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.

Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study

2020 ◽  
Vol 133 (5) ◽  
pp. 1324-1331 ◽  
Author(s):  
Rasmus W. Hansen ◽  
Christian B. Pedersen ◽  
Bo Halle ◽  
Anders R. Korshoej ◽  
Mette K. Schulz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Volume ◽  
Fluorescent Dyes ◽  
Aminolevulinic Acid ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Sodium Fluorescein ◽  
High Grade ◽  
Free Survival ◽  
High Grade Gliomas

OBJECTIVEMaximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, progression-free survival, and overall survival; and 2) to assess the influence of other risk factors on clinical outcome and screen for potential disadvantages of the dyes.METHODSA total of 209 patients with high-grade gliomas were included in this retrospective study. Resections were performed in the period from 2012 to 2017 using 5-ALA or fluorescein. Extent of resection was assessed as the difference in tumor volume between early postoperative and preoperative MRI studies. Tumor progression–free survival and overall survival were analyzed using an adjusted Cox proportional hazards model.RESULTSOne hundred fifty-eight patients were operated on with 5-ALA and 51 with fluorescein. The median duration of follow-up was 46.7 and 21.2 months, respectively. Covariables were evenly distributed. There was no statistically significant difference in volumetrically assessed median extent of resection (96.9% for 5-ALA vs 97.4% for fluorescein, p = 0.46) or the percentage of patients with residual tumor volume less than 0.175 cm3 (29.5% for 5-ALA vs 36.2% for fluorescein, p = 0.39). The median overall survival was 14.8 months for the 5-ALA group and 19.7 months for the fluorescein group (p = 0.06). The median adjusted progression-free survival was 8.7 months for the 5-ALA group and 9.2 months for the fluorescein group (p = 0.03).CONCLUSIONSFluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed.

scholarly journals Molecular and Metabolic Mechanisms Underlying Selective 5-Aminolevulinic Acid-Induced Fluorescence in Gliomas

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 580
Author(s):  
Jeffrey I. Traylor ◽  
Mark N. Pernik ◽  
Alex C. Sternisha ◽  
Samuel K. McBrayer ◽  
Kalil G. Abdullah
Keyword(s):  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Low Grade ◽  
Free Survival ◽  
Heme Synthesis ◽  
Preoperative Administration ◽  
Tissue Fluorescence ◽  
Specific Tissue

5-aminolevulinic acid (5-ALA) is a porphyrin precursor in the heme synthesis pathway. When supplied exogenously, certain cancers consume 5-ALA and convert it to the fluorogenic metabolite protoporphyrin IX (PpIX), causing tumor-specific tissue fluorescence. Preoperative administration of 5-ALA is used to aid neurosurgical resection of high-grade gliomas such as glioblastoma, allowing for increased extent of resection and progression free survival for these patients. A subset of gliomas, especially low-grade tumors, do not accumulate PpIX intracellularly or readily fluoresce upon 5-ALA administration, making gross total resection difficult to achieve in diffuse lesions. We review existing literature on 5-ALA metabolism and PpIX accumulation to explore potential mechanisms of 5-ALA-induced glioma tissue fluorescence. Targeting the heme synthesis pathway and understanding its dysregulation in malignant tissues could aid the development of adjunct therapies to increase intraoperative fluorescence after 5-ALA treatment.

The impact of extent of resection on malignant transformation of pure oligodendrogliomas

2014 ◽  
Vol 120 (2) ◽  
pp. 309-314 ◽  
Author(s):  
Laura A. Snyder ◽  
Andrew B. Wolf ◽  
Mark E. Oppenlander ◽  
Robert Bina ◽  
Jeffrey R. Wilson ◽  
...  
Keyword(s):  
Patient Population ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Malignant Progression ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii ◽  
Microsurgical Resection

