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

Abstract

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 h before skin incision. Tumor fluorescence was observed with Olympus or Storz 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 PPIX levels, limiting margin visualization. While current 5-ALA-PDD was insufficient for guiding resection in RAPN, further optimization may enhance its clinical utility.