Search Results (565)

Background/Objectives: Perirolandic brain metastases are challenging to resect because small deviations from the surgical corridor may cause sensorimotor deficits. This study evaluated the stage-specific value and limitations of general-purpose, non-navigated B-mode intraoperative ultrasonography (iUS) with MRI-based frameless neuronavigation in a consecutive surgical cohort of perirolandic metastases. Methods: In this single-center, single-surgeon retrospective case series, 15 consecutive adults underwent microsurgical resection of perirolandic brain metastases using MRI-based frameless neuronavigation and a general-purpose B-mode ultrasound system, without functional mapping or neurophysiological monitoring. Extent of resection was assessed on contrast-enhanced MRI obtained 24 to 36 h after surgery, and post-resection cavity iUS findings were compared descriptively with early postoperative MRI. Results: Gross-total resection was achieved in 13 patients (86.7%). iUS modified intraoperative targeting in 6 of 15 patients: the entry point was repositioned after findings consistent with intraoperative brain shift in 4, and the lesion was localized in interhemispheric corridors in 2. Post-resection iUS suspected residual tissue in 7 of 14 patients, but only 1 corresponded to residual tumor on MRI; a thin remnant on the motor cortex was not identified as suspicious for residual tumor on iUS. A new or worsened motor deficit occurred in 2 patients (13.3%); at follow-up, this was persistent at 20 months in 1 and partially improved in the other. No patient required reoperation, and there was no 30-day mortality. Conclusions: General-purpose B-mode iUS aided exposure confirmation and trajectory refinement but had limited value for excluding thin residual tumor. When functional mapping or neurophysiological monitoring is unavailable, it may provide accessible real-time anatomical guidance; however, because it lacks functional information, it should not be considered an alternative to these functional adjuncts. Full article

Glioblastoma (GBM) recurs predominantly from infiltrative disease that persists beyond the contrast-enhancing tumor (CET). This structured narrative review aims to define the invasive margin and peritumoral brain zone (PBZ) as a spatially organized molecular ecosystem, summarize the approaches used to interrogate this compartment, and evaluate how malignant-cell plasticity, host niches, and treatment-induced remodeling contribute to minimal residual disease and recurrence. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science identified the clinical, translational, preclinical, and review literature available through July 2026; evidence was synthesized qualitatively, with priority given to human tissue studies and single-cell or spatially resolved analyses. Across studies, the margin differs from both tumor core and normal brain and contains heterogeneous malignant states interacting with neural, vascular, immune, hypoxic, and extracellular-matrix-supported niches. Surgery, radiotherapy, and systemic treatment further reshape these interactions through inflammation, vascular injury, senescence, hypoxia, and fibrosis. The main translational challenge is therefore not simply to control the CET, but to identify biologically high-risk non-enhancing tissue and demonstrate that therapy reaches and modifies it. We propose three priorities: image-registered characterization of residual compartments, regional measurement of drug exposure and target engagement, and integration of local margin control with distributed and niche-directed treatment. Prospective validation is required before spatial PBZ biomarkers can guide routine care. Full article

Background/Objectives: Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults, characterized by highly infiltrative growth and poorly defined margins that hinder complete surgical resection. Fluorescence-guided surgery (FGS) can enhance intraoperative tumor visualization; however, currently available fluorophores often exhibit limited tumor specificity and inconsistent labeling. This study aimed to identify near-infrared (NIR) probes with improved glioblastoma selectivity using a high-throughput discovery approach. Methods: A chemically diverse library of 127 NIR oxazine probes was screened using automated fluorescence imaging across four GBM cell lines and a sarcoma control line. Top-performing probes were further evaluated in an orthotopic U251MG-GFP glioblastoma mouse model to assess blood–brain barrier penetration and tumor localization in vivo. Results: Five candidate probes exhibited strong, selective NIR fluorescence in GBM cells. In vivo imaging revealed that the lead probe, LGW01-44, achieved the highest tumor-to-brain contrast with minimal background signal. Ex vivo analysis of brain sections confirmed preferential accumulation of LGW01-44 within intracranial tumor tissue. Conclusions: These findings establish a scalable high-throughput platform for the discovery of tumor-selective NIR imaging agents and identify the oxazine probe LGW01-44 as a promising candidate for fluorescence-guided glioblastoma surgery. Full article

