Low plasma fibrinogen levels are associated with poor prognosis in cutaneous angiosarcoma of the head and neck.

Angiosarcoma of the head and neck (ASHN) is one of the most aggressive malignancies of the skin, but the prognostic factors are not well known because of its rarity. Recently, high plasma fibrinogen levels were reported to predict poor prognosis in several malignancies. In the present retrospective study, we suggest that low plasma fibrinogen levels predict poor prognosis for ASHN.

Characterizing circulating nucleosomes in the plasma of dogs with hemangiosarcoma.

BACKGROUND: Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.Q™ platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay. Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC. RESULTS: Dogs with hemangiosarcoma had a 6.6-fold increase in their median plasma nucleosome concentrations compared to controls (AUC 92.9 %). Elevated nucleosome concentrations were seen at all stages of disease and nucleosome concentrations increased with the stage of the disease. CONCLUSIONS: Plasma nucleosome concentrations are a reliable way to differentiate dogs with hemangiosarcoma from healthy dogs. Further testing is underway to better characterize cancer associated HSA circulating nucleosomes and optimize future diagnostics for canine HSA detection.

Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development.

BACKGROUND: High-level occupational vinyl chloride (VC) exposures have been associated with hepatic hemangiosarcoma, which typically develops following a long latency period. Although VC is genotoxic, a more comprehensive mode of action has not been determined and diagnostic biomarkers have not been established. The purpose of this study is to address these knowledge gaps through plasma metabolomics. METHODS: Plasma samples from polyvinyl chloride polymerization workers who developed hemangiosarcoma (cases, n = 15) and VC exposure-matched controls (n = 17) underwent metabolomic analysis. Random forest and bioinformatic analyses were performed. RESULTS: Cases and controls had similar demographics and routine liver biochemistries. Mass spectroscopy identified 606 known metabolites. Random forest analysis had an 82% predictive accuracy for group classification. 60 metabolites were significantly increased and 44 were decreased vs. controls. Taurocholate, bradykinin and fibrin degradation product 2 were up-regulated by greater than 80-fold. The naturally occurring anti-angiogenic phenol, 4-hydroxybenzyl alcohol, was down-regulated 5-fold. Top affected ontologies involved: (i) metabolism of bile acids, taurine, cholesterol, fatty acids and amino acids; (ii) inflammation and oxidative stress; and (iii) nicotinic cholinergic signaling. CONCLUSIONS: The plasma metabolome was differentially regulated in polyvinyl chloride workers who developed hepatic hemangiosarcoma. Ontologies potentially involved in hemangiosarcoma pathogenesis and candidate biomarkers were identified.

Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial.

BACKGROUND: We report here a correlation analysis conducted along with a phase II trial assessing bevacizumab in combination with weekly paclitaxel. METHODS: Circulating pro/anti-angiogenic factors were assessed on day 1 (D1) and day 8 (D8). The prognostic value for progression-free survival (PFS) was evaluated using a Cox model with biomarkers as continuous variables. RESULTS: Among the 51 patients enrolled and treated in this trial, biomarker analysis was performed for 42: 18 in Arm A (single-agent) and 24 in Arm B (combination). With a median follow-up of 46 months, PFS was 5.5 versus 5.7 months, respectively (p = 0.75). According to univariate analysis, factors associated with a poor PFS were as follows: visceral angiosarcoma, de novo angiosarcoma, and high PlGF and low VEGF-C baseline values. In multivariate analysis, de novo angiosarcoma (HR = 2.5; p = 0.024) and baseline VEGF-C value (HR = 0.7; p = 0.003) were significant prognostic factors. We observed a significant increase in circulating PlGF (< 0.001) and a decrease in VEGF (< 0.001) during bevacizumab treatment. An increase in FGF was associated with a poor outcome. CONCLUSIONS: De novo angiosarcoma and a low baseline level of VEGF-C were found to be associated with a poor prognosis. Addition of bevacizumab induces major changes in circulating biomarkers (VEGF and PlGF) in a short timeframe without impacting PFS. TRIAL REGISTRATION: Retrospectively registered on EudraCT N° 2009-017020-59 and NCT01303497 (February 24, 2011).

