Resection Of Gliomas Research Articles

Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro.

(1) Background: The protoporphyrin IX (PpIX)-mediated fluorescence-guided resection and interoperative photodynamic therapy (PDT) of remaining cells may be effective adjuvants to the resection of glioma. Both processes may be enhanced by increasing intracellular PpIX concentrations, which can be achieved through iron chelation. AP2-18 is a novel combinational drug, which ester-links a PpIX precursor (aminolaevulinic acid; ALA) to an iron-chelating agent (CP94). (2) Methods: Human glioma U-87 MG cells were cultured in 96-well plates for 24 h and incubated for 3 or 6 h with various test compound combinations: ALA (±) CP94, methyl aminolevulinate (MAL) (±) CP94 and AP2-18. PpIX fluorescence was measured at 0, 3 or 6 h with a Bio-tek Synergy HT plate reader, as well as immediately after irradiation with a 635 nm red light (Aktilite CL16 LED array), representing the PDT procedure. Cell viability post-irradiation was assessed using the neutral red assay. (3) Results: AP2-18 significantly increased PpIX fluorescence compared to all other test compounds. All treatment protocols effectively achieved PDT-induced cytotoxicity, with no significant difference between test compound combinations. (4) Conclusions: AP2-18 has potential to improve the efficacy of fluorescence-guided resection either with or without the subsequent intraoperative PDT of glioma. Future work should feature a more complex in vitro model of the glioma microenvironment.

5-Aminolevulinic acid fluorescence-guided endoscopic surgery for deep-seated intraparenchymal tumors

Aim The usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-assisted surgery for maximum resection of malignant gliomas has been established. However, its usefulness when combined with endoscopic surgery for deep-seated tumors has not been well established. In this study, whether 5-ALA photodynamic diagnosis (PDD) is feasible and useful for endoscopic surgery was investigated. Methods A specially designed endoscope for PDD that delivers white light or blue light (375–440 nm) as excitation light was used. The fluorescence emitted by the tumor was evaluated in the cavity during resection or at the tip of the sheath during biopsy. The intensity of fluorescence was classified into three categories: strong, vague, and negative. Results A total of 30 intraparenchymal tumors were observed with a neuroendoscope and 5-ALA PDD; 16 patients underwent resection, and 14 underwent biopsy. Overall, 67% (20/30) of tumors showed positive fluorescence of protoporphyrin IX. High-grade gliomas (HGGs) including glioblastoma (GBM) and anaplastic astrocytoma (AA) showed strong fluorescence in 47% (7/15), vague fluorescence in 33% (5/15), and negative fluorescence in 20% (3/15) of cases. Low-grade gliomas (LGGs) showed vague fluorescence in 33% (1/3) and negative fluorescence in 67% (2/3). Diffuse large B-cell lymphoma (DLBCL) showed vague fluorescence in 38% (3/8) and negative fluorescence in 63% (5/8). Metastatic tumors showed strong fluorescence in 25% (1/4) and vague fluorescence in 75% (3/4). In the comparison of fluorescence evaluation, a significant difference was observed only in the comparison between HGGs and DLBCL (p = 0.049). Conclusion These results suggest that 5-ALA PDD-assisted endoscopic surgery is feasible and useful for deep-seated intraparenchymal tumors.

NCMP-13. CONCURRENT WOUNDED GLIOMA SYNDROME AND DISTANT WOUNDED GLIOMA SYNDROME FOLLOWING A GROSS TOTAL RESECTION OF GLIOBLASTOMA MULTIFORME – A CASE REPORT