Brain tumor (BT) patients can experience neurological complications as a result of the disease itself or after exposure to anticancer treatment. It is already known that BT patients have a poor survival and quality of life due to tumor progression, but also to various complications. The neurological complications may represent obstacles in patient management and require multidisciplinary collaboration. Although new methods of surgery, radiation therapy and pharmacotherapy have been designed in the last few years in order to prevent, mitigate, or manage the adverse effects of classical therapies, the overall survival of patients with BTs, especially glioblastoma (GB), remain poor. In this review we provide an overview of the most commo022328n neurological complications of BTs, as well as tumor therapies. We present what is already known on the topic but also the newest clinical data, and the results of clinical trials from the last few years. We also make a summary of the strategies capable of managing or even preventing these adverse effects. Full article

As survival for cancer patients improves, the incidence of brain metastases has risen. This is likely due to improved systemic disease control, increased diligence in surveillance imaging in high-risk pathologies, improved neuro-imaging techniques and increased systemic screening for clinical trial enrollment. While there are well-established treatments for brain metastases, many patients will experience recurrence after definitive treatment. The management of these recurrent lesions is not well established and often varies on a per-patient basis, owing to the clinical complexity and variety of these patients. Patients with recurrent brain metastases have surgical procedural options to achieve local tumor control, including laser interstitial thermal therapy (LITT) repeat open surgical resection with or without placement of intracavity brachytherapy. Repeat resection can offer rapid improvement in neurological symptoms, performance status, and potentially survival. LITT is less invasive than a standard craniotomy but offers a chance at directed local treatment while still obtaining tissue for diagnostic purposes and achieving acceptable survival outcomes. Further study is needed to determine the role of LITT for recurrent brain metastases, but it is a useful tool, particularly for patients with deep-seated lesions who may not tolerate a large surgery. Intracavitary brachytherapy allows for the immediate delivery of highly conformal radiation to the surgical bed with excellent local control and low rates of radiation necrosis, even in previously irradiated patients. The decision regarding which of the above to employ for recurrent brain metastases will vary on a case-by-case basis, and further studies are needed to standardize their use for this growing problem. Full article

Melanoma is an aggressive skin cancer that has the potential to metastasize to the lymph nodes, lungs, liver, and brain. Therefore, the prevention and treatment of this condition are essential for achieving lower incidence rates and improving patient outcomes. Traditional treatment methods like surgery, radiation therapy, and chemotherapy have shown limited efficacy in the treatment of metastatic melanoma, and hence new treatment strategies have been developed. These recently developed treatment options include combining targeted therapies with immunotherapies to reduce drug resistance and improve overall effectiveness in preventing melanoma progression. Moreover, BRAF mutations are found in approximately 40–50% of cutaneous melanomas, and NRAS mutations in 15–25%, making these the two most common oncogenic drivers in the MAPK pathway. While alterations in other genes such as KRAS (~1.7%), HRAS (~1%), and MET (~2–4%) are relatively rare in melanoma, they still remain important to disease biology and are under investigation as potential therapeutic targets. These alterations may contribute to tumor progression, metastasis, and therapeutic resistance, highlighting the importance of continued investigation of targeted strategies in melanoma. This review aims to explore the role of each of these genes in melanoma, discusses their resistance mechanism, and summarizes preclinical and clinical trials involving drug combinations. By integrating current evidence on melanoma-associated genomic alterations with available targeted and immune approaches, this review aims to define molecular and clinical contexts that suggest potential treatment selections for melanoma patients. Full article