Object Recent evidence suggests that a greater extent of resection (EOR) extends malignant progression-free survival among patients with low-grade gliomas (LGGs). These studies, however, rely on the combined analysis of oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas—3 histological subtypes with distinct genetic and molecular compositions. To assess the value of EOR in a homogeneous LGG patient population and delineate its impact on LGG transformation, the authors examined its effect on newly diagnosed supratentorial oligodendrogliomas. Methods The authors identified 93 newly diagnosed adult patients with WHO Grade II oligodendrogliomas treated with microsurgical resection at Barrow Neurological Institute. Clinical, laboratory, and radiographic data were collected retrospectively, including 1p/19q codeletion status and volumetric analysis based on T2-weighted MRI. Results The median preoperative and postoperative tumor volumes and EOR were 29.0 cm3 (range 1.3–222.7 cm3), 5.2 cm3 (range 0–156.1 cm3), and 85% (range 6%–100%), respectively. Median follow-up was 75.4 months, and there were 14 deaths (15%). Progression and malignant progression were identified in 31 (33%) and 20 (22%) cases, respectively. A greater EOR was associated with longer overall survival (p = 0.005) and progression-free survival (p = 0.004); however, a greater EOR did not prolong the interval to malignant progression, even when controlling for 1p/19q codeletion. Conclusions A greater EOR is associated with an improved survival profile for patients with WHO Grade II oligodendrogliomas. However, for this particular LGG patient population, the interval to tumor transformation is not influenced by cytoreduction. These data raise the possibility that the capacity for microsurgical resection to modulate malignant progression is mediated through biological mechanisms specific to nonoligodendroglioma LGG histologies.

scholarly journals Endoscope-assisted fluorescence-guided resection allowing supratotal removal in glioblastoma surgery

2021 ◽  
Vol 50 (1) ◽  
pp. E3
Author(s):  
Christoph Bettag ◽  
Katharina Schregel ◽  
Philip Langer ◽  
Carolina Thomas ◽  
Daniel Behme ◽  
...  
Keyword(s):  
Contrast Enhancement ◽  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Histopathological Examination ◽  
Tumor Resection ◽  
Brain Parenchyma ◽  
Consecutive Series ◽  
Resection Cavity ◽  
The Mean ◽  
Supratotal Resection

OBJECTIVESeveral studies have proven the benefits of a wide extent of resection (EOR) of contrast-enhancing tumor in terms of progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma (GBM). Thus, gross-total resection (GTR) is the main surgical goal in noneloquently located GBMs. Complete tumor removal can be almost doubled by microscopic fluorescence guidance. Recently, a study has shown that an endoscope with a light source capable of inducing fluorescence allows visualization of remnant fluorescent tumor tissue even after complete microscopic fluorescence-guided (FG) resection, thereby increasing the rate of GTR. Since tumor infiltration spreads beyond the borders of contrast enhancement on MRI, the aim of this study was to determine via volumetric analyses of the EOR whether endoscope-assisted FG resection enables supratotal resection beyond the borders of contrast enhancement.METHODSThe authors conducted a retrospective single-center analysis of a consecutive series of patients with primary GBM presumed to be noneloquently located and routinely operated on at their institution between January 2015 and February 2018 using a combined microscopic and endoscopic FG resection. A 20-mg/kg dose of 5-aminolevulinic acid (5-ALA) was administered 4 hours before surgery. After complete microscopic FG resection, the resection cavity was scanned using the endoscope. Detected residual fluorescent tissue was resected and embedded separately for histopathological examination. Nonenhanced and contrast-enhanced 3D T1-weighted MR images acquired before and within 48 hours after tumor resection were analyzed using 3D Slicer. Bias field–corrected data were used to segment brain parenchyma, contrast-enhancing tumor, and the resection cavity for volume definition. The difference between the pre- and postoperative brain parenchyma volume was considered to be equivalent to the resected nonenhancing but fluorescent tumor tissue. The volume of resected tumor tissue was calculated from the sum of resected contrast-enhancing tumor tissue and resected nonenhancing tumor tissue.RESULTSTwelve patients with GBM were operated on using endoscopic after complete microscopic FG resection. In all cases, residual fluorescent tissue not visualized with the microscope was detected. Histopathological examination confirmed residual tumor tissue in all specimens. The mean preoperative volume of brain parenchyma without contrast-enhancing tumor was 1213.2 cm3. The mean postoperative volume of brain parenchyma without the resection cavity was 1151.2 cm3, accounting for a mean volume of nonenhancing but fluorescent tumor tissue of 62.0 cm3. The mean relative rate of the overall resected volume compared to the contrast-enhancing tumor volume was 244.7% (p < 0.001).CONCLUSIONSCombined microscopic and endoscopic FG resection of GBM significantly increases the EOR and allows the surgeon to achieve a supratotal resection beyond the borders of contrast enhancement in noneloquently located GBM.

scholarly journals Extent of resection of peritumoral diffusion tensor imaging–detected abnormality as a predictor of survival in adult glioblastoma patients

