KCa3.1 channel inhibition sensitizes malignant gliomas to temozolomide treatment

Malignant gliomas are among the most frequent and aggressive cerebral tumors, characterized by high proliferative and invasive indexes. Standard therapy for patients, after surgery and radiotherapy, consists of temozolomide (TMZ), a methylating agent that blocks tumor cell proliferation. Currently, there are no therapies aimed at reducing tumor cell invasion. Ion channels are candidate molecular targets involved in glioma cell migration and infiltration into the brain parenchyma. In this paper we demonstrate that: i) blockade of the calcium-activated potassium channel KCa3.1 with TRAM-34 has co-adjuvant effects with TMZ, reducing GL261 glioma cell migration, invasion and colony forming activity, increasing apoptosis, and forcing cells to pass the G2/M cell cycle phase, likely through cdc2 de-phosphorylation; ii) KCa3.1 silencing potentiates the inhibitory effect of TMZ on glioma cell viability; iii) the combination of TMZ/TRAM-34 attenuates the toxic effects of glioma conditioned medium on neuronal cultures, through a microglia dependent mechanism since the effect is abolished by clodronate-induced microglia killing; iv) TMZ/TRAM-34 co-treatment increases the number of apoptotic tumor cells, and the mean survival time in a syngeneic mouse glioma model (C57BL6 mice implanted with GL261 cells); v) TMZ/TRAM-34 co-treatment reduces cell viability of GBM cells and cancer stem cells (CSC) freshly isolated from patients.Taken together, these data suggest a new therapeutic approach for malignant glioma, targeting both glioma cell proliferating and migration, and demonstrate that TMZ/TRAM-34 co-treatment affects both glioma cells and infiltrating microglia, resulting in an overall reduction of tumor cell progression

Contrast-Enhanced Magnetic Resonance Cholangiography: Practical Tips and Clinical Indications for Biliary Disease Management

Since its introduction, MRCP has been improved over the years due to the introduction of several technical advances and innovations. It consists of a noninvasive method for biliary tree representation, based on heavily T2-weighted images. Conventionally, its protocol includes two-dimensional single-shot fast spin-echo images, acquired with thin sections or with multiple thick slabs. In recent years, three-dimensional T2-weighted fast-recovery fast spin-echo images have been added to the conventional protocol, increasing the possibility of biliary anatomy demonstration and leading to a significant benefit over conventional 2D imaging. A significant innovation has been reached with the introduction of hepatobiliary contrasts, represented by gadoxetic acid and gadobenate dimeglumine: they are excreted into the bile canaliculi, allowing the opacification of the biliary tree. Recently, 3D interpolated T1-weighted spoiled gradient echo images have been proposed for the evaluation of the biliary tree, obtaining images after hepatobiliary contrast agent administration. Thus, the acquisition of these excretory phases improves the diagnostic capability of conventional MRCP—based on T2 acquisitions. In this paper, technical features of contrast-enhanced magnetic resonance cholangiography are briefly discussed; main diagnostic tips of hepatobiliary phase are showed, emphasizing the benefit of enhanced cholangiography in comparison with conventional MRCP

Microglia control glutamatergic synapses in the adult mouse hippocampus

Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Late Sequelae: Gliotic Scar Formation-Postoperative MR Follow-Up in Grade II Oligoastrocytoma

Patient with surgically treated right temporo-fronto-insular grade II oligoastrocytoma. Postoperative follow-up performed late (at 6 months) with MR morphologic sequences and spectroscopy

TRAPIANTO EPATICO: VALUTAZIONE PRE- E POST-INTERVENTO

II trapianto di fegato rappresenta il trattamento di scelta per i pazienti affetti da insufficienza epatica acuta o cronica. \uc8 generalmente eseguito utilizzando organi prelevati da cadavere o parte dell'organo da un donatore vivente compatibile, generalmente il lobo destro nel caso di trapianto in adulto. L'imaging gioca un ruolo essenziale nella valutazione preoperatoria del ricevente e, nel caso di trapianto da donatore vivente, anche del potenziale donatore

