Laparoscopic Photodynamic Diagnosis of Ovarian Cancer Using 5-Aminolevulinic Acid in a Rat Model

• Published in: Gynecologic oncology 2002-10, Vol.87 (1), p.64-70
• Main Authors: Chan, John K., Monk, Bradley J., Cuccia, David, Pham, Huyen, Kimel, Sol, Gu, Mai, Hammer-Wilson, Marie J., Liaw, Lih-Huei L., Osann, Kathryn, DiSaia, Philip J., Berns, Michael, Tromberg, Bruce, Tadir, Yona
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - secondary; Aminolevulinic Acid; Animals; Biological and medical sciences; Endoscopy; Female; Female genital diseases; Fluorescence; Gynecology. Andrology. Obstetrics; Investigative techniques, diagnostic techniques (general aspects); Laparoscopy - methods; Medical sciences; Miscellaneous. Technology; Neoplasm Metastasis; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - pathology; Photosensitizing Agents; Rats; Rats, Inbred F344; Sensitivity and Specificity; Tumors
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1006/gyno.2002.6793

Objective. The objective of this study was to determine the efficacy and sensitivity of laparoscopic photodynamic diagnosis to detect 5-aminolevulinic acid (ALA)-induced fluorescent tumors in an animal model. Methods. Cancer cells were injected into the peritoneum of rats to induce peritoneal carcinomatosis. After 3–4 weeks, ALA was administered to establish fluorescence in tumor nodules. All intraperitoneal surfaces were inspected using fluorescence and white light laparoscopy. Suspicious lesions were then biopsied in vivo under either fluorescence or white light laparoscopic guidance. Fluorescence intensities of the cancerous lesions compared to normal tissues were determined. A pathologist blinded to our clinical impression analyzed all biopsied specimens. We compared the sensitivity of fluorescence and white light laparoscopic-guided detection of cancerous lesions and determined the clinical utility of fluorescent photodynamic diagnosis in detecting metastatic ovarian cancer. Results. Forty-three biopsies were performed in vivo under laparoscopic fluorescent guidance and 42 biopsies were taken using white light in various regions of the peritoneal surface from nine rats. Ten biopsies were also removed from nonfluorescent regions as nontumor controls. Cancerous lesions showed significantly higher fluorescent intensity compared to noncancerous lesions. Cancerous lesions that were difficult to differentiate from normal surrounding tissue under white light conditions were clearly detected by ALA-induced fluorescence. The average size of these metastatic lesions biopsied under fluorescent light was 1.0 mm (range: 0.3–2.5) compared to 1.5 mm (range: 0.5–2.9) with white light illumination ( P < 0.05). Conclusions. Fluorescent laparoscopic detection of micrometastatic ovarian cancer using ALA is significantly more sensitive than white-light laparoscopy in detecting smaller cancerous lesions in an ovarian cancer rat model. Human trials are indicated.