Pancreatic Cyst Fluid Vascular Endothelial Growth Factor A and Carcinoembryonic Antigen: A Highly Accurate Test for the Diagnosis of Serous Cystic Neoplasm

Rosalie A. Carr, Michele Yip-Schneider, Scott Dolejs, Bradley A. Hancock, Huangbing Wu, Milan Radovich, C. Schmidt

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 < 0.001). With a threshold of >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.

Original languageEnglish (US)
Pages (from-to)93-100
Number of pages8
JournalJournal of the American College of Surgeons
Volume225
Issue number1
DOIs
StatePublished - Jul 1 2017

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Pancreatic Cyst
Cyst Fluid
Carcinoembryonic Antigen
Vascular Endothelial Growth Factor A
Neoplasms
Sensitivity and Specificity
Pancreatic Ducts

ASJC Scopus subject areas

  • Surgery

Cite this

@article{7f53ee61cce84f688ca8b71c77afa856,
title = "Pancreatic Cyst Fluid Vascular Endothelial Growth Factor A and Carcinoembryonic Antigen: A Highly Accurate Test for the Diagnosis of Serous Cystic Neoplasm",
abstract = "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 < 0.001). With a threshold of >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.",
author = "Carr, {Rosalie A.} and Michele Yip-Schneider and Scott Dolejs and Hancock, {Bradley A.} and Huangbing Wu and Milan Radovich and C. Schmidt",
year = "2017",
month = "7",
day = "1",
doi = "10.1016/j.jamcollsurg.2017.05.003",
language = "English (US)",
volume = "225",
pages = "93--100",
journal = "Journal of the American College of Surgeons",
issn = "1072-7515",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Pancreatic Cyst Fluid Vascular Endothelial Growth Factor A and Carcinoembryonic Antigen

T2 - A Highly Accurate Test for the Diagnosis of Serous Cystic Neoplasm

AU - Carr, Rosalie A.

AU - Yip-Schneider, Michele

AU - Dolejs, Scott

AU - Hancock, Bradley A.

AU - Wu, Huangbing

AU - Radovich, Milan

AU - Schmidt, C.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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 < 0.001). With a threshold of >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.

AB - 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 < 0.001). With a threshold of >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.

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DO - 10.1016/j.jamcollsurg.2017.05.003

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