Three patients with advanced cutaneous angiosarcoma treated with eribulin: investigation of serum soluble CD163 and chemokine (C-X-C motif) ligand 10 as possible biomarkers predicting the biological behaviour of angiosarcoma.

Cutaneous angiosarcoma (CAS) is a highly aggressive vascular tumour that recurs locally and metastasizes early. Although chemoradiotherapy with taxanes shows a high response rate with prolonged survival, second-line therapy for advanced CAS remains contentious. This report describes three patients with advanced CAS treated with eribulin. In addition, we investigated serum soluble (s)CD163, chemokine (C-X-C motif) ligand 10 (CXCL10) and chemokine (C-C motif) ligand 2 levels at several time points of tumour progression in these patients, revealing serum levels of sCD163 and CXCL10 as potential biomarkers for progression of CAS.

Removal of hemangiosarcoma cells from canine blood with a cell salvage system and leukocyte reduction filter.

OBJECTIVE: To determine the ability of an intraoperative cell salvage (IOCS) system and a leukocyte reduction filter (LRF) to remove hemangiosarcoma (HSA) cells from canine blood. STUDY DESIGN: Cultured HSA cells were added to canine blood to simulate intraoperative hemorrhage and address hemoabdomen from ruptured splenic HSA. The blood/HSA cell mixture was processed through an IOCS, followed by LRF processing. SAMPLE POPULATION: Whole blood from 3 healthy dogs combined with cultured HSA cells. METHODS: The ability of quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), multiparameter flow cytometry, and cytologic examination to detect 50 HSA cells per milliliter of culture media was confirmed. RT-PCR, multiparameter flow cytometry, and cytologic examination were used to determine the presence of cultured HSA cells at 4 points during processing. RESULTS: HSA cells were found in all control samples and in all samples after IOCS but prior to LRF processing with all 3 cell detection methods. HSA cells were not found after IOCS/LRF processing with all 3 cell detection methods. CONCLUSION: IOCS combined with LRF processing is able to remove cultured HSA cells from canine blood. The addition of LRF to IOCS may allow application of IOCS in dogs with HSA. CLINICAL SIGNIFICANCE: A combination of IOCS and LRF processing may provide an alternative to allogeneic blood transfusion in dogs with hemoabdomen due to HSA.

A rare case of angiosarcoma with skull masses and erythropenia and thrombocytopenia: A case report and review of literature.

RATIONALE: Primary splenic angiosarcoma (PSA) is a rare, fatal neoplasm originating from sinusoidal vascular endothelial cells, and usually metastasizes and almost always has a poor prognosis. Surgical excision is the main treatment of this highly malignant disease. PATIENT CONCERNS: We reported a special case of a 68-year-old female who had a 6-month history of scalp masses. DIAGNOSIS: The patient was found to have 2 skull masses on computed tomography (CT). Laboratory findings revealed erythropenia and thrombocytopenia. Enhanced abdomen magnetic resonance imaging (MRI) showed multiple masses in liver and spleen. The pathological result of the skull masses was revealed to be metastatic angiosarcoma. INTERVENTIONS: The patient underwent surgical excision of skull masses, and no subsequent radiotherapy or chemotherapy was done. OUTCOMES: The patient died due to dyscrasia at August 12, 2015, with a survival of nearly 1 month. LESSONS: We highlight the importance for clinicians to be aware of this rare neoplasm, and to consider it in the differential diagnosis when encountering a skull mass. Early confirmation and treatment may improve the prognosis.

Clinical Usefulness of the Platelet-to Lymphocyte Ratio in Patients with Angiosarcoma of the Face and Scalp.

