5-Aminolevulinic Acid Fluorescence-Guided Resection of Intramedullary Ependymoma: Report of 9 Cases

2012 ◽  
Vol 72 (2) ◽  
pp. ons159-ons168 ◽  
Author(s):  
Tomoo Inoue ◽  
Toshiki Endo ◽  
Kenichi Nagamatsu ◽  
Mika Watanabe ◽  
Teiji Tominaga
Keyword(s):  
Spinal Cord ◽  
Aminolevulinic Acid ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Labeling Index ◽  
World Health ◽  
Histopathological Diagnosis ◽  
Glioma Surgery ◽  
Ki 67 ◽  
Grade Ii

Abstract BACKGROUND: Resection guided by 5-aminolevulinic acid (5-ALA) fluorescence has proved to be useful in intracranial glioma surgery. However, the effects of 5-ALA on spinal cord tumors remain unknown. OBJECTIVE: To evaluate the usefulness of 5-ALA fluorescence-guided resection of intramedullary ependymoma for achieving maximum tumor resection. METHODS: This study included 10 patients who underwent surgical resection of an intramedullary ependymoma. Nine patients were orally administered 5-ALA (20 mg/kg) 2 hours before the induction of anesthesia. 5-ALA fluorescence was visualized with an operating microscope. Tumors were removed in a standardized manner with electro-physiological monitoring. The extent of resection was evaluated on the basis of intra-operative findings and postoperative magnetic resonance imaging. Histopathological diagnosis was established according to World Health Organization 2007 criteria. Cell proliferation was assessed by Ki-67 labeling index. RESULTS: 5-ALA fluorescence was positive in 7 patients (6 grade II and 1 grade III) and negative in 2 patients (grade II). Intraoperative findings were dichotomized: Tumors covered by the cyst were easily separated from the normal parenchyma, whereas tumors without the cyst appeared to be continuous to the spinal cord. In these cases, 5-ALA fluorescence was especially valuable in delineating the ventral and cranial and caudal margins. Ki-67 labeling index was significantly higher in 5-ALA-positive cases compared with 5-ALA-negative cases. All patients improved neurologically or stabilized after surgery. CONCLUSION: 5-ALA fluorescence was useful for detecting tumor margins during surgery for intramedullary ependymoma. When combined with electrophysiological monitoring, fluorescence-guided resection could help to achieve maximum tumor resection safely.

The Ki-67 labeling index as a prognostic factor in Grade II oligoastrocytomas

2005 ◽  
Vol 102 (6) ◽  
pp. 1033-1039 ◽  
Author(s):  
Mark E. Shaffrey ◽  
Elana Farace ◽  
David Schiff ◽  
James M. Larner ◽  
Melike Mut ◽  
...  
Keyword(s):  
Labeling Index ◽  
World Health ◽  
Ki 67 ◽  
Content Type ◽  
Prognostic Utility ◽  
Grade Ii ◽  
Health Organization ◽  
The University ◽  
Grade Iii ◽  
Fine Print

Object. This study was conducted to determine whether proliferative tumor activity, as assessed using the Ki-67 immunohistochemical labeling index (LI), has prognostic utility for patients with Grade II oligoastrocytomas. Methods. The study period spans the years 1988 to 2000. In a retrospective analysis, the authors selected cases with biopsy-proven diagnoses of Grade II oligoastrocytomas on initial presentation. The authors added new patients to this group and followed all patients prospectively at the University of Virginia Neuro-Oncology Center. Twenty-three adult patients were followed for at least 1 year (median 40.3 months). Eleven patients with Grade II tumors and initial Ki-67 LIs less than 10% had a significantly longer median time to tumor progression (TTP, 51.8 months compared with 9.9 months) and a longer median survival (93.1 months compared with 16.1 months) than 12 patients with initial Ki-67 LIs of 10% or greater. Twelve patients with Grade III oligoastrocytomas had a mean TTP that was similar to the TTP of patients with Grade II tumors and high Ki-67 LIs (mean 4 months compared with 9.9 months) and duration of survival (13.3 months compared with 16.1 months). Conclusions. Patients with a Grade II oligoastrocytoma and a Ki-67 LI of 10% or greater have a much shorter TTP and potentially a poorer disease prognosis than expected—more similar to patients with a Grade III oligoastrocytoma. These results indicate that in the future a measure of proliferative activity should be taken into consideration along with the World Health Organization grading criteria for oligoastrocytomas.

scholarly journals SURG-18. 5-AMINOLEVULINIC ACID FLUORESCENCE (5-ALA) GUIDED RESECTION OF GLIOBLASTOMA, LESSON LEARNED FROM 19 CASES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi243-vi243
Author(s):  
Jinmo Cho
Keyword(s):  
Aminolevulinic Acid ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
High Grade ◽  
Total Resection ◽  
Glioma Surgery ◽  
Term Survival ◽  
Tumor Bed ◽  
Key Factor

