title: Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Al-Haddad
authors.affiliation: Department of Medicine, Jefferson Digestive Disease Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kowalski
authors.affiliation: Department of Medicine, Jefferson Digestive Disease Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Siddiqui
authors.affiliation: Nashville GI Associates, Nashville, Tennessee, USA.
authors.forename: Howard R
authors.initials: HR
authors.lastname: Mertz
authors.affiliation: Premier Gastroenterology of Texas, Dallas, Texas, USA.
authors.forename: Damien
authors.initials: D
authors.lastname: Mallat
authors.affiliation: Division of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Nadim
authors.initials: N
authors.lastname: Haddad
authors.affiliation: Division of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Malhotra
authors.affiliation: Division of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Sadowski
authors.affiliation: Northside Gastroenterology, Indianapolis, Indiana, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Lybik
authors.affiliation: Department of Medicine, University of Texas San Antonio, San Antonio, Texas, USA.
authors.forename: Sandeep N
authors.initials: SN
authors.lastname: Patel
authors.affiliation: Department of Medicine, University of Texas San Antonio, San Antonio, Texas, USA.
authors.forename: Emuejevoke
authors.initials: E
authors.lastname: Okoh
authors.affiliation: Department of Medicine, University of Texas San Antonio, San Antonio, Texas, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Rosenkranz
authors.affiliation: Connecticut GI, Hartford, Connecticut, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Karasik
authors.affiliation: Connecticut GI, Hartford, Connecticut, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Golioto
authors.affiliation: Digestive Health Associates of Texas, Dallas, Texas, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Linder
authors.affiliation: Wisconsin Center for Advanced Research, St. Luke's Medical Center, Milwaukee, Wisconsin, USA.
authors.forename: Marc F
authors.initials: MF
authors.lastname: Catalano
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D020420:Cyst Fluid / Q000737:chemistry*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D010181:Pancreatic Cyst / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods