**8. Confocal laser endomicroscopy**

Confocal laser endomicroscopy (CLE) allows for in vivo histological analysis of tissues in real time. The technique is being developed for the assessment of early pancreatic masses and the surveillance of precancerous lesions. A laser is used to illuminate the target tissue, which is then reflected back through a pinhole to the user. Local or systemic use of fluorescence agents, such as fluorescein can also be used to enhance the image. In endoscopy, CLE can either be done through an integrated endoscope tip, which has been useful for assessing and targeting biopsies of the luminal wall (e.g. oesophagus or stomach), or through needle-based CLE (nCLE), which uses a microfiber that can pass through a 19-gauge needle to assess tissue at the site of the needle tip.

nCLE has been studied mostly in investigation of pancreatic cystic lesions and shown to have an accuracy of 46–95% for diagnosing PC, with a low sensitivity 46–59%. Overall complication rate ranges from 0 to 2.5%; complications include bleeding, infection, pancreatitis and perforation [66]. Nakai et al. used a combination of EUS-guided cystoscopy (direct visualisation of the internal wall of a cystic lesion) and nCLE in the assessment of 30 patients with cystic pancreatic lesions. The sensitivity of cystoscopy was 90% for determining PCN vs. BPC, nCLE was 80% sensitive, and the combination of the two modalities was 100% sensitive [67].

**Author details**

Eva Segelov1,2

**References**

Cameron John McLaren1

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\*Address all correspondence to: cam.mclaren@gmail.com

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1 Monash Health, Melbourne, Australia

2 Monash University, Melbourne, Australia

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tionaldimensions.com/eLearn/endoscope/anatomy.php [cited 10 Dec 2017]

Kongkam et al. conducted a study to validate the CLE diagnostic criteria and found a 90.9% accuracy of EUS-nCLE among 22 patients [68]. They found malignant lesions displayed dark clumping with or without dilated vessels (<40 μm), while benign lesions were more likely to display white fibrous bands and normal acini. They also found good inter-observer agreement between the three blinded endoscopists (κ = 0.82) [68]. These results contrast that of Karstensen JG et al. (2018), who conducted a prospective, dual-centre study on 28 patients with pancreatic masses referred for EUS-FNA and found limited benefit above EUS-FNA alone by using the current proposed nCLE criteria. This study also found significant interobserver and intraobserver analysis of the proposed CLE criteria, suggesting the reproducibility of the procedure is currently suboptimal. They concluded that further development of the technology is needed to permit better delineation between benign and malignant disease [69]. More studies are required in this area before EUS-CLE can be recommended as an adjunct to EUS-FNA for routine analysis of solid pancreatic lesions.

The use of EUS-nCLE to enable direct visualisation of molecular expression with pancreatic cancers has also been explored. Nakai et al. have shown proof-of-concept in the ability to directly image EGFR and survivin expression in porcine models in vivo. This study utilised the direct injection of fluorescein isothiocyanate-labelled antibodies against EGFR and survivin into the pancreas 30 min before EUS-nCLE to highlight the expression of EGFR and survivin, and showed good correlation between the EUS-nCLE images and histological analysis of the porcine pancreas ex vivo [70]. The use of similarly labelled antibodies to KRAS could assist in the stratification of precancerous lesions and direct early-stage treatment.

What about a section on molecular diagnosis personalised therapy. You cannot tell me that this will not be important in the future. I know self-citation is frowned upon but we have published 3 articles in this space recently?
