scholarly journals Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Sadahiro Kaneko ◽  
Sadao Kaneko
Keyword(s):  
Malignant Glioma ◽  
Anticancer Agents ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas ◽  
Protoporphyrin Ix ◽  
Time Spectrum ◽  
Photodynamic Diagnosis ◽  
Promising Technique ◽  
New Methods ◽  
New Treatments

Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD.

scholarly journals COT-13 Luminance analysis of 5-aminolevulinic acid using Image J for malignant brain tumor

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi30-vi30
Author(s):  
Takashi Kon ◽  
Yusuke Kobayashi ◽  
Yosuke Sato ◽  
Katsuyoshi Shimizu ◽  
Tohru Mizutani
Keyword(s):  
Brain Tumor ◽  
Malignant Glioma ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas ◽  
Malignant Brain Tumor ◽  
Photodynamic Diagnosis ◽  
Tumor Surgery ◽  
Maximum Luminance ◽  
Brain Tumor Surgery ◽  
Average Maximum

Abstract Purpose: For malignant brain tumor surgery, photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) is useful for maximal removal of the tumor. Although it has the advantage of identifying the presence or absence of residual tumors during surgery, there are variations in positive rates, and the classification is limited, based on visual inspection such as Stummer’s classification (strong, vague, none). We analyzed the luminance of positive findings using software Image J for brain tumor surgery using 5-ALA, and we report the results. Materials and Methods: From April 2018 to March 2021, 31 patients with suspected malignant glioma before surgery were included. Intraoperative 5-ALA positive findings were analyzed by software Image J (Wayne Rasband: NIH), the luminance was measured with a histogram, and compared the maximum luminance titer. Results: Among the positive cases, the average maximum luminance value for malignant glioma was 101 (50–168), which consisted of 11 cases of Glioblastoma, 1 case of Oligodendroglioma, and 1 case of anaplastic astrocytoma. The average maximum brightness of metastatic brain tumors is lower than that of malignant gliomas, even if they are visually strong, 83.5 (28–121). Conclusions: Even if it is visually strong in the conventional Stummer classification, it may be possible to classify in detail by analyzing luminance with Image J. In addition, more objective index is necessary to classify the vague findings.

scholarly journals Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy

2021 ◽  
Vol 14 (3) ◽  
pp. 229
Author(s):  
Yo Shinoda ◽  
Daitetsu Kato ◽  
Ryosuke Ando ◽  
Hikaru Endo ◽  
Tsutomu Takahashi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Human Cancer ◽  
Meta Analysis ◽  
Protoporphyrin Ix ◽  
Cell Types ◽  
Amino Acid Derivative ◽  
Photodynamic Diagnosis

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.

Endoscopic identification and biopsy sampling of an intraventricular malignant glioma using a 5–aminolevulinic acid–induced protoporphyrin IX fluorescence imaging system

2007 ◽  
Vol 106 (3) ◽  
pp. 507-510 ◽  
Author(s):  
Yoji Tamura ◽  
Toshihiko Kuroiwa ◽  
Yoshinaga Kajimoto ◽  
Yoshihito Miki ◽  
Shin-Ichi Miyatake ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Malignant Glioma ◽  
Fluorescence Imaging ◽  
Aminolevulinic Acid ◽  
Imaging System ◽  
Protoporphyrin Ix ◽  
Intraventricular Tumor ◽  
Excitation Light ◽  
Fluorescence Imaging System ◽  
Cutoff Filter

✓Several neurosurgical studies have provided descriptions of the utility of fluorescence-guided tumor resection using a microscope. However, fluorescence-guided endoscopic detection of a deep-seated brain tumor has not yet been reported. The authors report their experience with an endoscopic biopsy procedure for a malignant glioma within the third ventricle using a 5–aminolevulinic acid (5-ALA)–induced protoporphyrin IX fluorescence imaging system. A 5-ALA–induced fluorescence image of an intraventricular tumor is barely visible with the typical fluorescence endoscopic system used in other clinical fields because the intensity of excitation light at wavelengths of 390 to 405 nm through a cutoff filter is too weak to delineate a brain tumor. The technique described in this study made use of a laser illumination system with a high-powered output that delivered a violet-blue light at wavelengths of 405 nm. In addition, a common ultraviolet cutoff filter was fitted between the endoscope and the high-sensitivity camera to block the backscattered excitation light. A 5-ALA–induced fluorescence endoscopy performed using this system allowed the intraventricular tumor to be clearly visualized as a red fluorescent lesion. Several biopsy specimens obtained from the fluorescent lesion provided a definitive histological diagnosis. The results indicate that this endoscopic system is useful in detecting an intraventricular fluorescent tumor.

scholarly journals 5-aminolaevulinic acid (5-ALA) accumulates in GIST-T1 cells and photodynamic diagnosis using 5-ALA identifies gastrointestinal stromal tumors (GISTs) in xenograft tumor models

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249650
Author(s):  
Makiko Sasaki ◽  
Mamoru Tanaka ◽  
Hiroshi Ichikawa ◽  
Taketo Suzuki ◽  
Hirotada Nishie ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Fluorescence Emission ◽  
Immunofluorescent Staining ◽  
Photodynamic Diagnosis ◽  
Submucosal Tumors ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Preferential Uptake ◽  
Clinical Potential

Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis.

