title: Development and Validation of a Multi-institutional Preoperative Nomogram for Predicting Grade of Dysplasia in Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas: A Report from The Pancreatic Surgery Consortium.
abstract: Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multiinstitutional dataset.
  
  
  
  IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of high-grade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another.
  
  
  
  Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type (MD)] and branch duct (BD) types based on preoperative imaging. Logistic regression modeling was used on a training subset to develop 2 independent nomograms (MD and BD) to predict low-risk (low- or intermediate-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma) disease. Model performance was then evaluated using an independent validation set.
  
  
  
  We identified 1028 patients who underwent resection for IPMNs [MD: n = 454 (44%), BD: n = 574 (56%)] during the 10-year study period. High-risk disease was present in 487 patients (47%). Patients with high-risk disease comprised 71% and 29% of MD and BD groups, respectively (P <0.0001). MD and BD nomograms were developed on the training set [70% of total (n = 720); MD: n = 318, BD: n = 402] and validated on the test set [30% (n = 308); MD: n = 136, BD: n = 172]. The presence of jaundice was almost exclusively associated with high-risk disease (57 of 58 patients, 98%). Cyst size >3.0 cm, solid component/mural nodule, pain symptoms, and weight loss were significantly associated with high-risk disease. C-indices were 0.82 and 0.81 on training and independent validation sets, respectively; Brier scores were 0.173 and 0.175, respectively.
  
  
  
  For patients with suspected IPMNs, we present an independently validated model for the prediction of high-risk disease.
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Attiyeh
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Del Castillo
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al Efishat
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Anne A
authors.initials: AA
authors.lastname: Eaton
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gönen
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Ruqayyah
authors.initials: R
authors.lastname: Batts
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pergolini
authors.affiliation: Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Neda
authors.initials: N
authors.lastname: Rezaee
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lillemoe
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Ferrone
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA.
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.affiliation: Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Weiss
authors.affiliation: Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: John L
authors.initials: JL
authors.lastname: Cameron
authors.affiliation: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: T Peter
authors.initials: TP
authors.lastname: Kingham
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.affiliation: Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000473:pathology* / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology* / Q000601:surgery; D002291:Carcinoma, Papillary / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D049451:Nomograms; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000601:surgery; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011446:Prospective Studies; D012372:ROC Curve; D012189:Retrospective Studies; D055815:Young Adult
keywords: cancer; dysplasia; intraductal papillary mucinous neoplasm; IPMN; nomogram; pancreas; the pancreatic surgery consortium