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Hillemanns, Peter; Wimberger, Pauline; Reif, Jessica; Stepp, Herbert und Klapdor, Rüdiger (2017): Photodynamic Diagnosis With 5-Aminolevulinic Acid for Intraoperative Detection of Peritoneal Metastases of Ovarian Cancer: A Feasibility and Dose Finding Study. In: Lasers in Surgery and Medicine, Bd. 49, Nr. 2: S. 169-176

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Abstract

Objective: With a prospective feasibility study, we aimed to analyse the effect of different time points for application and dosage of preoperative oral 5-aminolevulinic acid administration for photodynamic diagnosis of peritoneal metastases in ovarian cancer patients. Materials and Methods: In this prospective cohort study patients were randomly divided into three different groups. 5-Aminolevulinic acid was orally administered 3-14 hours before surgery using a dosage of 1 mg/kg, 4-9 hours using 10 mg/kg, and 9-16 hours using 10 mg/kg, respectively. Fluorescence was recorded intraoperatively using endoscopic equipment. The number and localization, of fluorescing nodules were documented. To analyze sensitivity and specificity samples from fluorescent and non-fluorescent tissues were evaluated histologically. Plasma protoporphyrin concentrations as well as any adverse events were assessed perioperatively. Results: In total, 26 patients suspected for ovarian cancer underwent intraoperative photodynamic diagnosis with 5-aminolevulinic acid. Most of them suffered from advanced cancer, 72% from FIGO-Stage IIIc. No severe adverse events were observed. Orally applied 5-aminolevulinic acid with a dosage of 1 mg/kg revealed no detectable fluorescence. However, at a dosage of 10 mg/kg fluorescence of metastatic tissue was significantly stronger than of non-affected tissue. If administered 4-9 hours preoperatively best detection rates for peritoneal metastases were obtained resulting in a sensitivity of 75% and a specificity of 100%. Conclusions: Photodynamic diagnosis with 5-aminolevulinic acid leads to safe and specific fluorescence detection of peritoneal metastases. 5-Aminolevulinic acid should be used at a dosage of at least 10 mg/kg 4-9 hours preoperatively. Further phase I-II studies are recommended. (C) 2016 Wiley-Blackwell Periodicals, Inc.

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