scholarly journals Cortical plasticity catalyzed by prehabilitation enables extensive resection of brain tumors in eloquent areas

2017 ◽  
Vol 126 (4) ◽  
pp. 1323-1333 ◽  
Author(s):  
Paola A. Rivera-Rivera ◽  
Marcos Rios-Lago ◽  
Sandra Sanchez-Casarrubios ◽  
Osman Salazar ◽  
Miguel Yus ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Behavioral Training ◽  
Brain Areas ◽  
Extensive Resection ◽  
Who Grade ◽  
Stimulation Intensity ◽  
Eloquent Areas ◽  
Cortical Electrical Stimulation

OBJECTIVE The extent of resection is the most important prognostic factor following brain glioma surgery. However, eloquent areas within tumors limit the extent of resection and, thus, critically affect outcomes. The authors hypothesized that presurgical suppression of the eloquent areas within a tumor by continuous cortical electrical stimulation, coupled with appropriate behavioral training (“prehabilitation”), would induce plastic reorganization and enable a more extensive resection. METHODS The authors report on 5 patients harboring gliomas involving eloquent brain areas within tumors as identified on intraoperative stimulation mapping. A grid of electrodes was placed over the residual tumor, and continuous cortical electrical stimulation was targeted to the functional areas. The stimulation intensity was adjusted daily to provoke a mild functional impairment while the function was intensively trained. RESULTS The stimulation intensity required to impair function increased progressively in all patients, and all underwent another operation a mean of 33.6 days later (range 27–37 days), when the maximal stimulation voltage in all active contacts induced no functional deficit. In all cases, a substantially more extensive resection of the tumor was possible. Intraoperative mapping and functional MRI demonstrated a plastic reorganization, and most previously demonstrated eloquent areas within the tumor were silent, while there was new functional activation of brain areas in the same region or toward the contralateral hemisphere. CONCLUSIONS Prehabilitation with continuous cortical electrical stimulation and appropriate behavioral training prior to surgery in patients with WHO Grade II and III gliomas affecting eloquent areas accelerate plastic changes. This can help maximize tumor resection and, thus, improve survival while maintaining function.

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.

scholarly journals Age is associated with unfavorable neuropathological and radiological features and poor outcome in patients with WHO grade 2 and 3 gliomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aleksandrs Krigers ◽  
Matthias Demetz ◽  
Claudius Thomé ◽  
Christian F. Freyschlag
Keyword(s):  
Older Patients ◽  
Group Analysis ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Lower Grade ◽  
Wild Type ◽  
Who Grade ◽  
Radiological Features ◽  
Age Related ◽  
Type Population

AbstractWith the rising life expectancy and availability of neuroimaging, increased number of older patients will present with diffuse and anaplastic gliomas. The aim of our study was therefore to investigate age-related prognostic clinical, neuropathological and radiological features of lower-grade gliomas. All consecutive patients with diffuse or anaplastic glioma WHO grade 2 and 3 who underwent first tumor resection between 2010 and 2018, were selected from the institutional neuro-oncological database and evaluated. The mean age of 55 males and 44 females was 46 years (SD ± 16). Wild-type IDH1 (p = 0.012), persistent nuclear ATRX expression (p = 0.012) and anaplasia (p < 0.001) were significantly associated with higher age. The CE volume before resection was found to be increased in older patients (r = 0.42, p < 0.0001), and CE rate was higher in the IDH wild-type population only (p = 0.02). The extent of resection did not differ with age. Overall, one year of life resulted in a PFS reduction of 9 days (p = 0.047); in IDH sub-group analysis, this dependency was confirmed only in wild-type tumors (p = 0.05). OS was significantly reduced in older patients (p = 0.033). In conclusion, behavior and prognosis of WHO grade 2 and 3 glioma were unfavorable in correlation to patient’s age, even if the extent of resection was comparable. Older age imparted a poorer PFS and higher CE rate only in the IDH wild-type population.

scholarly journals Orbit-associated tumors: navigation and control of resection using intraoperative computed tomography