2017 ◽  
Vol 126 (1) ◽  
pp. 234-241 ◽  
Author(s):  
Jiun-Lin Yan ◽  
Anouk van der Hoorn ◽  
Timothy J. Larkin ◽  
Natalie R. Boonzaier ◽  
Tomasz Matys ◽  
...  
Keyword(s):  
Overall Survival ◽  
Diffusion Tensor Imaging ◽  
Cox Regression ◽  
Aminolevulinic Acid ◽  
Diffusion Tensor ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Extensive Resection ◽  
Free Survival

OBJECTIVE Diffusion tensor imaging (DTI) has been shown to detect tumor invasion in glioblastoma patients and has been applied in surgical planning. However, the clinical value of the extent of resection based on DTI is unclear. Therefore, the correlation between the extent of resection of DTI abnormalities and patients' outcome was retrospectively reviewed. METHODS A review was conducted of 31 patients with newly diagnosed supratentorial glioblastoma who underwent standard 5-aminolevulinic acid–aided surgery with the aim of maximal resection of the enhancing tumor component. All patients underwent presurgical MRI, including volumetric postcontrast T1-weighted imaging, DTI, and FLAIR. Postsurgical anatomical MR images were obtained within 72 hours of resection. The diffusion tensor was split into an isotropic (p) and anisotropic (q) component. The extent of resection was measured for the abnormal area on the p, q, FLAIR, and postcontrast T1-weighted images. Data were analyzed in relation to patients' outcome using univariate and multivariate Cox regression models controlling for possible confounding factors including age, O6-methylguanine-DNA-methyltrans-ferase methylation status, and isocitrate dehydrogenase–1 mutation. RESULTS Complete resection of the enhanced tumor shown on the postcontrast T1-weighted images was achieved in 24 of 31 patients (77%). The mean extent of resection of the abnormal p, q, and FLAIR areas was 57%, 83%, and 59%, respectively. Increased resection of the abnormal p and q areas correlated positively with progression-free survival (p = 0.009 and p = 0.006, respectively). Additionally, a larger, residual, abnormal q volume predicted significantly shorter time to progression (p = 0.008). More extensive resection of the abnormal q and contrast-enhanced area improved overall survival (p = 0.041 and 0.050, respectively). CONCLUSIONS Longer progression-free survival and overall survival were seen in glioblastoma patients in whom more DTI-documented abnormality was resected, which was previously shown to represent infiltrative tumor. This highlights the potential usefulness and the importance of an extended resection based on DTI-derived maps.

scholarly journals Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas

2013 ◽  
Vol 71 (1) ◽  
pp. 31-34 ◽  
Author(s):  
André de Macedo Bianco ◽  
Flavio Key Miura ◽  
Carlos Clara ◽  
Jose Reynaldo W. Almeida ◽  
Clemar Correa da Silva ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Subtotal Resection ◽  
Low Grade ◽  
Brain Areas ◽  
Free Survival ◽  
Eloquent Areas ◽  
Eloquent Area ◽  
Extent Of Surgical Resection

A retrospective study of 81 patients with low-grade astrocytoma (LGA) comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS) and progression- free survival (PFS). Degree of tumor resection was classified as gross total resection (GTR), subtotal resection (STR) or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013), whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33). Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.

KAI-1 Expression in Pediatric High-Grade Osteosarcoma

2006 ◽  
Vol 9 (3) ◽  
pp. 219-224 ◽  
Author(s):  
Patrick J. Leavey ◽  
Charles Timmons ◽  
William Frawley ◽  
Donald Lombardi ◽  
Raheela Ashfaq
Keyword(s):  
Prognostic Markers ◽  
Clinical Phenotype ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Surface Proteins ◽  
High Grade ◽  
Free Survival ◽  
Treatment Groups ◽  
High Grade Osteosarcoma

Recent evidence implicates cell surface proteins of the tetraspanin superfamily in the process of metastasis whereas the downregulation of KAI-1, a member of the tetraspanin family, is associated with an aggressive clinical phenotype in several types of human cancers. To determine if expression of KAI-1-1 is associated with any known prognostic marker or clinical outcome in high-grade osteosarcoma, we examined 91 nondecalcified archival samples from 47 patients for the expression of KAI-1. Archival, paraffin-embedded, and decalcified pathologic samples were examined by immunohistochemistry and results were correlated to clinical outcomes and known prognostic markers. There were 46 samples from diagnostic biopsies (1 diagnostic sample was not available), 32 tumor resection samples, and 13 metastasis samples. Thirty-three percent (n = 30) of the samples expressed KAI-1 (16 biopsies, 9 resections, and 5 metastasis). KAI-1 expression was not significantly related to known prognostic markers or to either tumor necrosis after neoadjuvant therapy or the incidence of metastasis at diagnosis. KAI-1 expression was not significantly different between paired diagnostic tumor samples and either resection or metastasis tumor samples. Twenty-five patients remain alive at a median follow-up of 95 months. The overall and progression-free survival percentages at 5 years were 62% and 47% for KAI-1-positive patients and 49% and 38% for KAI-1-negative patients, respectively. This difference was not statistically significant. We conclude that KAI-1 is expressed in a proportion of high-grade osteosarcoma but is not of clinical significance and cannot be used to stratify treatment groups for these patients.

