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Journal of Nuclear Cardiology :... Dec 2023
Topics: Humans; Cardiovascular System; Molecular Imaging; Heart; Mediastinum
PubMed: 33655449
DOI: 10.1007/s12350-021-02534-9 -
Insights Into Imaging Jul 2023The paraspinal region encompasses all tissues around the spine. The regional anatomy is complex and includes the paraspinal muscles, spinal nerves, sympathetic chains,... (Review)
Review
The paraspinal region encompasses all tissues around the spine. The regional anatomy is complex and includes the paraspinal muscles, spinal nerves, sympathetic chains, Batson's venous plexus and a rich arterial network. A wide variety of pathologies can occur in the paraspinal region, originating either from paraspinal soft tissues or the vertebral column. The most common paraspinal benign neoplasms include lipomas, fibroblastic tumours and benign peripheral nerve sheath tumours. Tumour-like masses such as haematomas, extramedullary haematopoiesis or abscesses should be considered in patients with suggestive medical histories. Malignant neoplasms are less frequent than benign processes and include liposarcomas and undifferentiated sarcomas. Secondary and primary spinal tumours may present as midline expansile soft tissue masses invading the adjacent paraspinal region. Knowledge of the anatomy of the paraspinal region is of major importance since it allows understanding of the complex locoregional tumour spread that can occur via many adipose corridors, haematogenous pathways and direct contact. Paraspinal tumours can extend into other anatomical regions, such as the retroperitoneum, pleura, posterior mediastinum, intercostal space or extradural neural axis compartment. Imaging plays a crucial role in formulating a hypothesis regarding the aetiology of the mass and tumour staging, which informs preoperative planning. Understanding the complex relationship between the different elements and the imaging features of common paraspinal masses is fundamental to achieving a correct diagnosis and adequate patient management. This review gives an overview of the anatomy of the paraspinal region and describes imaging features of the main tumours and tumour-like lesions that occur in the region.
PubMed: 37466751
DOI: 10.1186/s13244-023-01462-1 -
Leukemia Nov 2023Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders....
Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217 alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequencing identified genetic lesions affecting ZNF217 in 33% of 157 PMBCL patients. Subsequent gene expression profiling (n = 120) revealed changes in cytokine and interferon signal transduction in ZNF217-aberrant PMBCL cases. In vitro, knockout of ZNF217 led to changes in chromatin accessibility interfering with binding motifs for crucial lymphoma-associated transcription factors. This led to disturbed expression of interferon-responsive and inflammation-associated genes, altered cell behavior, and aberrant differentiation. Mass spectrometry demonstrates that ZNF217 acts within a histone modifier complex containing LSD1, CoREST and HDAC and interferes with H3K4 methylation and H3K27 acetylation. Concluding, our data suggest non-catalytic activity of ZNF217, which directs histone modifier complex function and controls B cell differentiation-associated patterns of chromatin structure.
Topics: Humans; Histones; Trans-Activators; Interferons; Cell Line, Tumor; Mutation; Signal Transduction; Chromatin; Lymphoma, B-Cell
PubMed: 37648814
DOI: 10.1038/s41375-023-02013-9 -
Frontiers in Oncology 2023Diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) are aggressive histological subtypes of non-Hodgkin's lymphoma. Improved...
Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies.
INTRODUCTION
Diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) are aggressive histological subtypes of non-Hodgkin's lymphoma. Improved understanding of the underlying molecular pathogenesis has led to new classification and risk stratification tools, including the development of cell-free biomarkers through liquid biopsies. The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients.
MATERIALS AND METHODS
Blood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit.
RESULTS
Higher cfRNA concentrations were demonstrated in lymphoma patients compared to healthy controls. A large number of differentially abundant genes were identified between the cell-free transcriptomes of DLBCL patients, PMBCL patients, and healthy controls. Overlap analyses with matched FFPE samples showed that blood plasma has a unique transcriptomic profile that significantly differs from that of the tumor tissue. As a good concordance between tissue-derived gene expression and the immunohistochemistry Hans algorithm for cell-of-origin (COO) classification was demonstrated in the FFPE samples, but not in the plasma samples, a 64-gene cfRNA classifier was developed that can accurately determine COO in plasma. High plasma levels of a 9-gene signature (, , , , , , , , pseudogene) and a 5-gene signature (, , , , ) were significantly associated with inferior progression-free and overall survival in DLBCL patients, respectively, independent of the NCCN-IPI score.
