Response to tigilanol tiglate in dogs with mast cell tumors.

Background: Information regarding response rate to tigilanol tiglate for mast cell tumors in dogs is limited.

Objectives: Report the response rate and durability of tigilanol tiglate intratumoral treatment in dogs with mast cell tumors presented to veterinary oncologists.

Animals: One hundred forty-nine dogs; 151 individual tumors.

Sub-Internship Academy: Implementation and Evaluation of Single-Day Resident-Driven Focused Sub-Internship Preparation Course.

Objective: Strong performance in neurosurgical sub-internships is a vital component of a successful residency application and requires adequate familiarity with clinical knowledge and technical skills that may not be covered in standard medical school curricula. Accordingly, a need exists for immersive and comprehensive sub-internship preparation programs that respect time and resource limitations, are optimized based on longitudinal student feedback, provide opportunities for mentorship, and foster enthusiasm for neurosurgery. Therefore, residents at a single institution designed and implemented a comprehensive curriculum for a 1-day sub-internship academy.

The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma.

Biological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes.

Rapid tumor DNA analysis of cerebrospinal fluid accelerates treatment of central nervous system lymphoma.

Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown cause. Participants underwent genotyping of CSF-derived DNA using a quantitative polymerase chain reaction-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF, and H3F3A genes within 80 minutes of sample acquisition.

Glioblastoma-Infiltrating CD8+ T Cells Are Predominantly a Clonally Expanded GZMK+ Effector Population.

Unlabelled: Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared with matched blood, which was validated at the protein level.

Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

Background: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described.

Skull Base Tumors.

Objective: This article reviews the presenting features, molecular characteristics, diagnosis, and management of selected skull base tumors, including meningiomas, vestibular schwannomas, pituitary neuroendocrine tumors, craniopharyngiomas, chordomas, ecchordosis physaliphora, chondrosarcomas, esthesioneuroblastomas, and paragangliomas.

Latest Developments: Skull base tumors pose a management challenge given their complex location and, as a result, the tumors and treatment can result in significant morbidity. In most cases, surgery, radiation therapy, or both yield high rates of disease control, but the use of these therapies may be limited by the surgical accessibility of these tumors and their proximity to critical structures.

Neurological Surgery Residency Programs in the United States: A National Cross-Sectional Survey.

Background And Objectives: The Accreditation Council for Graduate Medical Education has approved 117 neurological surgery residency programs which develop and educate neurosurgical trainees. We present the current landscape of neurosurgical training in the United States by examining multiple aspects of neurological surgery residencies in the 2022-2023 academic year and investigate the impact of program structure on resident academic productivity.

Methods: Demographic data were collected from publicly available websites and reports from the National Resident Match Program.

Treatment of IgG4-related disease-associated hypertrophic pachymeningitis with intrathecal rituximab: a case report.

IgG4-related disease-associated hypertrophic pachymeningitis (IgG4RD-HP) is a fibroinflammatory autoimmune disorder in which diagnosis is difficult without biopsy. Guidance on management of disease refractory to glucocorticoids and intravenous rituximab is limited. We present the case of a 68-year-old woman with IgG4RD-HP who developed sensorineural hearing loss with associated bulky basilar pachymeningeal enhancement.

Pro- and anti-tumour activities of CD146/MCAM in breast cancer result from its heterogeneous expression and association with epithelial to mesenchymal transition.

CD146, also known as melanoma cell adhesion molecule (MCAM), is expressed in numerous cancers and has been implicated in the regulation of metastasis. We show that CD146 negatively regulates transendothelial migration (TEM) in breast cancer. This inhibitory activity is reflected by a reduction in MCAM gene expression and increased promoter methylation in tumour tissue compared to normal breast tissue.

Treatment of multiple synchronous canine mast cell tumours using intratumoural tigilanol tiglate.

Mast cell tumours (MCTs) are common canine skin neoplasia. While they generally occur as single tumours, multiple synchronous MCTs (msMCTs) of /non-metastatic origin are reported in a proportion of the patient population. Where there is no evidence of metastasis or lymphatic spread, MCTs are effectively controlled by surgery and other local therapies.

5-ALA fluorescence-guided resection of a recurrent anaplastic pleomorphic xanthoastrocytoma: illustrative case.