Fluorescence-Based Measurement of Real-Time Kinetics of Protoporphyrin IX After 5-Aminolevulinic Acid Administration in Human In Situ Malignant Gliomas

Neurosurgery ◽  
2019 ◽  
Vol 85 (4) ◽  
pp. E739-E746 ◽  
Author(s):  
Sadahiro Kaneko ◽  
Eric Suero Molina ◽  
Christian Ewelt ◽  
Nils Warneke ◽  
Walter Stummer
Keyword(s):  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas ◽  
Protoporphyrin Ix ◽  
Time Dependency ◽  
Average Maximum ◽  
Kinetics Of ◽  
Acid Administration ◽  
Time Point

Abstract BACKGROUND Five-aminolevulinic acid (5-ALA) is well established for fluorescence-guided resections of malignant gliomas by eliciting the accumulation of fluorescent protoporphyrin IX (PpIX) in tumors. Because of the assumed time point of peak fluorescence, 5-ALA is recommended to be administered 3 h before surgery. However, the actual time dependency of tumor fluorescence has not yet been evaluated in humans and may have important implications. OBJECTIVE To investigate the time dependency of PpIX by measuring fluorescence intensities in tumors at various time points during surgery. METHODS Patients received 5-ALA (20 mg/kg b.w.) 3 to 4 h before surgery. Fluorescence intensities (FI) and estimated tumor PpIX concentrations (CPPIX) were measured in the tumors over time with a hyperspectral camera. CPPIX was assessed using hyperspectral imaging and by evaluating fluorescence phantoms with known CPPIX. RESULTS A total of 201 samples from 68 patients were included in this study. On average, maximum values of calculated FI and CPPIX were observed between 7 and 8 h after 5-ALA administration. FI and CPPIX both reliably distinguished central strong and marginal weak fluorescence, and grade III compared to grade IV gliomas. Interestingly, marginal (weak) fluorescence was observed to peak later than strong fluorescence (8-9 vs 7-8 h). CONCLUSION In human in Situ brain tumor tissue, we determined fluorescence after 5-ALA administration to be maximal later than previously thought. In consequence, 5-ALA should be administered 4 to 5 h before surgery, with timing adjusted to internal logistical circumstances and factors related to approaching the tumor.

scholarly journals 5-Aminolevulinic Acid: Pitfalls of Fluorescence-guided Resection for Malignant Gliomas and Application for Malignant Glioma Therapy

2020 ◽  
Vol 42 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Junkoh YAMAMOTO ◽  
Takehiro KITAGAWA ◽  
Ryo MIYAOKA ◽  
Kohei SUZUKI ◽  
Seishiro TAKAMATSU ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas

scholarly journals What is the Surgical Benefit of Utilizing 5-Aminolevulinic Acid for Fluorescence-Guided Surgery of Malignant Gliomas?

Neurosurgery ◽  
2015 ◽  
Vol 77 (5) ◽  
pp. 663-673 ◽  
Author(s):  
Costas G. Hadjipanayis ◽  
Georg Widhalm ◽  
Walter Stummer
Keyword(s):  
Malignant Glioma ◽  
White Light ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas ◽  
Histopathological Diagnosis ◽  
Normal Brain ◽  
Extensive Literature ◽  
Predictive Values ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery

Abstract The current neurosurgical goal for patients with malignant gliomas is maximal safe resection of the contrast-enhancing tumor. However, a complete resection of the contrast-enhancing tumor is achieved only in a minority of patients. One reason for this limitation is the difficulty in distinguishing viable tumor from normal adjacent brain during surgery at the tumor margin using conventional white-light microscopy. To overcome this limitation, fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) has been introduced in the treatment of malignant gliomas. FGS permits the intraoperative visualization of malignant glioma tissue and supports the neurosurgeon with real-time guidance for differentiating tumor from normal brain that is independent of neuronavigation and brain shift. Tissue fluorescence after oral administration of 5-ALA is associated with unprecedented high sensitivity, specificity, and positive predictive values for identifying malignant glioma tumor tissue. 5-ALA-induced tumor fluorescence in diffusely infiltrating gliomas with non-significant magnetic resonance imaging contrast-enhancement permits intraoperative identification of anaplastic foci and establishment of an accurate histopathological diagnosis for proper adjuvant treatment. 5-ALA FGS has enabled surgeons to achieve a significantly higher rate of complete resections of malignant gliomas in comparison with conventional white-light resections. Consequently, 5-ALA FGS has become an indispensable surgical technique and standard of care at many neurosurgical departments around the world. We conducted an extensive literature review concerning the surgical benefit of using 5-ALA for FGS of malignant gliomas. According to the literature, there are a number of reasons for the neurosurgeon to perform 5-ALA FGS, which will be discussed in detail in the current review.