Abstract Surgery is the initial form of treatment for glioblastoma, and a maximum resection without impairing neurological function improves survival. Wounded Glioma Syndrome (WGS) is a clinical picture observed after the resection of high-grade tumors. This syndrome, developing within hours or a few days after glioma surgery, is characterized by hemorrhage into the surgical bed and cerebral edema, and at times occurring in areas distant from the site of the resection, i.e., Distant WGS. We report a case of an elderly male presenting with an acute-onset left leg weakness, with a large peripherally-enhancing mass with central non-enhancement suggestive of necrosis in the right frontal lobe. A gross total resection of the tumor was done, and the histopathologic evaluation yielded a high-grade glioma, favoring a diagnosis of Glioblastoma WHO Grade-IV. During the postoperative period, he was drowsy and was able to move the right extremities. He had a series of generalized tonic-clonic seizures three hours after the operation. After eight hours, the patient became comatose with signs of increasing intracranial pressure. A cranial CT revealed diffuse cerebral edema, and hemorrhage into the operative site in the right frontal lobe, as well as subarachnoid hemorrhages in the bilateral fronto-parietal sulci. There were also small hemorrhages seen in the left caudate head, midbrain and left hemipons. Death occurred the following day. This case report demonstrates an unusual case of a WGS with a concurrent Distant WGS in the brainstem after a gross total resection of a frontal lobe glioma. This case shows a significant uncommon sequela that a patient undergoing glioma surgery can present, leading to rapid deterioration and death. Resection of a glioma carries a significant risk, and its impact in the immediate postoperative period merits evaluation when planning the perioperative management, taking prompt action if these syndromes occur.

SURG-16. SAMPLING AND PROCESSING OF TUMOR TISSUE DURING RESECTION OF DIFFUSE INTRACRANIAL GLIOMA: INTERNATIONAL SURVEY AND RECOMMENDATIONS FOR STANDARDIZATION ON BEHALF OF FOUR RANO GROUPS

Abstract BACKGROUND Surgical resection represents the standard of care for newly diagnosed diffuse gliomas and allows neuropathological evaluation for diagnosis. Moreover, tissue specimens form the basis for research allowing the identification of pathogenetic mechanisms and targets. However, there is no consensus which tumor portions should be systematically sampled to achieve a genuinely representative evaluation in a condition characterized by intratumoral heterogeneity. Guidelines for biospecimen handling and long-term storage are also lacking, limiting comparative analyses between different biobanks. METHODS Four international RANO groups from the fields of surgical and medical neuro-oncology, radiation oncology, neuroimaging, and neuropathology aimed to generate a framework for tissue sampling and processing during resection of diffuse glioma. RESULTS A core committee of 21 representatives from the four RANO groups identified areas of interest based upon expert consensus and drafted recommendations for best practice guidelines. Those were eventually sent to 38 leading experts in the field for further evaluation using a two-staged eDelphi process, leading to refinement of the recommendations. Only recommendations which were scored as of ‘critical importance’ by ≥ 70% of the expert panelists were accepted. Consensus recommendations were developed for (I) tissue volume and (neuroimaging-based) tumor-specific regions from where the tumor should be sampled; (II) definitions how regions for sampling of non-contrast-enhancing tumor on MRI should be identified; (III) blood and CSF sampling; (IV) handling and storage to enable both neuropathological diagnosis and in-depth research analyses; and (V) the preferred sample labelling to avoid communication errors. These recommendations resulted in a sophisticated intraoperative workflow proposal to accurately depicture the tumor composition during sampling. CONCLUSION These RANO recommendations offer a framework to standardize the surgical and post-surgical workflow for prospective biobanking studies which will be presented together with the results of the eDelphi survey at the SNO meeting.

SURG-10. DEVELOPMENT OF 2 COMPLEMENTARY INNOVATIVE APPROACHES FOR REAL-TIME, LABEL-FREE INTRAOPERATIVE TUMOR DETECTION TO ENHANCE EXTENT OF RESECTION OF LOW GRADE GLIOMAS

Abstract Brain tumor surgery aims to maximize tumor resection while avoiding neurological deficits. Accurate characterization of tissue and delineation of resection margins are essential to achieve optimal surgical outcome. Hyperspectral imaging (HSI) and Real-time Rapid Evaporative Ionization Mass Spectrometry ( REIMS) are both novel technological adjuncts able to accurately detect intraoperatively zones of low grade glioma without substantially altering the surgical work flow. For HSI, we successfully demonstrate how an HSI system can interface with a clinically approved surgical microscope making use of the microscope’s available light sources and optical ports. We integrated the HSI system into the clinical workflow during brain surgery, specifically for resections of low-grade gliomas (LGG). During the study the acquired dataset was used to train an AI algorithm to detect LGG, providing 81% accuracy on unseen data. Real-time Rapid Evaporative Ionization Mass Spectrometry (REIMS) enables in-situ tissue characterization based on the mass spectrometric analysis of electrosurgical vapors generated during dissection. We demonstrate the use of REIMS for the molecular characterization of brain tumor tissue, thereby providing quasi real-time assessment of tumor type. A classification model containing 31 sampling points in normal brain tissue and 93 in glial tumor tissue provided 89.3% sensitivity and 91.1% specificity. Both techniques, HSI and REIMS display a high intraoperative diagnostic accuracy in terms of glioma tissue detection and are complementary, real-time and label-free methods which we developed and tested up to the stage of high Technology Readiness levels (TRL) of 7 and 5 respectively.

