Fukuoka consensus guidelines (FCG) have been examined for their roles in predicting advanced neoplasia (AN) in pancreatic cystic neoplasm (PCN) patients with mixed results. We aim to evaluate the utilities of both guidelines in a Chinese cohort with preoperatively diagnosed mucinous PCNs. METHODS: One hundred ninety-seven patients who underwent resections from 2008 to 2015 in Zhong Shan Hospital, Fudan University for suspected PCNs were retrospectively reviewed. Receiver operating characteristic (ROC) curves were calculated and compared to measure diagnostic value. RESULTS: Fifty-five patients were diagnosed with AN pathologically. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the SCG high-risk (SCGHR ) criteria were 87.3%, 28.2%, 32.0%, 85.1%, and 44.7%, respectively, and for the FCG high-risk (FCGHR ) criteria, they were 40.0%, 95.8%, 78.6%, 80.5%, and 80.2%, respectively. ROC curve comparison analyses showed that the FCGHR were superior to the SCGHR (P = 0.02). The performance of the FCGHR was enhanced with CA19-9 incorporated (P = 0.004). CONCLUSIONS: The FCG were superior to the SCG in this retrospective analysis, which could be further improved by the incorporation of CA19-9. However, the practical safety remains uncertain because of missed invasive carcinoma cases.

Hypernatremia and acute pancreatitis in chronic kidney disease: back to the salt mines. Questions.

BACKGROUND: Acute pancreatitis can be a life-threatening complication in patients with chronic kidney disease (CKD), especially in kidney transplant recipients. CASE DIAGNOSIS/TREATMENT: The patient was 7 years old when he received renal transplantation for CKD secondary to posterior urethral valves. Two years later, he presented with severe necrotizing pancreatitis (Ranson's score 5, Balthazar's score 8). Viral and genetic testing came back negative; pancreatitis was attributed to the patient's treatments (prednisone, trimethoprim-sulfamethoxazole, and everolimus). Twenty days later, necrotized pancreatic cysts had formed. Two drains were surgically inserted into the abdomen, and continuous cyst lavage was started with normal saline solution. Two days later, blood tests revealed severe hypernatremia and hypokalemia. We suspected unwanted peritoneal dialysis had occurred because of the high sodium chloride content and the absence of potassium in the normal saline solution being used for cyst lavage. We switched to a peritoneal dialysis solution for the lavage, leading to complete correction of hydroelectrolytic disorders. CONCLUSION: Acute pancreatitis is a frequent and potentially severe complication in CKD patients. It should be suspected in the presence of nonspecific symptoms, such as abdominal pain or vomiting. Rigorous monitoring of electrolytes is also mandatory for managing CKD patients with acute pancreatitis.

Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA.

BACKGROUND: Pancreatic cysts are common incidental findings with malignant potential, raising diagnostic and treatment dilemmas. AIMS: To determine the added value of KRAS and GNAS mutation analysis on cyst classification and decision making. METHODS: We analyzed 52 frozen samples of pancreatic cystic fluid obtained by EUS-FNA between 2008 and 2014. In addition to cytology and CEA, mutations of GNAS (exons 8 and 9) and KRAS (exons 2 and 3) genes were analyzed using Sanger sequencing. RESULTS: There were 52 patients, 67% females, with a mean age of 59 ± 15 years (29-91). Cysts were classified as mucinous in 21 patients (40%) (14 low-risk, seven malignant) and non-mucinous in 31 patients (60%). After EUS-FNA, 11 patients had surgery, six had chemotherapy or palliation, one had endoscopic drainage, and 34 are on follow-up after a mean of 57 months. KRAS mutation was detected in nine and GNAS in two samples. Patients harboring cysts with KRAS mutations were older (p = 0.01), cysts were more commonly mucinous (p = 0.001) and malignant (p = 0.01). KRAS mutations were present in both low-risk and malignant mucinous lesions. For identifying mucinous lesions, CEA > 192 ng/mL performed better (AUC ROC = 93%), whereas for malignant/high-risk mucinous lesions, EUS imaging had the best accuracy (AUC ROC = 88%). After molecular analysis, a modification in cyst classification occurred in ten patients, but was correct in only two, a pseudocyst re-classified as IPMN and a malignant cyst as a non-mucinous cyst. CONCLUSIONS: In this cohort of patients with pancreatic cysts, KRAS and GNAS mutations had no significant diagnostic benefit in comparison with conventional testing.