2016 ◽  
Vol 124 (5) ◽  
pp. 1319-1327 ◽  
Author(s):  
Nicole A. Terpolilli ◽  
Walter Rachinger ◽  
Mathias Kunz ◽  
Niklas Thon ◽  
Wilhelm H. Flatz ◽  
...  
Keyword(s):  
Skull Base ◽  
Clinical Symptoms ◽  
Intraoperative Imaging ◽  
Tumor Resection ◽  
Visual Outcome ◽  
Extent Of Resection ◽  
Who Grade ◽  
Intraoperative Ct ◽  
Intraoperative Computed Tomography ◽  
Skull Base Lesions

OBJECT Treatment of skull base lesions is complex and usually requires a multidisciplinary approach. In meningioma, which is the most common tumor entity in this region, resection is considered to be the most important therapeutic step to avoid tumor recurrence. However, resection of skull base lesions with orbital or optic nerve involvement poses a challenge due to their anatomical structure and their proximity to eloquent areas. Therefore the main goal of surgery should be to achieve the maximum extent of resection while preserving neurological function. In the postoperative course, medical and radiotherapeutic strategies may then be successfully used to treat possible tumor residues. Methods to safely improve the extent of resection in skull base lesions therefore are desirable. The current study reports the authors’ experience with the use of intraoperative CT (iCT) combined with neuronavigation with regard to feasibility and possible benefits of the method. METHODS Those patients with tumorous lesions in relationship to the orbit, sphenoid wing, or cavernous sinus who were surgically treated between October 2008 and December 2013 using iCT-based neuronavigation and in whom an intraoperative scan was obtained for control of resection were included. In all cases a second iCT scan was performed under sterile conditions after completion of navigation-guided microsurgical tumor resection. The surgical strategy was adapted accordingly; if necessary, resection was continued. RESULTS Twenty-three patients (19 with WHO Grade I meningioma and 4 with other lesions) were included. The most common clinical symptoms were loss of visual acuity and exophthalmus. Intraoperative control of resection by iCT was successfully obtained in all cases. Intraoperative imaging changed the surgical approach in more than half (52.2%) of these patients, either because iCT demonstrated unexpected residual tumor masses or because the second scan revealed additional tumor tissue that was not detected in the first scan due to overlay by osseous tumor parts; in these cases resection was continued. In the remaining cases resection was concluded as planned because iCT verified the surgeon’s microscopic estimation of tumor resection status. Postoperative visual outcome was favorable in more than 80% of patients. CONCLUSIONS Intraoperative CT allows control of resection in case of uncertainty and can help to improve the extent of maximal safe resection, especially in case of osseous tumor parts and masses within the orbit.

scholarly journals SURG-06. AWAKE CRANIOTOMY FOR BRAIN TUMOR IN PEDIATRIC PATIENTS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii462-iii462
Author(s):  
Carlos Almeida ◽  
Alessandra Levy Antoniazzi ◽  
Bruna Minniti Mançano ◽  
Marcus Matsushita ◽  
Rachel Eggers Bacci ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Pediatric Patients ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Awake Craniotomy ◽  
Cortical Mapping ◽  
Dysembryoplastic Neuroepithelial Tumor ◽  
Direct Stimulation ◽  
Who Grade ◽  
Mapping Procedure

Abstract BACKGROUND The challenge of surgery in neurooncology is to achieve the maximum extent of resection while preserving eloquent functions. Intra-operative cortical mapping during resection of a brain tumor allows direct stimulation in eloquent areas with a reduction in postoperative deficits. This procedure has been performed in adults and children down to the age of 11 years. There are only two cases reported on the literature of an 8-year-old and 9-year-old child submitted to an awake craniotomy for brain tumor resection. Pediatric patients are prone to more risks than adults because they become easily agitated after pain sensation. Extensive preparation for the procedure is essential for pediatric patients in order to avoid a lack of cooperation. CASE PRESENTATION: Two patients, with 9-year-old presented with seizures due to a tumor in the left temporoparietal region. In order to identify language and motor–controlling areas during resection, we proposed an awake craniotomy. Because of their ages, they were prepared by a multidisciplinary team. The children’s cooperation during the mapping procedure and tumor resection were exceptional. Postoperative cranial MRI confirmed partial resection of the lesion, whose remnant was located in the left motor area. No seizures occurred during the postoperative period, and both were discharged without a neurological disability on the fifth day after the surgery. Histology revealed a dysembryoplastic neuroepithelial tumor (WHO grade I). CONCLUSION Brain mapping during resection of a tumor in an awake pediatric patient is feasible and can be safely performed even in patients under 11-year-old.

