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 photo...

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Main Authors: Takashi Matsuoka, Issei Suzuki, Ryosuke Suzuki, Arinobu Fukunaga, Yoichiro Tohi, Yoshio Sugino, Takuya Okada, Mutsushi Kawakita
Format: Article
Language:English
Published: BMC 2025-06-01
Series:BMC Surgery
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Online Access:https://doi.org/10.1186/s12893-025-02987-6
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author Takashi Matsuoka
Issei Suzuki
Ryosuke Suzuki
Arinobu Fukunaga
Yoichiro Tohi
Yoshio Sugino
Takuya Okada
Mutsushi Kawakita
author_facet Takashi Matsuoka
Issei Suzuki
Ryosuke Suzuki
Arinobu Fukunaga
Yoichiro Tohi
Yoshio Sugino
Takuya Okada
Mutsushi Kawakita
author_sort Takashi Matsuoka
collection DOAJ
description 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.
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publishDate 2025-06-01
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spelling doaj-art-94c3f2cf0aa845fbbd7b3cd5ef10da302025-08-20T03:25:16ZengBMCBMC Surgery1471-24822025-06-0125111010.1186/s12893-025-02987-6Fluorescence by 5-aminolevulinic acid-induced protoporphyrin IX varies in tumor and normal tissues during robot-assisted partial nephrectomy for renal cell carcinomaTakashi Matsuoka0Issei Suzuki1Ryosuke Suzuki2Arinobu Fukunaga3Yoichiro Tohi4Yoshio Sugino5Takuya Okada6Mutsushi Kawakita7Department of Urology, Kobe City Medical Center General HospitalDepartment of Urology, Kobe City Medical Center General HospitalDepartment of Urology, Kobe City Medical Center General HospitalDepartment of Urology, Kobe City Medical Center General HospitalDepartment of Urology, Kobe City Medical Center General HospitalDepartment of Urology, Kobe City Medical Center General HospitalDepartment of Urology, Kobe City Medical Center General HospitalDepartment of Urology, Kobe City Medical Center General HospitalAbstract 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.https://doi.org/10.1186/s12893-025-02987-65-aminolevulinic acidPhotodynamic detectionProtoporphyrin IXRenal cell carcinomaRobot-assisted partial nephrectomyFluorescence imaging
spellingShingle Takashi Matsuoka
Issei Suzuki
Ryosuke Suzuki
Arinobu Fukunaga
Yoichiro Tohi
Yoshio Sugino
Takuya Okada
Mutsushi Kawakita
Fluorescence by 5-aminolevulinic acid-induced protoporphyrin IX varies in tumor and normal tissues during robot-assisted partial nephrectomy for renal cell carcinoma
BMC Surgery
5-aminolevulinic acid
Photodynamic detection
Protoporphyrin IX
Renal cell carcinoma
Robot-assisted partial nephrectomy
Fluorescence imaging
title Fluorescence by 5-aminolevulinic acid-induced protoporphyrin IX varies in tumor and normal tissues during robot-assisted partial nephrectomy for renal cell carcinoma
title_full Fluorescence by 5-aminolevulinic acid-induced protoporphyrin IX varies in tumor and normal tissues during robot-assisted partial nephrectomy for renal cell carcinoma
title_fullStr Fluorescence by 5-aminolevulinic acid-induced protoporphyrin IX varies in tumor and normal tissues during robot-assisted partial nephrectomy for renal cell carcinoma
title_full_unstemmed Fluorescence by 5-aminolevulinic acid-induced protoporphyrin IX varies in tumor and normal tissues during robot-assisted partial nephrectomy for renal cell carcinoma
title_short Fluorescence by 5-aminolevulinic acid-induced protoporphyrin IX varies in tumor and normal tissues during robot-assisted partial nephrectomy for renal cell carcinoma
title_sort fluorescence by 5 aminolevulinic acid induced protoporphyrin ix varies in tumor and normal tissues during robot assisted partial nephrectomy for renal cell carcinoma
topic 5-aminolevulinic acid
Photodynamic detection
Protoporphyrin IX
Renal cell carcinoma
Robot-assisted partial nephrectomy
Fluorescence imaging
url https://doi.org/10.1186/s12893-025-02987-6
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