• Mohammad A Al Efishat, Marc A Attiyeh, Anne A Eaton, Mithat Gönen, Denise Prosser, Anna E Lokshin, Castillo Carlos Fernández-Del CF Department of Surgery, Massachusetts General Hospital, Boston, MA., Keith D Lillemoe, Cristina R Ferrone, Ilaria Pergolini, Mari Mino-Kenudson, Neda Rezaee, Marco Dal Molin, Matthew J Weiss, John L Cameron, Ralph H Hruban, Michael I D'Angelica, T Peter Kingham, Ronald P DeMatteo, William R Jarnagin, Christopher L Wolfgang, and Peter J Allen.
• Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
• Ann. Surg. 2018 Aug 1; 268 (2): 340-347.

ObjectivePreliminary 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 DataIPMN 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.MethodsClinical 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.ResultsWithin 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).ConclusionsThis 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.

45 keywords...

hide…