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Neutrophil Gelatinase-Associated Lipocalin, Macrophage Inhibitory Cytokine 1, and Carbohydrate Antigen 19-9 in Pancreatic Juice: Pathobiologic Implications in Diagnosing Benign and Malignant Disease of the Pancreas

Kaur, Sukhwinder PhD*; Baine, Michael J. PhD; Guha, Sushovan MD, PhD; Ochi, Nobuo MD, PhD; Chakraborty, Subhankar MD, PhD*; Mallya, Kavita MS*; Thomas, Colleen MS§; Crook, Julia PhD§; Wallace, Michael B. MD; Woodward, Timothy A. MD; Jain, Maneesh PhD*; Singh, Shailender MD; Sasson, Aaron R. MD#; Skinner, Verna MS; Raimondo, Massimo MD; Batra, Surinder K. PhD*†

doi: 10.1097/MPA.0b013e31826a8597
Original Articles

Objective: Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1 (MIC-1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients with symptoms suggestive of pancreatic diseases.

Methods: A total of 105 chronic pancreatitis (CP), pancreatic cancer (PC), and nonpancreatic nonhealthy (patients with symptoms mimicking pancreatic disease but found to be free of any pancreatic disease) patients underwent endoscopic pancreatic juice collection after secretin stimulation. Neutrophil gelatinase-associated lipocalin and MIC-1 levels were measured by enzyme-linked immunosorbent assay, whereas CA19-9 was measured by radioimmunoassay.

Results: Neutrophil gelatinase-associated lipocalin, MIC-1, and CA19-9 were significantly elevated in the pancreatic juice of patients with CP and patients with PC as compared with nonpancreatic nonhealthy controls (P ≤ 0.034). Neutrophil gelatinase-associated lipocalin seemed most promising in differentiating diseased versus nondiseased pancreata (areas under the curve, 0.88–0.91), whereas MIC-1 was found to be higher in patients with PC than in patients with CP (P = 0.043). Interestingly, MIC-1 levels in diabetic patients with PC were higher than in nondiabetic patients with PC (P = 0.030) and diabetic patients with CP (P = 0.087). Carbohydrate antigen 19-9 showed the least ability to distinguish patient groups (areas under the curve, 0.61–0.76).

Conclusions: Pancreatic juice neutrophil gelatinase-associated lipocalin shows potential utility in establishing pancreatic etiology in the context of nonspecific symptoms, whereas MIC-1 may aid in differentiating PC from CP.

From the *Department of Biochemistry and Molecular Biology, and †Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE; ‡Department of Gastroenterology, Hepatology and Nutrition, MD Anderson Cancer Center, The University of Texas, Houston, TX; §Divisions of Biostatistics and ∥Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL; ¶Departments of Gastroenterology and #Surgery, University of Nebraska Medical Center, Omaha, NE.

Received for publication April 2, 2012; accepted July 18, 2012.

Reprints: Surinder K. Batra, PhD, Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198 (e-mail: sbatra@unmc.edu); and Massimo Raimondo, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL (e-mail: Raimondo.Massimo@mayo.edu).

Sukhwinder Kaur, PhD, Michael J. Baine, PhD, and Sushovan Guha, MD, PhD, contributed equally to this work.

Surinder K. Batra, Subhankar Chakraborty, Sukhwinder Kaur, Kavita Mallya, Michael J. Baine, Maneesh Jain, and Aaron R. Sasson are supported, in part, by grants from the National Institutes of Health (U01EDRN CA111294, R01 CA131944, and P50 SPORE CA127297). Sushovan Guha is supported by grants from MD Anderson Cancer Center McNair Foundation Scholar Award and the Cyrus Scholar Award. Massimo Raimondo is supported by Mayo Clinic Institutional Research Grant Award.

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the article apart from those disclosed.

No writing assistance was used in the production of this article.

Sukhwinder Kaur was involved in performing the biomarker assays at University of Nebraska Medical Center and writing the article. Michael J. Baine was involved in the assay interpretation, study design, and writing of the article. Sushovan Guha was involved in study design and performing the biomarker assays at MD Anderson Cancer Center. Nobuo Ochi was involved in performing the neutrophil gelatinase-associated lipocalin assays at MD Anderson Cancer Center. Subhankar Chakraborty was involved in the study design and writing of the article. Kavita Mallya was involved in the performance of the biomarker assays at the University of Nebraska Medical Center. Colleen Thomas and Julia Crook were involved in the statistical analysis of the data. Michael B. Wallace was involved in collection of secretin-stimulated exocrine pancreatic secretions samples for the study. Timothy A. Woodward was involved in the collection of secretin-stimulated exocrine pancreatic secretions samples for the study. Maneesh Jain was involved in interpretation of the University of Nebraska Medical Center assays and the writing of the article. Verna Skinner acted as the clinical study coordinator for this work. Massimo Raimondo was involved in the study design and collection of secretin-stimulated exocrine pancreatic secretions samples for the study. Surinder K. Batra was involved in the study design and writing of the article.

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