Validation of diagnostic characteristics of needle based confocal laser endomicroscopy in differentiation of pancreatic cystic lesions

Somashekar G Krishna, Benjamin Swanson, Phil A Hart, Samer El-Dika, Jon P Walker, Sean T McCarthy, Ahmad Malli, Zarine K Shah, Darwin L Conwell, Somashekar G Krishna, Benjamin Swanson, Phil A Hart, Samer El-Dika, Jon P Walker, Sean T McCarthy, Ahmad Malli, Zarine K Shah, Darwin L Conwell

Abstract

Background and aims: Endoscopic ultrasound (EUS)-guided needle-based Confocal Laser Endomicroscopy (nCLE) characteristics of pancreatic cystic lesions (PCLs) have been identified in studies where the gold standard surgical histopathology was available in a minority of patients. There are diverging reports of interobserver agreement (IOA) and paucity of intraobserver reliability (IOR). Thus, we sought to validate current EUS-nCLE criteria of PCLs in a larger consecutive series of surgical patients. Methods: A retrospective analysis of patients who underwent EUS-nCLE at a single center was performed. For calculation of IOA (Fleiss' kappa) and IOR (Cohen's kappa), blinded nCLE-naïve observers (n = 6) reviewed nCLE videos of PCLs in two phases separated by a 2-week washout period. Results: EUS-nCLE was performed in 49 subjects, and a definitive diagnosis was available in 26 patients. The overall sensitivity, specificity, and accuracy for diagnosing a mucinous PCL were 94 %, 82 %, and 89 %, respectively. The IOA for differentiating mucinous vs. non-mucinous PCL was "substantial" (κ = 0.67, 95 %CI 0.57, 0.77). The mean (± standard deviation) IOR was "substantial" (κ = 0.78 ± 0.13) for diagnosing mucinous PCLs. Both the IOAs and mean IORs were "substantial" for detection of known nCLE image patterns of papillae/epithelial bands of mucinous PCLs (IOA κ = 0.63; IOR κ = 0.76 ± 0.11), bright particles on a dark background of pseudocysts (IOA κ = 0.71; IOR κ = 0.78 ± 0.12), and fern-pattern or superficial vascular network of serous cystadenomas (IOA κ = 0.62; IOR κ = 0.68 ± 0.20). Three (6.1 % of 49) patients developed post-fine needle aspiration (FNA) pancreatitis. Conclusion: Characteristic EUS-nCLE patterns can be consistently identified and improve the diagnostic accuracy of PCLs. These results support further investigations to optimize EUS-nCLE while minimizing adverse events.

Study registration: NCT02516488.

Conflict of interest statement

Competing interests: There are no relevant conflicts of interest to report for any author.

Figures

Fig. 1
Fig. 1
Study flow chart. EUS-nCLE: endoscopic ultrasound guided needle based confocal laser endomicroscopy. IOA: interobserver agreement.
Fig. 2
Fig. 2
EUS-guided needle based confocal endomicroscopy of intraductal papillary mucinous neoplasms (IPMN): “Finger-like” papillary projections representing the central fibrovascular core (black arrows) and overlying epithelium (white arrows) of the papillae. a, c In vivo EUS-nCLE imaging of branch duct IPMN. b, d surgical histopathology: b, magnification × 40; d, magnification × 10.
Fig. 3
Fig. 3
EUS-guided needle based confocal endomicroscopy of mucinous cystic neoplasm (MCN). a, b MCN with low grade dysplasia. EUS-nCLE image (a) demonstrates a solitary epithelial band (white arrow) correlating with representative histology (b, magnification × 10). c, d MCN with high grade dysplasia. EUS-nCLE image (c) reveals a thicker epithelial band (white arrow) relating to representative histology (d, magnification × 40).
Fig. 4
Fig. 4
EUS-guided needle based confocal endomicroscopy (nCLE) in pancreatic cystic lesions. a Schematic diagram of the “fern-pattern” of vascularity in serous cystadenoma. b, c nCLE images of the “fern-pattern” of vascularity.
Fig. 5
Fig. 5
EUS-guided needle based confocal endomicroscopy of pancreatic cysts. a Pseudocysts lack an underlying epithelium and demonstrate multiple clusters of bright, floating, heterogeneous particles representing inflammatory debris and cells (autofluorescent macrophages: green arrows). Due to lack of vascularity, the background is dark. b Lymphoepithelial cyst revealing squamous type epithelium (orange arrows). c Epidermoid cyst also revealing squamous type epithelial cells (yellow arrows). d Lymphoepithelial cyst with abundant keratin (blue arrows).

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