10 research outputs found
Prostaglandin E2: A Pancreatic Fluid Biomarker of Intraductal Papillary Mucinous Neoplasm Dysplasi
Background
With the increased frequency of diagnostic imaging, pancreatic cysts are now detected in >3% of American adults. Most of these are intraductal papillary mucinous neoplasms (IPMNs) with well-established but variable malignant potential. A biomarker that predicts malignant potential or dysplastic grade would help determine which IPMNs require removal and which can be observed safely. We previously reported that pancreatic fluid prostaglandin E2 (PGE2) levels might have promise as a predictor of IPMN dysplasia and we seek to validate those results in the current study.
Study Design
Pancreatic cyst/duct fluid was prospectively collected from 100 patients with IPMN undergoing pancreatic resection. Surgical pathology revealed 47 low-/moderate-grade, 34 high-grade, and 20 invasive IPMNs. The PGE2 levels were assessed by ELISA and correlated with IPMN dysplasia grade, demographics, clinical radiologic/pathologic variables, acute/chronic pancreatitis, and NSAID use.
Results
Mean pancreatic cyst fluid PGE2 levels in high-grade and invasive IPMNs were significantly higher than low-/moderate-grade IPMNs (3.5 and 4.4 pg/μL, respectively, vs 1.2 pg/μL; p 192 ng/mL, PGE2 at a threshold of 0.5 pg/μL demonstrated 78% sensitivity, 100% specificity, and 86% accuracy for detection of high-grade/invasive IPMN.
Conclusions
Our results validate pancreatic cyst fluid PGE2 as an indicator of IPMN dysplasia, especially in select patients with preoperative pancreatic cyst fluid CEA >192 ng/mL. The inclusion of PGE2/CEA in a diagnostic biomarker panel can facilitate more optimal treatment stratification of IPMN patients
Pancreatic Cyst Fluid Vascular Endothelial Growth Factor A and Carcinoembryonic Antigen: A Highly Accurate Test for the Diagnosis of Serous Cystic Neoplasm
Background
Accurate differentiation of pancreatic cystic lesions is important for early detection and prevention of pancreatic cancer, as well as avoidance of unnecessary surgical intervention. Serous cystic neoplasms (SCNs) have no malignant potential, but can mimic the following premalignant mucinous cystic lesions: mucinous cystic neoplasm and intraductal papillary mucinous neoplasm (IPMN). We recently identified vascular endothelial growth factor (VEGF)-A as a novel pancreatic fluid biomarker for SCN. We hypothesize that combining cyst fluid CEA with VEGF-A will improve the diagnostic accuracy of VEGF-A.
Methods
Pancreatic cyst/duct fluid was collected from consenting patients undergoing surgical cyst resection with corresponding pathologic diagnoses. Pancreatic fluid VEGF-A and CEA levels were detected by ELISA.
Results
One hundred and forty-nine patients with pancreatic cystic lesions met inclusion criteria. Pathologic diagnoses included pseudocyst (n = 14), SCN (n = 26), mucinous cystic neoplasm (n = 40), low-/moderate-grade IPMN (n = 34), high-grade IPMN (n = 20), invasive IPMN (n = 10), and solid pseudopapillary neoplasm (n = 5). Vascular endothelial growth factor A was significantly elevated in SCN cyst fluid compared with all other diagnoses (p 5,000 pg/mL, VEGF-A alone has 100% sensitivity and 83.7% specificity to distinguish SCNs from other cystic lesions. With a threshold of ≤10 ng/mL, CEA alone identifies SCN with 95.5% sensitivity and 81.5% specificity. Sensitivity and specificity of the VEGF-A/CEA combination are 95.5% and 100%, respectively. The c-statistic increased from 0.98 to 0.99 in the receiver operating characteristic analysis when CEA was added to VEGF-A alone.
Conclusions
Although VEGF-A alone is a highly accurate test for SCN, the combination of VEGF-A with CEA approaches the gold standard for pathologic diagnosis, importantly avoiding false positives. Patients with a positive test indicating benign SCN can be spared a high-risk surgical pancreatic resection
Circulating Thrombospondin-2 enhances prediction of malignant intraductal papillary mucinous neoplasm
Background
IPMNs are cystic pancreatic lesions with variable malignant potential. Thrombospondin-2 (THBS2)—an endogenous, anti-angiogenic matrix glycoprotein—may modulate tumor progression. We hypothesized that circulating levels of THBS2 could aid in preoperative prediction of malignant IPMN.
Methods
Preoperative serum/plasma samples were procured from patients undergoing surgery. Circulating levels of THBS2 were measured (enzyme-linked immunosorbent assay) and compared to surgical pathology IPMN dysplastic grade.