Glioblastoma (GBM) is the most common and aggressive primary brain tumor, characterized by poor prognosis and a median survival of 12–18 months despite standard therapies such as surgery, radiation, and temozolomide chemotherapy. Its high cellular heterogeneity, along with complex mechanisms of therapy resistance, presents significant challenges for effective treatment. Conventional systemic chemotherapy is limited by the blood–brain barrier (BBB), systemic toxicity, and insufficient drug penetration into the tumor microenvironment. Emerging therapeutic strategies aim to overcome these barriers through novel chemotherapeutic agents, targeted therapies, immunotherapies, and smart drug delivery systems. Endovascular drug delivery, particularly super-selective intra-arterial cerebral infusion (SSIACI), offers a minimally invasive approach to directly target the tumor vasculature, potentially increasing drug concentration at the tumor site while reducing systemic exposure. Complementary techniques, such as MR-guided focused ultrasound, hyperosmotic disruption, and nanoparticle-based carriers, are being explored to enhance BBB penetration and retention of therapeutics within the tumor. Ongoing clinical trials and translational studies provide insights into optimizing these approaches, with future directions focused on precision medicine, biomarker-driven patient selection, and combination therapies. Integrating endovascular strategies with innovative chemotherapies and immunotherapies may transform GBM management, but further research is required to establish their efficacy and safety in clinical practice. Full article

Background/Objectives: Data on the value of tumor debulking surgery are scarce. We aimed to examine whether tumor debulking surgery followed by non-surgical treatment (cases) improves survival compared to non-surgical treatment alone (controls) in patients with head and neck cancer (HNC). Methods: We performed a systematic review of studies published in the databases PubMed, Scopus and Cochrane Central Register of Controlled Trials up to 10 December 2024. Studies evaluating tumor debulking surgery followed by non-surgical treatment and reporting survival (local recurrence, disease-free survival or overall survival) in subjects with HNC were included; case reports were excluded. We assessed the quality of observational studies with the Newcastle–Ottawa Scale. Results: Among 11 retrospective small studies, three case–control studies (one of high quality, i.e., 7/9, and two of moderate quality, i.e., 6/9 and 5/9) suggested longer survival in 72 cases with predominantly squamous cell carcinoma (SCC) than in 40 controls with predominantly SCC. However, these survival benefits cannot be attributed solely to tumor debulking surgery, as confounding by indication is the most likely explanation. In supraglottic laryngeal SCC, one study reported a local recurrence-free survival rate and overall survival of 80% and 88%, respectively, in 25 cases compared with 86% and 77%, respectively, in 24 controls. In sarcomas, local recurrence-free survival was 25%, 65% and 100% for unknown resection margins, wide local excision and radical excision, respectively. Conclusions: The heterogeneous data indicate the need for higher-quality research. It would be interesting to investigate whether an attempt to surgically debulk paranasal sinus tumors while preserving adjacent vital organs (e.g., the orbit and/or brain) should be incorporated into the treatment strategy for patients with extended paranasal sinus squamous cell carcinoma. Tumor debulking surgery did not improve survival in supraglottic laryngeal SCC or head and neck soft tissue sarcomas. Full article

