BOLD Coupling between Lesioned and Healthy Brain Is Associated with Glioma Patients’ Recovery

Predicting functional outcomes after surgery and early adjuvant treatment is difficult due to the complex, extended, interlocking brain networks that underpin cognition. The aim of this study was to test glioma functional interactions with the rest of the brain, thereby identifying the risk factors of cognitive recovery or deterioration. Seventeen patients with diffuse non-enhancing glioma (aged 22–56 years) were longitudinally MRI scanned and cognitively assessed before and after surgery and during a 12-month recovery period (55 MRI scans in total after exclusions). We initially found, and then replicated in an independent dataset, that the spatial correlation pattern between regional and global BOLD signals (also known as global signal topography) was associated with tumour occurrence. We then estimated the coupling between the BOLD signal from within the tumour and the signal extracted from different brain tissues. We observed that the normative global signal topography is reorganised in glioma patients during the recovery period. Moreover, we found that the BOLD signal within the tumour and lesioned brain was coupled with the global signal and that this coupling was associated with cognitive recovery. Nevertheless, patients did not show any apparent disruption of functional connectivity within canonical functional networks. Understanding how tumour infiltration and coupling are related to patients’ recovery represents a major step forward in prognostic development.

The white matter is a pro-differentiative niche for glioblastoma

Glioblastomas are hierarchically organised tumours driven by glioma stem cells that retain partial differentiation potential. Glioma stem cells are maintained in specialised microenvironments, but whether, or how, they undergo lineage progression outside of these niches remains unclear. Here we identify the white matter as a differentiative niche for glioblastomas with oligodendrocyte lineage competency. Tumour cells in contact with white matter acquire pre-oligodendrocyte fate, resulting in decreased proliferation and invasion. Differentiation is a response to white matter injury, which is caused by tumour infiltration itself in a tumoursuppressive feedback loop. Mechanistically, tumour cell differentiation is driven by selective white matter upregulation of SOX10, a master regulator of normal oligodendrogenesis. SOX10 overexpression or treatment with myelination-promoting agents that upregulate endogenous SOX10, mimic this response, leading to niche-independent pre-oligodendrocyte differentiation and tumour suppression in vivo. Thus, glioblastoma recapitulates an injury response and exploiting this latent programme may offer treatment opportunities for a subset of patients.

The hormonal suppression as first-line treatment of lingual thyroid: A case report

Ectopic thyroid gland is a rare anomaly in the development of the thyroid gland. It is defined as any thyroid tissue that is not found on its usual topography. We present the case of a 62-year-old patient with difficulty swallowing solid food, occasional sore throat, hoarse voice, and difficulty speaking. The patient was in hypothyroid status. Thyroid scintigraphy and magnetic resonance imaging visualized a nodular mass on the base of the tongue, suprahyoid, and mediosagittal. The pathohistological finding revealed normal thyroid tissue with few colloidal changes, ruled out tumour infiltration and specific inflammatory process. She received hormonal suppression treatment as a first-line treatment. The patient showed significant improvement in symptoms with reduction of the dyspnea and the dysphagia and normalization of thyroid hormone tests.

The white matter is a pro-differentiative microenvironment for glioblastoma

SummaryGlioblastomas are hierarchically organised tumours driven by glioma stem cells that retain partial differentiation potential. Glioma stem cells are maintained in specialised microenvironments, but how they undergo lineage progression outside of these niches remains unclear. Here we identify the white matter as a differentiative niche for glioblastomas with oligodendrocyte lineage competency. Tumour cells in contact with white matter acquire pre-oligodendrocyte-like fate, resulting in decreased proliferation and invasion. Differentiation is a response to white matter injury, which is caused by tumour infiltration itself in a tumoursuppressive feedback loop. Mechanistically, tumour cell differentiation is driven by selective white matter upregulation of SOX10, a master regulator of normal oligodendrogenesis. SOX10 overexpression or treatment with myelination-promoting agents that upregulate endogenous SOX10, mimic this response, leading to white matter-independent pre-oligodendrocyte-like differentiation and tumour suppression in vivo. Thus, glioblastoma recapitulates an injury response and exploiting this latent programme may offer treatment opportunities for a subset of patients.

Quantitative MRI using relaxometry in malignant gliomas detects contrast enhancement in peritumoral oedema

Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R1), transverse relaxation (R2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R1-difference-map. The quantitative R1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.

Kidney as a Target Organ in Cardiac Oncology

The review addresses the problem of kidney lesions in patients with cardiovascular and oncological diseases. In the context of the current spread of cardiovascular and oncological pathologies, a growing number of patients reveal comorbid and/or polymorbid renal dysfunctions. In confluence with cardiovascular disorders, kidney lesions are manifested in various types of the cardiorenal syndrome. In current knowledge, the heart and kidneys are highly interdependent and interact across several interfaces in a complex feedback system. The kidneys can both play a target role and back-influence cardiac functions and pathology. Evidently, the development of acute kidney lesions and / or chronic renal dysfunctions worsens the prognosis of the primary disease and elevates risks of developing acute cardiovascular disorders. Combined cardiovascular and oncological pathologies are nowadays more common. Numerous patients with malignant neoplasms develop renal pathologies due to tumour infiltration or exposure to tumour metabolites, as well as indirectly through the nephrotoxic effect of antitumour chemotherapy and/or radiation therapy. Many studies show that acute kidney lesions and/or chronic renal disorders contribute independently to the severity of cancer and mortality rate. In recent decades, the level of serum creatinine is used as a marker of acute kidney damage, which although harbours inherent weaknesses of being responsive to a spectrum of renal and extra-renal factors and having a delay of 48–72 h of elevation in the blood after exposure to the trigging factor. In this respect, the development of novel kidney-specific lesion biomarkers continues. Among such candidate agents is the kidney injury molecule KIM-1.

BIMG-17. EFFECTS OF THE TUMOUR MICROENVIRONMENT ON PROTOPORPHYRIN IX ACCUMULATION IN GLIOBLASTOMA

Glioblastoma is the most common primary brain tumour and has a poor prognosis. The median survival is less than two years despite clinical intervention that usually involves the resection of the tumour volume, chemotherapy and radiotherapy. Achieving gross-total resection is challenging due to poorly defined boundaries as a result of tumour infiltration. Fluorescence-guided surgery (FGS) utilises an apparently selective accumulation of protoporphyrin IX (PPIX) that occurs in areas of glioblastoma after administration of the metabolite, 5-aminolevulinic acid (5-ALA). 5-ALA and the fluorescent metabolite, PPIX, sit within the endogenous heme biosynthetic pathway, which suggests that FGS is not only an important clinical tool, but also highlights differing metabolic phenotypes naturally present throughout the tumour. Genetic and mechanistic studies into this phenomenon have shown that differential expression of metabolite transporters, altered activity of the heme pathway enzymes and variable nutrient availability are all factors in the accumulation of PPIX. However, little is known about the cellular driving force for the uptake of 5-ALA and subsequent conversion into PPIX. Our data suggest that different microenvironments within the tumour alter the activity of the heme biosynthetic pathway, resulting in differential fluorescence in glioblastoma. It paves the way for work to alter the glioblastoma microenvironment in order to further improve the use of FGS in guiding surgery across these devastating tumours.