A Prospective In-Vivo Human Pilot Study to Assess Confocal Laser Endomicroscopy Characteristics of Upper Tract Urothelial Carcinoma

This study is a prospective, mono-center observational human, in vivo pilot study to assess in-vivo CLE characteristics of normal urothelium, benign urothelium and urothelial carcinoma (low-grade, high-grade or CIS) of the upper urinary tract. Eligible patients have a suspect tumour in the upper urinary tract and are scheduled for a diagnostic URS. Eligible patients will be informed about this study by their urologist. Information about the study will be provided both verbally and in written form.

CLE images are recorded using a probe-based system (Cellvizio 100 series, Mauna Kea Technologies, Paris, France). The probe has a diameter of 0,85 mm, hereby enabling passage through the working channel of ureterorenoscope. It has a depth of tissue penetration of 50 µm, a field of view of 320 µm and a resolution of 3,5 µm. Images are collected at a scan rate of 12 frames per second. Using the Cellvizio Viewer system, we can observe mucosal microarchitecture with an increased field of view through mosaic post processing. This system also enables virtual staining of mucosal structures to further enhance tissue contrast.

A fluorescent contrast agent is needed to obtain CLE images. Fluorescein (fluoresceinedinatrium, Fresenius Kabi, Zeist, Nederland), a non-toxic and commonly used fluorescent dye will be administered through the working channel of the ureterorenoscope into the pyelocaliceal system (3 - 5 mL 0.1% fluorescein diluted in saline) and left indwelling for 5 minutes to stain the extracellular matrix.

In this study patients will undergo one CLE measurement during the planned diagnostic URS. We measure on average 2 regions of interest per patient. If a patient has multiple tumours we will do multiple measurements. The measurement duration per patient adds maximally 10 minutes during the URS. At a later stage two independent non-blinded observers will review the CLE images. The CLE images of the diagnostic URS are qualitatively compared with histopathology from diagnostic biopsies, and if performed also with pathology from the therapeutic nephroureterectomy.

Based on the UTUC diagnosis from the diagnostic URS, in general about one third of the patients are indicated for a therapeutic radical nephroureterectomy. The other two thirds of the UTUC patients are treated with endoscopic treatment. If patients undergo several ureterorenoscopies, they may be approached for CLE measurements at consecutive ureterorenoscopies.