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The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
Cerebral vascular anatomy and physiology
Knowledge of normal cerebral vascular anatomy and physiology is critical for both recognizing and safely managing a range of neurosurgical conditions through either open or endovascular techniques. In this article we summarize the key features of the arterial supply and venous drainage of the brain along with their main clinical significance.
Human ventromedial prefrontal cortex is necessary for prosocial motivation.
Ventromedial prefrontal cortex (vmPFC) is vital for decision-making. Functional neuroimaging links vmPFC to processing rewards and effort, while parallel work suggests vmPFC involvement in prosocial behaviour. However, the necessity of vmPFC for these functions is unknown. Patients with rare focal vmPFC lesions (n = 25), patients with lesions elsewhere (n = 15) and healthy controls (n = 40) chose between rest and exerting effort to earn rewards for themselves or another person. vmPFC damage decreased prosociality across behavioural and computational measures. vmPFC patients earned less, discounted rewards by effort more, and exerted less force when another person benefited, compared to both control groups. Voxel-based lesion mapping revealed dissociations between vmPFC subregions. While medial damage led to antisocial behaviour, lateral damage increased prosocial behaviour relative to patients with damage elsewhere. vmPFC patients also showed reduced effort sensitivity overall, but reward sensitivity was limited to specific subregions. These results reveal multiple causal contributions of vmPFC to prosocial behaviour, effort and reward.
Comparison of intranasal medication delivery devices before and after functional endoscopic sinus surgery using Phacon sinus surgery models
AbstractObjectiveFunctional endoscopic sinus surgery for chronic rhinosinusitis improves sinus drainage and intranasal medication delivery. This study compares medication delivery with commonly used devices in normal and altered anatomy (post functional endoscopic sinus surgery) using sinus surgery models (Phacon).MethodsMedication delivery was simulated via nasal drops, nasal spray and an irrigation device (Neilmed Sinus Rinse). Coverage was then calculated from endoscopic pictures taken at various anatomical sites in the normal nose and post functional endoscopic sinus surgery.ResultsIn the normal nose, nasal spray did not penetrate the sphenoid sinus, and drops bypassed the vestibule anteriorly. Neilmed Sinus Rinse provided superior coverage at the sphenoid site following sphenoidectomy and the frontal site following Draf III. After ethmoidectomy, nasal drops overall provided less coverage than the other methods.ConclusionNeilmed Sinus Rinse generally provided the best distribution, followed by the nasal spray and then nasal drops. The type and extent of surgery also affects medication delivery.
Metastatic meningioma: a case series and systematic review.
BACKGROUND: Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for a more comprehensive review of these patients to improve our understanding of this rare phenomenon and its prevalence globally. Here we describe our institution's experience of patients presenting with metastatic meningiomas. We further perform a systematic review of the existing literature to explore common features of this rare manifestation of meningioma and review the efficacy of current treatments. METHODS: We performed a retrospective clinical review of all adult patients with metastatic meningioma managed at our institution over the past 20 years, identifying 6 patients. We then performed a systematic review of cases of metastatic meningioma in the literature ranging from the years 1886 to 2022. A descriptive analysis was then conducted on the available data from 1979 onward, focusing on the grade and location of the primary tumor as well as the latency period to, and location of, the metastasis. RESULTS: In total, we analyzed 155 cases. Fifty-four percent of patients initially presented with a primary meningioma located in the convexity. The most common site of metastasis was the lung. Risk factors associated with a shorter time to metastasis were male sex and a high initial grade of the tumor. Regarding treatment, the addition of chemotherapy was the most common adjunct to the standard management of surgery and radiotherapy. Despite an exhaustive review we were unable to identify effective treatments. The majority of published cases came from centers situated in high-income countries (84%) while only 16% came from lower- and middle-income countries. CONCLUSIONS: Metastatic meningiomas pose a pertinent, and likely underestimated, clinical challenge within modern neurosurgery. To optimize management, timely identification of these patients is important. More research is needed to explore the mechanisms underlying these tumors to better guide the development of effective screening and management protocols. However, screening of each meningioma patient is not feasible, and at the heart of this challenge is the inability to control the primary disease. Ultimately, a consensus is needed as to how to correctly screen for and manage these patients; genomic and epigenomic approaches could hold the answer to finding druggable targets.
