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

Somashekar G. Krishna, Phil A. Hart, John M. DeWitt, Christopher J. DiMaio, Pradermchai Kongkam, Bertrand Napoleon, Mohamed O. Othman, Damien Meng Yew Tan, Sebastian G. Strobel, Peter P. Stanich, Anand Patel, Anjuli K. Luthra, Megan Q. Chan, Alecia M. Blaszczak, Dana Lee, Samer El-Dika, Sean T. McCarthy, Jon P. Walker, Christina A. Arnold, Kyle PorterDarwin L. Conwell

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2 Scopus citations

Abstract

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). Methods: 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). Results: 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. Conclusions: 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.)

Original languageEnglish (US)
Pages (from-to)551-563.e5
JournalGastrointestinal endoscopy
Volume91
Issue number3
DOIs
StatePublished - Mar 2020

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Gastroenterology

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    Krishna, S. G., Hart, P. A., DeWitt, J. M., DiMaio, C. J., Kongkam, P., Napoleon, B., Othman, M. O., Yew Tan, D. M., Strobel, S. G., Stanich, P. P., Patel, A., Luthra, A. K., Chan, M. Q., Blaszczak, A. M., Lee, D., El-Dika, S., McCarthy, S. T., Walker, J. P., Arnold, C. A., ... Conwell, D. L. (2020). EUS-guided confocal laser endomicroscopy: prediction of dysplasia in intraductal papillary mucinous neoplasms (with video). Gastrointestinal endoscopy, 91(3), 551-563.e5. https://doi.org/10.1016/j.gie.2019.09.014