Abstract BACKGROUND 5-ALA is known as useful tool for high grade glioma resection and the accumulation extent of 5-ALA is known as far beyond gadolinium enhancement. Extent of resection is key factor for favorable outcome and long-term survival for high grade glioma patients and 5-ALA might increase extent of resection. We present our experience of 5-ALA guided glioma surgeries METHODS Total 19 patients were performed 5-ALA guided surgery. They ingested 20mg/kg, four hours before craniotomy. We tried to perform supra-total resection rather than gross total resection according to the tumor consistency and if the tumor located relatively non-eloquent area, we tried to perform lobectomy rather than lesionectomy. After tumor resection, we inspect the tumor bed under 5-ALA fluorescence, and we confirmed the complete loss of fluorescence on the tumor resected bed. We check the MRI within 48 hour after operation and assess the extent of resection RESULTS Among the 19 patients, 15 patients were confirmed glioblastoma and 3 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. We confirmed all enhancing lesion was completely removed, however, 2 patients show residual non-enhancing lesion in post-operative MRI. Two patients suffered temporary hemiparesis and 2 patients show permanent visual field defect. CONCLUSION 5-ALA is useful tool for glioma surgery. Resection extent could be increased, however, non-enhancing lesion in the high grade gliomas, might be missed under 5-ALA guidance.

scholarly journals Indications of 5-Aminolevulinic Acid and Intraoperative MRI in Glioma Surgery: First Cases in Latin America in a Single Reference Center

2018 ◽  
Vol 37 (02) ◽  
pp. 088-094
Author(s):  
Ricardo Ramina ◽  
Erasmo Silva Júnior ◽  
Felipe Constanzo ◽  
Maurício Coelho Neto
Keyword(s):  
Aminolevulinic Acid ◽  
Complete Resection ◽  
World Health ◽  
Awake Surgery ◽  
Glioma Surgery ◽  
Who Grade ◽  
Combined Use ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Introduction The improvement on the extent of resection (EOR) of gliomas with the combination of 5-aminolevulinic acid (5-ALA) and intraoperative magnetic resonance imaging (iMRI) has been demonstrated in previous studies. We present our results with the combined use of 5-ALA and (iMRI) in the surgery of glial lesions. Methods A total of 64 cases of patients with intracranial gliomas who underwent image-guided surgery using 5-ALA with and without (iMRI) were reviewed. All patients underwent an early postoperative MRI to evaluate the EOR. Other intra-operative techniques (awake surgery, electrophysiological stimulation and monitoring) were also performed according to the location of the tumor. Results A total of 18 tumors did not show intraoperative 5-ALA fluorescence (according to the World Health Organization [WHO] classification of tumors, 2 WHO-grade I, 14 WHO-grade II, 1 WHO-grade III and 1 WHO-grade IV), and 46 tumors showed intraoperative 5-ALA fluorescence (3 WHO-grade II, 3 WHO-grade III, 40 WHO-grade IV). In 28 of the 46 5-ALA positive cases, a safe 5-ALA free resection was achieved. In the 5-ALA negative cases, the (iMRI) findings guided the EOR, and complete resection was achieved in 11 cases. Complete resection was opted out in gliomas infiltrating eloquent areas. Conclusions The combined use of 5-ALA and IMRI showed improved results in glioma surgery, offering the safest maximal EOR. In the 5-ALA positive cases (mostly high-grade), fluorescence was a more useful tool. In the 5- ALA negative cases (mostly low-grade), the (iMRI) was decisive to guide the EOR of the tumor.

scholarly journals Ki-67 immunostaining in astrocytomas: Association with histopathological grade – A South Indian study

2016 ◽  
Vol 7 (04) ◽  
pp. 510-514 ◽  
Author(s):  
Nandish Vastrad Shivaprasad ◽  
Suchitha Satish ◽  
Sunila Ravishankar ◽  
Manjunath Gubbi Vimalambike
Keyword(s):  
Biological Marker ◽  
World Health ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
Ki 67 ◽  
Histopathological Grade ◽  
South Indian ◽  
Significant Difference ◽  
Grade Ii ◽  
Histopathological Grading

