Esmee I M L Liem1, Jan Erik Freund2, Cemile Dilara Savci-Heijink3, Jean J M C H de la Rosette4, Guido M Kamphuis2, Joyce Baard2, Joseph C Liao5, Ton G van Leeuwen6, Theo M de Reijke2, Daniel Martijn de Bruin7. 1. Department of Urology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: e.i.liem@amc.uva.nl. 2. Department of Urology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 3. Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 4. Department of Urology, Istanbul Medipol University, Istanbul, Turkey; Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 5. Department of Urology, Stanford University School of Medicine, Stanford, California, USA. 6. Department of Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 7. Department of Urology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Abstract
BACKGROUND: Cystoscopy enables the visualisation of suspicious bladder lesions but lacks the ability to provide real-time histopathologic information. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic images. This high-resolution optical imaging technique may enable real-time tumour grading during cystoscopy. OBJECTIVE: To validate and adapt CLE criteria for bladder cancer diagnosis and grading. DESIGN, SETTING, AND PARTICIPANTS: Prospectively, 73 patients scheduled for transurethral resection of bladder tumour(s) were included. CLE imaging was performed intraoperatively prior to en bloc resection. Histopathology was the reference standard for comparison. INTERVENTION: Cystoscopic CLE imaging. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three independent observers evaluated the CLE images to classify tumours as low- or high-grade urothelial carcinoma (UC), or benign lesions. Interobserver agreement was calculated with Fleiss kappa analysis and diagnostic accuracy with 2×2 tables. RESULTS AND LIMITATIONS: Histopathology of 66 lesions (53 patients) revealed 25 low-grade UCs, 27 high-grade UCs, and 14 benign lesions. For low-grade UC, most common features were papillary configuration (100%), distinct cell borders (81%), presence of fibrovascular stalks (79%), cohesiveness of cells (77%), organised cell pattern (76%), and monomorphic cells (67%). A concordance between CLE-based classification and histopathology was found in 19 cases (76%). For high-grade UC, pleomorphic cells (77%), indistinct cell borders (77%), papillary configuration (67%), and disorganised cell pattern (60%) were the most common features. A concordance with histopathology was found in 19 cases (70%). In benign lesions, the most prevalent features were disorganised cell pattern (57%) and pleomorphic cells (52%), and a concordance with histopathology was found in four cases (29%). CONCLUSIONS: The CLE criteria enable identification of UC. CLE features correlate to histopathologic features that may enable real-time tumour grading. However, flat lesions remain difficult to classify. PATIENT SUMMARY: Confocal laser endomicroscopy may enable real-time cancer differentiation during cystoscopy, which is important for prognosis and disease management.
BACKGROUND: Cystoscopy enables the visualisation of suspicious bladder lesions but lacks the ability to provide real-time histopathologic information. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic images. This high-resolution optical imaging technique may enable real-time tumour grading during cystoscopy. OBJECTIVE: To validate and adapt CLE criteria for bladder cancer diagnosis and grading. DESIGN, SETTING, AND PARTICIPANTS: Prospectively, 73 patients scheduled for transurethral resection of bladder tumour(s) were included. CLE imaging was performed intraoperatively prior to en bloc resection. Histopathology was the reference standard for comparison. INTERVENTION: Cystoscopic CLE imaging. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three independent observers evaluated the CLE images to classify tumours as low- or high-grade urothelial carcinoma (UC), or benign lesions. Interobserver agreement was calculated with Fleiss kappa analysis and diagnostic accuracy with 2×2 tables. RESULTS AND LIMITATIONS: Histopathology of 66 lesions (53 patients) revealed 25 low-grade UCs, 27 high-grade UCs, and 14 benign lesions. For low-grade UC, most common features were papillary configuration (100%), distinct cell borders (81%), presence of fibrovascular stalks (79%), cohesiveness of cells (77%), organised cell pattern (76%), and monomorphic cells (67%). A concordance between CLE-based classification and histopathology was found in 19 cases (76%). For high-grade UC, pleomorphic cells (77%), indistinct cell borders (77%), papillary configuration (67%), and disorganised cell pattern (60%) were the most common features. A concordance with histopathology was found in 19 cases (70%). In benign lesions, the most prevalent features were disorganised cell pattern (57%) and pleomorphic cells (52%), and a concordance with histopathology was found in four cases (29%). CONCLUSIONS: The CLE criteria enable identification of UC. CLE features correlate to histopathologic features that may enable real-time tumour grading. However, flat lesions remain difficult to classify. PATIENT SUMMARY: Confocal laser endomicroscopy may enable real-time cancer differentiation during cystoscopy, which is important for prognosis and disease management.
Authors: Luigi A M J G van Riel; Abel Swaan; Christophe K Mannaerts; Rob A A van Kollenburg; C Dilara Savci Heijink; Theo M de Reijke; Daniel M de Bruin; Jan Erik Freund Journal: Technol Cancer Res Treat Date: 2022 Jan-Dec