QOL-04. CHANGES IN FUNCTIONAL CONNECTIVITY AFTER SURGERY ARE ASSOCIATED WITH DECLINE IN FUNCTIONAL INDEPENDENCE IN PATIENTS WITH ELOQUENT GLIOMA

Abstract It is unknown whether patient independence following resection of eloquent glioma is associated with postoperative functional connectomic changes. Fifteen patients with left perisylvian glioma underwent resting-state fMRI and neuropsychological evaluation before and about 1 month after resection. Functional independence was measured with the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living scale (IADL). Manual dexterity testing (Grooved Pegboard; N = 13), neurologic motor exam (N = 12), and performance status (KPS; N = 14) were also obtained. Graph theoretical analysis was used to calculate functional brain network properties. Postoperative need for assistance in at least 1 activity on the IADL increased from baseline in 80% of patients, most commonly in Transportation (67%), followed by Shopping (60%), Financial Management (47%), Cooking (47%), Medication Management (33%), and Phone Use (33%). Overall need for assistance (Total IADL score) significantly increased postoperatively (Mdn change = 4, p = .006). Need for assistance on the PSMS only increased in 27% of patients, with rates less than 15% across all functions. Total PSMS scores did not differ pre- and postoperatively (Mdn change = 0). KPS scores worsened in 40% of patients. None had gross motor worsening, though fine manual dexterity declined in 7% for the left and 23% for the right hand. Increased connectomic properties were significantly associated (Spearman ρ) with greater need for assistance on the IADL [Local Efficiency: Total (.72), Shopping (.71), Cooking (.64), Financial Management (.64); Clustering Coefficient: Phone Use (.63); Betweenness Centrality: Phone Use (.63); all p < .01]. PSMS and IADL ratings were not associated with KPS, manual dexterity, pre/postoperative FLAIR volume, or extent of resection. This study demonstrated that increases in certain functional connectomic properties after surgery are associated with greater need for assistance in instrumental activities in the postoperative period. Connectivity increases have also been associated with poorer cognitive outcome in this population, though specific properties involved may differ.

SURG-28. MULTI-STAGE, OPEN CRANIAL APPROACHES FOR RESECTION OF PRIMARY INTRACRANIAL NEOPLASMS: A SYSTEMATIC REVIEW OF THE HISTORY AND CURRENT APPLICATIONS

Abstract Staged surgery for skull base lesions has been utilized to facilitate maximal safe resection and optimize outcomes while minimizing morbidity and complications. Conversely, staged surgery for primary intraparenchymal neoplasms is less commonly performed and has not been reported as extensively within the literature. As such, we performed a systematic review to examine the unique surgical indications for staging, timing between stages, specific surgical approaches utilized, and postoperative complications of staged surgery for primary intra-axial neoplasms. METHODS: A literature search was conducted in August 2021 using PubMed, Web of Science, and Cochrane databases using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. Titles and abstracts were evaluated independently by 2 authors, after which articles were selected for final analysis based on application of strict inclusion criteria during full text screen. Each included article was then qualitatively assessed and relevant variables—including operative approaches, timing, and outcomes—were extracted for synthesis. RESULTS: Of 115 results, 7 articles were included for final analysis and consisted of 17 pediatric and 4 adult patients. Staged approaches were more commonly utilized in the pediatric patient population for resection of astrocytoma and glioma. Pediatric patients had a timing of surgeries ranging from 5–10 days between operations, compared with 18 days to 4 months in adult patients. Complications in pediatric patients were most commonly hemiparesis, hydrocephalus, cranial nerve VI and VII palsies, truncal ataxia, and cerebellar mutism, while complications in adult patients included language and abstract thinking deficits, respiratory failure, and motor weakness. CONCLUSION: This study reports the first comprehensive review of staged surgical procedures for primary, intra-axial cranial neoplasms. There exists a large degree of heterogeneity in complications resulting from staged surgeries for intra-axial neoplasms, which are similar to complications associated with single-stage surgery for intraparenchymal lesions as well as multi-stage surgeries for skull base lesions.