Novel Biomarkers for Pancreatic Cysts.

With increased utilization and ongoing advancements in cross-sectional abdominal imaging, the identification of a pancreatic cyst has become a frequent finding. While many pancreatic cysts are associated with a benign clinical course, others may transform into pancreatic ductal adenocarcinoma. However, distinguishing a benign from a malignant pancreatic cyst or pancreatic cyst with malignant potential on the basis of standard clinical findings, imaging parameters and ancillary studies can be challenging. Hence, a significant interest within the past decade has been the identification of novel biomarkers to accurately classify and prognosticate a pancreatic cyst. Within this review, we discuss novel DNA, miRNA, protein and metabolite biomarkers, and their relevance in clinical practice. In addition, we focus on future areas of research that have the potential to change pancreatic cyst management.

American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data.

BACKGROUND AND AIMS: The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts. METHODS: The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN. RESULTS: Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value. CONCLUSIONS: The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI surveillance. The results of an alternative approach with integrative molecular testing are encouraging but require further validation.

Lymphoepithelial cysts of the pancreas. Can preoperative imaging distinguish this benign lesion from malignant or pre-malignant cystic pancreatic lesions?

CONTEXT: Lymphoepithelial cysts of the pancreas are rare true benign cystic tumors of the pancreas of uncertain etiology. Cystic neoplasms of the pancreas present a significant diagnostic dilemma in differentiating benign from premalignant or malignant variants. Since the first description of lymphoepithelial cysts in 1985, 109 cases have been reported in the literature. We describe 6 cases of this rare tumor, the preoperative imaging results, and a review the literature. PATIENTS: Five males and one female ranging in age from 47 to 76 years underwent resection for lymphoepithelial cysts. Five patients presented with abdominal pain related to the lesion and in one patient the lesion was discovered incidentally. Four patients had elevated serum CA 19-9 levels. Pre-operative imaging with a CT scan and MRI of the abdomen typically revealed a well defined hypodense mass with Hounsfield units (HU) in the range of 15 to 20. One patient had papillary projections into the lesion. The mean size was 3.3 cm (ranging from 1.8 cm to 4 cm). All lesions were exophytic off the pancreatic parenchyma (1 cyst was located in the head of the pancreas, 2 were in the body, and 3 were in the tail region). Pre-operative EUS-guided/CT-guided needle aspiration, when performed, was not diagnostic. All patients underwent resection (one pancreaticoduodenectomy, five left pancreatectomies) to remove these cystic neoplasms. Pathology revealed a cyst lined by non-dysplastic squamous cells surrounded by sheets of benign lymphocytes. No evidence of malignancy was found. CONCLUSION: Lymphoepithelial cysts of the pancreas are rare and are characteristically seen in men. While a hypodense mass (less than 20 HU) with papillary projections should be considered suspicious for lymphoepithelial cyst, a definitive diagnosis cannot be made solely based on preoperative imaging. EUS-guided biopsy coupled with biochemical/tumor marker studies are increasingly being used as a diagnostic tool to help differentiate between the various types of cystic pancreatic neoplasms. Imaging findings of lymphoepithelial cysts are non-specific and hence surgical resection is often required to rule out the presence of a malignant or pre-malignant cystic pancreatic lesion. In true lymphoepithelial cysts, malignant transformation is not seen and patients who have these cysts are not at increased risk of developing a pancreatic malignancy.

K-ras mutations correlate with atypical cytology and elevated CEA levels in pancreatic cystic neoplasms.