CONCLUSION
Total RNA sequencing of blood plasma samples allows the analysis of the cell-free transcriptome in DLBCL and PMBCL patients and demonstrates its unexplored potential in identifying diagnostic, cell-of-origin, and prognostic cfRNA biomarkers.
PubMed: 37954086
DOI: 10.3389/fonc.2023.1221471 -
Annals of Palliative Medicine May 2024Superior vena cava (SVC) syndrome occurs due to obstructed blood flow through the SVC. It can present clinically on a spectrum, between asymptomatic and life-threatening... (Review)
Review
Superior vena cava (SVC) syndrome occurs due to obstructed blood flow through the SVC. It can present clinically on a spectrum, between asymptomatic and life-threatening emergency. Patients commonly report a feeling of fullness in the head, facial, neck and upper extremity edema, and dyspnea. On imaging, patients commonly have superior mediastinal widening and pleural effusion. The majority of cases are due to malignant causes, with non-small cell lung cancer, small cell lung cancer, and lymphoma the most commonly associated malignancies. When evaluating patients, a complete staging workup is recommended, as it will determine whether treatment should be definitive/curative or palliative in intent. If the patient requires urgent treatment of venous obstruction, such as in the cases of acute central airway obstruction, severe laryngeal edema and/or coma from cerebral edema, direct opening of the occlusion by endovascular stenting and angioplasty with thrombolysis should be considered. Such an approach can provide immediate relief of symptoms before cancer-specific therapies are initiated. The intent of treatment is to manage the underlying disease while palliating symptoms. Treatment approaches most commonly employ chemotherapy and/or radiation therapy depending on the primary histology. Mildly hypofractionated radiation regimens are most commonly employed and achieve high rates of symptomatic responses generally within 2 weeks of initiating therapy.
Topics: Superior Vena Cava Syndrome; Humans; Palliative Care; Lung Neoplasms
PubMed: 38600814
DOI: 10.21037/apm-23-573 -
Blood Advances Aug 2023Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell...
Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 vs 51 days) and OS (387 vs 131 days) were significantly longer in patients with late (>180 days) vs early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of patients treated with CPI. Most patients (83%) died, commonly because of progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of patients with aggressive B-cell lymphoma treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post-CAR-T outcomes.
Topics: Humans; Receptors, Chimeric Antigen; Retrospective Studies; Neoplasm Recurrence, Local; Lymphoma, Large B-Cell, Diffuse; Immunotherapy, Adoptive
PubMed: 37026796
DOI: 10.1182/bloodadvances.2023010016 -
Diagnostics (Basel, Switzerland) Jul 2023Dual-energy computed tomography (DECT) can improve the differentiation of material by using two different X-ray energy spectra, and may provide new imaging techniques to... (Review)
Review
Dual-energy computed tomography (DECT) can improve the differentiation of material by using two different X-ray energy spectra, and may provide new imaging techniques to diagnostic radiology to overcome the limitations of conventional CT in characterizing tissue. Some techniques have used dual-energy imaging, which mainly includes dual-sourced, rapid kVp switching, dual-layer detectors, and split-filter imaging. In iodine images, images of the lung's perfused blood volume (PBV) based on DECT have been applied in patients with pulmonary embolism to obtain both images of the PE occluding the pulmonary artery and the consequent perfusion defects in the lung's parenchyma. PBV images of the lung also have the potential to indicate the severity of PE, including chronic thromboembolic pulmonary hypertension. Virtual monochromatic imaging can improve the accuracy of diagnosing pulmonary vascular diseases by optimizing kiloelectronvolt settings for various purposes. Iodine images also could provide a new approach in the area of thoracic oncology, for example, for the characterization of pulmonary nodules and mediastinal lymph nodes. DECT-based lung ventilation imaging is also available with noble gases with high atomic numbers, such as xenon, which is similar to iodine. A ventilation map of the lung can be used to image various pulmonary diseases such as chronic obstructive pulmonary disease.
PubMed: 37443688
DOI: 10.3390/diagnostics13132295