scholarly journals Could Primary Tumor Resection Improve Survival in Metastatic Breast Cancer?

2021 ◽  
Vol 9 (07) ◽  
pp. 422-428
Author(s):  
Rafaela Aparecida Dias de Oliveira ◽  
Lyvia Aparecida Dias de Oliveira ◽  
Marília Davoli Abella Goulart ◽  
Maria Clara Faustino Linhares
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Systemic Therapy ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Tumor Resection ◽  
Free Survival

Introduction: In advanced breast cancer, local treatment is considered palliative. However, although there are some polemic opinions about the surgical treatment, some of the latest studies have emphasized that in advanced cases primary tumor resection (PTR) is related to better outcomes. This review aims to evaluate how resection of the original tumor impacts women with metastatic breast cancer, considering the most recent studies about this subject. Methods: The search was performed in MEDLINE, Scopus, PMC, Current Contents and Wiley Online Library databases; 23 articles - from 2016 to 2019 - were selected and 11 were included in this review. As inclusion criteria were considered: studies presenting outcomes about resection of the primary tumor, comparison between chemotherapy/ hormone therapy/ targeted cancer therapies and surgical intervention, studies published from 2016 to 2019 and available in English, Spanish or Portuguese. We excluded those which did not approach PTR, did not present outcomes of interest (progression-free survival comparison between PTR and systemic therapy) or only discussed systemic therapy, as well as those published before 2016. Results: It was reported in 6 studies that progression-free survival is better on those who underwent surgery. PTR was also related to longer median overall survival in women submitted to surgery, up to 16 months higher when compared to the ones who were not. Enhanced survival even pertained to surgical groups regardless of tumor size.  Conclusion: Based in the analysis, PTR in metastatic breast cancer can be related to higher overall survival.

scholarly journals Robotic-Assisted Digital Exoscope for Resection of Cerebral Metastases: A Case Series

2021 ◽  
Author(s):  
Alexander J Schupper ◽  
Gabrielle Price ◽  
Constantinos G Hadjipanayis
Keyword(s):  
Case Series ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Neurological Complications ◽  
Primary Treatment ◽  
Complete Resection ◽  
Cerebral Metastases ◽  
Discharge Disposition ◽  
Tumor Tissues ◽  
Postoperative Symptoms

Abstract BACKGROUND Surgical resection is the primary treatment for cerebral metastases with safe complete resection as the goal. The robotically assisted digital surgical exoscope is a novel system with advanced visualization methods with recent applications in neurosurgery. OBJECTIVE To evaluate the outcomes for patients with cerebral metastases undergoing resection with the surgical exoscope. METHODS Data were retrospectively collected from patients with cerebral metastases where resection was achieved with using the surgical exoscope from 2016 to 2020. Demographics, clinical, imaging, and operative and outcome findings were collected. The relationship between perioperative data and discharge disposition as well as progression-free survival (PFS) and 12 mo overall survival (OS) was assessed. RESULTS A total of 31 patients (19 males) with a median patient age 63 yr (range 38-80) were included. Average pre- and postoperative volumes were 18.1 cc and 0.75 cc, respectively. Mean depth of the resected lesions was 0.6 cm (range 0-3.6 cm). Complete resection was achieved in 64.5% of patients. The mean extent of resection was 96.7%, with 71.0% achieving PFS at 6 mo. Overall PFS rate was 58.1% and the OS rate at 12 mo was 83.9%. Neurological complications included motor (35.5%) and sensory (12.9%) deficits, with 12 patients reporting no postoperative symptoms. CONCLUSION The surgical exoscope can delineate tumor tissues with high resolution, as shown by a gross total resection achieved for the majority of cases in our series. Postoperative complications and patient outcomes were similar to those reported with use of the operative microscope. Use of the exoscope can provide optimal visualization and delineation of cerebral metastases.

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