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Item Osteoglophonic dysplasia: A ‘common’ mutation in a rare disease(Wiley Online Library, 2010-08) Sow, AJ; Ramli, R.; Latiff, ZA; Ichikawa, S.; Gray, AK; Nordin, R.; Abd Jabar, MN; Primuharsa Putra, SHA; Siar, CH; Econs, MJ; Department of Medicine, IU School of MedicineItem Pancreatic Fluid Interleukin-1β Complements Prostaglandin E2 and Serum Carbohydrate Antigen 19-9 in Prediction of Intraductal Papillary Mucinous Neoplasm Dysplasia(Wolters Kluwer, 2019-09-01) Simpson, Rachel E.; Yip-Schneider, Michele T.; Flick, Katelyn F.; Wu, Huangbing; Colgate, Cameron L.; Schmidt, C. Max; Surgery, School of MedicineObjectives: 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.Item Prostaglandin E2: A Pancreatic Fluid Biomarker of Intraductal Papillary Mucinous Neoplasm Dysplasi(Elsevier, 2017) Yip-Schneider, Michele T.; Carr, Rosalie A.; Wu, Huangbing; Schmidt, C. Max; Department of Surgery, School of MedicineBackground 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 < 0.0016). At a threshold of 1.1 pg/μL, PGE2 was 63% sensitive, 79% specific, and 71% accurate for detection of high-grade/invasive IPMNs. When tested in the subset of IPMN patients with preoperative pancreatic cyst fluid CEA >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.