CTNI-40. A MULTICENTER, RETROSPECTIVE ANALYSIS OF PROGNOSTIC FACTORS IN INTRACRANIAL H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA IN ADULTS

Abstract H3 K27M-mutant glioma were first described as a new grade IV entity in the 2016 WHO classification. Current studies have focused on its common pediatric appearance, increasing the need to better understand this entity in adults. Here we report a multicentric, retrospective analysis of 70 diffuse midline glioma in adults. We included molecularly confirmed H3K27M-mutant glioma in patients >18 years of age between 2015-2022. Clinical-, radiological- and surgical features were analyzed. Univariate and multivariate analyses were then performed to identify prognostic factors. The study was approved by the ethics committee (PV4904). Overall, 70 patients were identified, with a mean age of 36.13 years at the initial diagnosis. Median overall survival was 13.62 + 14 months. H3K27M-mutated glioma showed a midline involvement in 61.4%. Clinically, obstructive hydrocephalus was observed in almost half of the patients (46.3%). Gross total resection (GTR) was achieved in 14.5% of all patients. 30.4% had a subtotal resection (STR), and 55.1% received a biopsy. Intraoperative cryo-section resulted in low-grade glioma in 25%, high-grade glioma in 63.9% and no tumor in 11.1%. Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location site in the mesencephalon/metencephalon showed a significantly longer survival (8.3 vs. 16.2 months, p = 0.009). Preoperative Karnofsky Performance Score (KPS) below 80 showed a reduced OS (6 vs. 11.24 months, p = 0.03). Patients, who received resection (GTR/STR) showed no significant survival benefit compared with biopsied patients (9.6 vs. 8 months, p = 0.4817). The present study describes surgical features of DMG with H3K27M mutation in one of the most extensive multicentric studies to date in adult patients. Our data show that location and preoperative KPS impact OS significantly in DMG. Furthermore, in our dataset resection of K27M-mutated glioma provided no significant survival benefit compared with biopsy.

INNV-24. MACHINE LEARNING-BASED SPECTROSCOPIC TISSUE DIFFERENTIATION IN FLUORESCENCE-GUIDED NEUROSURGERY

Abstract Maximal resection of malignant gliomas is hindered by difficulty in distinguishing tumor margins. Fluorescence-guided resection with 5-ALA assists in reaching this goal. Previously, we characterized five fluorophore emissions that accurately represent any spectrum measured from human brain tumor biopsies with a wide-field hyperspectral device. In this study, the effectiveness of these five spectra was explored for different tumor classification tasks in 891 hyperspectral widefield measurements of 184 patients harboring low- (n=30) and high-grade gliomas (n=115), non-glial primary brain tumors (n=19), radiation necrosis (n=2), miscellaneous (n=10) and metastases (n=8), which corresponds to up to 15000 spectra for a given test. The statistical differences in fluorophore abundances between classes were determined and visualized using dimensionality reduction techniques, including principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE). Three machine-learning models were trained to classify tumor type (12 classes), grade (3 classes), and glioma margins (3 classes). Five algorithms were tested with varying hyperparameters for each classification task. We explored whether PCA projection onto five different axes than fluorophore abundances can provide more information for visualization and classification. The abundances of the five a priori fluorophore spectra matched or outperformed the five optimal PCA components for all classification tasks. These five axes capture 96-99% of the variance in the dataset. Using random forests and multilayer perceptrons, the classifiers achieved average test accuracies of 74-82%, 79%, and 81%, respectively. All five fluorophore abundances varied between tumor margin type as well as between grades (p < 0.01). For tissue type, at least four of five fluorophore abundances were found to be significantly different (p < 0.01) between all classes. These results demonstrate the differing contribution of fluorophores in different tissue classes tissue, as well as the five fluorophores value as potential optical biomarkers, opening new opportunities for intraoperative classification systems in fluorescence-guided neurosurgery.

Unraveling the blue shift in porphyrin fluorescence in glioma: The 620 nm peak and its potential significance in tumor biology.

