Management Strategies and Outcomes in Primary Liver Angiosarcoma.

OBJECTIVES: Primary hepatic angiosarcoma is a rare tumor of the liver that originates from endothelial and fibroblastic tissue, with poor prognosis and lack of standardized treatment. We retrospectively analyzed the clinical characteristics and treatment outcomes of 23 patients with primary liver angiosarcoma treated at an academic sarcoma center. METHODS: We screened all patients with primary liver angiosarcoma treated at Stanford between 2000 and 2022. Data was collected from EPIC electronic medical records and included patient demographics, tumor characteristics, treatment modalities, and patient outcomes. Statistical analysis was completed using Python 3.0, while survival curves were generated using the Kaplan-Meier method and Lifelines Packages. RESULTS: There were nearly equal numbers of males (11) and females (12) in our study, with most patients aged 70 to 79 at diagnosis. The median overall survival (OS) was 6 months (range 0.07 to 222.6 mo). The 2- and 5-year OS were both 38.6%. 71% of patients received systemic treatment with chemotherapy, while 29% received immunotherapy. Local treatment with surgery or radioembolization was performed in 14% of patients. Three patients in our study displayed particularly improved OS and received various treatments, which ranged from hepatic resection to ipilimumab/nivolumab. CONCLUSION: Our study demonstrated that primary liver angiosarcoma has poor outcomes despite treatment. Surgical resection with negative margins is the only curative modality. However, most patients present with advanced disease and are not surgical candidates. Further research is needed to identify more effective systemic therapy options for this devastating disease.

Cutaneous Angiosarcoma of the Head and Neck-A Retrospective Analysis of 47 Patients.

Cutaneous angiosarcoma (CAS) is a rare and aggressive malignant tumor with blood vessel or lymphatic-type endothelial differentiation. It has a poor prognosis with lack of standardized treatment options. This study retrospectively evaluated the clinical characteristics and treatment outcomes of 47 patients with CAS of the head and neck treated at an academic sarcoma center. Patient data were collected from the electronic medical records. 62% of patients were male with the scalp being the most commonly affected area (64%). The majority of patients presented with localized disease (53%). Median overall survival (OS) was 3.4 years with an OS of 36% at 5 years. There was a statistically significant increase in OS for patients who underwent surgery compared to those who did not (5.4 vs. 2.8 years). In contrast, radiotherapy (RT) or chemotherapy did not significantly increase OS. 45% of patients had recurrence of disease during their treatment course with a median time to recurrence of 22.8 months. There was not a significant difference in OS for patients who underwent immunotherapy compared to those who underwent chemotherapy, although only a few patients received immunotherapy. We found that surgery was an effective treatment modality in patients with easily resectable disease, while RT, chemotherapy, and immunotherapy did not significantly improve OS.

Bempedoic acid: a novel oral LDL-cholesterol lowering agent.

An elevated LDL-cholesterol is a potent risk factor for atherosclerotic cardiovascular disease (ASCVD). Invariably, pharmacotherapy is required to get high risk patients to goal. The cornerstone of such therapy is the statin class of drugs. Recently Bempedoic Acid (BA), a first in class ATP-citrate lyase inhibitor was approved for LDL-C reduction based on the CLEAR trials in which BA was superior to Placebo. In addition to lowering LDL-C it also lowers apoB and hsCRP levels. BA appears to be very efficacious in combination with ezetimibe especially in statin intolerant patients. However the reduction in LDL-C is modest, it lowers HDL-C levels, causes hyperuricemia and an elevated creatinine. The ongoing Outcomes trial examining ASCVD events with BA will firmly establish the role of BA in our arsenal for the management of ASCVD if positive.

Neutrophil and monocyte ratios to high-density lipoprotein-cholesterol and adiponectin as biomarkers of nascent metabolic syndrome.

Background Metabolic syndrome (MetS) continues to be a significant problem globally, affecting nearly 35% of adults in the USA. Whilst there is no ideal biomarker that captures this disorder, high sensitivity C-reactive protein (hsCRP) appears to be most widely accepted. We examined the ratios between neutrophils (PMNs) and monocytes to high-density lipoprotein (HDL)-cholesterol and adiponectin, two anti-inflammatory proteins, in patients with nascent MetS without the confounding of diabetes, atherosclerotic cardiovascular diseases (ASCVD), smoking or lipid therapy to determine if they were also valid biomarkers of MetS. Materials and methods Patients with nascent MetS (n = 58) and matched controls (n = 44) were recruited from Sacramento County. Fasting blood samples were obtained for complete blood counts, basic metabolic panel, lipid profile, insulin and adiponectin. Ratios of PMNs and monocytes to HDL-C and adiponectin were calculated and compared statistically. Results The PMN:HDL-C, monocyte:HDL-C, PMN:adiponectin and monocyte:adiponectin ratios were significantly increased in patients with MetS and increased with increasing severity of MetS. Receiver operating characteristic (ROC) curve analysis showed that both the PMN:HDL-C and monocyte:HDL-C areas under the curve (AUCs) significantly added to the CRP AUC. Also both the ratios correlated with cardio-metabolic features of MetS, hsCRP and insulin resistance. Conclusions Our data indicates that ratios of neutrophils and monocytes to HDL-C are significantly increased in patients with nascent MetS and both ratios appear to be better predictors of MetS than hsCRP alone. These important preliminary findings need to be confirmed in large prospective databases.

Metabolic syndrome is an inflammatory disorder: A conspiracy between adipose tissue and phagocytes.

Metabolic syndrome (MetS) describes a cluster of cardio-metabolic factors that predispose to type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). While 35% of Americans suffer from this disorder, the specific pathways related to this disease are largely underexplored. The prevailing consensus is that inflammatory pathways contribute to the pathogenesis of this disease, and therefore new research has uncovered how inflammation plays a critical role in the development and progression of MetS. The purpose of this review is to understand the role of major inflammatory mechanisms and their role in MetS. Our review identifies that adipose tissue (AT) contributes to the inflammatory pathways through the release of pro-inflammatory adipokines such as leptin and chemerin and dysregulation of anti-inflammatory adiponectin. Chemokines and cytokines deriving from monocytes are also altered and promote inflammation and insulin resistance. Circulating inflammatory biomarkers including C-reactive protein (CRP), fibrinogen, Serum amyloid A (SAA), cytokines, and chemokines have also been linked to the pathogenesis of MetS. Researchers have identified the significance of CRP levels in predicting future sequelae of MetS such as ASCVD. Mast cells in subcutaneous adipose tissue (SAT) promote both inflammation and fibrosis. Thus, both AT and phagocyte activity define MetS as an inflammatory disorder.

Exploratory metabolomics of metabolic syndrome: A status report.

Metabolic syndrome (MetS) is as a cluster of cardio-metabolic factors that greatly increase the risk of chronic diseases such as type II diabetes mellitus and atherosclerotic cardiovascular disease. In the United States, obesity, physical inactivity, aging, and genetics (to a minor extent) have arisen as risk factors for developing MetS. Although 35% of American adults suffer from MetS, its pathogenesis largely remains unknown. Worse, there is a lack of screening and optimum therapy for this disease. Researchers have consequently turned towards metabolomics to identify biomarkers to better understand MetS. The purpose of this review is to characterize various metabolites and their potential connections to MetS. Numerous studies have also characterized MetS as a disease of increased inflammation, and therefore this review also explores how metabolites play a role in various inflammatory pathways. Our review explores a broad range of metabolites including biogenic amines, branched chain amino acids, aromatic amines, phosphatidylcholines, as well as a variety of other molecules. We will explore their biochemical pathways and their potential role in serving as biomarkers.