The Journal of Urology
Volume 182, Issue 4 , Pages 1299-1305, October 2009

Optical Biopsy of Human Bladder Neoplasia With In Vivo Confocal Laser Endomicroscopy

  • Geoffrey A. Sonn

      Affiliations

    • Department of Urology, Stanford University School of Medicine, Stanford, California
  • ,
  • Sha-Nita E. Jones

      Affiliations

    • Department of Urology, Stanford University School of Medicine, Stanford, California
  • ,
  • Tatum V. Tarin

      Affiliations

    • Department of Urology, Stanford University School of Medicine, Stanford, California
  • ,
  • Christine B. Du

      Affiliations

    • Department of Urology, Stanford University School of Medicine, Stanford, California
  • ,
  • Kathleen E. Mach

      Affiliations

    • Department of Urology, Stanford University School of Medicine, Stanford, California
  • ,
  • Kristin C. Jensen

      Affiliations

    • Department of Pathology, Stanford University School of Medicine, Stanford, California
    • Veterans Affairs Palo Alto Health Care System, Palo Alto, California
  • ,
  • Joseph C. Liao

      Affiliations

    • Department of Urology, Stanford University School of Medicine, Stanford, California
    • Stanford Cancer Center, Stanford University School of Medicine, Stanford, California
    • Veterans Affairs Palo Alto Health Care System, Palo Alto, California
    • Corresponding Author InformationCorrespondence and requests for reprints: Department of Urology, Stanford University School of Medicine, 300 Pasteur Drive, S-287, Stanford, California 94305-5118 (telephone: 650-852-3284; FAX: 650-849-0319)
    • Recipient of Stanford University Cancer Center Developmental Cancer Research Award.

Received 29 January 2009 published online 14 August 2009.

Purpose

Confocal laser endomicroscopy is a new endoscopic imaging technology that could complement white light cystoscopy by providing in vivo bladder histopathology. We evaluated confocal laser endomicroscopy by imaging normal, malignant appearing and indeterminate bladder mucosa in a pilot study.

Materials and Methods

Patients scheduled to undergo transurethral resection of bladder tumors were recruited during a 3-month period. After standard cystoscopy fluorescein was administered intravesically and/or intravenously as a contrast dye. A 2.6 mm probe based confocal laser endomicroscope was passed through a 26Fr resectoscope to image normal and abnormal appearing areas. The images were collected with 488 nm excitation at 8 to 12 frames per second. The endomicroscopic images were compared with standard hematoxylin and eosin analysis of transurethral resection of bladder tumor specimens.

Results

Of the 27 recruited patients 8 had no cancer, 9 had low grade tumors, 9 had high grade tumors and 1 had a low grade tumor with a high grade focus. Endomicroscopic images demonstrated clear differences between normal mucosa, and low and high grade tumors. In normal urothelium larger umbrella cells are seen most superficially followed by smaller intermediate cells and the less cellular lamina propria. In contrast, low grade papillary tumors demonstrate densely arranged but normal-shaped small cells extending outward from fibrovascular cores. High grade tumors show markedly irregular architecture and cellular pleomorphism.

Conclusions

We report the first study to our knowledge of in vivo confocal laser endomicroscopy in the urinary tract. Marked differences among normal urothelium, low grade tumors and high grade tumors were visualized. Pending further clinical investigation and technological improvement, confocal laser endomicroscopy may become a useful adjunct to conventional cystoscopy.

Key Words: microscopy, confocal, urinary bladder neoplasms, anatomy and histology, biopsy

Abbreviations and Acronyms: TURBT, transurethral resection of bladder tumor

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 To view the accompanying video, please see the online version of this article (Volume 182, Number 4) at www.jurology.com.

 Study received institutional review board approval.

 Clinical Trial Registration NCT00801762 (www.clinicaltrials.gov).

PII: S0022-5347(09)01513-4

doi:10.1016/j.juro.2009.06.039

The Journal of Urology
Volume 182, Issue 4 , Pages 1299-1305, October 2009