Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial

Stummer, Walter; Pichlmeier, Uwe; Meinel, Thomas; Wiestler, Otmar D.; Zanella, Friedhelm E.; Reulen, H. J.

doi:10.1016/s1470-2045(06)70665-9

Cited by 2,982 publications

(2,358 citation statements)

References 21 publications

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“…Application of 5-aminolevulinic acid (5-ALA or ALA) for detection of highly malignant brain tumors has gained increasing popularity among the neurosurgeons in the recent years following extensive studies by Stummer et al on the effectiveness of the method to increase gross total resection of the glioblastomas, an infiltrative and highly malignant brain tumor [1,2]. Accordingly, the gross total resection of glioblastoma was reported to have increased from 44% to 78% using fluorescence guidance leading to five months longer survival [2].…”

Section: Introductionmentioning

confidence: 99%

Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Haj‐Hosseini

Richter

Hallbeck

et al. 2015

Photodiagnosis and Photodynamic Therapy

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Section: Introductionmentioning

confidence: 99%

Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Haj‐Hosseini

Richter

Hallbeck

et al. 2015

Photodiagnosis and Photodynamic Therapy

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“…Therefore, fluorescence-based techniques, such as the detection of inherent tissue markers, have gained acceptance mostly in endoscopic diagnoses, and use mostly ultraviolet excitation. Due to the few tissue components that exhibit significant autofluorescence, tissues are often stained with specific fluorophores such as 5-aminolevulinic acid (ALA) [9] or indocyanine green (ICG) [10] to increase sensitivity and specificity, particularly for invivo observations.…”

Section: Introductionmentioning

confidence: 99%

Molecular pathology via IR and Raman spectral imaging

Diem¹,

Mazur²,

Lenau³

et al. 2013

Journal of Biophotonics

177

115

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Journal of BIOPHOTONICSDuring the last 15 years, vibrational spectroscopic methods have been developed that can be viewed as molecular pathology methods that depend on sampling the entire genome, proteome and metabolome of cells and tissues, rather than probing for the presence of selected markers. First, this review introduces the background and fundamentals of the spectroscopies underlying the new methodologies, namely infrared and Raman spectroscopy. Then, results are presented in the context of spectral histopathology of tissues for detection of metastases in lymph nodes, squamous cell carcinoma, adenocarcinomas, brain tumors and brain metastases. Results from spectral cytopathology of cells are discussed for screening of oral and cervical mucosa, and circulating tumor cells. It is concluded that infrared and Raman spectroscopy can complement histopathology and reveal information that is available in classical methods only by costly and time-consuming steps such as immunohistochemistry, polymerase chain reaction or gene arrays. Due to the inherent sensitivity toward changes in the bio-molecular composition of different cell and tissue types, vibrational spectroscopy can even provide information that is in some cases superior to that of any one of the conventional techniques.Schematic of spectral histopathology (SHP) process: diagnostic algorithm is developed by spectral data of well documented specimens and subsequently applied to unknown dataset.

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“…As already shown by various groups, the administration of 5-aminolevulinic acid (5-ALA) leads to a highly selective accumulation of protoporphyrin IX (PpIX) in high-grade malignant gliomas. [22][23][24] A tumor-related deficient blood brain barrier and an altered activity level of several enzymes including ferrochelatase, which catalyzes the conversion of PpIX to heme, are central reasons for this phenomenon. [25] Tumor recognition with 5-ALA-induced PpIX is already effectively used for fluorescence-guided resection of malignant gliomas using surgical microscopes [22,23,26] or fiber optical probes [27,28].…”

Section: Introductionmentioning

confidence: 99%

“…[22][23][24] A tumor-related deficient blood brain barrier and an altered activity level of several enzymes including ferrochelatase, which catalyzes the conversion of PpIX to heme, are central reasons for this phenomenon. [25] Tumor recognition with 5-ALA-induced PpIX is already effectively used for fluorescence-guided resection of malignant gliomas using surgical microscopes [22,23,26] or fiber optical probes [27,28]. It leads to a significantly increased complete resection rate of these diffusely growing tumors and to a significantly enhanced progression-free survival rate after 6 months, translating into a progression-free survival prolongation of 1.5 months as compared to conventional white light resection.…”

Section: Introductionmentioning

confidence: 99%

“…It leads to a significantly increased complete resection rate of these diffusely growing tumors and to a significantly enhanced progression-free survival rate after 6 months, translating into a progression-free survival prolongation of 1.5 months as compared to conventional white light resection. [23] The method has also been tested on excised tissue samples during stereotactic biopsy using surgical microscopes [21,[29][30][31]. In the latter case, the diagnostic yield of the fluorescent samples was always 100% (total n = 98).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence‐guided stereotactic biopsy of brain tumors

Markwardt

Haj‐Hosseini

Hollnburger

et al. 2015

Journal of Biophotonics

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Fluorescence diagnosis may be used to improve the safety and reliability of stereotactic brain tumor biopsies using biopsy needles with integrated fiber optics. Based on 5-aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence, vital tumor tissue can be localized in-vivo during the excision procedure to reduce the number of necessary samples for a reliable diagnosis.In this study, the practical suitability of two different PpIX excitation wavelengths (405 nm, 633 nm) was investigated on optical phantoms. Violet excitation at 405 nm provides a 50-fold higher sensitivity for the bulk tumor; this factor increases up to 100 with decreasing fluorescent volume as shown by ray tracing simulations. Red excitation at 633 nm, however, is noticeably superior with regard to blood layers obscuring the fluorescence. Experimental results on the signal attenuation through blood layers of well-defined thicknesses could be confirmed by ray tracing simulations. Typical interstitial fiber probe measurements were mimicked on agarose-gel phantoms. Even in direct contact, blood layers of 20 -40 µm between probe and tissue must be expected, obscuring 405-nm-excited PpIX fluorescence almost completely, but reducing the 633-nm-excited signal only by 25.5%. Thus, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of highgrade gliomas in stereotactic biopsy.

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Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial

Cited by 2,982 publications

References 21 publications

Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Molecular pathology via IR and Raman spectral imaging

405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence‐guided stereotactic biopsy of brain tumors

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