Objective: Intracranial infection is a severe complication that can occur following neurosurgery, and early diagnosis is crucial for improving patient prognosis. In this study, we aimed to investigate, from an exploratory perspective, whether the immune microenvironment of intraoperative cerebrospinal fluid (CSF) is associated with postoperative intracranial infection (PII) in patients undergoing craniotomy for benign brain tumors. Methods: A total of 134 patients undergoing neurosurgery for benign brain tumors were included and categorized into an infection group (n = 18) and a non-infection group (n = 116). CSF samples were collected aseptically immediately after dural opening during surgery. The concentrations of 16 cytokines, including monocyte chemoattractant protein-1 (MCP-1); macrophage inflammatory protein-1α (MIP-1α) and MIP-1β; interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, and IL-17; interferon (IFN)-α and IFN-γ; tumor necrosis factor-α (TNF-α); and granulocyte colony-stimulating factor (G-CSF), were quantified using Cytometric Bead Array (CBA) technology. An independent samples t-test was used for normally distributed data, while the Mann–Whitney U test was applied for non-normally distributed data. Group comparisons were performed using independent-samples t-tests or Mann–Whitney U tests for continuous variables and χ² tests or Fisher’s exact tests for categorical variables. The Benjamini–Hochberg false discovery rate (FDR) correction was applied to all 16 cytokines to control for multiple testing. Receiver operating characteristic (ROC) curve analysis was performed to assess discriminatory capacity. Statistical significance was defined as p < 0.05. Results: PII developed in 18 of 134 patients (13.4%). Age (47.78 vs. 54.86, p = 0.028) and operative duration (390 vs. 244 min, p = 0.005) showed differences in unadjusted analyses. In the unadjusted comparisons, MCP-1 and IL-4 levels were found to be significantly lower in the infection group (MCP-1: 57.78 vs. 116.03 pg/mL, p = 0.003; IL-4: 24.38 vs. 28.18 pg/mL, p = 0.032). No cytokine remained significant after FDR correction. The ROC analysis showed that age and IL-4 demonstrated mild discriminatory performance, with AUC values of 0.665 (95% CI 0.526–0.803, p = 0.025) and 0.657 (95% CI 0.540–0.774, p = 0.032), while MCP-1 and operative duration demonstrated modest discriminatory performance, with AUC values of 0.716 (95% CI 0.595–0.838, p = 0.003) and 0.708 (95% CI 0.578–0.838, p = 0.002). Conclusions: In this study, single-point intraoperative CSF cytokines were not significantly associated with PII after stringent correction for multiple testing, and did not provide a validated clinical prediction tool. The unadjusted and direction-corrected findings for MCP-1 and IL-4 remain exploratory and require validation. Full article

Background: Glioblastoma (used to be called glioblastoma multiforme—GBM) is the most common and aggressive brain tumor, having the lowest overall survival rate. Initial focal neurological deficits are primarily attributable to surrounding edema; however, as tumor invasion progresses, these deficits become more pronounced and permanent. The standard treatment for newly diagnosed glioblastoma is represented by cytoreductive neurosurgery followed by the Stupp Protocol. Postoperative recovery of the patient with glioblastoma is a long-term process that should include, for overall more acceptable outcomes, neurorehabilitation. This review aims to bring together evidence from neuro-oncology, neurosurgery, and neurorehabilitation in order to better understand the factors associated with recovery, functional status, and quality of life (QoL) after glioblastoma surgery. Our work also aimed to update the related knowledge base and to attempt to optimize the related protocols in patients with operated cerebral glioblastoma. Methods: For these purposes, we conducted a systematic literature review to assess the current state of research referring to the above-mentioned topic. We have used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA—widely recognized internationally) methodology. We used, in this respect, specific keyword combinations/“syntaxes” for searching literature in the domain, in four international databases. Results: Following PRISMA screening, 14 studies met the predefined eligibility criteria. Additional manual reference screening and complementary searches identified further relevant publications, resulting in a total of 22 included articles. Together, the reviewed work addressed a diverse range of topics relevant to postoperative glioblastoma management, including the potential role of multidisciplinary rehabilitation, cognitive interventions, neuromodulation approaches, and functional assessment strategies in improving postoperative outcomes and QoL in glioblastoma patients, while emphasizing that this interdisciplinary domain warrants more extended approaches. Discussion and Conclusions: Despite the relatively limited and largely exploratory available information, neurorehabilitation may contribute to improved functional outcomes and QoL in patients with glioblastoma. Full article

