Multi-institutional validation study of pancreatic cyst fluid protein analysis for prediction of high-risk intraductal papillary mucinous neoplasms of the pancreas Journal Article


Authors: Al Efishat, M. A.; Attiyeh, M. A.; Eaton, A. A.; Gönen, M.; Prosser, D.; Lokshin, A. E.; Castillo, C. F. D.; Lillemoe, K. D.; Ferrone, C. R.; Pergolini, I.; Mino-Kenudson, M.; Rezaee, N.; Dal Molin, M.; Weiss, M. J.; Cameron, J. L.; Hruban, R. H.; D'Angelica, M. I.; Kingham, T. P.; DeMatteo, R. P.; Jarnagin, W. R.; Wolfgang, C. L.; Allen, P. J.
Article Title: Multi-institutional validation study of pancreatic cyst fluid protein analysis for prediction of high-risk intraductal papillary mucinous neoplasms of the pancreas
Abstract: Objective: Preliminary work by our group suggested that proteins within the pancreatic cyst fluid (CF) may discriminate degree of IPMN dysplasia. We sought to externally validate these markers and determine whether their inclusion in a preoperative clinical nomogram could increase diagnostic accuracy. Summary Background Data: IPMN is the most common radiographically identifiable precursor to pancreatic cancer; however, the timing and frequency of its malignant progression are unknown, and there are currently no reliable preoperative tests that can determine the grade of dysplasia in IPMN. Methods: Clinical and radiographic data, as well as CF samples, were obtained from 149 patients who underwent resection for IPMN at 1 of 3 institutions. High-risk disease was defined as the presence of high-grade dysplasia or invasive carcinoma. Multianalyte bead array analysis (Luminex) of CF was performed for 4 protein markers that were previously associated with high-risk disease. Logistic regression models were fit on training data, with and without adjustment for a previously developed clinical nomogram and validated with an external testing set. The models incorporating clinical risk score were presented graphically as nomograms. Results: Within the group of 149 resected patients, 89 (60%) had low-risk disease, and 60 (40%) had high-risk disease. All 4 CF markers (MMP9, CA72-4, sFASL, and IL-4) were overexpressed in patients with high-risk IPMN (P < 0.05). Two predictive models based on preselected combinations of CF markers had concordance indices of 0.76 (Model-1) and 0.80 (Model-2). Integration of each CF marker model into a previously described clinical nomogram leads to increased discrimination compared with either the CF models or nomogram alone (c-indices of 0.84 and 0.83, respectively). Conclusions: This multi-institutional study validated 2 CF protein marker models for preoperative identification of high-risk IPMN. When combined with a clinical nomogram, the ability to predict high-grade dysplasia was even stronger. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Keywords: pancreas; biomarkers; cyst fluid; dysplasia; intraductal papillary mucinous neoplasms
Journal Title: Annals of Surgery
Volume: 268
Issue: 2
ISSN: 0003-4932
Publisher: Lippincott Williams & Wilkins  
Date Published: 2018-08-01
Start Page: 340
End Page: 347
Language: English
DOI: 10.1097/sla.0000000000002421
PROVIDER: scopus
PMCID: PMC5764837
PUBMED: 28700444
DOI/URL:
Notes: Article -- Export Date: 1 August 2018 -- Source: Scopus
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MSK Authors
  1. Ronald P Dematteo
    585 Dematteo
  2. Mithat Gonen
    681 Gonen
  3. Peter Allen
    421 Allen
  4. William R Jarnagin
    566 Jarnagin
  5. T Peter Kingham
    276 Kingham
  6. Anne Austin Eaton
    112 Eaton
  7. Marc   Attiyeh
    20 Attiyeh