Background: 5-aminolevulinic acid (5-ALA)-induced fluorescence of neoplastic tissue is known to occur in a number of high-grade gliomas. This fluorescence helps surgeons maximize safe resection by distinguishing previously indiscernible neoplastic tissue from brain parenchyma. Still, the effectiveness of 5-ALA has not been fully explored for all central nervous system tumors.

Pituitary surgery in Cushing's disease: first line treatment and role of reoperation.

Cushing's disease is the most common cause of endogenous hypercortisolemia, and transsphenoidal surgery remains the first line therapy for removal of the ACTH-secreting adenoma. While post-operative remission rates are high in experienced hands, there remains a 2% risk of recurrence per year. Patients with the highest chance for cure are those with small, non-invasive tumors that are visible on pre-operative MRI and identified during surgery and are performed by high-volume pituitary neurosurgeons.

Sprouting Angiogenesis in Human Pituitary Adenomas.

Introduction: Angiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors.

Materials And Methods: 219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR.

Quality of life after long-term biochemical control of acromegaly.

Purpose: To assess long-term quality of life (QoL) in patients with sustained biochemical control of acromegaly, comparing those receiving vs not receiving pharmacotherapy (primary analysis); to assess change in QoL over time (secondary analysis).

Methods: Cross-sectional study, with a secondary longitudinal component, of 58 patients with biochemically controlled acromegaly. All had participated in studies assessing QoL years previously, after having undergone surgery ± radiotherapy.

The Prolactin per Unit Tumor Volume Ratio Accurately Distinguishes Prolactinomas From Secondary Hyperprolactinemia due to Stalk Effect.

Objective: The prolactin levels alone are insufficient to distinguish between some cases of prolactinomas and stalk effect. We aimed to formally characterize the relationship between serum prolactin and prolactinoma volume, determine a cutoff for prolactin/mm that accurately distinguishes prolactinomas from stalk effect, and validate this cutoff in a cohort selected to include ambiguous prolactin values ranging from 50 to 150 ng/mL.

Methods: We used the Research Patient Data Registry and transsphenoidal surgery database in our institution to retrospectively identify adult patients with clinically nonfunctioning (NF) tumors (primary analysis, n = 279; validation cohort, n = 10) and prolactinomas (primary analysis, n = 94; validation cohort, n = 18).

Tigilanol Tiglate-Mediated Margins: A Comparison With Surgical Margins in Successful Treatment of Canine Mast Cell Tumours.

Tigilanol tiglate (TT) is a novel small molecule registered as a veterinary pharmaceutical for intratumoural treatment of canine mast cell tumours (MCTs). The drug has a multifactorial mode of action resulting in rapid destruction of the treated tumour by haemorrhagic necrosis and subsequent slough of the necrotic tumour to reveal a tissue deficit that is left to heal by second intention with minimal to no veterinary intervention. Here we introduce the concept of TT-mediated margins, the calculated margin of tissue loss analogous to surgically applied margins to help clinicians conceptualise tissue deficits formed following tumour destruction by TT relative to surgical excision.

The Upregulation of Molecules Related to Tumor Immune Escape in Human Pituitary Adenomas.

Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas.

Intratumoural Treatment of 18 Cytologically Diagnosed Canine High-Grade Mast Cell Tumours With Tigilanol Tiglate.

Canine high-grade mast cell tumours (HGMCT) are associated with a poor prognosis, are inherently more invasive, and have higher rates of local recurrence. The primary aim of this retrospective study was to assess the efficacy of intratumoural tigilanol tiglate (TT) as a local treatment option. Eighteen dogs with mast cell tumours (MCT) cytologically diagnosed by veterinary pathologists as either high-grade or suspected high-grade MCT were treated with TT.

Microscale dynamics of electrophysiological markers of epilepsy.

Objective: Interictal discharges (IIDs) and high frequency oscillations (HFOs) are established neurophysiologic biomarkers of epilepsy, while microseizures are less well studied. We used custom poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) microelectrodes to better understand these markers' microscale spatial dynamics.

Methods: Electrodes with spatial resolution down to 50 µm were used to record intraoperatively in 30 subjects.

Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling.

Metastasis requires tumour cells to cross endothelial cell (EC) barriers using pathways similar to those used by leucocytes during inflammation. Cell surface CD99 is expressed by healthy leucocytes and ECs, and participates in inflammatory transendothelial migration (TEM). Tumour cells also express CD99, and we have analysed its role in tumour progression and cancer cell TEM.