Glioblastoma (GBM) remains the most lethal primary brain tumor in adults, with a median overall survival of approximately 15–20 months despite multimodal treatment including surgery, chemoradiation, and Tumor Treating Fields (TTFields). While the survival benefit of TTFields was established by the EF-14 phase III trial, their biological effects extend well beyond the canonical anti-mitotic mechanism and encompass extensive interactions with the GBM tumor microenvironment (TME). This review provides an integrated mechanistic analysis of TTFields–TME interactions in GBM, with a distinctive focus on their convergence with radiotherapy. We examine how TTFields activate innate immune sensing through cGAS/STING and AIM2 inflammasome pathways, drive immunogenic cell death, reprogram tumor-associated macrophages, and prime adaptive T cell responses. We further address TTFields effects on glioma stem cells, blood–brain barrier permeability, and intracellular signaling governing invasion, angiogenesis, and autophagy. Critically, we develop the mechanistic and clinical case for TTFields-radiotherapy combinations, highlighting convergent mechanisms of DNA repair impairment, mitotic catastrophe, and innate immune activation. Practical considerations for concurrent clinical implementation are discussed alongside a research agenda centered on optimal timing, hypofractionation, and predictive biomarkers. Available evidence—largely preclinical—suggests that TTFields may act as a TME-remodeling platform whose potential is most likely to be realized through mechanistically informed combinations. Full article

Background/Objectives: Strict hemodynamic stability is critical during supratentorial craniotomy. This systematic review and meta-analysis aimed to evaluate the efficacy of magnesium sulfate (MgSO₄) as a multimodal adjuvant on intraoperative hemodynamics, opioid consumption, and biomarker outcomes in this setting. Methods: We systematically searched PubMed, Scopus, EBSCO, and the Cochrane Library for randomized controlled trials (RCTs) comparing perioperative MgSO₄ administration to placebo or standard care in adult patients undergoing elective supratentorial craniotomy. Results: Meta-analysis of nine included RCTs using a random-effects model demonstrated that MgSO₄ significantly reduced intraoperative mean arterial pressure (mean difference [MD]: −4.65 mmHg; 95% confidence interval [CI]: −7.76 to −1.55; p = 0.0033; I² = 73.6%). Furthermore, MgSO₄ administration significantly lowered postoperative serum S100B levels (standardized MD [SMD]: −0.81; 95% CI: −1.24 to −0.38; p = 0.0002, I² = 0.0%), indicating mitigated cellular neural damage, and decreased perioperative fentanyl consumption (standardized MD: −1.01; 95% CI: −1.45 to −0.57; p < 0.0001; I² = 0.0%). Intraoperative blood loss volume did not differ significantly between groups (MD: −85.03 mL; 95% CI: −331.42 to 161.37; p = 0.4952; I² = 92.5%). Conclusions: MgSO₄ is a safe and effective multimodal adjuvant for supratentorial craniotomy, providing significant hemodynamic stability, opioid-sparing effects, and preliminary biochemical evidence suggestive of neuroprotection without compromising intraoperative hemostasis. Full article

Background and Clinical Significance: Thyroid cancer is increasing, particularly the differentiated type, with decreasing incidence of the anaplastic type. Anaplastic thyroid carcinoma (ATC) is a rare, aggressive, and often lethal form. It frequently presents with metastatic disease, regional and systemic, with common distant metastasis to the lung, bone, brain, and adrenal, and rarely to other places; Case presentation: A 74-year-old Arab male presented with symptomatic anemia and melena and was admitted for investigation of the cause. The patient was found to have a large retrosternal goiter and gastric tumor. CT scan showed a pedunculated, nonobstructive mass, suggestive of a GIST or leiomyoma. The neck mass presented with compressive symptoms. He underwent a combined neck and abdominal surgical resection based on a multidisciplinary team decision, as prior biopsies were not conclusive. The final pathology report identified similar tumors in the two specimens and suggested an anaplastic thyroid carcinoma as the primary tumor with metastasis to the stomach. Furthermore, the workup, including a PET scan 2 weeks post-surgery, revealed widespread metastases in the bone, lung, and liver, and the treatment was palliative. He was followed up in the outpatient clinic for 4 and a half months post-operatively. The patient developed sepsis and cardiopulmonary arrest and died; Conclusions: ATC can metastasize to many places in the body, including the stomach (as shown in our case), which can cause significant upper gastrointestinal bleeding and anemia. Metastatic ATC carries a poor prognosis; thus, physicians need to keep a high index of suspicion in approaching similar cases. A multidisciplinary approach for the management is of utmost importance for appropriate treatment. This disease’s pathology, behavior, and targeted new treatment modalities must be explored further. Full article

