Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis

Table 1

Summary of the studies applying CLE for esophageal lesion screening and diagnosis (“per biopsy” or “per patient” analysis).

Author and year	Country		Mean age or range	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)	Main findings
Barrett’s esophagus
Kiesslich et al. 2006 [20]	Germany	63 patients; 156 biopsies	58.7	92.9; n/a	98.4; n/a	92.9; n/a	98.4; n/a	97.4; n/a	CLE may be helpful in the management of patients with BE because gastric, Barrett’s epithelium, and Barrett’s associated neoplastic changes can be diagnosed with high accuracy.
Pohl et al. 2008 [21]	Germany	38 patients; 201 biopsies	62.1	75; 80	57.9; 94.1	n/a; 44.4	91.7; 98.8	60.9; 93.3	CLE showed a high NPV for the diagnosis of endoscopically invisible neoplasia in BE.
Dunbar et al. 2009 [22]	USA	39 patients	64	n/a	n/a	n/a	n/a	n/a	CLE increases diagnostic yield for neoplasia and reduces the number of mucosal biopsies.
Wallace et al. 2010 [23]	USA; Germany; France	5 patients; 20 biopsies	38–86	n/a; 88	n/a; 96	n/a; n/a	n/a; n/a	n/a; 92	pCLE has very high accuracy and reliability for the diagnosis of neoplasia in BE.
Bajbouj et al. 2010 [24]	Germany	68 patients; 703 biopsies	60	60; 12	95; 95	67; 18	93; 92	n/a; n/a	pCLE can be regarded as noninferior to endoscopic biopsy but, for its low PPV and sensitivity, may currently not replace standard biopsy techniques for the diagnosis of BE and associated neoplasia.
Sharma et al. 2011 [25]	USA; France; Germany	101 patients; 874 biopsies	65.1	n/a; 62.5	n/a; 92.7	n/a; 57.7	n/a; 94.0	n/a; n/a	pCLE combined with HD-WLE significantly improved the ability to detect neoplasia in BE patients compared with HD-WLE.
Jayasekera et al. 2012 [26]	Australia	50 patients; 1117 biopsies	66	n/a; 75.7	n/a; 80.0	n/a; 98.1	n/a; 19.4	n/a; 79.9	Minimal additional diagnostic impact of CLE above HD-WLE and NBI in the assessment of BE.
Wallace et al. 2012 [27]	USA; France; UK	164 patients	67.9; 69.6	n/a	n/a	n/a	n/a	n/a	The addition of pCLE to high-definition white light imaging does not improve diagnostic accuracy nor clinical outcomes in patients undergoing ablation or resection for BE.
Nguyen et al. 2012 [28]	USA	18 patients	72.6	n/a	n/a	n/a	n/a	n/a	Endoscopists with minimal experience in CLE can effectively use this technology for targeted biopsy, decreasing the need for intense tissue sampling without lowering the diagnostic yield in detecting dysplasia.
Bertani et al. 2013 [29]	Italy	100 patients	59.7	100	83	67	100	n/a	Incident dysplasia can be more frequently detected by pCLE than by HD-WLE in BE. The higher dysplasia detection rate provided by pCLE could improve the efficacy of BE surveillance programs.
Trovato et al. 2013 [30]	Italy	48 patients; 422 biopsies	54	83.3; 93.3	95.2; 98.2	71.4; 66.6	97.6; 99.7	93.7; 98.1	CLE can provide in vivo diagnosis of Barrett tumor-associated esophagus leading to significant improvements in screening and monitoring of in vivo BE.
Canto et al. 2014 [31]	USA Germany	192 patients; 978 biopsies	62	95; 86	92; 93	77; 65	98; 98	93; 92	Real-time CLE and TB after HD-WLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision-making by altering the diagnosis and guiding therapy.
Squamous cell carcinoma
Pech et al. 2008 [32]	Germany	21 patients	64	100	87.5	93	100	95	CLE is able to provide virtual histology of early squamous cell cancers with a high degree of accuracy and can facilitate rapid diagnosis during routine endoscopy.
Liu et al. 2009 [33]	China	27 patients	61.1	n/a	n/a	n/a	n/a	n/a	CLE can be used to distinguish cancerous from normal epithelium, which gives it potential value for early detection of esophageal carcinoma.
Iguchi et al. 2009 [34]	Japan	15 patients	65.9	n/a	n/a	n/a	n/a	n/a	Scoring and quantification of CLE images may be useful for the differential diagnosis and determination of superficial invasion by squamous cell carcinoma.
Reflux esophagitis, nonerosive reflux disease (NERD)
Venkatesh et al. 2012 [35]	Australia	23 patients	7.6; 12	n/a	n/a	n/a	n/a	n/a	Measurement of the S-P distance by CLE will enable real-time diagnosis of GERD-related esophagitis during ongoing endoscopy.
Chu et al. 2012 [36]	China	46 patients	48.12; 45.23	n/a	n/a	n/a	n/a	n/a	CLE represents a useful and potentially significant improvement over standard endoscopy to examine the microalterations of the esophagus in vivo.