In glioma surgery, the low-density infiltration zone of tumors is difficult to detect by any means. While, for instance, 5-aminolevulinic acid (5-ALA)-induced fluorescence is a well-established surgical procedure for maximizing resection of malignant gliomas, a cell density in tumor tissue of 20-30% is needed to observe visual fluorescence. Hyperspectral imaging is a powerful technique for the optical characterization of brain tissue, which accommodates the complex spectral properties of gliomas. Thereby, knowledge about the signal source is essential to generate specific separation (unmixing) procedures for the different spectral characteristics of analytes and estimate compound abundances. It was stated that protoporphyrin IX (PpIX) fluorescence consists mainly of emission peaks at 634 nm (PpIX634) and 620 nm (PpIX620). However, other members of the substance group of porphyrins fluoresce similarly to PpIX due to their common tetrapyrrole core structure. While the PpIX634 signal has reliably been assigned to PpIX, it has not yet been analyzed if PpIX620 might result from a different porphyrin rather than being a second photo state of PpIX. We thus reviewed more than 200,000 spectra from various tumors measured in almost 600 biopsies of 130 patients. Insufficient consideration of autofluorescence led to artificial inflation of the PpIX620 peak in the past. Recently, five basis spectra (PpIX634, PpIX620, flavin, lipofuscin, and NADH) were described and incorporated into the analysis algorithm, which allowed more accurate unmixing of spectral abundances. We used the improved algorithm to investigate the PpIX620 signal more precisely and investigated coproporphyrin III (CpIII) fluorescence phantoms for spectral unmixing. Our findings show that the PpIX634 peak was the primary source of the 5-ALA-induced fluorescence. CpIII had a similar spectral characteristic to PpIX620. The supplementation of 5-ALA may trigger the increased production of porphyrins other than PpIX within the heme biosynthesis pathway, including that of CpIII. It is essential to correctly separate autofluorescence from the main PpIX634 peak to analyze the fluorescence signal. This article highlights the need for a comprehensive understanding of the spectral complexity in gliomas and suggests less significance of the 620 nm fluorescence peak for PpIX analysis and visualization.

Role of amide proton transfer imaging in maximizing tumor resection in malignant glioma: a possibility to take the place of 11C-methionine positron emission tomography.

Amide proton transfer (APT) imaging has been proposed as a technique to assess tumor metabolism. However, the relationship between APT imaging and other quantitative modalities including positron emission tomography (PET) has not been investigated in detail. This study aimed to evaluate the clinical usefulness of APT imaging in determining the metabolic status of malignant glioma and to compare findings with those from 11C-methionine (Met)-PET. This research analyzed APT imaging data from 20 consecutive patients with malignant glioma treated between January 2022 and July 2023. Patients underwent tumor resection and correlations between tumor activity and intensity of APT signal were investigated. We also compared 11C-Met-PET and APT imaging for the same regions of the perifocal tumor invasion area. Clear, diagnostic APT images were obtained from all 20 cases. Mean APT intensity (APTmean) was significantly higher in the glioblastoma (GBM), IDH wild type group (27.2 ± 12.8%) than in other gliomas (6.0 ± 4.7%; p < 0.001). The cut-off APTmean to optimally distinguish between GBM and other malignant gliomas was 12.8%, offering 100% sensitivity and 83.3% specificity. These values for APTmean broadly matched the tumor-to-contralateral normal brain tissue ratio from 11C-Met-PET analysis (r = 0.66). The APT signal was also observed in the gadolinium non-contrast region on T1-weighted imaging, appearing to reflect the surrounding tumor-infiltrated area. APT imaging can be used to evaluate the area of tumor invasion, similar to 11C-Met-PET. APT imaging revealed low invasiveness in patients and was useful in preoperative planning for tumor resection, facilitating maximum tumor resection including the tumor invasive area.

