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Introduction: The treatment of spinal chordomas presents a significant challenge due to their resistance to both radiotherapy and chemotherapy as well as the complexity of the surgical procedures required. This study presents a series of cases of primary spinal chordomas, focusing on the development of a personalized therapeutic strategy that is tailored to each patient's unique clinical status. This approach aims to ensure that treatments are optimally aligned with the patient's overall prognosis and surgical eligibility. Methods: This retrospective study analyzed 14 patients with primary spinal chordomas treated at our institution. We evaluated surgical strategies, clinical outcomes, and survival rates, The therapeutic strategy was formulated after interdisciplinary conferences with sarcoma management specialists. Data were collected on patient demographics, surgical details, postoperative outcomes, and follow-up status. Results: All patients presented with neurological deficits preoperatively, which generally improved post-surgery. The study included a detailed analysis of two distinct surgical approaches: five patients underwent en bloc resection with dorsal stabilization and nine received decompression only. Patients undergoing en bloc resection showed a reduced need for additional surgery due to the comprehensive removal of the tumor. As anticipated, 40% of the patients who underwent decompression experienced tumor progression within the first three months. However, given the poor overall prognosis, the objective of maintaining neurological function was achieved. Conclusions: Surgical en bloc resection offers a viable and effective intervention for spinal chordomas, enhancing neurological function. It is imperative to tailor treatment strategies to individual prognoses, integrating insights from multidisciplinary discussions that meticulously evaluate surgical risks. This collaborative approach aids in selecting the most appropriate surgical technique tailored to each patient's specific condition. [ABSTRACT FROM AUTHOR]

Introduction: The management of spinal sarcomas is complex, given their widespread involvement and high recurrence rates. Despite consensus on the need for a multidisciplinary approach with surgery at its core, there is a lack of definitive guidelines for clinical decision-making. This study examines a case series of primary spinal sarcomas, focusing on the surgical strategies, clinical results, and survival data to inform and guide therapeutic practices. Methods: We conducted a retrospective analysis of patients who underwent surgical resection for primary spinal sarcomas between 2005 and 2022. The study focused on gathering data on patient demographics, surgical details, postoperative complications, overall hospital stay, and mortality within 90 days post-surgery. Results: The study included 14 patients with a primary diagnosis of spinal sarcoma, with an average age of 48.6 ± 12.6 years. Chondrosarcoma emerged as the most common tumor type, representing 57.1% of cases, followed by Ewing sarcoma at 35.7%, and synovial sarcoma at 7.1%. Patients with chondrosarcoma were treated with en-bloc resection, while the patient with synovial sarcoma underwent intra-lesional excision and those with Ewing sarcoma received decompression and tumor debulking. Postoperative assessments revealed significant improvements in neurological conditions. Notably, functional status as measured by the Karnofski Performance Index (KPI), improved substantially post-surgery (from 61.4 to 80.0%) The mean follow-up was 34.9 ± 9.2 months. During this time period one patient experienced fatal bleeding after en-bloc resection complications involving the vena cava. None of the patient needed further surgery. Conclusions: Our 16-year study offers vital insights into managing primary spinal sarcomas, showcasing the effectiveness of surgical intervention, particularly en-bloc resection. Despite their rarity and complexity, our multidisciplinary treatment approach yields improved outcomes and highlights the potential for refined surgical strategies to become standardized care in this challenging domain. [ABSTRACT FROM AUTHOR]

Purpose: Surgery for recurrent glioma provides cytoreduction and tissue for molecularly informed treatment. With mostly heavily pretreated patients involved, it is unclear whether the benefits of repeat surgery outweigh its potential risks. Methods: Patients receiving surgery for recurrent glioma WHO grade 2–4 with the goal of tissue sampling for targeted therapies were analyzed retrospectively. Complication rates (surgical, neurological) were compared to our institutional glioma surgery cohort. Tissue molecular diagnostic yield, targeted therapies and post-surgical survival rates were analyzed. Results: Between 2017 and 2022, tumor board recommendation for targeted therapy through molecular diagnostics was made for 180 patients. Of these, 70 patients (38%) underwent repeat surgery. IDH-wildtype glioblastoma was