Angiosarcoma of the face and scalp (ASFS) is an extremely aggressive tumor that frequently metastasizes, often leading to death. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are inflammatory markers that predict outcome of various cancers. We aimed to examine the relationship between pretreatment inflammatory markers and ASFS outcome. We included 17 patients with ASFS and a control group of 56 age- and gender-matched healthy individuals. Total white blood counts, neutrophil, lymphocyte, monocyte, and platelet counts were recorded; NLR, PLR, and LMR were calculated. Kaplan-Meier curves were used to calculate overall survival (OS) and distant metastasis-free survival (DMFS). Optimal cut-off values for each inflammatory marker were calculated using receiver operating curve analysis. Median follow-up was 22 months (range, 6-75). There was a statistically significant difference in absolute neutrophil counts and NLR between patient and control groups. Two-year OS and DMFS rates were 41% and 35%, respectively. In patients with tumors < 10 cm, PLR was highly correlated with DMFS, with the 2-year DMFS for those with a high PLR being 50% compared with 100% for those with a low PLR (p = 0.06). This study suggests that PLR is superior to NLR and LMR, and is a clinically useful marker in patients with ASFS with small tumors.

Hallazgos de imagen de las masas cardíacas (parte II): tumores malignos y lesiones pseudotumorales / Imaging findings in cardiac masses (part II): malignant tumors and pseudotumors

Los tumores cardíacos malignos son menos frecuentes que los tumores benignos; pueden ser primarios y secundarios. Los secundarios o metastásicos son entre 20 y 40 veces más frecuentes que los primarios, con una incidencia estimada del 0,05%. Las lesiones pseudotumorales no neoplásicas pueden presentarse como masas cardíacas con características de imagen que pueden plantear el diagnóstico con neoplasias. El objetivo de este trabajo es presentar los tumores cardíacos malignos y las lesiones pseudotumorales haciendo hincapié en los hallazgos en TC y RM y en las características que permiten diferenciarlos de los tumores cardíacos benignos (AU)

Malignant heart tumors are less common than benign ones. They can be primary or secondary. Secondary or metastatic heart tumors are 20 to 40 times more common than primary malignant heart tumors, which have an estimated incidence of 0.05%. Non-neoplastic pseudotumors can present as cardiac masses, with imaging characteristics than can suggest the diagnosis of a tumor. The aim of this article is to describe and illustrate malignant heart tumors and pseudotumors, stressing the CT and MRI findings that make it possible to differentiate them from benign cardiac tumors (AU)

MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases.

Malignant endothelial proliferative diseases including human angiosarcoma (AS) and canine hemangiosarcoma (HSA) are serious diseases with a grave prognosis. Establishing liquid biopsy-based biomarkers for screening has definite clinical utility; however, plasma miRNAs up- or down-regulated in these sarcomas have been unclear. For identifying possible diagnostic plasma miRNAs for these sarcomas, we investigated whether plasma miR-214 and miR-126, which miRNAs play important roles in angiogenesis and tumorigenesis, were elevated in malignant endothelial proliferative diseases. For this investigation, human angiosarcoma and canine hemangiosarcoma cell lines and clinical plasma samples of canine hemangiosarcoma were examined by performing miRNA qRT-PCR. We report here that human angiosarcoma and canine hemangiosarcoma cell lines over-secreted miR-214 and miR-126 via microvesicles; in addition, their levels in the plasma samples from canines with hemangiosarcoma were increased. Moreover, the surgical resection of primary tumors decreased the levels of plasma miR-214 and miR-126. Our findings suggest that these malignant endothelial proliferative diseases over-secreted miR-214 and miR-126, thus suggesting that these miRNAs have potential as diagnostic biomarkers for malignant endothelial proliferative diseases in canine and possible in human angiosarcoma.

Case report of primary splenic angiosarcoma with hepatic metastases.

Primary splenic angiosarcoma (PSA) is the most unusual type of malignancy with early multifocal metastasis through hematogenous spread. PSA is generally believed to originate from splenic sinusoidal vascular endothelium with a high rate of metastasis and to have a poor prognosis. Its etiology and pathogenetic mechanisms have not yet been clearly described. Thus far, only approximately 200 cases have been reported. PSA has variable symptomatology with the potential to present with life-threatening complications. The diagnosis of PSA is challenging; and often late. PSA should be considered in the differential diagnosis of patients with splenomegaly and anemia of unknown etiology. Surgical treatment with splenectomy is considered the only curative intervention for potential long-term disease-free survival. Early diagnosis and treatment are very important. It is important that clinical doctors improve the understanding of PSA. Herein, we report one rare case of PSA with hepatic metastases, along with a review of the current literature.

