Following the light in glioma surgery: a comparison of sodium fluorescein and 5-aminolevulinic acid as surgical adjuncts in glioma resection

2020 ◽  
Vol 63 (6) ◽  
Author(s):  
Jorge Navarro-Bonnet ◽  
Paola Suarez-Meade ◽  
Desmond A. Brown ◽  
Kaisorn L. Chaichana ◽  
Alfredo Quinones-Hinojosa
Keyword(s):  
Aminolevulinic Acid ◽  
Sodium Fluorescein ◽  
Glioma Surgery ◽  
Glioma Resection

scholarly journals Characteristics of Fluorescent Intraoperative Dyes Helpful in Gross Total Resection of High-Grade Gliomas—A Systematic Review

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1100
Author(s):  
Marek Mazurek ◽  
Bartłomiej Kulesza ◽  
Filip Stoma ◽  
Jacek Osuchowski ◽  
Sławomir Mańdziuk ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Aminolevulinic Acid ◽  
High Grade Glioma ◽  
Light Filter ◽  
Gross Total Resection ◽  
High Grade ◽  
Total Resection ◽  
Glioma Surgery ◽  
Glioma Resection ◽  
Intraoperative Fluorescence

Background: A very important aspect in the treatment of high-grade glioma is gross total resection to reduce the risk of tumor recurrence. One of the methods to facilitate this task is intraoperative fluorescence navigation. The aim of the study was to compare the dyes used in this technique fluorescent intraoperative navigation in terms of the mechanism of action and influence on the treatment of patients. Methods: The review was carried out on the basis of articles found in PubMed, Google Scholar, and BMC search engines, as well as those identified by searched bibliographies and suggested by experts during the preparation of the article. The database analysis was performed for the following phrases: “glioma”, “glioblastoma”, “ALA”, “5ALA”, “5-ALA”, “aminolevulinic acid”, ”levulinic acid”, “fluorescein”, “ICG”, “indocyanine green”, and “fluorescence navigation”. Results: After analyzing 913 citations identified on the basis of the search criteria, we included 36 studies in the review. On the basis of the analyzed articles, we found that 5-aminolevulinic acid and fluorescein are highly effective in improving the percentage of gross total resection achieved in high-grade glioma surgery. At the same time, the limitations resulting from the use of these methods are marked—higher costs of the procedure and the need to have neurosurgical microscope in combination with a special light filter in the case of 5-aminolevulinic acid (5-ALA), and low specificity for neoplastic cells and the dependence on the degree of damage to the blood–brain barrier in the intensity of fluorescence in the case of fluorescein. The use of indocyanine green in the visualization of glioma cells is relatively unknown, but some researchers have suggested its utility and the benefits of using it simultaneously with other dyes. Conclusion: The use of intraoperative fluorescence navigation with the use of 5-aminolevulinic acid and fluorescein allows the range of high-grade glioma resection to be increased.

Sodium Fluorescein-Guided Gross Total Resection of Pediatric Exophytic Brainstem Glioma: 2-Dimensional Operative Video

2020 ◽  
Author(s):  
Christopher Markosian ◽  
Catherine A Mazzola ◽  
Luke D Tomycz
Keyword(s):  
Normal Tissue ◽  
Clinical Case ◽  
Aminolevulinic Acid ◽  
Significant Risk ◽  
Gross Total Resection ◽  
Subtotal Resection ◽  
Sodium Fluorescein ◽  
Total Resection ◽  
Term Survival ◽  
Patient Consent

Abstract Brainstem gliomas comprise 10% to 20% of pediatric intracranial tumors.1 Gross total resection is associated with the greatest long-term survival.1 However, due to the eloquence of surrounding brain tissue, an aggressive resection is not always achievable and can be associated with significant risk.2 Sodium fluorescein can be used to help differentiate between tumor and normal tissue.3,4 In this operative video, we demonstrate the step-by-step technique to utilize fluorescence in surgically resecting an exophytic glioma arising from the midbrain in a 16-yr-old male. Technical nuances are highlighted in this operative video, including the use of the YELLOW 560 (Zeiss) filter to differentiate fluorescent tumor from normal tissue as well as strategic splitting of the tentorium to expose the supratentorial component of the tumor. A decrease in motor potentials of the right leg during the case did not translate into neurological worsening postoperatively; at 3-mo follow-up, the patient attests to better strength and coordination on his affected side. In summary, sodium fluorescein can be used as a critical adjunctive tool for successful surgery in the case of a brainstem tumor. Alternatives to this procedure included gross total resection with 5-aminolevulinic acid, subtotal resection with chemotherapy, and active monitoring, but were not chosen due to their limitations in this clinical case.5-7  Appropriate patient consent was obtained to perform this procedure and present this clinical case and surgical video for academic purposes.

scholarly journals Ex vivo ultrasonic samples of human brain tumors in the molecular era

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Alastair J Kirby ◽  
José P Lavrador ◽  
Istvan Bodi ◽  
Francesco Vergani ◽  
Ranjeev Bhangoo ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Cellular Proliferation ◽  
Aminolevulinic Acid ◽  
Ex Vivo ◽  
Methylation Status ◽  
Protoporphyrin Ix ◽  
Intratumor Heterogeneity ◽  
Power Relationship ◽  
Surgical Biopsy ◽  
Glioma Surgery

