Fluorescence by 5-aminolevulinic acid-induced protoporphyrin Ⅸ varies in tumor and normal tissues during robot-assisted partial nephrectomy for renal cell carcinoma.

Background Partial nephrectomy is the gold standard for small renal cell carcinoma (RCC). Robot-assisted partial nephrectomy (RAPN), introduced in 2004, has gained acceptance as a minimally invasive approach. Determining resection margins in complex cases remains a challenge. 5-ALA, a photosensitizer metabolized to protoporphyrin IX (PPⅨ), induces red fluorescence under blue light, aiding tumor detection. Although effective in other malignancies, its utility in renal tumors is not well established. METHODS Between May 2016 and August 2017, 19 patients underwent RAPN using photodynamic diagnosis (PDD) at our institution with the da Vinci Surgical System Si®. Patients received 20 mg/kg 5-ALA in 50 mL water orally, 0‒12 hours before skin incision. Tumor fluorescence was observed with Olympus or Stolz camera systems under excitation wavelengths for characteristic red fluorescence during surgery. We evaluated 5-ALA and protoporphyrin IX (PPⅨ) levels in tumor and normal tissues by high-performance liquid chromatography (HPLC). Statistical analyses were performed using Mann‒Whitney U tests with GraphPad Prism 5. A p-value of less than 0.05 was considered statistically significant. RESULTS Tumor pathology revealed clear cell RCC in 17 and chromophobe RCC in two cases. Only one clear cell RCC tumor showed fluorescence under excitation wavelengths before renal artery clamping; however, normal peri-tumoral tissues also demonstrated fluorescence. In three cases, including this one, fluorescence was observed in both tumor and normal tissues ex vivo within a dark box. In the ex vivo analysis, two cases exhibited fluorescence in the tumor tissue without fluorescence in the normal tissue, while one exhibited the reverse. Accumulation of 5-ALA and PPIX in resected tissue specimens was measured in six cases. Although statistical significance was not reached due to the small sample size (p = 0.057, Mann-Whitney U test), PPIX concentrations tended to be higher in fluorescence-positive tumors than in fluorescence-negative ones. CONCLUSIONS Both tumors and normal tissues exhibited heterogeneous concentrations of PPⅨ, resulting in variable fluorescence intensity, making it challenging to differentiate tumor margins. Photodynamic diagnosis by 5-ALA administration is inadequate to determine the resection margin in RAPN.