Results
164 patients underwent THBS2 testing (100 Low/Moderate-IPMN; 64 High-Grade/Invasive-IPMN). Circulating THBS2 (mean ± SD) was greater in High-Grade/Invasive-IPMN than Low/Moderate-grade IPMN (26.6 ± 12.7 ng/mL vs. 20.4 ± 8.2 ng/mL; P < 0.001). THBS2 (AUC = 0.65) out-performed CA19-9 (n = 144; AUC = 0.59) in predicting IPMN grade. The combination of THBS2, CA19-9, radiographic main-duct involvement, main-duct diameter, age, sex, and BMI (AUC 0.82; n = 137) provided a good prediction model for IPMN grade.
Conclusion
Circulating THBS2 is correlated with IPMN dysplasia grade. THBS2 alone did not strongly predict IPMN grade but rather strengthened prediction models for High-Grade/Invasive IPMN when combined with other clinical/biomarker data
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-1β 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)-1β 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-1β (Enzyme-Linked Immunosorbent Assay). Patients had surgical pathology-proven IPMN. Threshold values (PGE2 [>1100 pg/mL], IL-1β [>20 pg/mL], serum CA 19–9 [>36 U/mL]) were determined.
Results:
Levels of IL-1β were higher in high-grade (HGD)/Invasive-IPMN (n = 42) compared to 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 to 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-1β (AUC, 0.789) provided 89% specificity and 82% positive predictive value (PPV) for HGD/Invasive-IPMN. Elevated levels of all three provided 100% Specificity and PPV for HGD/Invasive-IPMN.
Conclusion:
Cyst fluid PGE2, IL-1β, 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
Performance of Candidate Urinary Biomarkers for Pancreatic Cancer - Correlation with Pancreatic Cyst Malignant Progression?
Background
Intraductal papillary mucinous neoplasms (IPMN) are precursors of pancreatic cancer. Potential biomarkers of IPMN progression have not been identified in urine. A few urinary biomarkers were reported to be predictive of pancreatic ductal adenocarcinoma (PDAC). Here, we seek to assess their ability to detect high-risk IPMN.
Methods
Urine was collected from patients undergoing pancreatic resection and healthy controls. TIMP-1(Tissue Inhibitor of Metalloproteinase-1), LYVE-1(Lymphatic Vessel Endothelial Receptor 1), and PGEM(Prostaglandin E Metabolite) levels were determined by ELISA and analyzed by Kruskal-Wallis.
Results
Median urinary TIMP-1 levels were significantly lower in healthy controls (n = 9; 0.32 ng/mg creatinine) compared to PDAC (n = 13; 1.95) but not significantly different between low/moderate-grade (n = 20; 0.71) and high-grade/invasive IPMN (n = 20; 1.12). No significant difference in urinary LYVE-1 was detected between IPMN low/moderate (n = 16; 0.37 ng/mg creatinine) and high/invasive grades (n = 21; 0.09). Urinary PGEM levels were not significantly different between groups.
Conclusions
Urinary TIMP-1, LYVE-1, and PGEM do not correlate with malignant potential of pancreatic cysts
Pancreatic cyst fluid glucose: rapid, inexpensive, and accurate diagnosis of mucinous pancreatic cysts
Background
The most widely accepted biochemical test for preoperative differentiation of mucinous from benign, nonmucinous pancreatic cysts is cyst fluid carcinoembryonic antigen. However, the diagnostic accuracy of carcinoembryonic antigen ranges from 70% to 86%. Based on previous work, we hypothesize that pancreatic cyst fluid glucose may be an attractive alternative to carcinoembryonic antigen.
Methods
Pancreatic cyst fluid was collected during endoscopic or operative intervention. Diagnoses were pathologically confirmed. Glucose and carcinoembryonic antigen were measured using a patient glucometer and automated analyzer/enzyme-linked immunosorbent assay. Sensitivity, specificity, accuracy, and receiver operator characteristic analyses were performed.
Results
Cyst fluid samples from 153 patients were evaluated (mucinous: 25 mucinous cystic neoplasms, 77 intraductal papillary mucinous neoplasms, 4 ductal adenocarcinomas; nonmucinous: 21 serous cystic neoplasms, 9 cystic neuroendocrine tumors, 14 pseudocysts, 3 solid pseudopapillary neoplasms). Median cyst fluid glucose was lower in mucinous versus nonmucinous cysts (19 vs 96 mg/dL; P 192 ng/mL was 58% sensitive, 96% specific, and 69% accurate. Area under the curve for glucose and CEA were similar at 0.91 and 0.92.
Conclusion
Cyst fluid glucose has significant advantages over carcinoembryonic antigen and should be considered for use as a routine diagnostic test for pancreatic mucinous cysts