Supplementary Figure 1 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 1 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 2 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 2 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 1 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 1 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 2 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 2 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Table 1 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Table 1 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 4 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 4 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Data from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
<div>Abstract<p>Glioblastoma, the most malignant type of primary brain tumor, is one of the solid cancers where cancer stem cells have been isolated, and studies have suggested resistance of those cells to chemotherapy and radiotherapy. Here, we report the establishment of CSC-enriched cultures derived from human glioblastoma specimens. They grew as neurospheres in serum-free medium with epidermal growth factor and fibroblast growth factor 2, varied in the level of CD133 expression and very efficiently formed highly invasive and/or vascular tumors upon intracerebral implantation into immunodeficient mice. As a novel therapeutic strategy for glioblastoma-derived cancer stem–like cells (GBM-SC), we have tested oncolytic herpes simplex virus (oHSV) vectors. We show that although <i>ICP6</i> (<i>UL39</i>)–deleted mutants kill GBM-SCs as efficiently as wild-type HSV, the deletion of <i>γ34.5</i> significantly attenuated the vectors due to poor replication. However, this was significantly reversed by the additional deletion of <i>α47</i>. Infection with oHSV G47Δ (<i>ICP6<sup>−</sup>, γ34.5<sup>−</sup>, α47<sup>−</sup></i>) not only killed GBM-SCs but also inhibited their self-renewal as evidenced by the inability of viable cells to form secondary tumor spheres. Importantly, despite the highly invasive nature of the intracerebral tumors generated by GBM-SCs, intratumoral injection of G47Δ significantly prolonged survival. These results for the first time show the efficacy of oHSV against human GBM-SCs, and correlate this cytotoxic property with specific oHSV mutations. This is important for designing new oHSV vectors and clinical trials. Moreover, the new glioma models described in this study provide powerful tools for testing experimental therapeutics and studying invasion and angiogenesis. [Cancer Res 2009;69(8):3472–81]</p></div>
Supplementary Figure 3 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 3 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 4 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Supplementary Figure 4 from Human Glioblastoma–Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
Cancer vaccine trial evaluations: immunobridging and potential immunological endpoints.
Therapeutic cancer vaccines are an emerging class of immunotherapy, but challenges remain in effectively adapting approved vaccines to a growing number of adjuvants, combination therapies, and antigen-selection methods. Phase III clinical trials remain the gold standard in determining clinical benefit, but are slow and resource intensive, whilst radiological surrogates often fail to reliably predict clinical benefit. Using immunological surrogates of efficacy, deployed in 'immunobridging trials', could present a viable alternative, safely speeding up cancer vaccine development in a cost-effective manner. Whilst this approach has proven successful in infectious disease vaccines, identifying reliable immunological correlates of protection has proven difficult for cancer vaccines. Most clinical trials, which present the richest source of data to establish a correlate, rely on peripheral blood samples and standard immunoassays that are ill-equipped to capture the complexity of the vaccine-induced anti-tumour response. This review is the first to outline the importance and challenges of establishing immunological surrogates for cancer vaccines in the context of immunobridging trials, evaluating current immunoassay methods, and highlighting the need for techniques that can characterize tumour-infiltrating lymphocytes and the suppressive tumour microenvironment across a range of patients. The authors propose adapting trial designs for surrogate discovery, including combining phase I/II trials and the use of multi-omics approaches. Successful immunological surrogate development could enable future immunobridging trials to accelerate the optimization of approved cancer vaccines without requiring new phase III trials, promoting faster clinical implementation of scientific advances and patient benefits.