Dr. Jen-Jane Liu Profile

Dr. Jen-Jane Liu

at Stanford Health Care

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Publications (2)

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Proceedings Article | 9 February 2012 Paper

Next generation of optical diagnostics for bladder cancer using probe-based confocal laser endomicroscopy

Jen-Jane Liu, Timothy Chang, Ying Pan, Shelly Hsiao, Kathleen Mach, Kristin Jensen, Joseph Liao

Proceedings Volume 8207, 820716 (2012) https://doi.org/10.1117/12.907623

KEYWORDS: Bladder, Bladder cancer, Cancer, Tumors, Diagnostics, Confocal microscopy, Tissues, Control systems, Endomicroscopy, Imaging systems

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Real-time imaging with confocal laser endomicroscopy (CLE) probes that fit in standard endoscopes has emerged as a clinically feasible technology for optical biopsy of bladder cancer. Confocal images of normal, inflammatory, and neoplastic urothelium obtained with intravesical fluorescein can be differentiated by morphologic characteristics. We compiled a confocal atlas of the urinary tract using these diagnostic criteria to be used in a prospective diagnostic accuracy study. Patients scheduled to undergo transurethral resection of bladder tumor underwent white light cystoscopy (WLC), followed by CLE, and histologic confirmation of resected tissue. Areas that appeared normal by WLC were imaged and biopsied as controls. We imaged and prospectively analyzed 135 areas in 57 patients. We show that CLE improves the diagnostic accuracy of WLC for diagnosing benign tissue, low and high grade cancer. Interobserver studies showed a moderate level of agreement by urologists and nonclinical researchers. Despite morphologic differences between inflammation and cancer, real-time differentiation can still be challenging. Identification of bladder cancer-specific contrast agents could provide molecular specificity to CLE. By using fluorescently-labeled antibodies or peptides that bind to proteins expressed in bladder cancer, we have identified putative molecular contrast agents for targeted imaging with CLE. We describe one candidate agent - anti-CD47 - that was instilled into bladder specimens. The tumor and normal urothelium were imaged with CLE, with increased fluorescent signal demonstrated in areas of tumor compared to normal areas. Thus, cancer-specificity can be achieved using molecular contrast agents ex vivo in conjunction with CLE.

Proceedings Article | 23 February 2011 Paper

Real time diagnosis of bladder cancer with probe-based confocal laser endomicroscopy

Jen-Jane Liu, Katherine Wu, Winifred Adams, Shelly Hsiao, Kathleen Mach, Andrew Beck, Kristin Jensen, Joseph Liao

Proceedings Volume 7902, 79021V (2011) https://doi.org/10.1117/12.874243

KEYWORDS: Confocal microscopy, Bladder cancer, Diagnostics, Bladder, Tumors, Tissues, Endomicroscopy, Biopsy, Video, Image processing

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Probe-based confocal laser endomicroscopy (pCLE) is an emerging technology for in vivo optical imaging of the urinary tract. Particularly for bladder cancer, real time optical biopsy of suspected lesions will likely lead to improved management of bladder cancer. With pCLE, micron scale resolution is achieved with sterilizable imaging probes (1.4 or 2.6 mm diameter), which are compatible with standard cystoscopes and resectoscopes. Based on our initial experience to date (n = 66 patients), we have demonstrated the safety profile of intravesical fluorescein administration and established objective diagnostic criteria to differentiate between normal, benign, and neoplastic urothelium. Confocal images of normal bladder showed organized layers of umbrella cells, intermediate cells, and lamina propria. Low grade bladder cancer is characterized by densely packed monomorphic cells with central fibrovascular cores, whereas high grade cancer consists of highly disorganized microarchitecture and pleomorphic cells with indistinct cell borders. Currently, we are conducting a diagnostic accuracy study of pCLE for bladder cancer diagnosis. Patients scheduled to undergo transurethral resection of bladder tumor are recruited. Patients undergo first white light cystocopy (WLC), followed by pCLE, and finally histologic confirmation of the resected tissues. The diagnostic accuracy is determined both in real time by the operative surgeon and offline after additional image processing. Using histology as the standard, the sensitivity, specificity, positive and negative predictive value of WLC and WLC + pCLE are calculated. With additional validation, pCLE may prove to be a valuable adjunct to WLC for real time diagnosis of bladder cancer.

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