diagnosed in 48 patients (69%), followed by IDH-mutant astrocytoma (n = 13; 19%) and oligodendroglioma (n = 9; 13%). Gross total resection (GTR) was achieved in 50 patients (71%). Tissue was processed for next-generation sequencing in 64 cases (91%), and for DNA methylation analysis in 58 cases (83%), while immunohistochemistry for mTOR phosphorylation was performed in 24 cases (34%). Targeted therapy was recommended in 35 (50%) and commenced in 21 (30%) cases. Postoperatively, 7 patients (11%) required revision surgery, compared to 7% (p = 0.519) and 6% (p = 0.359) of our reference cohorts of patients undergoing first and second craniotomy, respectively. Non-resolving neurological deterioration was documented in 6 cases (10% vs. 8%, p = 0.612, after first and 4%, p = 0.519, after second craniotomy). Median survival after repeat surgery was 399 days in all patients and 348 days in GBM patients after repeat GTR. Conclusion: Surgery for recurrent glioma provides relevant molecular diagnostic information with a direct consequence for targeted therapy under a reasonable risk of postoperative complications. With satisfactory postoperative survival it can therefore complement a multi-modal glioma therapy approach. [ABSTRACT FROM AUTHOR]

Introduction: Brain tumor surgery represents a critical and high-risk area within the field of neurosurgery. Our study aims to offer a comprehensive analysis of adverse events (AEs) from a prospectively maintained database at a leading neurosurgical tertiary center, with a specific focus on different types of tumor entities. Methods: From January 2022 to September 2023, our study focused on adult patients, who underwent surgery for intracranial tumors. Each patient in this demographic was thoroughly assessed for adverse events (AEs) by their attending physicians at discharge. An AE was defined as any event occurring within the first 30 days post-surgery. Results: A total of 1173 patients with an average age of 57.4 ± 15.3 years underwent surgical procedures. The majority of these surgeries were elective, accounting for 93.4% (1095 out of 1173), while emergency surgeries constituted 13.9% (163 out of 1173). The incidence of surgery-related AEs was relatively low at 12.7%. The most common surgical indications were meningioma and glioma pathologies, representing 31.1% and 28.2% of cases, respectively. Dural leaks occurred in 1.5% of the cases. Postoperative hemorrhage was a significant complication, especially among glioma patients, with ten experiencing postoperative hemorrhage and eight requiring revision surgery. The overall mortality rate stood at 0.8%, corresponding to five patient deaths. Causes of death included massive postoperative bleeding in one patient, pulmonary embolism in two patients, and tumor progression in two others. Conclusions: Surgical interventions for intracranial neoplasms are inherently associated with a significant risk of adverse events. However, our study's findings reveal a notably low mortality rate within our patient cohort. This suggests that thorough documentation of AEs, coupled with proactive intervention strategies in neurosurgical practices, can substantially enhance patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Brain tumor surgery represents a critical and high-risk area within the field of neurosurgery. Our study aims to offer a comprehensive analysis of adverse events (AEs) from a prospectively maintained database at a leading neurosurgical tertiary center, with a specific focus on different types of tumor entities. Methods: From January 2022 to September 2023, our study focused on adult patients, who underwent surgery for intracranial tumors. Each patient in this demographic was thoroughly assessed for adverse events (AEs) by their attending physicians at discharge. An AE was defined as any event occurring within the first 30 days post-surgery. Results: A total of 1173 patients with an average age of 57.4 ± 15.3 years underwent surgical procedures. The majority of these surgeries were elective, accounting for 93.4% (1095 out of 1173), while emergency surgeries constituted 13.9% (163 out of 1173). The incidence of surgery-related AEs was relatively low at 12.7%. The most common surgical indications were meningioma and glioma pathologies, representing 31.1% and 28.2% of cases, respectively. Dural leaks occurred in 1.5% of the cases. Postoperative hemorrhage was a significant complication, especially among glioma patients, with ten experiencing postoperative hemorrhage and eight requiring revision surgery. The overall mortality rate stood at 0.8%, corresponding to five patient deaths. Causes of death included massive postoperative bleeding in one patient, pulmonary embolism in two patients, and tumor progression in two others. Conclusions: Surgical interventions for intracranial neoplasms are inherently associated with a significant risk of adverse events. However, our study’s findings reveal a notably low mortality rate within our patient cohort. This suggests that thorough documentation of