ABSTRACT Background: Astrocytomas are the most common primary tumor of the central nervous system. The distinction between different tumor grades can be tested despite criteria given by the World Health Organization (WHO). Ki-67 is a potent biological marker used in grading of astrocytomas, which estimates growth of the neoplasm quantitatively and will help in predicting prognosis accurately. Objectives: The aim of this was to study the proliferative activity using Ki-67 immunostaining and to assess the relationship of Ki-67 staining with the histopathological grading of astrocytomas. Patients and Methods: Thirty cases of histologically proven astrocytomas were studied. The histopathological grade was assessed using the 2007 WHO criteria. Immunohistochemistry for Ki-67 was done on paraffin-embedded wax sections. P < 0.05 was considered statistically significant. Results: Thirty cases of astrocytomas studied showed a male preponderance (M:F = 1.72:1) with a mean age of 48.1 years. Of these, Grade I, (n = 1, 3.33%), Grade II, (n = 7, 23.3%), Grade III (n = 6, 20%), and Grade IV (n = 16, 53.3%) astrocytomas were analyzed. The mean Ki-67 labeling index (LI) in Grades I, II, III, and IV was 0.02, 0.81, 9.14, and 17.81, respectively. Statistically significant difference was seen in the Ki-67 LI of low-grade (Grade II) and high-grade astrocytomas (Grades III and IV). There was concordance between histopathological grading and Ki-67 LI in 27 (90%) and discordance in 3 (10%) cases. Conclusion: Ki-67 LI varies considerably in different grades of astrocytomas and considerable overlaps can be observed between them. It can be of great help in situations where there is a lack of correlation between clinical parameters and histopathological diagnosis. Determination of Ki-67 LI should constitute a part of routine investigations in patients with astrocytomas.

scholarly journals SURG-39. 5-AMINOLEVULINIC ACID FLUORESCENCE (5-ALA) GUIDED RESECTION OF GLIOBLASTOMA, LESSON LEARNED FROM 26 CASES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii211-ii212
Author(s):  
Jinmo Cho
Keyword(s):  
Aminolevulinic Acid ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
High Grade ◽  
Total Resection ◽  
Glioma Surgery ◽  
Term Survival ◽  
Tumor Bed ◽  
Key Factor

Abstract INTRODUCTION 5-ALA is known as useful tool for high grade glioma resection and the accumulation extent of 5-ALA is known as far beyond gadolinium enhancement. Extent of resection is key factor for favorable outcome and long-term survival for high grade glioma patients and 5-ALA might increase extent of resection. We present our experience of 5-ALA guided glioma surgeries. MATERIALS AND METHODS Total 26 patients were performed 5-ALA guided surgery. They ingested 20mg/kg, four hours before craniotomy. We tried to perform supra-total resection rather than gross total resection according to the tumor consistency and if the tumor located relatively non-eloquent area, we tried to perform lobectomy rather than lesionectomy. After tumor resection, we inspect the tumor bed under 5-ALA fluorescence, and we confirmed the complete loss of fluorescence on the tumor resected bed. We check the MRI within 48 hour after operation and assess the extent of resection. RESULTS Among the 26 patients, 22 patients were confirmed glioblastoma and 3 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. We confirmed all enhancing lesion was completely removed, however, 4 patients show residual non-enhancing lesion in post-operative MRI. Two patients suffered temporary hemiparesis and 2 patients show permanent visual field defect. CONCLUSION 5-ALA is useful tool for glioma surgery. Resection extent could be increased, however, non-enhancing lesion in the high grade gliomas, might be missed under 5-ALA guidance.

scholarly journals Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts

2016 ◽  
Vol 140 (5) ◽  
pp. 437-448 ◽  
Author(s):  
Joo Young Kim ◽  
Seung-Mo Hong
Keyword(s):  
World Health Organization ◽  
Neuroendocrine Tumors ◽  
Classification Scheme ◽  
Neuroendocrine Cells ◽  
Labeling Index ◽  
World Health ◽  
World Health Organization Classification ◽  
Clinicopathologic Characteristics ◽  
Ki 67 ◽  
Health Organization

Context.—Gastrointestinal (GI) and pancreatobiliary tracts contain a variety of neuroendocrine cells that constitute a diffuse endocrine system. Neuroendocrine tumors (NETs) from these organs are heterogeneous tumors with diverse clinical behaviors. Recent improvements in the understanding of NETs from the GI and pancreatobiliary tracts have led to more-refined definitions of the clinicopathologic characteristics of these tumors. Under the 2010 World Health Organization classification scheme, NETs are classified as grade (G) 1 NETs, G2 NETs, neuroendocrine carcinomas, and mixed adenoneuroendocrine carcinomas. Histologic grades are dependent on mitotic counts and the Ki-67 labeling index. Several new issues arose after implementation of the 2010 World Health Organization classification scheme, such as issues with well-differentiated NETs with G3 Ki-67 labeling index and the evaluation of mitotic counts and Ki-67 labeling. Hereditary syndromes, including multiple endocrine neoplasia type 1 syndrome, von Hippel-Lindau syndrome, neurofibromatosis 1, and tuberous sclerosis, are related to NETs of the GI and pancreatobiliary tracts. Several prognostic markers of GI and pancreatobiliary tract NETs have been introduced, but many of them require further validation. Objective.—To understand clinicopathologic characteristics of NETs from the GI and pancreatobiliary tracts. Data Sources.—PubMed (US National Library of Medicine) reports were reviewed. Conclusions.—In this review, we briefly summarize recent developments and issues related to NETs of the GI and pancreatobiliary tracts.

