Experience in the use of confocal laser endomicroscopy for the diagnosis of bladder papillary tumors


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Abstract

Introduction. Visual confirmation of suspicious changes in the urinary tract mucosa is the cornerstone in the diagnosis of urothelial cancer. However, with bladder tumors, it is impossible to obtain histopathological data during cystoscopy both in white light and in photodynamic and narrow-spectrum modes, as well as with computerized chromoendoscopy. Confocal laser endomicroscopy (probe-based confocal laser endomicroscopy – pCLE) is an optical imaging technique that provides high-resolution in vivo imaging and real-time evaluation of urothelial lesions.

Aim. To assess the diagnostic capabilities of pCLE in papillary bladder tumors and compare its results with standard pathomorphological study.

Materials and methods. A total of 38 patients (27 men, 11 women, aged 41–82 years) with primary bladder tumors diagnosed on the imaging methods were included in the study. For the diagnosis and treatment, all patients underwent transurethral resection (TUR) of the bladder. When a standard white light cystoscopy with assessment of the entire urothelium, 10% sodium fluorescein was administrated intravenously as a contrast dye. pCLE was performed with CystoFlexTMUHD 2.6 mm (7.8 Fr) probe, which was passed through the 26 Fr resectoscope using a telescope bridge to visualize normal and pathological urothelial lesions. A laser with a wavelength of 488 nm and a speed of 8 to 12 frames per second allowed to obtain an endomicroscopic image. These images were compared with standard histopathological analysis using hematoxylin-eosin (H&E) staining of tumor fragments removed during TUR of the bladder.

Results. Based on real-time pCLE, 23 patients had a diagnosis of low-grade urothelial carcinoma, while in 12 patients the endomicroscopic picture corresponded to high-grade urothelial carcinoma, 2 patients had typical changes for inflammatory process and 1 case of carcinoma in situ was suspected, which was confirmed by histopathological study. Endomicroscopic images demonstrated clear differences between normal bladder mucosa and high- and low-grade tumors. In the normal urothelium, the larger umbrella cells are located most superficially, followed by smaller intermediate cells, as well as the lamina propria with blood vessels network. In contrast, low-grade urothelial carcinoma is characterized by denser, normal-shaped small cells located superficially than a central fibrovascular core. High-grade urothelial carcinoma exhibits markedly irregular cell architecture and cellular pleomorphism.

Conclusion. pCLE is a promising new method for in-vivo diagnosing of bladder cancer. Our results show its potential for endoscopic determination of the histological characteristics of bladder tumors and the ability to differentiate between benign and malignant processes, as well as the histological grade of tumor cells.

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About the authors

M. A. Shoaydarov

A.I. Burnazyan SRC FMBC, FMBA of Russia

Email: dr.shoaydarov@yahoo.com
ORCID iD: 0000-0002-3136-2114

urologist, Ph.D. student at the Department of Urology and Andrology

Russian Federation, Moscow

A. G. Martov

GBUZ “City clinical hospital named after D.D. Pletnev of the Health Department c. Moscow; A.I. Burnazyan SRC FMBC, FMBA of Russia; Lomonosov Moscow State University

Author for correspondence.
Email: martovalex@mail.ru
ORCID iD: 0000-0001-6324-6110

Ph.D., MD, corresponding member of RAS, Professor, Head of the Department of Urology and Andrology; Head of the urologic department No2; leading researcher at the Department of Urology and Andrology of Medical Scientific and Educational Center

Russian Federation, Moscow; Moscow; Moscow

A. S. Andronov

GBUZ “City clinical hospital named after D.D. Pletnev of the Health Department c. Moscow; A.I. Burnazyan SRC FMBC, FMBA of Russia

Email: dr.andronov@mail.ru
ORCID iD: 0000-0002-5492-6808

Ph.D., associate professor at the Department of Urology and Andrology; urologist at the Urologic department No2

Russian Federation, Moscow; Moscow

S. V. Dutov

GBUZ “City clinical hospital named after D.D. Pletnev of the Health Department c. Moscow; A.I. Burnazyan SRC FMBC, FMBA of Russia

Email: hammerwise@gmail.com
ORCID iD: 0000-0002-5384-355X

Ph.D., assistant at the Department of Urology and Andrology; urologist at the Urologic department No2

Russian Federation, Moscow; Moscow

V. M. Pominalnaya

Loginov Moscow Clinical Scientific Center of Moscow Health Department

Email: vika.pominalnaya74@mail.ru
ORCID iD: 0000-0003-4420-9052

Ph.D., pathologist at the Department of the Pathology

Russian Federation, Moscow

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig.1. The principle of operation of the confocal laser endomicroscope (explanations in the text)

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3. Fig.2. Confocal laser endomicroscopy with a MiniprobeTM CystoFlexTM UHD probe. A - unchanged mucosa of the urothelium, B - papillary tumor of the bladder

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4. Fig.3. Confocal laser endomicroscopy. Left - endoscopic picture in white light (WLC). Right - Cellvizio® endomicroscopic image, real-time tumor scan

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5. Fig.4. Endomicroscopic picture of a "healthy urothelium". A - umbrella cells, B - intermediate cells, C - lamina propria propria, the arrow indicates the movement of erythrocytes in the vessels

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6. Fig.5. A, Endomicroscopic (pCLE) image of a low grade papillary urothelial carcinoma with a central fibrovascular core and well organized urothelial cells. B - pathological picture: staining with hematoxylin and eosin (H&E)

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7. Fig.6. A, Endomicroscopic (pCLE) picture of high grade papillary urothelial carcinoma with extensive architectural disorder and cellular irregularity. B - pathological picture: staining with hematoxylin and eosin (H&E)

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