Appraisal of needle-based confocal laser endomicroscopy in the diagnosis of pancreatic cysts

Table 1 Outcome, diagnostic accuracies, and risk of pancreatitis for major trials investigating role of endoscopic ultrasound-guided needle based confocal laser endomicroscopy needle based confocal laser endomicroscopy in diagnosis of pancreatic cystic lesions

Study	Outcome	Patients, n	Surgery, n (%)	SN	SP	PPV	NPV	Accuracy	Pancreatitis rate (%)
INSPECT[21]	Neoplastic cystic lesions	Total: 66	14 (21.2)	59	100	100	50	71	3.0
DETECT[17]	Mucinous cystic lesion	Total: 30	2 (6.0)	80	100	100	80	89	6.62
		High certainty: 181
CONTACT[22]	Serous cystadenoma	Total: 31	7 (22.5)	69	100	100	82	87	3.2

¹High-certainty patients included in analysis of diagnostic accuracy;

²Patient underwent both, needle based cystoscopy and confocal endomicroscopy. SN: Sensitivity; SP: Specificity; PPV: Positive predictive value; NPV: Negative predictive value.

Table 2 Developing role of endoscopic ultrasound guided needle based confocal laser endomicroscopy in diagnosis of pancreatic cystic lesions: Review of recently presented abstracts at international gastroenterology conferences (Digestive Disease Week and American College of Gastroenterology scientific meeting)

	Study objectives	Patient, n	Pancreatitis and other complications	Accuracy data	Conclusions
Napoleon et al[23]	To evaluate feasibility and assess complication rate of nCLE in CPLs	Total: 141	Minor pancreatitis: 2 (1.45%)	NA	Main technical limitation observed when cyst interrogation requires approach through second part of the duodenum
CONTACT study		Technical feasibility: 93% (131 patients)
DDW 2015			Intracystic bleeding without extravasation - 10%
	Prospective study
Kadayifci et al[28]	To assess the safety, feasibility and diagnostic value of EUS guided nCLE for CPLs	Total: 11	No pancreatitis reported	The sensitivity, specificity, and accuracy for mucinous cyst (findings of papillae) were 57%, 100%, and 70% respectively	nCLE for pancreatic cysts was safe and feasible. nCLE has low sensitivity but high specificity for mucinous cysts
DDW 2015		Procedure successful: 10
	Retrospective
Bertani et al[26] DDW 2015	To validate prior described nCLE findings typical of IPMN lesions	Total: 9	No pancreatitis reported	Finger-like projections were observed in 7 of 7 IPMN lesions	nCLE imaging identified common criteria for diagnosis of IPMN
	Retrospective
Krishna et al[25]	To validate prior described diagnostic nCLE imaging patterns	Total: 32	Pancreatitis: 3.1% (1 patient)	Sensitivity, specificity, and accuracy for IPMN were 89%, 100%, and 96% respectively	Promising technology providing diagnosis of mucinous cysts
DDW 2015		Inclusion: 26
		Surgery: 7 (27%)
	Retrospective
				Sensitivity, specificity, and accuracy for SCA were 90%, 100%, and 96% respectively
Sejpal et al[27]	To validate prior described nCLE findings for diagnosis of pancreatic cysts	Total: 19	No pancreatitis reported	Sensitivity, specificity, and accuracy for IPMN were 80%, 100%, and 95% respectively	Possibly treating pseudocysts after nCLE examination bypass fluid analysis
DDW 2015
	Retrospective
Joshi et al[36]	To validate available nCLE criteria for diagnosis of CPLs	Total: 16	No pancreatitis reported	Improved confidence in diagnosing type of cyst in 80% of patients	Can impact in management and avoiding unnecessary surgeries for pancreatic cysts
ACG 2014
Napoleon et al[37]	To investigate and describe nCLE characteristics of CPLs	Total: 31	No pancreatitis reported	NA	nCLE images could help in the differentiation of IPMNs, MCN and SCA
CONTACT study		Inclusion: 16
DDW 2014
	Prospective

DDW: Digestive Disease Week; ACG: American College of Gastroenterology; CPL: Cystic pancreatic lesions; NA: Not available; IPMN: Intraductal papillary mucinous neoplasm; MCN: Mucinous cystic neoplasm; SCA: Serous cystadenoma.

Table 3 Summary of endoscopic ultrasound-guided needle based confocal laser endomicroscopy findings: INSPECT[21], DETECT[17], and CONTACT[22] trials

Parenchymal structures
Blood vessels	Thin or thick white bands; networking of blood vessels
Acinar cells	Dark lobular structures
Adipose cells	Grey oval structures
Pancreatic ductal epithelium	Thin grey bands
Fibrous strands	Ultrathin bright bands
Epithelial structures
Villous structures	Finger-like papillary projections, dark ring with white core (cross section)
Wall (fibrous)	Paucicellular, avascular wall
Neoplasia	Dark aggregates of cells
Cyst luminal structures
Inflammatory cells	Clusters of bright, floating, heterogeneous particles
Red blood cells	Small black particles
Debris	Bright white fixed spots or large dark round floating particles with varying sizes

Table 4 Proposed criteria for diagnosis of pancreatic cystic lesions and correlative histology

Intraductal papillary mucinous neoplasm (Figure 1A)
Finger like projections	Central fibrovascular core and overlying epithelium viewed in parallel
Dark rings	Central fibrovascular core and overlying epithelium viewed in transection
Parallel thick bands	Alternating papillae with central fibrovascular core and overlying epithelium
Absence of “superficial vascular network”
Absence of “bright, floating, heterogeneous particles”
Serous cystadenoma (Figure 1B)
“Superficial vascular network”	Dense and tortuous appearing network of multiple blood vessels under cuboidal epithelium. Observed in both macrocystic and septa separating microcysts
Multiple blood vessels
Absence of finger like projections
Pseudocyst1 (Figure 1C)
Clusters of bright, floating, heterogeneous particles
Absence of finger like projections
Mucinous cystadenoma1 (Figure 1D)
Solitary epithelial bands	Epithelium (columnar, tall cells) lining the cysts
Large caliber blood vessels
Clusters of bright particles	Epithelial cells and inflammatory elements

¹Needs validation.