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.)
Graphical abstract
Graphical Abstract
Abbreviations:
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)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: September 19, 2019
Accepted:
September 10,
2019
Received:
June 26,
2019
Footnotes
If you would like to chat with an author of this article, you may contact Dr Krishna at [email protected]
DISCLOSURE: Dr DiMaio has been a consultant and speaker for Boston Scientific and Medtronic. Dr Othman has been a consultant for Boston Scientific and consultant and speaker for Olympus. Dr Napoleon has received grant support from and been a consultant for Mauna Kea Technologies and has been a consultant for Boston Scientific and speaker for Olympus. All other authors disclosed no financial relationships.
See CME section; p. 698.
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© 2020 by the American Society for Gastrointestinal Endoscopy
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- EUS-guided confocal laser endomicroscopy: Can we use thick and wide for diagnosis of early cancer?Gastrointestinal EndoscopyVol. 91Issue 3
- PreviewIn 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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