Intra-hepatic spillage of gallstones as a late complication of laparoscopic cholecystectomy : MR imaging findings

BACKGROUND: Spillage of gallstones in the abdominal cavity may rarely occur during the course of laparoscopic cholecystectomy. Dropped gallstones in the peritoneal and extra-peritoneal cavity are usually asymptomatic. However, they may lead to abscess formation with an estimated incidence of about 0.3%. Common locations of the abscess are in the abdominal wall followed by the intra-abdominal cavity, usually in the sub-hepatic or retro-peritoneum inferior to the sub-hepatic space. CASE REPORT: We hereby describe an unusual case of infected spilled gallstones in the right sub-phrenic space, prospectively detected on abdominal MRI performed two years after laparoscopic cholecystectomy, in a patient with only a mild right-sided abdominal complaint. CONCLUSIONS: This case highlights the role of MRI in suggesting the right diagnosis in cases with vague or even absent symptomatology. In our case the patient's history together with high quality abdomen MRI allowed the correct diagnosis. Radiologists should be aware of this rare and late onset complication, even after many years from surgery as an incidental finding in almost asymptomatic patients

MRI of Hepatic Epithelioid Hemangioendothelioma (HEH).

Purpose To investigate magnetic resonance imaging (MRI) characteristics of hepatic epithelioid hemangionendothelioma (HEH). Materials and Methods The study was exempted from formal Ethics Committee approval due to its retrospective and noninvasive nature. Eleven patients with histology-proven HEH were collected from six different institutions in a 5-year time period. In all patients a contrast-enhanced MR study was available. Two experienced reviewers in consensus retrospectively noted potential MR findings of HEH. Reviewers separately analyzed morphological findings, tumor signal intensity, HEH contrast enhancement pattern, and tumor appearance on hepatobiliary phase and diffusion-weighted imaging (DWI). The frequency of various findings was calculated. Results The most frequent presentation was a peripheral distribution of the lesions (72.7%), target appearance on T2-weighted images (63.6%), low signal intensity on T1-weighted images (63.6%), ring or target-like enhancement at dynamic study (63.6%), and coalescence of nodules and capsular retraction (45.4%). Lack of hepatobiliary enhancement (5/8 patients) or "entrapment" hepatobiliary enhancement (3/8 patients) as well as target appearance at DWI (5/6 patients) was also observed in our series. Conclusion Although quite variable imaging appearances were seen, a target appearance on the T2-weighted image, ring or target enhancement at dynamic study, lack of enhancement or "entrapment" at hepatobiliary phase, and target appearance on DWI are frequent findings of HEH. © 2013 Wiley Periodicals, Inc

Multiparametric MRI for Prostate Cancer Detection: New Insights into the Combined Use of a Radiomic Approach with Advanced Acquisition Protocol

Prostate cancer (PCa) is a disease affecting an increasing number of men worldwide. Several efforts have been made to identify imaging biomarkers to non-invasively detect and characterize PCa, with substantial improvements thanks to multiparametric Magnetic Resonance Imaging (mpMRI). In recent years, diffusion kurtosis imaging (DKI) was proposed to be directly related to tissue physiological and pathological characteristic, while the radiomic approach was proven to be a key method to study cancer imaging phenotypes. Our aim was to compare a standard radiomic model for PCa detection, built using T2-weighted (T2W) and Apparent Diffusion Coefficient (ADC), with an advanced one, including DKI and quantitative Dynamic Contrast Enhanced (DCE), while also evaluating differences in prediction performance when using 2D or 3D lesion segmentation. The obtained results in terms of diagnostic accuracy were high for all of the performed comparisons, reaching values up to 0.99 for the area under a receiver operating characteristic curve (AUC), and 0.98 for both sensitivity and specificity. In comparison, the radiomic model based on standard features led to prediction performances higher than those of the advanced model, while greater accuracy was achieved by the model extracted from 3D segmentation. These results provide new insights into active topics of discussion, such as choosing the most convenient acquisition protocol and the most appropriate postprocessing pipeline to accurately detect and characterize PCa