Abstract Background Gliomas are composed of multiple clones of tumor cells. This intratumor heterogeneity contributes to the ability of gliomas to resist treatment. It is vital that gliomas are fully characterized at a molecular level when a diagnosis is made to maximize treatment effectiveness. Methods We collected ultrasonic tissue fragments during glioma surgery. Large tissue fragments were separated in the operating theater and bathed continuously in oxygenated artificial cerebrospinal fluid to keep them alive. The ex vivo tissue fragments were transferred to a laboratory and incubated in 5-aminolevulinic acid (5-ALA). 5-ALA is metabolized to Protoporphyrin IX (PpIX), which accumulates in glioma cells and makes them fluorescent. The molecular and neuropathological features of the PpIX fluorescent ultrasonic tissue fragments were studied. Results We show that PpIX fluorescence can rapidly identify tissue fragments infiltrated by glioma in the laboratory. Ultrasonic tissue fragments from the tumor core provided molecular and neuropathological information about the glioma that was comparable to the surgical biopsy. We characterized the heterogeneity within individual gliomas by studying ultrasonic tissue fragments from different parts of the tumor. We found that gliomas exhibit a power relationship between cellular proliferation and tumor infiltration. Tissue fragments that deviate from this relationship may contain foci of more malignant glioma. The methylation status of the O6-methylguanine DNA methyltransferase gene promoter varied within each glioma. Conclusions Ex vivo ultrasonic tissue fragments can be rapidly screened for glioma infiltration. They offer a viable platform to characterize heterogeneity within individual gliomas, thereby enhancing their diagnosis and treatment.

Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence

2007 ◽  
Vol 106 (6) ◽  
pp. 1070-1074 ◽  
Author(s):  
Yoshinaga Kajimoto ◽  
Toshihiko Kuroiwa ◽  
Shin-Ichi Miyatake ◽  
Tsugumichi Ichioka ◽  
Minoru Miyashita ◽  
...  
Keyword(s):  
High Risk ◽  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Superior Sagittal Sinus ◽  
Residual Tumor ◽  
Strong Fluorescence ◽  
Glioma Surgery ◽  
Risk Of Recurrence ◽  
Sagittal Sinus ◽  
Atypical Meningiomas

✓It has been established that fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is useful in glioma surgery. The authors report on a 65-year-old woman who had a huge atypical left-hemisphere meningioma, which extended into the skull and to the superior sagittal sinus and demonstrated fluorescence in response to administration of 5-ALA. After the tumor was removed, the operative field was observed under the fluorescent mode of a fluorescence surgical microscopy system. Several minute areas of residual tumor tissue were visualized as strong fluorescence behind the vein and sinus, in a part of the hypertrophic dura, and along the edge of the skull. These remnants were completely removed. The authors concluded that fluorescence-guided resection using 5-ALA is useful in cases of atypical meningiomas with a high risk of recurrence.

Efficacy of 5-aminolevulinic acid-induced fluorescence detection in malignant glioma surgery

2004 ◽  
Vol 1268 ◽  
pp. 1290
Author(s):  
Takashi Maruyama ◽  
Yoshihiro Muragaki ◽  
Masahiko Tanaka ◽  
Hiroshi Iseki ◽  
Ichiro Sakuma ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Fluorescence Detection ◽  
Aminolevulinic Acid ◽  
Glioma Surgery

FLGS-01. Development of novel topical fluorescent probe for intraoperative rapid detection of glioma

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi225-vi226
Author(s):  
Shota Tanaka ◽  
Yosuke Kitagawa ◽  
Mako Kamiya ◽  
Takenori Shimizu ◽  
Yasuteru Urano ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Fluorescent Probe ◽  
Rapid Detection ◽  
Aminolevulinic Acid ◽  
Characteristic Curve ◽  
Screening Method ◽  
Tumor Resection ◽  
Phase Iii ◽  
Glioma Surgery ◽  
Two Dimensional Gel Electrophoresis

Abstract PURPOSE Fluorescence imaging is an important surgical adjunct in malignant glioma surgery. 5-aminolevulinic acid (5-ALA) has been proven effective for radical tumor resection and extended progression-free survival in a phase III randomized trial and therefore integrated into surgery for malignant glioma. Importantly, however, some limitations still exist in its use, which include false positivity and false negativity as well as inability of re-administration. In this study, we aimed to develop a novel, spray-type fluorescent probe using hydroxymethyl rhodamine green (HMRG) as a fluorescent scaffold. METHODS We have previously established a fluorescent probe library comprised of more than 320 kinds of HMRG probes. They have HMRG as a fluorescent scaffold with various types of dipeptides attached to it. Primary probe screening was performed using the homogenized tumor samples from patients with glioblastoma operated at our institution. Secondary screening followed using the selected probes and fresh tumor samples obtained from patients with glioblastoma operated from 2016 until 2018. Diced electrophoresis gel (DEG) assay, two-dimensional gel electrophoresis followed by a multi-well plate-based fluorometric assay, was performed to identify responsible enzymes for the selected probe. Further experiments with inhibitors, real-time PCR, immunohistochemistry, and western blotting were performed for confirmation. RESULTS Proline-arginine-HMRG (PR-HMRG) was selected as a candidate probe based upon the above two-step screenings. It achieved 79.4% accuracy in receiver operating characteristic curve analysis. Calpain-1 was found to be responsible to cleave PR-HMRG probe by DEG-proteome analysis. Calpain-1 protein was highly expressed in tumor tissues which reacted to PR-HMRG probe. CONCLUSIONS Our innovative screening method was able to find PR-HMRG as a novel fluorescent probe effective for rapid detection of glioblastoma. A preclinical study is planned to assess the efficacy and safety of the selected probe.