Glioblastoma therapy in the elderly and the importance of the extent of resection regardless of age

2012 ◽  
Vol 116 (2) ◽  
pp. 357-364 ◽  
Author(s):  
Ági Oszvald ◽  
Erdem Güresir ◽  
Matthias Setzer ◽  
Hartmut Vatter ◽  
Christian Senft ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Elderly Patients ◽  
Clinical Status ◽  
Combined Treatment ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Karnofsky Performance Scale ◽  
Extensive Resection ◽  
Younger Patients

Object The objective of this study was to analyze whether age influences the outcome of patients with glioblastoma and whether elderly patients with glioblastoma can tolerate the same aggressive treatment as younger patients. Methods Data from 361 consecutive patients with newly diagnosed cerebral glioblastoma (2000–2006) who underwent regular follow-up evaluation from initial diagnosis until death were prospectively entered into a database. Patients underwent resection (complete, subtotal, or partial) or biopsy, depending on tumor size, location, and Karnofsky Performance Scale score. Following surgery, all patients underwent adjuvant treatment consisting of radiotherapy, chemotherapy, or combined treatment. Patients older than 65 years of age were defined as elderly (146 total). Results Two hundred thirty-four patients underwent tumor resection (complete 26%, subtotal 29%, and partial 45%). One hundred twenty-seven underwent biopsy. Mean patient age was 61 years, and overall survival was 11.6 ± 12.1 months. The overall survival of elderly patients (9.1 ± 11.6 months) was significantly lower than that of younger patients (14.9 ± 16.7 months; p = 0.0001). Stratifying between resection or biopsy, age was a negative prognostic factor in patients undergoing biopsy (4.0 ± 7.1 vs 7.9 ± 8.7 months; p = 0.007), but not in patients undergoing tumor resection (13.0 ± 8.5 vs 13.3 ± 14.5 months; p = 0.86). Survival of elderly patients undergoing complete tumor resection was 17.7 ± 8.1 months. Conclusions In this series of patients with glioblastoma, age was a prognostic factor in patients undergoing biopsy, but not in patients undergoing resection. Tumor location and patient clinical status may prohibit extensive resection, but resection should not be withheld from patients only on the basis of age. In elderly patients with glioblastoma, undergoing resection to the extent feasible, followed by adjuvant therapies, is warranted.

scholarly journals SURG-14. AWAKE CRANIOTOMY VS CRANIOTOMY UNDER GENERAL ANESTHESIA FOR GLIOBLASTOMAS: EVALUATING THE IMPACT ON OVERALL SURVIVAL AND RISK OF RECURRENCE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii206-ii206
Author(s):  
Mario Moro
Keyword(s):  
Overall Survival ◽  
General Anesthesia ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Neurological Deficits ◽  
Awake Surgery ◽  
Tumor Control ◽  
Risk Of Recurrence ◽  
Eloquent Areas ◽  
The Impact

Abstract Maximum safe resection for eloquent glioblastomas (GBMs) is the maximum tumor resection achievable without causing neurological deficits. Although challenging, it must be considered the therapeutic target for GBMs. Indeed, the extension of resection positively correlates with the overall survival and recurrences risk. Awake surgery (AS) has become paramount for achieving maximum safe resection for tumors in eloquent areas. However, there is not a unanimous consensus on the extent of resection of eloquent GBMs, especially for what concerns the so-called supratotal resection (i.e.: resection over the contrast-enhancing limits of the lesion). Recently, several studies focused their attention on the residual tumor volume as estimated from T1-contrast enhanced sequences, but few analyzed the outcomes of patients with a more extended resection. Some authors speculated that increased surgical aggressiveness, thus removing peritumoral edematous area, correlates with improved overall survival and tumor control, without increasing adverse events rates. This study aimed to assess, through quantitative volumetric analysis, the outcomes of a prospectively collected cohort of patients with primary GBM located in eloquent areas. We furtherly subdivided our population into two treatment groups: awake surgery (AS) and general anesthesia (GA) craniotomies. We analyzed the overall outcomes, especially for what concerns MRI T2-Flair signal extent of resection, related to patients’ survival and recurrences formation. Eventually, we stratified our analysis by type of treatment (awake surgery vs. general anesthesia) to rule out any significant differences in survival and postoperative GBMs behaviors. Our data confirmed extensive that T2-Flair resection (EOR≥30%) and AS could improve overall survival and reduce risk of recurrence without, at the same time, causing an increase of surgical and medical complications

scholarly journals Lighting Up the Tumor—Fluorescein-Guided Resection of Gangliogliomas