Big endothelin-1 as a tumour marker for canine haemangiosarcoma.

Haemangiosarcoma (HSA) is an important malignant neoplasm of dogs that originates from vascular endothelial cells. This study explored the suitability of using serum big endothelin-1 (ET-1) as a tumour marker for canine spontaneous HSA. Serum big ET-1 was measured in dogs with splenic HSA (n = 14), splenic malignant tumours other than HSA (n = 10), benign splenic lesions (n = 11) and normal healthy dogs (n = 17) by ELISA. Serum big ET-1 levels in dogs with HSA were significantly (P < 0.01) higher than in other dogs. High sensitivity (100%, 95% confidence interval 86-100%) and specificity (95%, 95% confidence interval 86-95%) for HSA diagnosis were obtained using a cut-off of 17 pg/mL according to receiver operating characteristic (ROC) curves (area under ROC curve 0.93). PPET1, ETA, VEGF and Hif1-α mRNA expression, measured by real-time PCR, were elevated in HSA compared with normal tissues. These findings suggest that elevated serum big ET-1 could be used as a diagnostic marker for canine HSA.

Serum vascular endothelial growth factor in dogs with haemangiosarcoma and haematoma.

Splenic haemangiosarcomas are frequently seen in dogs. Because of their bad prognosis differentiation from other benign splenic lesions are of prognostic importance. However, because haemangiosarcoma is a tumour of the vascular system, it was hypothesised that vascular endothelial growth factor (VEGF) might play a major role in tumour growth and might thus be increased in the blood of affected dogs. The aim of this study was to investigate the clinical relevance of differences in serum VEGF concentrations between dogs with splenic haemangiosarcomas and those with non-malignant splenic lesions (haematomas) and healthy subjects using a canine ELISA. Serum VEGF levels were significantly higher in dogs with splenic masses compared with healthy dogs, but did not differ significantly between dogs with haemangiosarcomas and haematomas. VEGF has a potential clinical utility as a diagnostic marker for dogs with splenic lesions but may not be useful to differentiate among the various splenic lesions.

Low level of baseline circulating VEGF-A is associated with better outcome in patients with vascular sarcomas receiving sorafenib: an ancillary study from a phase II trial.

We have carried out a stratified phase II study of sorafenib (So) in patients with advanced angiosarcoma (n = 32) and epithelioid hemangioendothelioma (n = 13). This report concerns the correlative analysis of the predictive values of circulating pro/anti-angiogenetic biomarkers. Using the ELISA method (R&D Systems), circulating biomarkers (VEGF-A, in picograms per milliliter), thrombospondin-1 (TSP1, in micrograms per milliliter), stem cell factor (SCF, in picograms per milliliter), placental growth factor (PlGF, in picograms per milliliter), VEGF-C (in picograms per milliliter), and E-selectin (in nanograms per milliliter) were measured before So treatment and after 7 days. VEGF-A (mean value 475 vs. 541, p = 0.002), TSP1 (16 vs. 24, p = 0.0002), and PlGF (20.9 vs. 40.7, p = 0.0001) significantly increased during the treatment. Treatment did not affect the levels of SCF, VEGF-C, and E-selectin. Only two biomarkers were associated with better outcome as follows: VEGF-A and PlGF. Best objective response and non-progression at 180 days were associated with low level of VEGF-A at baseline (p = 0.04 and 0.03, respectively). There was a correlation between the circulating level of VEGF-A and time to progression (TTP) (r = -0.47, p = 0.001). Best objective response and non-progression at 180 days were not associated with baseline level of PIGF, but there was a correlation between the circulating level of PIGF at baseline and TTP. Low level of VEGF-A at baseline (<500) was significantly associated with better outcome.

Disease distribution in canine patients with acanthocytosis: 123 cases.