5-Aminolevulonic Acid, a New Tumor Contrast Agent: Anesthesia Considerations in Patients Undergoing Craniotomy

5-aminolevulinic acid (ALA) is used during resection of malignant gliomas due to its fluorescence properties and has been shown to render resection more effective than resection without ALA guidance. The aim of this narrative review is to categorize the adverse effects of ALA relevant to anesthesia providers. Intraoperative hypotension, porphyria-related side effects, alterations in blood chemistry and coagulation, photosensitivity, and increased levels of liver enzymes have all been reported. We also sought to examine the impact of dosage and timing of oral administration on efficacy of ALA and on these side effects. Twenty-seven studies met our inclusion criteria of patients undergoing craniotomy for glioma resection using ALA and occurrence of at least one adverse effect. The results of these studies showed that there was heterogeneity in levels of intraoperative hypotension, with some reporting an incidence as high as 32%, and that hypotension was associated with antihypertensive medication use. Clinical symptoms of porphyria, such as gastrointestinal disturbance, were less commonly reported. Photosensitivity of the skin after 5-ALA administration was well documented particularly in patients exposed to light; however, adverse effects on the eye were not adequately studied. Elevation in liver enzymes was a common finding postoperatively but was often clinically insignificant. The timing of oral administration presents practical issues for the preoperative management of patients undergoing resection with ALA. We provide guidance for perioperative management of patients who receive ALA for brain tumor resection. Controlled studies with adequate statistical power are required to further understand and prevent the adverse effects of ALA.

Awake Mapping of Supplementary Motor Area Networks for Maximal Safe Resection of Left Superior Frontal Gyrus Low-Grade Glioma.

Awake Mapping of Supplementary Motor Area Networks for Maximal Safe Resection of Left Superior Frontal Gyrus Low-Grade Glioma.

Factors Related to the Recurrence of Low-grade Gliomas

Abstract Objective To identify the determining factors for reoperation in patients with low-grade gliomas, taking into account the degree of resection, and to analyze the histological aspects, observing possible transformations with signs of malignancy in the tissue samples. Materials and Methods The sample consisted of 40 cases of low-grade glioma that were operated on at Hospital das Clínicas de Botucatu between 2013 and 2019. Results The mean follow-up was of 37 months, and the sample was composed of 28 men and 12 women with a mean age at the first surgery of 43.1 ± 15.6 years. Epileptic seizures were observed in 31 (77.5%) patients. According to the histological classification, half of the patients presented oligodendroglioma (50%), of grade II in most cases (97.5%). Total or subtotal resection was achieved in 22 (55%) patients. Only one patient underwent radiotherapy, and two underwent chemotherapy. Reoperation was performed in 20 (50%) patients. The median interval between the first surgery and the reapproach was of 16 (range: 0–77) months. In the second approach, the histological classification was of astrocytoma in 4 (20%) cases, oligoastrocytoma in another 4 (20%), oligodendroglioma in 7 (35%), and glioblastoma in 5 (25%) cases. The only variable associated with the need for reoperation was the degree of resection after the first surgery (p = 0.013). Conclusions Total resection of low-grade gliomas, when feasible, should be performed to avoid recurrence.

Application of intraoperative ultrasound in the resection of high-grade gliomas

The incidence of gliomas is approximately 3–5/100,000, with high-grade gliomas accounting for approximately 30–40% of these tumors. Surgery is a confirmed positive factor in prolonging the survival of these patients, and a larger resection range means a longer survival time. Therefore, surgery for high-grade glioma patients should aim to maximize the extent of resection while preserving neurological function to achieve a better quality of life. There is consensus regarding the need to lengthen progression-free survival (PFS) and overall survival (OS) times. In glioma surgery, methods such as intraoperative computed tomography (ICT), intraoperative magnetic resonance imaging (IMRI), navigation, 5-aminolevulinic acid (5-ALA), and intraoperative ultrasound (IOUS) are used to achieve an expanded resection during the surgical procedure. IOUS has been increasingly used in the surgery of high-grade gliomas and various tumors due to its convenient intraoperative use, its flexible repeatability, and the relatively low cost of operating room construction. With the continuous upgrading of ultrasound equipment, IOUS has been able to better assist surgeons in achieving an increased extent of resection. This review aims to summarize the application of ultrasound in the surgery of high-grade gliomas in the past decade, its improvement in patient prognosis, and its prospects.