INTRODUCTION: Benign pancreatic cystic neoplasms are important precursors to pancreatic adenocarcinoma, and offer the opportunity to prevent cancer. Conversely, prevention only occurs with surgical resection associated with significant morbidity and mortality, while the natural history of small cystic neoplasms is a slow and uncertain progression to malignancy. Markers that predict progression to malignancy are needed. Cyst fluid DNA analysis including K-ras mutations may predict more aggressive natural history of pancreatic cystic neoplasms. METHODS: Sixty patients with pancreatic cysts measuring less than 3 cm without solid component or pancreatic ductal dilation underwent EUS with fine needle aspiration. Nine had surgical resection. Cyst fluid was tested for cytology, CEA levels, and DNA analysis including K-ras mutations, and eight loss of heterozygosity mutations. Mutations were correlated with findings of atypia and CEA levels. RESULTS: Cyst fluid K-ras mutation was found in 30% of patients. Patients with mutated K-ras were more likely to have atypia on cytology or pathology (39 vs. 14%) and higher CEA (median 591 vs. 42) compared to wild-type K-ras. K-ras mutants were more likely to have two or more loss of heterozygosity mutations. Loss of heterozygosity mutations did not correlate with atypia or CEA levels. CONCLUSIONS: Cyst fluid K-ras mutation correlates with other markers of aggressive cyst behavior. EUS with cyst DNA analysis may alter management of smaller pancreatic cysts when surgery might otherwise be deferred. Further studies of cyst fluid DNA and long-term outcomes are needed.

Macrophage inhibitory cytokine-1/growth differentiation factor-15 in premalignant and neoplastic tumours in a high-risk pancreatic cancer cohort.

BACKGROUND: Pancreatic cancer (PC) is a leading cause of cancer related mortality worldwide, with poor survival due to late diagnosis. Currently, biomarkers have limited use in early diagnosis of PC. Macrophage inhibitory cytokine-1 or growth differentiation factor-15 (MIC-1/GDF15) has been implicated as a potential serum biomarker in PC and other malignancies. AIM: To determine the role of MIC-1/GDF15 in detecting pre-malignant pancreatic lesions and neoplastic tumours in an asymptomatic high-risk cohort part of Australian Pancreatic Cancer Screening Program. METHODS: A feasibility prospective single centre cohort study was performed. Participants recruited for yearly surveillance with endoscopic ultrasound (EUS) had serial fasting blood samples collected before EUS for MIC-1/GDF15, C-reactive protein and carbohydrate antigen 19-9. Patients were stratified into five groups based on EUS findings: Normal; pancreatic cysts, branch-duct intraductal papillary mucinous neoplasm; diffuse non-specific abnormalities; and neoplastic tumours. MIC-1/GDF15 serum levels were quantified using ELISA. Participants in whom EUS demonstrated abnormalities but not malignancy were closely followed up with magnetic resonance imaging (MRI) or computed tomography. RESULTS: One hundred twenty participants were prospectively recruited from 2011-2018. Forty-seven participants (39.2%) had an abnormal EUS and five participants (4.2%) were diagnosed with neoplastic tumours, three by EUS (two pancreatic and one liver) and two by MRI/computed tomography (breast cancer, bladder cancer), which were performed for follow up of abnormal EUS. Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operator characteristic curve analysis [area under curve (AUC) = 0.814, P = 0.023]. Baseline serum MIC-1/GDF15 had moderate predictive capacity for branch-duct intraductal papillary mucinous neoplasm (AUC = 0.644) and neoplastic tumours noted on EUS (AUC = 0.793), however this was not significant (P = 0.188 and 0.081 respectively). Serial serum MIC-1/GDF15 did not demonstrate a significant percentage change between a normal and abnormal EUS (P = 0.213). Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours (Median = 1039.6, interquartile range = 727.0-1977.7) compared to those diagnosed with a benign lesion (Median = 570.1, interquartile range = 460.7-865.2) on EUS and MRI (P = 0.012). CONCLUSION: In this pilot study MIC-1/GDF15 has predictive capacity for neoplastic tumours in asymptomatic individuals with a genetic predisposition for PC. Further imagining may be warranted in patients with abnormal EUS and raised serum MIC-1/GDF15. Larger multicentric prospective studies are required to further define the role of MIC-1/GDF15 as a serological biomarker in pre-malignant pancreatic lesions and neoplastic tumours.

Is there an indication for initial conservative management of pancreatic cystic lesions?