Quantification of Glioma Removal by Intraoperative High-Field Magnetic Resonance Imaging: An Update

Neurosurgery ◽  
2011 ◽  
Vol 69 (4) ◽  
pp. 852-863 ◽  
Author(s):  
Daniela Kuhnt ◽  
Oliver Ganslandt ◽  
Sven-Martin Schlaffer ◽  
Michael Buchfelder ◽  
Christopher Nimsky
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
High Field ◽  
Tumor Volume ◽  
Tumor Resection ◽  
World Health ◽  
Incomplete Resection ◽  
Resonance Imaging ◽  
Glioma Surgery ◽  
Who Grade

Abstract BACKGROUND: The beneficial role of the extent of resection (EOR) in glioma surgery in correlation to increased survival remains controversial. However, common literature favors maximum EOR with preservation of neurological function, which is shown to be associated with a significantly improved outcome. OBJECTIVE: In order to obtain a maximum EOR, it was examined whether high-field intraoperative magnetic resonance imaging (iMRI) combined with multimodal navigation contributes to a significantly improved EOR in glioma surgery. METHODS: Two hundred ninety-three glioma patients underwent craniotomy and tumor resection with the aid of intraoperative 1.5 T MRI and integrated multimodal navigation. In cases of remnant tumor, an update of navigation was performed with intraoperative images. Tumor volume was quantified pre- and intraoperatively by segmentation of T2 abnormality in low-grade and contrast enhancement in high-grade gliomas. RESULTS: In 25.9% of all cases examined, additional tumor mass was removed as a result of iMRI. This led to complete tumor resection in 20 cases, increasing the rate of gross-total removal from 31.7% to 38.6%. In 56 patients, additional but incomplete resection was performed because of the close location to eloquent brain areas. Volumetric analysis showed a significantly (P &lt; .01) reduced mean percentage of tumor volume following additional further resection after iMRI from 33.5% ± 25.1% to 14.7% ± 23.3% (World Health Organization [WHO] grade I, 32.8% ± 21.9% to 6.1% ± 18.8%; WHO grade II, 24.4% ± 25.1% to 10.8% ± 11.0%; WHO grade III, 35.1% ± 27.3% to 24.8% ± 26.3%; WHO grade IV, 34.2% ± 23.7% to 1.2% ± 16.2%). CONCLUSION: MRI in conjunction with multimodal navigation and an intraoperative updating procedure enlarges tumor-volume reduction in glioma surgery significantly without higher postoperative morbidity.

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.

scholarly journals The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
World Health ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Grade Ii ◽  
The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

Endoscopic Fluorescence-Guided Resection Increases Radicality in Glioblastoma Surgery

2019 ◽  
Vol 18 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Christoph Bettag ◽  
Abdelhalim Hussein ◽  
Daniel Behme ◽  
Theoni Maragkou ◽  
Veit Rohde ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Histopathological Examination ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Complete Resection ◽  
Free Survival ◽  
Resected Tissue ◽  
Microsurgical Resection

Abstract BACKGROUND Several studies have proven the benefit of a greater extent of resection on progression-free survival and overall survival in glioblastoma (GBM). Possible reasons for incomplete tumor resection might be wrong interpretation of fading fluorescence or overseen fluorescent tumor tissue by a lacking line of sight between tumor tissue and the microscope. OBJECTIVE To evaluate if an endoscope being capable of inducing fluorescence might overcome some limitations of microscopic fluorescence-guided (FG) resection. METHODS 5-Aminolevulinic acid (20 mg/kg) was given 4 h before surgery. Microsurgical resection of all fluorescent tissue was performed. Then, the resection cavity was scanned with the endoscope. Fluorescent tissue, not being visualized by the microscope, was additionally removed and histopathologically examined separately. Neuronavigation was used for defining the sites of additional tumor resection. All patients underwent magnetic resonance imaging within 48 h after surgery. RESULTS Twenty patients with GBM were operated using microscopic and endoscopic FG resection. In all patients, additional fluorescent tissue was detected with the endoscope. This tissue was completely resected in 19 patients (95%). Eloquent localization precluded complete resection in the remaining patient. In 19 patients (95%), histopathological examination confirmed tumor in the additionally resected tissue. In 19 patients (95%), complete resection was confirmed. In all patients, endoscopic FG resection reached beyond the borders of contrast-enhancing tumor. CONCLUSION Endoscopic FG resection of GBM allows increasing the complete resection rate substantially and therefore is a useful adjunct to microscopic FG resection.

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