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

Research output: Contribution to journalArticle

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)
JournalGastrointestinal endoscopy
DOIs
StateAccepted/In press - Jan 1 2019

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Lasers
Needles
Confidence Intervals
Neoplasms
Darkness
Area Under Curve
Logistic Models
Pancreatic Cyst
Sensitivity and Specificity
ROC Curve
Multicenter Studies
Cell Biology
Adenocarcinoma
Software
Clinical Trials
Prospective Studies
Liver

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Gastroenterology

Cite this

EUS-guided confocal laser endomicroscopy : prediction of dysplasia in intraductal papillary mucinous neoplasms (with video). / Krishna, Somashekar G.; Hart, Phil A.; DeWitt, John M.; DiMaio, Christopher J.; Kongkam, Pradermchai; Napoleon, Bertrand; Othman, Mohamed O.; Yew Tan, Damien Meng; Strobel, Sebastian G.; Stanich, Peter P.; Patel, Anand; Luthra, Anjuli K.; Chan, Megan Q.; Blaszczak, Alecia M.; Lee, Dana; El-Dika, Samer; McCarthy, Sean T.; Walker, Jon P.; Arnold, Christina A.; Porter, Kyle; Conwell, Darwin L.

In: Gastrointestinal endoscopy, 01.01.2019.

Research output: Contribution to journalArticle

Krishna, SG, Hart, PA, DeWitt, JM, DiMaio, CJ, Kongkam, P, Napoleon, B, Othman, MO, Yew Tan, DM, Strobel, SG, Stanich, PP, Patel, A, Luthra, AK, Chan, MQ, Blaszczak, AM, Lee, D, El-Dika, S, McCarthy, ST, Walker, JP, Arnold, CA, Porter, K & Conwell, DL 2019, 'EUS-guided confocal laser endomicroscopy: prediction of dysplasia in intraductal papillary mucinous neoplasms (with video)', Gastrointestinal endoscopy. https://doi.org/10.1016/j.gie.2019.09.014
Krishna, Somashekar G. ; Hart, Phil A. ; DeWitt, John M. ; DiMaio, Christopher J. ; Kongkam, Pradermchai ; Napoleon, Bertrand ; Othman, Mohamed O. ; Yew Tan, Damien Meng ; Strobel, Sebastian G. ; Stanich, Peter P. ; Patel, Anand ; Luthra, Anjuli K. ; Chan, Megan Q. ; Blaszczak, Alecia M. ; Lee, Dana ; El-Dika, Samer ; McCarthy, Sean T. ; Walker, Jon P. ; Arnold, Christina A. ; Porter, Kyle ; Conwell, Darwin L. / EUS-guided confocal laser endomicroscopy : prediction of dysplasia in intraductal papillary mucinous neoplasms (with video). In: Gastrointestinal endoscopy. 2019.
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title = "EUS-guided confocal laser endomicroscopy: prediction of dysplasia in intraductal papillary mucinous neoplasms (with video)",
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-na{\"i}ve 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.)",
author = "Krishna, {Somashekar G.} and Hart, {Phil A.} and DeWitt, {John M.} and DiMaio, {Christopher J.} and Pradermchai Kongkam and Bertrand Napoleon and Othman, {Mohamed O.} and {Yew Tan}, {Damien Meng} and Strobel, {Sebastian G.} and Stanich, {Peter P.} and Anand Patel and Luthra, {Anjuli K.} and Chan, {Megan Q.} and Blaszczak, {Alecia M.} and Dana Lee and Samer El-Dika and McCarthy, {Sean T.} and Walker, {Jon P.} and Arnold, {Christina A.} and Kyle Porter and Conwell, {Darwin L.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.gie.2019.09.014",
language = "English (US)",
journal = "Gastrointestinal Endoscopy",
issn = "0016-5107",
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TY - JOUR

T1 - EUS-guided confocal laser endomicroscopy

T2 - prediction of dysplasia in intraductal papillary mucinous neoplasms (with video)

AU - Krishna, Somashekar G.

AU - Hart, Phil A.

AU - DeWitt, John M.

AU - DiMaio, Christopher J.

AU - Kongkam, Pradermchai

AU - Napoleon, Bertrand

AU - Othman, Mohamed O.

AU - Yew Tan, Damien Meng

AU - Strobel, Sebastian G.

AU - Stanich, Peter P.

AU - Patel, Anand

AU - Luthra, Anjuli K.

AU - Chan, Megan Q.

AU - Blaszczak, Alecia M.

AU - Lee, Dana

AU - El-Dika, Samer

AU - McCarthy, Sean T.

AU - Walker, Jon P.

AU - Arnold, Christina A.

AU - Porter, Kyle

AU - Conwell, Darwin L.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.)

AB - 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.)

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