BACKGROUND: The management of small pancreatic cystic lesions presents a clinical challenge. METHODS: We reviewed our experience with 78 patients who presented with a cystic pancreatic lesion who underwent operative management between 1995 and 2005. Data on cyst characteristics were analyzed in the context of pathologic findings following resection. RESULTS: Among 78 patients, there were 55 (71%) females; median age 63 years. Patients presented with: an incidental finding (48%), pain (40%), acute pancreatitis (4%), other (8%). Operations were distal pancreatectomy (n = 47), pancreaticoduodenectomy (n = 16), and other (n = 15). Most patients had a non-malignant lesion (n = 65, 83%) (mucinous cystadenoma (n = 29), serous cystadenoma (n = 15), IPMN without invasion (n = 8), pseudocyst (n = 8), other benign (n = 5)). Malignant lesions (adenocarcinoma, neuroendocrine tumor, and other) were found in 13 patients (17%). The risk of malignancy increased with size: <3 cm (n = 25), 4%; 3-5 cm (n = 23), 13%; and >5 cm (n = 30), 30%. Pre-operative cyst fluid cytology was performed in 41 patients. The negative predictive value (NPV) of cytology for malignancy was 88% and the positive predictive value (PPV) was 80%. The NPV of CA 19-9 for malignancy was 90%; the PPV was 50%. CONCLUSIONS: Initial conservative management of small cystic pancreatic lesions may be indicated in selected patients.

Circulating Leptin and Branched Chain Amino Acids-Correlation with Intraductal Papillary Mucinous Neoplasm Dysplastic Grade.

BACKGROUND: The most common type of mucinous pancreatic cyst that may progress to pancreatic cancer is intraductal papillary mucinous neoplasm (IPMN). Low-risk IPMN with low-/moderate-grade dysplasia may be safely watched, whereas high-risk IPMN with high-grade dysplasia or invasive components should undergo resection. However, there is currently no reliable means of making this distinction. We hypothesize that blood concentrations of insulin resistance biomarkers may aid in the differentiation of low- and high-risk IPMN. METHODS: Plasma/serum was collected from consented patients undergoing pancreatic resection. IPMN diagnosis and dysplastic grade were confirmed by surgical pathology. The study included 235 IPMN (166 low/moderate grade, 39 high grade, 30 invasive). Circulating levels of leptin, branched chain amino acids (BCAA), and retinol-binding protein-4 (RBP-4) were measured by enzyme-linked immunoassay and correlated with surgical pathology. RESULTS: Circulating leptin levels (mean ± SE) were significantly higher in patients with low/moderate IPMN than in high-grade/invasive IPMN (15,803 ± 1686 vs. 10,275 ± 1228 pg/ml; p = 0.0086). Leptin levels were positively correlated with BMI (r = 0.65, p < 0.0001) and were higher in females (p < 0.0001). Stratified analysis showed that mean leptin levels were significantly different between low/moderate and high/invasive IPMNs only in females (24,383 ± 2748 vs. 16,295 ± 2040 pg/ml; p = 0.020). Conversely, circulating BCAA levels were lower in low/moderate IPMN than in high-grade/invasive IPMN (0.38 ± 0.007 vs. 0.42 ± 0.01 mM; p = 0.011). No significant differences in RBP-4 levels were observed. CONCLUSIONS: Circulating leptin in females and BCAA correlates with IPMN dysplastic grade and, if combined with clinical characteristics, have the potential to improve clinical decision-making.

Pancreatic Fluid Interleukin-1ß Complements Prostaglandin E2 and Serum Carbohydrate Antigen 19-9 in Prediction of Intraductal Papillary Mucinous Neoplasm Dysplasia.

OBJECTIVES: We sought to determine if interleukin (IL)-1ß and prostaglandin E2 (PGE2) (inflammatory mediators in pancreatic fluid) together with serum carbohydrate antigen (CA) 19-9 could better predict intraductal papillary mucinous neoplasm (IPMN) dysplasia than individual biomarkers alone. METHODS: Pancreatic cyst fluid (n = 92) collected via endoscopy or surgery (2003-2016) was analyzed for PGE2 and IL-1ß (enzyme-linked immunosorbent assay). Patients had surgical pathology-proven IPMN. Threshold values (PGE2 [>1100 pg/mL], IL-1ß [>20 pg/mL], and serum CA 19-9 [>36 U/mL]) were determined. RESULTS: Levels of IL-1ß were higher in high-grade dysplasia (HGD)/invasive-IPMN (n = 42) compared with low/moderate IPMN (n = 37) (median [range], 54.6 [0-2671] vs 5.9 [0-797] pg/mL; P < 0.001; area under curve [AUC], 0.766). Similarly, PGE2 was higher in HGD/invasive IPMN (n = 45) compared with low/moderate IPMN (n = 47) (median [range], 1790 [20-15,180] vs. 140 [10-14,630] pg/mL; P < 0.001; AUC, 0.748). Presence of elevated PGE2 and IL-1ß (AUC, 0.789) provided 89% specificity and 82% positive predictive value (PPV) for HGD/invasive IPMN. Elevated levels of all 3 provided 100% specificity and PPV for HGD/invasive IPMN. CONCLUSIONS: Cyst fluid PGE2, IL-1ß, and serum CA 19-9 in combination optimize specificity and PPV for HGD/invasive IPMN and may help build a panel of markers to predict IPMN dysplasia.