2020 ◽  
Vol 9 (8) ◽  
pp. 2405 ◽  
Author(s):  
Julius Höhne ◽  
Francesco Acerbi ◽  
Jacopo Falco ◽  
Mehmet Osman Akçakaya ◽  
Nils Ole Schmidt ◽  
...  
Keyword(s):  
Contrast Enhancement ◽  
Tumor Resection ◽  
Radical Resection ◽  
Extent Of Resection ◽  
University Hospital ◽  
World Health ◽  
Subtotal Resection ◽  
Anesthesia Induction ◽  
Fluorescein Sodium ◽  
Who Grade

(1) Background: Gangliogliomas comprise a small number of brain tumors. They usually present as World Health Organization (WHO) grade I, and they delineate on gadolinium-enhanced MRI; the surgical goal is wide radical resection, and the course thereafter is usually benign. Fluorescein sodium (FL) tends to accumulate in areas with altered blood–brain barrier (BBB). Thus far, the results provided by prospective and retrospective studies show that the utilization of this fluorophore may be associated with better visualization and improvement of resection for several tumors of the central nervous system. In this study, we retrospectively studied the effect of fluorescein sodium on visualization and resection of gangliogliomas. (2) Methods: Surgical databases in three neurosurgical departments (Regensburg University Hospital; Besta Institute, Milano, Italy; and Liv Hospital, Istanbul, Turkey), with approval by the local ethics committee, were retrospectively reviewed to find gangliogliomas surgically removed by a fluorescein-guided technique by the aid of a dedicated filter on the surgical microscope from April 2014 to February 2020. Eighteen patients (13 women, 5 men; mean age 22.9 years, range 3 to 78 years) underwent surgical treatment for gangliogliomas during 19 operations. Fluorescein was intravenously injected (5 mg/kg) after general anesthesia induction. Tumors were removed using a microsurgical technique with the YELLOW 560 Filter (YE560) (KINEVO/PENTERO 900, Carl Zeiss Meditec, Oberkochen, Germany). (3) Results: No side effects related to fluorescein occurred. In all tumors, contrast enhancement on preoperative MRI correlated with bright yellow fluorescence during the surgical procedure (17 gangliogliomas WHO grade I, 1 ganglioglioma WHO grade II). Fluorescein was considered helpful by the operating surgeon in distinguishing tumors from viable tissue in all cases (100%). Biopsy was intended in two operations, and subtotal resection was intended in one operation. In all other operations considered preoperatively eligible, gross total resection (GTR) was achieved in 12 out of 16 (75%) instances. (4) Conclusions: The use of FL and YE560 is a readily available method for safe fluorescence-guided tumor resection, possibly visualizing tumor margins intraoperatively similar to contrast enhancement in T1-weighted MRI. Our data suggested a positive effect of fluorescein-guided surgery on intraoperative visualization and extent of resection during resection of gangliogliomas.

scholarly journals Russian Intraoperative Naming Test: a Standardized Tool to Map Noun and Verb Production during Awake Neurosurgeries

2016 ◽  
Vol 3 (4) ◽  
pp. 4-25 ◽  
Author(s):  
Olga Dragoy ◽  
◽  
Anna Chrabaszcz ◽  
Valeria Tolkacheva ◽  
Svetlana Buklina
Keyword(s):  
Tumor Tissue ◽  
Tumor Resection ◽  
Linguistic Knowledge ◽  
Language Function ◽  
Extensive Resection ◽  
Eloquent Areas ◽  
Communication Disabilities ◽  
Brain Tumor Resection ◽  
Mapping Language ◽  
Naming Test