Deferoxamine may enhance 5-aminolevulinic acid-based fluorescence in glioma surgery

2017 ◽  
Vol 6 (S6) ◽  
pp. S1088-S1090
Author(s):  
Hirohito Yano ◽  
Jun Shinoda ◽  
Toru Iwama
Keyword(s):  
Aminolevulinic Acid ◽  
Glioma Surgery

scholarly journals SURG-32. THE USE OF 5-AMINOLEVULINIC ACID IN LOW-GRADE GLIOMA RESECTION: A SYSTEMATIC REVIEW

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi246-vi246
Author(s):  
Ahmad Almekkawi ◽  
Tarek El Ahmadieh ◽  
Karl Abi-Aad ◽  
Salah Aoun ◽  
Najib EL Tecle ◽  
...  
Keyword(s):  
Systematic Review ◽  
Quality Index ◽  
Aminolevulinic Acid ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Visualization Technology ◽  
Glioma Resection

Abstract BACKGROUND 5-aminolevulinic acid is a reliable tool for optimizing high-grade glioma resection. However, its efficacy in low-grade glioma resection remains unclear. OBJECTIVE To study the role of 5-aminolevulinic acid in low-grade glioma resection and assess positive fluorescence rates and effect on the extent of resection. METHODS A systematic review of PubMed, Google Scholar, and Cochrane was performed from the date of inception to February 1, 2019. Studies that correlated 5-aminolevulinic acid fluorescence with low-grade glioma in the setting of operative resection were selected. Studies with biopsy only were excluded. Positive fluorescence rates were calculated. Quality index of the selected papers using the Downs and Black criteria checklist was provided. RESULTS Twelve articles met the selection criteria with 244 histologically-confirmed low-grade glioma patients who underwent microsurgical resection. All patients received 20 mg/kg body weight of 5-aminolevulinic acid. Only 60 patients (n=60/244; 24.5%) demonstrated visual intra-operative 5-aminolevulinic acid fluorescence. The extent of resection was reported in 4 studies, however, the data combined low- and high-grade tumors. Only 2 studies reported on tumor location. Only 3 studies reported on clinical outcomes. The Zeiss OPMI Pentero microscope was most commonly used across all studies. The average quality index was 14.58 (range: 10–17) which correlated with an overall good quality. CONCLUSION There is an overall low correlation between 5-aminolevulinic acid fluorescence and low-grade glioma. Advances in visualization technology and using standardized fluorescence quantification methods may further improve the visualization and reliability of 5-aminolevulinic acid fluorescence in low-grade glioma resection.

FLUORESCENCE OF NON-NEOPLASTIC, MAGNETIC RESONANCE IMAGING-ENHANCING TISSUE BY 5-AMINOLEVULINIC ACID

Neurosurgery ◽  
2007 ◽  
Vol 61 (5) ◽  
pp. E1101-E1104 ◽  
Author(s):  
Shin-Ichi Miyatake ◽  
Toshihiko Kuroiwa ◽  
Yoshinaga Kajimoto ◽  
Minoru Miyashita ◽  
Hidekazu Tanaka ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Demyelinating Disease ◽  
Aminolevulinic Acid ◽  
Radiation Necrosis ◽  
Malignant Tumors ◽  
Central Nervous System Disease ◽  
Resonance Imaging ◽  
Glioma Surgery ◽  
System Disease

Abstract OBJECTIVE It has been established that fluorescence-guided resection using 5-aminolevulinic acid is useful in glioma surgery. In this study, we describe three cases in which even perinecrotic tissue could be recognized as fluorescence positive. METHODS Three cases of central nervous system disease, showing gadolinium enhancement on magnetic resonance imaging scans, were operated on with the aid of fluorescence derived from 5-aminolevulinic acid. Two of these were diagnosed as radiation necrosis and the other as a neurodegenerative demyelinating disease. RESULTS In all cases, at least some parts of the gadolinium-enhanced area could be labeled as fluorescence positive, whereas centers of necrotic tissue were negative for fluorescence. Histologically, cell infiltration was marked in each case that showed fluorescence activity. CONCLUSION Both malignant tumors and the perinecrotic area in radiation necrosis or neurodegenerative disease can be labeled as fluorescence positive using 5-aminolevulinic acid.

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