[Cystic pancreatic tumors: diagnostics and new biomarkers]. / Zystische Pankreastumoren: Diagnostik und neue Biomarker.

Mortality due to pancreatic ductal adenocarcinoma (PDAC) will increase in the near future. The only curative treatment for PDAC is radical resection; however, even small carcinomas exhibit micrometastases leading to early relapse. Accordingly, detection of premalignant precursor lesions is important. In essence, PDAC develops from three precursor lesions: pancreatic intraepithelial lesions (PanIN), intraductal papillary-mucinous neoplasia (IPMN) and mucinous-cystic neoplasia (MCN). Together with serous cystic neoplasia (SCN) and solid pseudopapillary neoplasia (SPN), these cystic lesions constitute the most common cystic neoplasms in the pancreas. In the case of IPMN, main and branch duct IPMN have to be differentiated because of a markedly different malignancy potential. While main duct IPMN and MCN have a high malignancy transformation rate, branch duct IPMNs are more variable with respect to malignant transformation. This shows that differential diagnosis of cystic lesions is important; however, this is often very difficult to accomplish using conventional imaging. Novel biomarkers and diagnostic tools based on the molecular differences of cystic pancreatic lesions could be helpful to differentiate these lesions and facilitate early diagnosis. The aim is to distinguish the premalignant cysts from strictly benign cystic lesions and a timely detection of malignant transformation. This article provides an overview on the molecular characteristics of cystic pancreatic lesions as a basis for improved diagnostics and the development of new biomarkers.

Serum Carbohydrate Antigen 19-9 in Differential Diagnosis of Benign and Malignant Pancreatic Cystic Neoplasms: A Meta-Analysis.

BACKGROUND: Using serum carbohydrate antigen 19-9 (CA 19-9) in discriminating between benign and malignant pancreatic disease remains controversial. We aim to evaluate the diagnostic value of serum CA 19-9 in predicting malignant pancreatic cystic lesions. METHODS: Eligible studies were identified through searching MEDLINE and EMBASE prior to March 2016. Studies were assessed for quality using the Quality Assessment for Studies of Diagnostic Accuracy, 2nd version (QUADAS-2). Pooled sensitivity and specificity with 95% confidence interval (CI) were calculated using random-effects models. Summary receiver operator characteristic (SROC) curves and the area under curve (AUC) were performed. RESULTS: A total of thirteen studies including 1437 patients were enrolled in this meta-analysis. The pooled sensitivity and specificity were 0.47(95% CI: 0.35-0.59), and 0.88(95% CI: 0.86-0.91), respectively, and the AUC was 0.87(95% CI, 0.84-0.90). Meta-regression analysis showed that sample size, region and reference standards were not the main sources of heterogeneity. CONCLUSIONS: Serum CA 19-9 has satisfying pooled specificity while poor pooled sensitivity for discriminating benign from malignant PCNs. It deserves to be widely used as complementary to other clinical diagnostic methods.

Transient eosinophilia associated with pancreatitis and pseudocyst formation.

Eosinophilia is frequently associated with allergic rhinitis, asthma, drug reactions, parasitic infections, malignant neoplasms, collagen vascular diseases, skin diseases, and pulmonary infiltrates. It has been infrequently described in conjunction with pancreatic diseases and not before, to my knowledge, with pseudocyst formation. A patient with alcohol-related pancreatitis manifested a transient eosinophilia during development of a massive pancreatic pseudocyst. Although he was atopic, with a greatly elevated serum IgE level, there was no recent contact with the specific allergen to which he was sensitized. This constellation of alcohol-related pancreatitis with pseudocyst formation, atopy with elevated serum IgE level, and transient eosinophilia is an interesting coincidence.