AEs, coupled with proactive intervention strategies in neurosurgical practices, can substantially enhance patient outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to compare and assess clinical outcomes of spinal metastasis with epidural spinal cord compression (MESCC) in patients aged 65–79 years and ≥ 80 years with an acute onset of neurological illness who underwent laminectomy. A second goal was to determine morbidity rates and potential risk factors for mortality. This retrospective review of electronic medical records at a single institution was conducted between September 2005 and December 2020. Data on patient demographics, surgical characteristics, complications, hospital clinical course, and 90-day mortality were also collected. Comorbidities were assessed using the age-adjusted Charlson comorbidity index (CCI). A total of 99 patients with an overall mean age of 76.2 ± 3.4 years diagnosed with MESCC within a 16-year period, of which 65 patients aged 65–79 years and 34 patients aged 80 years and older were enrolled in the study. Patients aged 80 and over had higher age-adjusted CCI (9.2 ± 2.1) compared to those aged 65–79 (5.1 ± 1.6; p < 0.001). Prostate cancer was the primary cause of spinal metastasis. Significant neurological and functional decline was more pronounced in the older group, evidenced by Karnofsky Performance Index (KPI) scores (80+ years: 47.8% ± 19.5; 65–79 years: 69.0% ± 23.9; p < 0.001). Despite requiring shorter decompression duration (148.8 ± 62.5 min vs. 199.4 ± 78.9 min; p = 0.004), the older group had more spinal levels needing decompression. Median survival time was 14.1 ± 4.3 months. Mortality risk factors included deteriorating functional status and comorbidities, but not motor weakness, surgical duration, extension of surgery, hospital or ICU stay, or complications. Overcoming age barriers in elderly surgical treatment in MSCC patients can reduce procedural delays and has the potential to significantly improve patient functionality. It emphasizes that age should not be a deterrent for spine surgery when medically necessary, although older MESCC patients may have reduced survival. [ABSTRACT FROM AUTHOR]

Free flap reconstruction is the standard of care for extensive defects of the head and neck area. In this study, two types of free flaps, the antero-lateral thigh flap (ALT) and the vastus lateralis muscle flap, were compared. The primary endpoint was flap success, secondary endpoints were complication rates, hospitalization and surgery time. Cases with defect situations of the scalp and consecutive microvascular free flap reconstructions using either ALT flaps or vastus lateralis muscle flaps between 2014 and 2022 were retrospectively analyzed. Indications, perioperative handling and outcomes were compared. Twenty patients were included in the analysis. Ten patients (50%) received a free flap reconstruction using an ALT flap and ten patients (50%) received a vastus lateralis flap. A simultaneous two-team approach was possible in each case and the flap success rate was 100% with the need for one successful anastomosis revision. The mean defect size in our cohort was 147 ± 46 cm2. There were no significant differences in surgery time, duration of hospitalization or complication rate between both cohorts. Both free flaps, the ALT and the vastus lateralis flap, are suitable for the closure of large scalp defects. They provide high success rates, short surgery times without the need for patient repositioning and low donor-site morbidity. The vastus lateralis muscle flap bares the advantage of being perforator-independent and allows for the preparation of long vessels for anastomosis if needed while baring the disadvantage of a prolonged period of healing via granulation or the need for secondary surgery in terms of covering by split-thickness skin grafts which may interfere with necessary adjuvant treatment in oncological patients. [ABSTRACT FROM AUTHOR]

Injury to vascular structures such as the internal carotid artery (ICA) is a rare but catastrophic complication of minimally invasive transsphenoidal surgery. Thorough preoperative planning, and knowledge of anatomical landmarks, such as the intercarotid distance (ICD) reduce this risk. Numerous anatomical studies have been conducted regarding the transsphenoidal approach, but none have taken racial disparities into account. Since differences of the cranium, especially of the skull base exist, we sought to analyze anatomical differences of the sellar region in thin sliced T2-weighted MRI scans of 187 (87 male and 100 female) Asian, African American and Caucasian patients provided by the 'Human Connectome Project' (HCP). We found significant differences in the ICD between males and females across all races. Furthermore, we found that the ICD was up to 2.4 mm smaller in the Caucasian cohort compared to the African American/Asian cohort. These findings indicate that racial disparities regarding the sellar anatomy should be considered in patients undergoing pituitary surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: The preoperative risk estimation of non-enhancing suspected "low-grade" glioma (NEG) is key in determining the optimal timing of diagnosis and treatment to delay malignant progression and avoid undertreatment. The updated 2021 WHO classification brought new facets to glioma grading. Therefore, we sought to identify preoperative risk factors of malignancy in NEG by considering molecular criteria, including IDH mutation and CDKN2A/B deletion status. A total of 72 NEG patients were analyzed, and a high prevalence of malignant gliomas was detected considering both the traditional WHO grading (WHO grade 3 + 4) and the integrated molecular classification (IDHwt glioblastoma WHO grade 4 and IDHmut astrocytoma WHO grade 4). Easily determinable preoperative factors (age, T2/FLAIR mismatch sign, and SVZ involvement) were identified by uni- and multivariate analyses and incorporated into a score. The score estimates the probability of an NEG harboring a malignant glioma. Finally, the score was validated in a cohort of 40 NEG patients and proved to be a better prediction model than the Pignatti score or the T2/FLAIR mismatch sign. The preoperative grading of non-enhancing glioma (NEG) remains challenging. Herein, we analyzed clinical and magnetic resonance imaging (MRI) features to predict malignancy in NEG according to the 2021 WHO classification and developed a clinical score, facilitating risk estimation. A discovery cohort (2012–2017, n = 72) was analyzed for MRI and clinical features (T2/FLAIR mismatch sign, subventricular zone (SVZ) involvement, tumor volume, growth rate, age, Pignatti score, and symptoms). Despite a "low-grade" appearance on MRI, 81% of patients were classified as WHO grade 3 or 4. Malignancy was then stratified by: (1) WHO grade (WHO grade 2 vs. WHO grade 3 + 4) and (2) molecular criteria (IDHmut WHO grade 2 + 3 vs. IDHwt glioblastoma + IDHmut astrocytoma WHO grade 4). Age, Pignatti score, SVZ involvement, and T2/FLAIR mismatch sign predicted malignancy only when considering molecular criteria, including IDH mutation and CDKN2A/B deletion status. A multivariate regression confirmed age and T2/FLAIR mismatch sign as independent predictors (p = 0.0009; p = 0.011). A "risk estimation in non-enhancing glioma" (RENEG) score was derived and tested in a validation cohort (2018–2019, n = 40), yielding a higher predictive value than the Pignatti score or the T2/FLAIR mismatch sign (AUC of receiver operating characteristics = 0.89). The prevalence of malignant glioma was high in this series of NEGs, supporting an upfront diagnosis and treatment approach. A clinical score with robust test performance was developed that identifies patients at risk for malignancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients diagnosed with isocitrate dehydrogenase (IDH)-mutated brain tumors frequently suffer from seizures, and the seizures were shown to promote tumor growth. Anti-seizure medications (antiepileptic drugs) might be able to break this vicious circle. However, it is not yet known which antiepileptic drugs might have additional anti-tumor effects. In this study, 20 commonly used antiepileptic drugs were tested on patient-derived tumor models. Only oxcarbazepine promoted additional tumor cell killing, making it an interesting drug to use in this special population of brain tumor patients. Patients diagnosed with isocitrate dehydrogenase mutant (IDHmut) gliomas suffer frequently from seizures. Although the clinical course is less aggressive than that of its IDH wildtype counterpart, recent discoveries have shown that epileptic activity can promote tumor proliferation. However, it is not known if antiepileptic drugs confer additional value by inhibiting tumor growth. In this study, the antineoplastic properties of 20 FDA-approved antiepileptic drugs (AEDs) were tested in six patient-derived IDHmut glioma stem-like cells (GSCs). Cell proliferation was assessed using the CellTiterGlo-3D assay. Two of the screened drugs (oxcarbazepine and perampanel) demonstrated an antiproliferative effect. A subsequent eight-point dose–response curve proved the dose-dependent growth inhibition for both drugs, but only oxcarbazepine reached an IC50 value below 100 µM in 5/6 GSCs (mean 44.7 µM; range 17.4–98.0 µM), approximating the possible cmax for oxcarbazepine in patient serums. Furthermore, the treated GSC spheroids were 82% smaller (mean volume 1.6 nL vs. 8.7 nL; p = 0.01 (live/deadTM fluorescence staining)), and the apoptotic events increased by more than 50% (caspase-3/7 activity; p = 0.006). Taken together, this drug screen of a large series of antiepileptic drugs identified oxcarbazepine as a potent proapoptotic drug in IDHmut GSCs, which combines antiepileptic and antineoplastic properties to treat this seizure-prone patient population. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively identify and quantify neurosurgical adverse events (AEs) in a tertiary care hospital. Methods: From January 2021 to December 2021, all patients treated in our department received a peer-reviewed AE-evaluation form at discharge. An AE was defined as any event after surgery that resulted in an undesirable clinical outcome, which is not caused by the underlying disease, that prolonged patient stay, resulted in readmission, caused a new neurological deficit, required revision surgery or life-saving intervention, or contributed to death. We considered AEs occurring within 30 days after discharge. AEs were categorized in wound event, cerebrospinal fluid (CSF) event, CSF shunt malfunction, post-operative infection, malpositioning of implanted material, new neurological deficit, rebleeding, and surgical goal not achieved and non-neurosurgical AEs. Results: 2874 patients were included. Most procedures were cranial (45.1%), followed by spinal (33.9%), subdural (7.7%), CSF (7.0%), neuromodulation (4.0%), and other (2.3%). In total, there were 621 AEs shared by 532 patients (18.5%). 80 (2.8%) patients had multiple AEs. Most AEs were non-neurosurgical (222; 8.1%). There were 172 (6%) revision surgeries. Patients receiving cranial interventions had the most AEs (19.1%) although revision surgery was only necessary in 3.1% of patients. Subdural interventions had the highest revision rate (12.6%). The majority of fatalities was admitted as an emergency (81/91 patients, 89%). Ten elective patients had lethal complications, six of them related to surgery (0.2%). Conclusion: This study presents the one-year results of a prospectively compiled AE database. Neurosurgical AEs arose in one in five patients. Although the need for revision surgery was low, the rate of AEs highlights the importance of a systematic AE database to deliver continued high-quality in a high-volume center. [ABSTRACT FROM AUTHOR]

The discovery of the isocitrate dehydrogenase (IDH) mutation in glioma led to a paradigm shift on how we see glioma biology. Difficulties in cultivating IDH mutant glioma stem cells (IDHmut GSCs) resulted in a paucity of preclinical models in IDHmut glioma, limiting the discovery of new effective chemotherapeutic agents. To fill this gap, we used six recently developed patient-derived IDHmut GSC lines and performed a large-scale drug screening with 147 Food and Drug Administration (FDA)-approved anticancer drugs. GSCs were subjected to the test compounds for 72 h in concentrations ranging from 0.0001 to 1 µM. Cell viability was assessed by CellTiterGlo and the induction of apoptosis by flow cytometry with Annexin V/propidium iodide staining. The initial screen was performed with two IDHmut GSC lines and identified seven drugs (bortezomib, carfilzomib, daunorubicin, doxorubicin, epirubicin, omacetaxine, plicamycin) with a substantial antiproliferative activity, as reflected by half maximal inhibitory concentrations (IC50) below 1 µM and maximum inhibitory effects (Emax) below 25%. These findings were validated in an additional four IDHmut GSC lines. The candidate drugs, of which plicamycin and omacetaxine are known to cross the blood brain barrier, were used for subsequent cell death analyses. A significant induction of apoptosis was observed at IC50 values of the respective drugs. In summary, we were able to identify seven FDA-approved drugs that should be further taken into clinical investigations for the treatment of IDHmut gliomas. [ABSTRACT FROM AUTHOR]

Glioma growth is often accompanied by a hypoxic microenvironment favorable for the induction and maintenance of the glioma stem cell (GSC) phenotype. Due to the paucity of cell models of Isocitrate Dehydrogenase 1 mutant (IDH1mut) GSCs, biology under hypoxic conditions has not been sufficiently studied as compared to IDH1 wildtype (IDH1wt) GSCs. We therefore grew well-characterized IDH1mut (n = 4) and IDH1wt (n = 4) GSC lines under normoxic (20%) and hypoxic (1.5%) culture conditions and harvested mRNA after 72 h. Transcriptome analyses were performed and hypoxia regulated genes were further analyzed using the expression and clinical data of the lower grade glioma cohort of The Cancer Genome Atlas (LGG TCGA) in a confirmatory approach and to test for possible survival associations. Results show that global expression changes were more pronounced in IDH1wt than in IDH1mut GSCs. However, when focusing on known hypoxia-regulated gene sets, enrichment analyses showed a comparable regulation in both IDH1mut and IDH1wt GSCs. Of 272 significantly up-regulated genes under hypoxic conditions in IDH1mut GSCs a hypoxia-related survival score (HRS-score) of five genes (LYVE1, FAM162A, WNT6, OTP, PLOD1) was identified by the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm which was able to predict survival independent of age, 1p19q co-deletion status and WHO grade (II vs. III) in the LGG TCGA cohort and in the Rembrandt dataset. Altogether, we were able to identify and validate a novel hypoxia-related survival score in IDH1mut GSCs consisting of five hypoxia-regulated genes which was significantly associated with patient survival independent of known prognostic confounders. [ABSTRACT FROM AUTHOR]