Rapid Passive Gamma Mapping as an Adjunct to Electrical Stimulation Mapping for Functional Localization in Resection of Primary Brain Neoplasms

We examined the utility of passive high gamma mapping (HGM) as an adjunct to conventional awake brain mapping during glioma resection. We compared functional and survival outcomes before and after implementing intraoperative HGM. This was a retrospective cohort study of 75 patients who underwent a first-time, awake craniotomy for glioma resection. Patients were stratified by whether their operation occurred before or after the implementation of a U.S. Food and Drug Administration-approved high-gamma mapping tool in July2017. The preimplementation and postimplementation cohorts included 28 and 47 patients, respectively. Median intraoperative time (261 vs. 261 minutes, P= 0.250) and extent of resection (97.14% vs. 98.19%, P= 0.481) were comparable between cohorts. Median Karnofsky performance status at initial follow-up was similar between cohorts (P= 0.650). Multivariable Cox regression models demonstrated an adjusted hazard ratio for overall survival of 0.10 (95% confidence interval: 0.02-0.43, P= 0.002) for the postimplementation cohort relative to the preimplementation cohort. Progression-free survival adjusted for insular involvement showed an adjusted hazard ratio of 1.00 (95% confidence interval: 0.49-2.06, P= 0.999) following HGM implementation. Falling short of statistical significance, prevalence of intraoperative seizures and/or afterdischarges decreased after HGM implementation as well (12.7% vs. 25%, P=0.150). Our results tentatively indicate that passive HGM is a safe and potentially useful adjunct to electrical stimulation mapping for awake cortical mapping, conferring at least comparable functional and survival outcomes with a nonsignificant lower rate of intraoperative epileptiform events. Considering the limitations of our study design and patient cohort, further investigation is needed to better identify optimal use cases for HGM.

Intraoperative and postoperative complications for repeat high-grade glioma resections with concurrent chemotherapy: patient series.

High-grade gliomas are aggressive primary brain tumors, the most common of which is glioblastoma multiforme. Despite advances in treatment, the prognosis for these patients remains poor. The most common chemotherapeutic agents used in the treatment of this pathology include temozolomide (TMZ), procarbazine, lomustine, and vincristine. It is unclear whether chemotherapy should be held during resection for high-grade gliomas, because the perioperative risk profile is not clearly defined. The authors report a case series of 18 surgeries to investigate the effects of concurrent TMZ and lomustine chemotherapy on surgical complications in patients undergoing repeat resection for recurrent high-grade gliomas. The authors found no postoperative infections, self-limiting postoperative complications, or excessive intraoperative blood loss and found one intraoperative complication. There may not be a need to pause TMZ and lomustine chemotherapy during recurrent resections for high-grade gliomas, and continuing these medications throughout the perioperative period may be appropriate. This case series suggests that patients receiving TMZ and lomustine chemotherapy who need a repeat resection for recurrent high-grade gliomas should consider remaining on their chemotherapy regimen because it has been shown in the literature to improve recurrence-free survival time.

Preconditioning of the motor network with repetitive navigated transcranial magnetic stimulation (rnTMS) to improve oncological and functional outcome in brain tumor surgery: a study protocol for a randomized, sham-controlled, triple-blind clinical trial

BackgroundThe extent of resection of glioma is one of the most important predictors of the survival duration of patients after surgery. The presence of eloquent areas within or near a tumor often limits resection, as resection of these areas would result in functional loss and reduced quality of life. The aim of this randomized, triple-blind, sham-controlled study is to investigate the capability of repetitive navigated transcranial magnetic stimulation (rnTMS) over the primary motor cortex to facilitate the functional reorganization of the motor network.MethodsOne hundred forty-eight patients with tumors in movement-relevant areas will be included in this randomized, sham-controlled, bicentric, triple-blind clinical trial. Patients considered at high risk for postoperative motor deficits according to an initial nTMS assessment will receive inhibitory rnTMS at 1 Hz for 30 min followed by a short motor training of 10 min. Stimulation will be applied to the fiber endings of the corticospinal tract closest to the tumor based on individualized tractography. Stimulation will be performed twice daily for each 30 min for 5–28 days depending on the individually available time between study inclusion and surgery. The intervention is controlled by a sham stimulation group (1:1 randomization), where a plastic adapter will be placed on the coil. We expect a comparable or better motor status 3 months postoperatively as measured by the British Medical Research Council (BMRC) score for the affected upper extremity (non-inferiority) and a higher rate of gross total resections (superiority) in the rnTMS compared to the sham group.DiscussionThe generated reorganization of the brain’s areas for motor function should allow a more extensive and safer removal of the tumor while preserving neurological and motor function. This would improve both survival and quality of life of our patients.Trial registrationDRKS.de DRKS00017232. Registered on 28 January 2020.