scholarly journals Usefulness of Intraoperative Photodynamic Diagnosis Using 5-Aminolevulinic Acid for Meningiomas With Cranial Invasion: Technical Case Report

2008 ◽  
Vol 62 (suppl_1) ◽  
pp. ONSE102-ONSE104 ◽  
Author(s):  
Morofuji Yoichi ◽  
Matsuo Takayuki ◽  
Hayashi Yukishige ◽  
Suyama Kazuhiko ◽  
Nagata Izumi
Keyword(s):  
Tumor Invasion ◽  
Clinical Presentation ◽  
Aminolevulinic Acid ◽  
Histopathological Examination ◽  
Subcutaneous Tissue ◽  
Malignant Gliomas ◽  
Frontal Bone ◽  
Photodynamic Diagnosis ◽  
Computed Tomographic ◽  
First Case

Abstract Objective: We present a case of a meningioma in which photodynamic diagnosis (PDD) using 5-aminolevulinic acid was very useful in identifying the cranial involvement. Clinical Presentation: An 83-year-old woman presented with a bony, hard, immobile bulge in her left forehead. Computed tomographic scans showed a thickening in the left frontal bone with a flat mass underneath. Magnetic resonance imaging scans revealed that enhancing lesions spread to the dura mater and subcutaneous tissue around the thickened frontal bone, reaching the upper margin of the left orbit. Intervention: Intraoperative PDD using 5-aminolevulinic acid indicated the optimal extent of the excision by showing clear fluorescence of affected tissues. The tumor was totally resected and diagnosed as an atypical meningioma. Histopathological examination confirmed the consistency of the extent of tumor invasion with affected lesions on PDD. Conclusion: To the best of our knowledge, this is the first case demonstrating the efficacy of PDD using 5-aminolevulinic acid for a meningioma with cranial invasion. Additional studies are warranted, as shown in cases of malignant gliomas.

scholarly journals Interstitial Photodynamic Therapy Using 5-ALA for Malignant Glioma Recurrences

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1767
Author(s):  
Stefanie Lietke ◽  
Michael Schmutzer ◽  
Christoph Schwartz ◽  
Jonathan Weller ◽  
Sebastian Siller ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Prognostic Factors ◽  
Malignant Glioma ◽  
Treatment Response ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas ◽  
Target Volume ◽  
Risk Profile ◽  
Who Grade ◽  
Interstitial Photodynamic Therapy

Interstitial photodynamic therapy (iPDT) using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) as a cytotoxic photosensitizer could be a feasible treatment option for malignant gliomas. In a monocentric cohort of consecutive patients treated between 2006 and 2018, a risk profile analysis of salvage iPDT for local malignant glioma recurrences and associated outcome measures are presented here. It was considered indicated in patients with circumscribed biopsy-proven malignant glioma recurrences after standard therapy, if not deemed eligible for safe complete resection. A 3D treatment-planning software was used to determine the number and suitable positions of the cylindrical diffusing fibers placed stereotactically to ensure optimal interstitial irradiation of the target volume. Outcome measurements included the risk profile of the procedure, estimated time-to-treatment-failure (TTF), post-recurrence survival (PRS) and prognostic factors. Forty-seven patients were treated, of which 44 (median age, 49.4 years, range, 33.4–87.0 years, 27 males) could be retrospectively evaluated. Recurrent gliomas included 37 glioblastomas (WHO grade IV) and 7 anaplastic astrocytomas (WHO grade III). Thirty (68.2%) tumors were O-6-methylguanine-DNA methyltransferase (MGMT)-methylated, 29 (65.9%)—isocitrate dehydrogenase (IDH)-wildtype. Twenty-six (59.1%) patients were treated for their first, 9 (20.5%)—for their second, 9 (20.5%)—for the third or further recurrence. The median iPDT target volume was 3.34 cm3 (range, 0.50–22.8 cm3). Severe neurologic deterioration lasted for more than six weeks in one patient only. The median TTF was 7.1 (95% confidence interval (CI), 4.4–9.8) months and the median PRS was 13.0 (95% CI, 9.2–16.8) months. The 2- and 5-year PRS rates were 25.0% and 4.5%, respectively. The treatment response was heterogeneous and not significantly associated with patient characteristics, treatment-related factors or molecular markers. The promising outcome and acceptable risk profile deserve further prospective evaluation particularly to identify mechanisms and prognostic factors of favorable treatment response.

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