BACKGROUND: An acanthocyte is an abnormally shaped erythrocyte. In veterinary medicine, acanthocytes have historically been associated with canine hemangiosarcoma. In human medicine, acanthocytes are rarely observed with neoplastic disease and are more commonly associated with a variety of hereditary and acquired diseases. OBJECTIVES: The purpose of the study was to determine what disease processes are associated with the presence of acanthocytes in the peripheral blood of dogs. METHODS: Medical records for dogs presented to the Veterinary Teaching Hospital of Colorado State University during January 2004 through June 2008 with acanthocytes documented in their CBCs were retrospectively reviewed. RESULTS: A total of 123 dogs were included, 66 of which were diagnosed with neoplastic disease, most commonly hemangiosarcoma (n = 12), osteosarcoma (n = 11), and lymphoma (n = 11). The remaining 57 dogs had nonneoplastic disease, most commonly observed were gastrointestinal (n = 13), musculoskeletal (n = 8), renal (n = 8), and immune-mediated diseases (n = 7). No statistically significant difference was detected between percent acanthocytes present in dogs with neoplastic and nonneoplastic diseases. CONCLUSION: Acanthocytosis was observed with a variety of neoplastic and nonneoplastic diseases. While clearly commonly associated, the presence of acanthocytes in a blood smear should not be considered pathognomonic for hemangiosarcoma in dogs.

Schistocytes, echinocytes, iron deficiency anemia, and thrombocytopenia - hematologic manifestations of splenic angiosarcoma.

Splenic angiosarcoma is a rare and aggressive malignancy with an incidence of less than one per million and a fatality rate over 90%.  Early diagnosis is of great importance for optimal management.  Here, we report the case of a patient with splenic angiosarcoma who presented with prominent schistocytes, echinocytes, thrombocytopenia, and iron deficiency anemia, which in combination with radiographic evidence of a splenic mass, raised the suspicion for angiosarcoma and resulted in a prompt surgical intervention with curative intent. Resolution of the hematologic findings following splenectomy suggests that patients with this malignancy should be monitored for recurrent hematologic abnormalities as they may herald recurrence of the disease. We present a literature review on the hematologic manifestations that is associated with this malignant disease.

Hyperferritinemia in dogs with splenic hemangiosarcoma.

Serum ferritin concentration increases in dogs in association with various diseases. In this study, we measured serum ferritin levels in dogs with splenic masses, using a sandwich ELISA assay. Eleven dogs with hemangiosarcoma (HSA), six with hematoma, 1 with hemangioma and 3 with lymphoma were enrolled. All dogs with HSA had serum ferritin concentrations above the normal limit (1,357 ng/ml, mean + 2× standard deviation of normal). Increased serum ferritin concentrations have also been observed in few cases of hematoma, hemangioma and lymphoma. Therefore, hyperferritinemia is not specific for splenic HSA, but may have clinical usefulness as a sensitive test for the disease. Further evaluation of serum ferritin concentrations in dogs with splenic HSA is needed.

Elevated protoporphyrin in patients with skin cancer receiving taxane chemotherapy.

BACKGROUND: Docetaxel and paclitaxel are both taxanes used for treatment of various malignant tumors. Only two case reports have described photohypersensitivity induced by docetaxel and paclitaxel in association with porphyrin aberrations. OBJECTIVES: To examine whether aberrations in the biosynthesis of porphyrins and photohypersensitivity occur among patients receiving taxanes. MATERIALS & METHODS: We examined porphyrin aberrations and photohypersensitivity in 8 patients with skin cancers who received docetaxel or paclitaxel chemotherapy in our department. RESULTS: Aberrations in erythrocyte protoporphyrin were detected in 4 patients, while no such aberration was detected in the control group. Photohypersensitivity to Ultraviolet B (UVB) was detected in 2 patients; one was related to an elevated synthesis of protoporphyrin but the other was not. Photohypersensitivity to Ultraviolet A (UVA) or visible light was not detected. CONCLUSION: Docetaxel and paclitaxel chemotherapy seemed to induce aberrations in porphyrin biosynthesis, although an elevated synthesis of porphyrin did not necessarily cause photohypersensitivity.