title: Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos).
abstract: OBJECTIVE
  EUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis.
  
  
  METHODS
  Six endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (n = 23) or clinical (n = 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used.
  
  
  RESULTS
  A total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κ = 0.81 (almost perfect); 95% CI, 0.71-0.90; and κ = 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κ = 0.83 (almost perfect); 95% CI, 0.73-0.92; and κ = 0.85 ± 0.11 (almost perfect), respectively.
  
  
  CONCLUSIONS
  EUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.).
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Somashekar G
authors.initials: SG
authors.lastname: Krishna
authors.affiliation: Pancreas Biliary Center, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Brugge
authors.affiliation: Division of Gastroenterology, Department of Medicine, Indiana University Hospital, Indianapolis, Indiana, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Dewitt
authors.affiliation: Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Pradermchai
authors.initials: P
authors.lastname: Kongkam
authors.affiliation: Department of Gastroenterology, Ramsay Générale de Santé, Hôpital privé Jean Mermoz, Lyon, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Napoleon
authors.affiliation: Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas, University Hospital OMNI, Guayaquil, Ecuador.
authors.forename: Carlos
authors.initials: C
authors.lastname: Robles-Medranda
authors.affiliation: Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.
authors.forename: Damien
authors.initials: D
authors.lastname: Tan
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Samer
authors.initials: S
authors.lastname: El-Dika
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: McCarthy
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Walker
authors.affiliation: Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Dillhoff
authors.affiliation: Department of General Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Manilchuk
authors.affiliation: Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Swanson
authors.affiliation: Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Zarine K
authors.initials: ZK
authors.lastname: Shah
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Phil A
authors.initials: PA
authors.lastname: Hart
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Darwin L
authors.initials: DL
authors.lastname: Conwell
mesh_terms: D000328:Adult; D000368:Aged; D018293:Cystadenoma, Serous / Q000000981:diagnostic imaging / Q000473:pathology*; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D019160:Endosonography / Q000379:methods*; D005260:Female; D006801:Humans; D000069416:Intravital Microscopy; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D008875:Middle Aged; D009339:Needles; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000473:pathology*; D015588:Observer Variation; D010181:Pancreatic Cyst / Q000000981:diagnostic imaging / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D012189:Retrospective Studies