Surgical, functional, and oncological considerations regarding awake resection for giant diffuse lower-grade glioma of more than 100 cm3.

Surgery for giant diffuse lower-grade gliomas (LGGs) is challenging, and very few data have been reported on this topic in the literature. In this article, the authors investigated surgical, functional, and oncological aspects in patients who underwent awake resection for large LGGs with a volume > 100 cm3. The authors retrospectively reviewed a consecutive cohort of patients who underwent surgery in an awake condition for an LGG (WHO grade 2 with possible foci of grade 3 transformation) with a volume > 100 cm3. A total of 108 patients were included, with a mean age of 36.1 ± 8.5 years. The mean presurgical LGG volume was 136.7 ± 34.5 cm3. In all but 2 patients a disconnection resective surgery up to functional boundaries was possible thanks to active patient collaboration during the awake period. At 3 months of follow-up, all but 1 patient had a normal neurological examination, with a mean Karnofsky Performance Status (KPS) score of 89.8 ± 10.36. In all patients with preoperative epilepsy, there was postoperative control or significant reduction of seizure events. Moreover, 85.1% of patients returned to work. The mean extent of resection (EOR) was 88.9% ± 7.0%, with a mean residual tumor volume (RTV) of 16.3 ± 12.0 cm3 (median RTV 15 cm3). Pathological examination revealed 73 grade 2 gliomas (67.6%; 26 oligodendrogliomas and 47 astrocytomas) and 35 gliomas with foci of grade 3 (32.4%; 19 oligodendrogliomas and 16 astrocytomas). During the postoperative period, 93.6% of patients underwent adjuvant chemotherapy with a median interval between surgery and first chemotherapy of 14 months (IQR 2-26 months), and 55% of patients had radiotherapy with a median interval of 38.5 months (IQR 18-59.8 months). At the last follow-up, 69.7% of patients were still alive with a median follow-up of 62 months (IQR 36-99 months). Overall survival (OS) rates at 1, 5, and 10 years were 100% (95% CI 0.99-1), 80% (95% CI 0.72-0.9), and 58% (95% CI 0.45-0.73), respectively. The median OS was 138 months. In multivariable Cox regression analysis, RTV was established as the only independent prognostic factor for survival. With the application of rigorous surgical methodology based on functional-guided resection, resection of giant LGGs (volume > 100 cm3) can be reproducibly achieved during surgery with patients under awake mapping with both favorable functional results (< 1% permanent neurological worsening) and favorable long-term oncological outcomes (median OS > 11 years, with a more significant benefit when the RTV is < 15 cm3).

Intraoperative Navigated Three-Dimensional Ultrasound Guidance Improves Resection in Gliomas Compared with Standard Two-Dimensional Ultrasound—Results from a Comparative Cohort Study

Intraoperative ultrasound is a promising tool for intraoperative tumor resection control. Navigated three-dimensional US (n3DUS) has many benefits over standard two-dimensional US (2DUS). Two cohorts (2DUS and n3DUS) of patients with histologically confirmed adult diffuse gliomas undergoing US-guided resection control were compared. The primary outcomes assessed were extent of resection and morbidity. Multivariate analysis was performed to account for tumor characteristics (delineation and eloquence) and surgeon experience, which could confound the results. n3DUS was used more often (n= 252) than 2DUS (n= 86). Tumor delineation was similar in 2DUS and n3DUS cohorts, although the n3DUS cohort included more nonenhancing, histologically lower grade (2-3) gliomas and had more gliomas located in eloquent regions; also, n3DUS was more often used by senior surgeons. Gross total resection (GTR) rates were 47%, and major morbidity was 9.5%. On multivariate analysis, after controlling for all other variables between the 2 groups, patients with well-delineated tumors, patients with prior treatment, and patients who underwent n3DUS were more likely to have GTR (adjusted odds ratios 3.0, 1.8, and 2.2, respectively), whereas patients with tumors in eloquent locations were half as likely (adjusted odds ratio 0.5) to have GTR. Eloquent located tumors were likely to be associated with higher neurological morbidity, although major morbidity was not significantly different. Good delineation, noneloquent location, and use of n3DUS was associated with a higher probability of GTR in glioma surgery. Surgeons' experience did not influence the extent of resection. Morbidity was predominantly associated with eloquent location, independent of all other factors.