Laparoscopic fluorescence detection of ovarian carcinoma metastases using 5‐aminolevulinic acid‐induced protoporphyrin IX

• Published in: Cancer 2004-04, Vol.100 (8), p.1650-1656
• Main Authors: Löning, Martin, Diddens, Heyke, Küpker, Wolfgang, Diedrich, Klaus, Hüttmann, Gereon
• Format: Article
• Language: English
• Subjects: 5‐aminolevulinic acid (ALA); Adult; Aged; Aminolevulinic Acid - administration & dosage; Biological and medical sciences; Female; Fluorescence; fluorescence detection; Humans; Infusions, Parenteral; Laparoscopy; Medical sciences; Middle Aged; ovarian carcinoma; Ovarian Neoplasms - pathology; Peritoneal Neoplasms - diagnosis; Peritoneal Neoplasms - secondary; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - analysis; Protoporphyrins - analysis; second look; Sensitivity and Specificity; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.20155

BACKGROUND The aim of the current clinical study was to evaluate the in vivo fluorescence detection of ovarian carcinoma metastases in a second‐look laparoscopic procedure after intraperitoneally applied 5‐aminolevulinic acid (ALA). METHODS Five hours before laparoscopic surgery, ALA was applied intraperitoneally via short infusion in a concentration of 30 mg/kg bodyweight in a sterile, 1% solution. Application of ALA resulted in the endogenous production of the fluorescent photosensitizer, protoporphyrin IX (PP IX). The Combilight PDD 5133 system served as a light source, permitting the switch from white light mode to blue light mode to excite the PP IX accumulated in the ovarian tissue specimens. By means of blue light illumination, intraperitoneally located red fluorescent lesions, which were suspected to be metastases, underwent a biopsy. In addition, several biopsy specimens were taken from nonfluorescent areas of the peritoneal cavity. RESULTS In 13 of 29 patients, ovarian carcinoma was confirmed histologically or cytologically. In 12 of these patients, metastases were visible by red fluorescence. In total, 123 biopsies were performed. Comparison of histologic assessment of the biopsy specimens with the fluorescence detection showed that strong red fluorescence had a sensitivity of 92% for detecting tumor tissue on specimens. In only 2% of all biopsy specimens was endometriosis observed in benign tissue specimens using fluorescence. In four of 13 patients with ovarian carcinoma, lesions were detected under fluorescence, which were not observed under white light illumination. CONCLUSIONS Laparoscopic fluorescence detection of endogenous PP IX after intraperitoneal application of ALA may provide a higher sensitivity of finding peritoneal metastases of epithelian ovarian carcinoma compared with conventional laparoscopy. Direct visualization of in vivo fluorescence after ALA application may improve the early detection of intraperitoneal ovarian carcinoma micrometastases. The high tissue selectivity of PP IX accumulation in tumor tissue specimens also offers the opportunity for therapeutic approaches using photodynamic therapy in the future. Cancer 2004. © 2004 American Cancer Society. After intraperitoneal application of 5‐aminolevulinic acid in patients with ovarian carcinoma, laparoscopic fluorescence imaging allowed the very early detection of intraperitoneal micrometastases with high sensitivity and specificity.