Background: Brain metastases are the most common intracranial tumors in adults and are traditionally considered well-demarcated lesions amenable to complete surgical resection. Nonetheless, increasing histopathological evidence demonstrates that metastatic cells may infiltrate beyond the contrast-enhancing margin into surrounding brain parenchyma, challenging the reliability of conventional imaging for defining true tumor boundaries. Confocal laser endomicroscopy (CLE) using Sodium Fluorescein (SF) has emerged as a novel intraoperative imaging modality capable of providing real-time, high-resolution optical biopsies, potentially improving margin assessment during metastasis surgery. Methods: A systematic literature search was performed according to PRISMA guidelines across PubMed, Embase, Scopus, Cochrane Library, and Google Scholar up to 3 March 2026. Studies evaluating intraoperative CLE with SF in adult patients with brain metastases were included. Data regarding study design, patient population, CLE system, imaging characteristics, and diagnostic performance were extracted. Risk of bias was assessed using the QUADAS-2 tool. Results: Ten studies met the inclusion criteria for qualitative synthesis, comprising over 650 patients; however, most studies included heterogeneous intracranial tumor populations, with only a subset specifically involving brain metastases. CLE enabled real-time visualization of tumor microarchitecture and demonstrated high sensitivity for tumor detection, frequently exceeding 90% in prospective studies. Specificity varied across studies, reflecting challenges in distinguishing tumor infiltration from reactive tissue at the tumor–brain interface. The MetInfilt trial highlighted that infiltrative growth patterns are common in brain metastases and can be visualized intraoperatively using CLE. Additional studies demonstrated that fluorescein-based CLE allows differentiation of tumor zones and may facilitate targeted margin assessment; however, evidence demonstrating improvement in clinically meaningful outcomes such as extent of resection, local recurrence, progression-free survival, or overall survival remains limited. Conclusions: Confocal laser endomicroscopy using SF represents a promising intraoperative adjunct for assessing tumor margins in brain metastasis surgery. By enabling real-time microscopic visualization of the metastasis–brain interface, CLE may support a more biologically informed surgical strategy. Full article

Glioblastoma recurrence remains nearly universal despite maximal safe surgical resection and multimodal adjuvant therapy. Beyond tumor debulking, resection induces profound local brain microenvironment alterations, including sterile neuroinflammation, blood–brain barrier disruption, extracellular matrix remodeling, and rapid activation of innate immune pathways. Among resident immune populations, microglia emerge as central regulators of the post-resection microenvironment, influencing inflammatory signaling, tissue repair, and tumor–host interactions. Activated microglia accumulate at the resection margin, where they adopt highly plastic functional states shaped by cytokine gradients, metabolic stress, hypoxia, and tumor-derived mediators. This dynamic activation landscape establishes bidirectional crosstalk with residual glioblastoma cells, promoting invasion, angiogenesis, maintenance of stem-like phenotypes, and suppression of anti-tumor immunity. As a result, microglial responses contribute to a permissive microenvironment that supports therapeutic resistance and tumor regrowth. Importantly, the perioperative period represents a short but important opportunity to modify microglial activity. Targeted therapeutic strategies, including pharmacologic modulation, local drug delivery systems, immunometabolic approaches, and gene- and cell-based therapies, may help alter the tumor microenvironment. This narrative review synthesizes current mechanistic insights into microglial dynamics following glioblastoma resection and evaluates emerging therapeutic strategies targeting microglial function. We further discuss integration with standard-of-care treatments and highlight evolving biomarker platforms for monitoring microglial states. Ultimately, targeting microglial plasticity represents a biologically grounded and clinically actionable strategy to improve outcomes after glioblastoma surgery. Full article