To minimize permanent postoperative deficits, functional mapping with direct electrical stimulation (DES) is becoming a gold standard when a brain tumor resection must be performed near or within eloquent areas. Due to the devastating impact of communication disabilities, language is one of the most commonly mapped functions. However, standardized linguistic protocols for intraoperative use are still scarce. Here we present the first Russian standardized naming test for mapping noun and verb production during awake neurosurgeries. Its development has been informed by modern (psycho)linguistic knowledge and DES requirements. The test was clinically piloted in a sample of 23 patients who underwent awake craniotomy, with results showing high relevance of the test in combination with DES for mapping language-relevant cortical and subcortical sites. The use of the test intraoperatively enabled extensive resection of tumor tissue while preserving language function in most of the tested patients. The test materials and protocols are freely available online

Proliferation-dominant high-grade astrocytoma: survival benefit associated with extensive resection of FLAIR abnormality region

2020 ◽  
Vol 132 (4) ◽  
pp. 998-1005 ◽  
Author(s):  
Haihui Jiang ◽  
Yong Cui ◽  
Xiang Liu ◽  
Xiaohui Ren ◽  
Mingxiao Li ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Characteristic Curve ◽  
Extent Of Resection ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
High Grade ◽  
Extensive Resection ◽  
High Grade Astrocytoma

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.

Intraoperative assessment of isocitrate dehydrogenase mutation status in human gliomas using desorption electrospray ionization–mass spectrometry

2020 ◽  
Vol 132 (1) ◽  
pp. 180-187 ◽  
Author(s):  
Clint M. Alfaro ◽  
Valentina Pirro ◽  
Michael F. Keating ◽  
Eyas M. Hattab ◽  
R. Graham Cooks ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Isocitrate Dehydrogenase ◽  
Tumor Resection ◽  
Desorption Electrospray Ionization ◽  
Extent Of Resection ◽  
Ionization Mass ◽  
Idh Mutation ◽  
Mutation Status ◽  
Desi Ms

OBJECTIVEThe authors describe a rapid intraoperative ambient ionization mass spectrometry (MS) method for determining isocitrate dehydrogenase (IDH) mutation status from glioma tissue biopsies. This method offers new glioma management options and may impact extent of resection goals. Assessment of the IDH mutation is key for accurate glioma diagnosis, particularly for differentiating diffuse glioma from other neoplastic and reactive inflammatory conditions, a challenge for the standard intraoperative diagnostic consultation that relies solely on morphology.METHODSBanked glioma specimens (n = 37) were analyzed by desorption electrospray ionization–MS (DESI-MS) to develop a diagnostic method to detect the known altered oncometabolite in IDH-mutant gliomas, 2-hydroxyglutarate (2HG). The method was used intraoperatively to analyze tissue smears obtained from glioma patients undergoing resection and to rapidly diagnose IDH mutation status (< 5 minutes). Fifty-one tumor core biopsies from 25 patients (14 wild type [WT] and 11 mutant) were examined and data were analyzed using analysis of variance and receiver operating characteristic curve analysis.RESULTSThe optimized DESI-MS method discriminated between IDH-WT and IDH-mutant gliomas, with an average sensitivity and specificity of 100%. The average normalized DESI-MS 2HG signal was an order of magnitude higher in IDH-mutant glioma than in IDH-WT glioma. The DESI 2HG signal intensities correlated with independently measured 2HG concentrations (R2 = 0.98). In 1 case, an IDH1 R132H–mutant glioma was misdiagnosed as a demyelinating condition by frozen section histology during the intraoperative consultation, and no resection was performed pending the final pathology report. A second craniotomy and tumor resection was performed after the final pathology provided a diagnosis most consistent with an IDH-mutant glioblastoma. During the second craniotomy, high levels of 2HG in the tumor core biopsies were detected.CONCLUSIONSThis study demonstrates the capability to differentiate rapidly between IDH-mutant gliomas and IDH-WT conditions by DESI-MS during tumor resection. DESI-MS analysis of tissue smears is simple and can be easily integrated into the standard intraoperative pathology consultation. This approach may aid in solving differential diagnosis problems associated with low-grade gliomas and could influence intraoperative decisions regarding extent of resection, ultimately improving patient outcome. Research is ongoing to expand the patient cohort, systematically validate the DESI-MS method, and investigate the relationships between 2HG and tumor heterogeneity.

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