Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic acid-induced protoporphyrin IX: pathological study

Utsuki, Satoshi; Miyoshi, Norio; Oka, Hiroyuki; Miyajima, Yoshiteru; Shimizu, Satoru; Suzuki, Sachio; Fujii, Kiyotaka

doi:10.1007/s10014-007-0223-3

Cited by 95 publications

(71 citation statements)

References 15 publications

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“…20 In a series of 11 metastatic brain tumors, Utsuki et al reported 5-ALA positivity for 82% of metastases. 41 Also in our series, the rate of 5-ALA fluorescence positivity in metastases from breast cancer was high (71%, n = 5/7). 5-ALA fluorescence was positive in only 1 of 4 urothelial carcinoma metastases.…”

Section: -Ala Fluorescence In Brain Metastasessupporting

confidence: 52%

“…Others have reported positive 5-ALA fluorescence in peri-tumor areas surrounding brain metastases. 20,36,41 These reports and our own findings indicate that more studies are needed to elucidate the potential role of 5-ALA in improving resection margins in various entities of brain metastasis. We used 5-ALA fluorescence as an immediate intraoperative indicator of tumor tissue in patients undergoing diagnostic biopsy.…”

Section: Clinical Value Of 5-ala-guided Resection Of Primary Brain Tumentioning

confidence: 64%

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Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Marbacher

Klinger

Schwyzer

et al. 2014

FOC

137

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Object The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

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Section: -Ala Fluorescence In Brain Metastasessupporting

confidence: 52%

Section: Clinical Value Of 5-ala-guided Resection Of Primary Brain Tumentioning

confidence: 64%

Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Marbacher

Klinger

Schwyzer

et al. 2014

FOC

137

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“…This PPIX may be found in surrounding tissues where no tumor cells exist [7]. This phenomenon is thought to be due to PPIX produced in tumor cells leaking out of the cells [8]. Also, more highly-concentrated porphyrin, particularly coproporphyrin, is reportedly excreted in the urine of brain tumor patients than by volunteers without brain tumors given 5-ALA, since porphyrins including PPIX leak out of tumor cells [5].…”

Section: Discussionmentioning

confidence: 99%

Preoperative Prediction of Whether Intraoperative Fluorescence of Protoporphyrin IX Can Be Achieved by 5-Aminolevulinic Acid Administration

Utsuki¹,

Oka²,

Kijima³

et al. 2012

IJCM

Self Cite

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Protoporphyrin IX (PPIX) fluorescence-guided brain tumor resection, using 5-aminolevulinic acid (5-ALA), is among the most valuable tools for determining tumor removal area. However, PPIX fluorescence is not necessarily achieved during an operation visually even when 5-ALA is used, and we do not know until tumor exposure to the excitation light of the ultraviolet region whether PPIX fluorescence has been achieved. When a particular biopsy and frozen section diagnosis is made, the reason for lack of PPIX fluorescence in the tissue cannot be judged. We do not know whether the tumor fails to fluoresce or no fluorescence is seen because it is not the main body of the tumor. We investigated whether the presence or absence of tumor fluorescence could be predicted by examining urinary porphyrin before surgery, at the time of intraoperative fluorescence diagnosis using 5-ALA. The urine of brain tumor patients 2 hours after 5-ALA administration was irradiated with a 405 ± 1 nm laser light. The patients were divided into a fluorescent urine group and negative fluorescent urine group. Red fluorescence was observed in response to the 405 ± 1 nm laser beam for all tumors in the fluorescent urine group. Clear red fluorescence was not observed even with 405 ± 1 nm laser beam irradiation in any tumors in the negative fluorescent urine group. Preoperative prediction of the intraoperative fluorescence of PPIX can be achieved by observation of urine 2 hours after 5-ALA administration with exposure to a 405 ± 1 nm laser light.

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“…In particular, ALA-PDD is officially approved as a standard procedure of diagnostics by fluorescence navigation in brain tumors 7 and bladder cancer 8 . ALA is an endogenous natural amino acid and a common precursor of chlorophyll in plants and bilirubin in animals.…”

Section: Discussionmentioning

confidence: 99%

“…Despite recent advances in surgical methods, such as laparoscopic radical prostatectomy (LRP) and robotic-assisted radical prostatectomy (RARP), there has not been enough of an improvement in the rate of positive surgical margin (PSM) in radical prostatectomy. [4][5][6] Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (ALA; ALA-PDD) is clinically recognized as an effective procedure of the detection for various cancers, such as brain tumor 7 and bladder cancer. 8 Fluorescence navigation by PDD provides good visualization and detection of PSM during surgery, leads to improved surgical curability and subsequent prognosis in these cancers.…”

Section: Introductionmentioning

confidence: 99%

Photodynamic diagnosis of positive margin during radical prostatectomy: Preliminary experience with 5‐aminolevulinic acid

Fukuhara¹,

Inoue²,

Satake³

et al. 2011

Int J of Urology

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Objectives:To investigate the feasibility of intraoperative photodynamic diagnosis (PDD) by 5-aminolevulinic acid (ALA) for the identification of positive surgical margins (PSM) during retropubic radical prostatectomy (RRP) in patients with prostate cancer (PCa). Methods: Intraoperative PDD was carried out in 16 patients with pathologically confirmed PCa by biopsy of the apex, or carrying >25% of probability of extraprostatic extension as defined by Japan PC Table. Before operation, 1.0 g of ALA was given orally. During open RRP, the resection margins inside the body were examined by PDD system with a fluorescence laparoscope. After their removal, 12 harvested prostates were divided and also investigated by PDD. Red fluorescentpositive lesions were biopsied and compared with the pathological result. Results: All 16 patients were fluorescence-negative inside the body, and negative margins were pathologically confirmed during PDD. Among the 43 specimens of 12 cases obtained by biopsy under PDD, 11 specimens (25.6%) were pathologically diagnosed as malignant tissue (adenocarcinoma, 10 specimens; high grade prostatic intraepithelial neoplasia, 1 specimen) and 19 specimens (44.2%) were evaluated as positive fluorescence by PDD with a sensitivity of 81.8%, a specificity of 68.8% and a predictive accuracy of 72.1%. No side-effects were observed and the procedures were well tolerated. Conclusions: PDD mediated by ALA during RRP might be a feasible and safe modality for detection of surgical margins. Further prospective randomized studies with larger populations are required.

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Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic acid-induced protoporphyrin IX: pathological study

Cited by 95 publications

References 15 publications

Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

Preoperative Prediction of Whether Intraoperative Fluorescence of Protoporphyrin IX Can Be Achieved by 5-Aminolevulinic Acid Administration

Photodynamic diagnosis of positive margin during radical prostatectomy: Preliminary experience with 5‐aminolevulinic acid

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