Rapid 3D Reconstruction Guided Embolization for Catastrophic Bleeding Following Vacuum Assisted Breast Biopsy; A Case Report and Review of the Literature

The most clinically significant complication associated with stereotactic core needle biopsy of the breast is hematoma formation, which only occurs in less than 1% of biopsies and may require treatment. Cases of uncontrollable bleeding, refractory to repeated compression, resulting from biopsy are exceedingly rare. We present a case of catastrophic, uncontrollable bleeding and large hematoma formation resulting from stereotactic vacuum-assisted breast biopsy of a breast mass identified in screening mammography. Percutaneous embolization was planned and guided using 3D reconstructions from computed tomographic angiography, and bleeding was successfully controlled with micro-coil embolization

Abducens Nerve Palsy as Initial Presentation of Multiple Myeloma and Intracranial Plasmacytoma

Central Nervous System (CNS) involvement in multiple myeloma and/or multifocal solitary plasmacytoma is rare. Although they are unique entities, multiple myeloma (MM) and plasmacytoma represent a spectrum of plasma cell neoplastic diseases that can sometimes occur concurrently. Plasmacytomas very often present as late-stage sequelae of MM. In this case report, we report a 53-year-old female presenting with right abducens cranial nerve (CN) VI palsy as an initial presentation secondary to lesion of the right clivus

Poly-ADP-Ribose-Polymerase as a Therapeutic Target in Paediatric Diffuse Intrinsic Pontine Glioma and Paediatric High Grade Astrocytoma

Paediatric high-grade astrocytomas (pHGA) and diffuse-intrinsic-pontine-gliomas (DIPG) are devastating paediatric malignancies for which there are no effective therapies. Previous evidence found Poly-ADP-Ribose-Polymerase 1 (PARP1) over-expressed in DIPG and pHGA. Immunohistochemical and western-blot analysis was performed on pHGA and DIPG patient tumour samples and cell lines to establish PARP1 expression. Three PARP inhibitors, Veliparib, Olaparib, and Niraparib, were used to study PARP inhibition in multiple pHGA and DIPG cell lines and intracranial xenografts. PARP1 was expressed in the majority of pHGA and DIPG patient samples and cell lines and PARP inhibition in vitro resulted in growth arrest and/or apoptosis. Niraparib was the most effective monotherapeutic agent. Niraparib reduced the rate of DNA repair and sensitized cells in vitro to ionizing radiation (IR). In vivo, Niraparib when combined with IR, inhibited PARP1 and extended survival by 40%. Therefore, PARP1 may serve as a potential therapeutic target in pHGA and DIPG.M.Sc

Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as Drivers of Neoplastic Change

The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states—cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism—termed “aerobic glycolysis”. Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids. To date, several molecules, termed “oncometabolites”, have been identified to be elevated in cancer cells and arise from mutations in nuclear encoded mitochondrial enzymes. Furthermore, there is evidence that oncometabolites can affect mitochondrial dynamics. It is believed that oncometabolites can assist in reprogramming enzymatic pathways and providing cancer cells with selective advantages. In this review, we will touch upon the effects of normal and aberrant mitochondrial metabolism in normal and cancer cells, the advantages of metabolic reprogramming, effects of oncometabolites on metabolism and mitochondrial dynamics and therapies aimed at targeting oncometabolites and metabolic aberrations

Targeting reduced mitochondrial DNA quantity as a therapeutic approach in pediatric high-grade gliomas

Background: Despite increased understanding of the genetic events underlying pediatric high-grade gliomas (pHGGs), therapeutic progress is static, with poor understanding of nongenomic drivers. We therefore investigated the role of alterations in mitochondrial function and developed an effective combination therapy against pHGGs. Methods: Mitochondrial DNA (mtDNA) copy number was measured in a cohort of 60 pHGGs. The implication of mtDNA alteration in pHGG tumorigenesis was studied and followed by an efficacy investigation using patient-derived cultures and orthotopic xenografts. Results: Average mtDNA content was significantly lower in tumors versus normal brains. Decreasing mtDNA copy number in normal human astrocytes led to a markedly increased tumorigenicity in vivo. Depletion of mtDNA in pHGG cells promoted cell migration and invasion and therapeutic resistance. Shifting glucose metabolism from glycolysis to mitochondrial oxidation with the adenosine monophosphate-activated protein kinase activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) or the pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA) significantly inhibited pHGG viability. Using DCA to shift glucose metabolism to mitochondrial oxidation and then metformin to simultaneously target mitochondrial function disrupted energy homeostasis of tumor cells, increasing DNA damage and apoptosis. The triple combination with radiation therapy, DCA and metformin led to a more potent therapeutic effect in vitro and in vivo. Conclusions: Our results suggest metabolic alterations as an onco-requisite factor of pHGG tumorigenesis. Targeting reduced mtDNA quantity represents a promising therapeutic strategy for pHGG

Abducens Nerve Palsy as Initial Presentation of Multiple Myeloma and Intracranial Plasmacytoma

Central Nervous System (CNS) involvement in multiple myeloma and/or multifocal solitary plasmacytoma is rare. Although they are unique entities, multiple myeloma (MM) and plasmacytoma represent a spectrum of plasma cell neoplastic diseases that can sometimes occur concurrently. Plasmacytomas very often present as late-stage sequelae of MM. In this case report, we report a 53-year-old female presenting with right abducens cranial nerve (CN) VI palsy as an initial presentation secondary to lesion of the right clivus.Medicine, Faculty ofNon UBCReviewedFacult

Retrospective single-center analysis of surgical treatment of patients with primary mitral insufficiency

The aim – to evaluate the results of the surgical treatment of primary mitral insufficiency (MIS) in single-centre study during three years. Materials and methods. The results of the mitral valve surgery performed from January 2010 to December 2012 in 144 consecutive patients with primary MIS have been analyzed. Registration of all parameters was performed using data of in-patient case reports. Severity of MIS and NYHA functional class (FC) before and after surgery were evaluated. Results. Degenerative channges were a most frequent (54.2 %) cause of MIS. Chordal rupture most a most frequent immediate cause (53.5 %). Mitral valve repair was performed in 51 (35.4 %) patients, replacement – in 93 (64.6 %) patients. The duration of the in-hospital stay in the group of repair treatment was 14 (6–73) days, after replacement – 21.5 (8–63) days (p < 0.05). NYHA FC improved after surgery in 57 (39.7 %) persons, worsened – in 9 (6.3 %), remained stable im more than half of patients. This shows efficiency of pre-surgery drug preparation. Conclusions. The duration of the in-hospital stay depended on type of the surgery and didn’t depend on NYHA FC. It was lower after mitral valve repair. Severity of MR decreased in all patients after mitral valve repair