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Item Fluid analysis prior to surgical resection of suspected mucinous pancreatic cysts. A single centre experience(AME Publishing Company, 2011-12) Al-Rashdan, Abdullah; Schmidt, C. Max; Al-Haddad, Mohammad; McHenry, Lee; LeBlanc, Julia Kim; Sherman, Stuart; Dewitt, JohnObjective EUS-FNA cytology and fluid analysis are frequently utilized to evaluate pancreatic cysts. Elevated cyst fluid CEA is usually indicative of a mucinous pancreatic cyst but whether CEA or amylase values can subclassify various mucinous cysts is unknown. The purpose of this study is to determine whether cyst fluid CEA and amylase obtained by EUS-FNA can differentiate between mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs). Methods Using our prospective hospital EUS and surgical databases, we identified all patients who underwent EUS of a pancreatic cyst prior to surgical resection, in the last 10 years. Cysts were pathologically sub-classified as MCNs or IPMNs; all other cysts were considered non-mucinous. Values of cyst fluid CEA and amylase were correlated to corresponding surgical histopathology and compared between the two groups. Results 134 patients underwent surgery for pancreatic cysts including 82 (63%) that also had preoperative EUS. EUS-FNA was performed in 61/82 (74%) and cyst fluid analysis in 35/61 (57%) including CEA and amylase in 35 and 33 patients, respectively. Histopathology in these 35 cysts demonstrated nonmucinous cysts in 10 and mucinous cysts in 25 including: MCNs (n=9) and IPMNs (n=16). Cyst fluid CEA (p=0.19) and amylase (p=0.64) between all IPMNs and MCNs were similar. Between branched duct IPMNs and MCNs alone, cyst fluid CEA (p=0.34) and amylase (p=0.92) were also similar. Conclusion In this single center study, pancreatic cyst fluid amylase and CEA levels appeared to be of limited value to influence the differential of mucinous pancreatic cysts. Larger studies are recommended to evaluate this role further.Item Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts(Thieme, 2015-02) Al-Haddad, Mohammad A.; Kowalski, Thomas; Siddiqui, Ali; Mertz, Howard R.; Mallat, Damien; Haddad, Nadim; Malhotra, Nidhi; Sadowski, Brett; Lybik, Mark J.; Patel, Sandeep N.; Okoh, Emuejevoke; Rosenkranz, Laura; Karasik, Michael; Golioto, Michael; Linder, Jeffrey; Catalano, Marc F.; Department of Medicine, IU School of MedicineBackground and study aims: Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts. Patients and methods: Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n = 492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis (“benign”/“statistically indolent” vs. “statistically higher risk [SHR]”/ “aggressive”) or an International Consensus Guideline (Sendai 2012) criteria model for “surveillance” vs. “surgery.” The Cox proportional hazards model determined hazard ratios for malignancy. Results: Benign and statistically indolent IMP diagnoses had a 97 % probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both P < 0.0001). Sendai surveillance criteria had a 97 % probability of benign follow-up for up to 7 years and 8 months, but for surgical criteria the hazard ratio was only 9.0 (P < 0.0001). In patients who met Sendai surgical criteria, benign and statistically indolent IMP diagnoses had a > 93 % probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both P < 0.0001). Conclusion: IMP more accurately determined the malignant potential of pancreatic cysts than a Sendai 2012 guideline management criteria model. IMP may improve patient management by justifying more relaxed observation in patients meeting Sendai surveillance criteria. IMP can more accurately differentiate between the need for surveillance or surgery in patients meeting Sendai surgical criteria.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.