Original article Clinical endoscopy| Volume 91, ISSUE 3, P551-563.e5, March 2020

EUS-guided confocal laser endomicroscopy: prediction of dysplasia in intraductal papillary mucinous neoplasms (with video)

Published:September 19, 2019DOI:https://doi.org/10.1016/j.gie.2019.09.014

      Background and Aims

      Previous studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of intraductal papillary mucinous neoplasms (IPMNs). We sought to derive EUS-guided nCLE criteria for differentiating IPMNs with high-grade dysplasia/adenocarcinoma (HGD-Ca) from those with low/intermediate-grade dysplasia (LGD).


      We performed a post hoc analysis of consecutive IPMNs with a definitive diagnosis from a prospective study evaluating EUS-guided nCLE in the diagnosis of pancreatic cysts. Three internal endosonographers reviewed all nCLE videos for the patients and identified potential discriminatory EUS-guided nCLE variables to differentiate HGD-Ca from LGD IPMNs (phase 1). Next, an interobserver agreement (IOA) analysis of variables from phase 1 was performed among 6 blinded external nCLE experts (phase 2). Last, 7 blinded nCLE-naïve observers underwent training and quantified variables with the highest IOA from phase 2 using dedicated software (phase 3).


      Among 26 IPMNs (HGD-Ca in 16), the reference standard was surgical histopathology in 24 and cytology confirmation of metastatic liver lesions in 2 patients. EUS-guided nCLE characteristics of increased papillary epithelial “width” and “darkness” were the most sensitive variables (90%; 95% confidence interval [CI], 84%-94% and 91%; 95% CI, 85%-95%, respectively) and accurate (85%; 95% CI, 78%-90% and 84%; 95% CI, 77%-89%, respectively) with substantial (κ = 0.61; 95% CI, 0.51-0.71) and moderate (κ = 0.55; 95% CI, 0.45-0.65) IOAs for detecting HGD-Ca, respectively (phase 2). Logistic regression models were fit for the outcome of HGD-Ca as predictor variables (phase 3). For papillary width (cut-off ≥50 μm), the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.95, respectively. For papillary darkness (cut-off ≤90 pixel intensity), the sensitivity, specificity, and AUC for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.90, respectively.


      In this derivation study, quantification of papillary epithelial width and darkness identified HGD-Ca in IPMNs with high accuracy. These quantifiable variables can be used in multicenter studies for risk stratification of IPMNs. (Clinical trial registration number: NCT02516488.)

      Graphical abstract


      AGA (American Gastroenterology Association), AUC (area under the receiver operating characteristic curve), BD (branch duct), CEA (carcinoembryonic antigen), CI (confidence interval), HGD-Ca (high-grade dysplasia or adenocarcinoma), ICG (International Consensus Guidelines), IOA (interobserver agreement), IPMN (intraductal papillary mucinous neoplasm), LGD (low- and/or intermediate-grade dysplasia), nCLE (needle-based confocal laser endomicroscopy), PCL (pancreatic cystic lesion), SD (standard deviation)
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      Linked Article

      • EUS-guided confocal laser endomicroscopy: Can we use thick and wide for diagnosis of early cancer?
        Gastrointestinal EndoscopyVol. 91Issue 3
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          In this issue of Gastrointestinal Endoscopy, Krishna et al1 report their investigation of the use of EUS–needle-based confocal laser endomicroscopy (EUS-nCLE) for differentiating intraductal papillary mucinous neoplasms (IPMNs) with high-grade dysplasia or adenocarcinoma (HGD-Ca) from those with low- to intermediate-grade dysplasia. They performed a post hoc analysis of a series of consecutive IPMNs with a definitive diagnosis. In their study, the authors performed 3 phases of evaluation of IPMNs for determining the EUS-nCLE criteria.
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