RESUMO
OBJECTIVES: To evaluate the utilization of hematopathology resources within our enterprise on axillary lymph node core biopsy (AxLNCB) specimens, particularly those obtained in the context of breast cancer screening. METHODS: The utilization of hematopathology resources was determined for all AxLNCB specimens over a 30-month period from across our enterprise, and chart review was performed for select patient demographics and radiographic features. The AxLNCB cases with benign histology were reviewed for subtyping of histologic patterns. RESULTS: Of the total 594 AxLNCB specimens, 61.6% were benign and 38.6% malignant. Of malignant cases, only 9.3% contained any hematologic malignancy, yet 94% of all cases received tissue triage for lymphoma, and 81% were reviewed at least in part by a hematopathologist. Six clinical parameters were found to independently predict risk of hematologic malignancy: male sex (P = .041), bilateral lymphadenopathy (P = .004), diffuse cortical thickening (P = .005), lack of breast cancer (P = .001), older age (P < .001), and history of hematologic malignancy (P < .001). CONCLUSIONS: Our enterprise overused hematopathology resources in the evaluation of AxLNCB performed in the study period. Our process could improve from the application of a simple tool generated from this cohort to predict percent risk of the specimen containing hematologic malignancy using patient characteristics easily found via routine chart review.
RESUMO
Arsenoplatins are adducts of two chemically important anticancer drugs, cisplatin and arsenic trioxide, that have a Pt(II) bond to an As(III) hydroxide center. Screens of the NCI-60 human tumor cell lines reveal that arsenoplatin-1 (AP-1), [Pt(µ-NHC(CH3)O)2ClAs(OH)2], the first representative of this novel class of anticancer agents, displays a superior activity profile relative to the parent drugs As2O3 or cisplatin in a majority of cancer cell lines tested. These activity profiles are important because the success of arsenic trioxide in blood cancers (such as APL) has not been seen in solid tumors due to the rapid clearance of arsenous acid from the body. To understand the biological chemistry of these compounds, we evaluated interactions of AP-1 with the two important classes of biomolecules-proteins and DNA. The first structural studies of AP-1 bound to model proteins reveal that platinum(II) binds the Nε of His in a manner that preserves the Pt-As bond. We find that AP-1 readily enters cells and binds to DNA with an intact Pt-As bond (Pt:As ratio of 1). At longer incubation times, however, the Pt:As ratio in DNA samples increases, suggesting that the Pt-As bond breaks and releases the As(OH)2 moiety. We conclude that arsenoplatin-1 has the potential to deliver both Pt and As species to a variety of hematological and solid cancers.
Assuntos
Antineoplásicos/farmacologia , Trióxido de Arsênio/análogos & derivados , Cisplatino/análogos & derivados , Compostos Organoplatínicos/farmacologia , Antineoplásicos/química , Trióxido de Arsênio/química , Trióxido de Arsênio/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/química , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Compostos Organoplatínicos/química , Relação Estrutura-AtividadeRESUMO
Platinum drugs (cisplatin, oxaliplatin, and carboplatin) and arsenic trioxide are the only commercial inorganic non-radioactive anticancer drugs approved by the US Food and Drug Administration. Numerous efforts are underway to take advantage of the synergy between the anticancer activity of cisplatin and arsenic trioxide - two drugs with strikingly different mechanisms of action. These include co-encapsulation of the two drugs in novel nanoscale delivery systems as well as the development of small molecule agents that combine the activity of these two inorganic materials. Several of these new molecular entities containing Pt-As bonds have broad anticancer activity, are robust in physiological buffer solutions, and form stable complexes with biopolymers. This review summarizes results from a number of preclinical studies involving the combination of cisplatin and As2O3, co-encapsulation and nanoformulation efforts, and the chemistry and cytotoxicity of the first member of platinum anticancer agents with an arsenous acid moiety bound to the platinum(II) center: arsenoplatins.
RESUMO
Cardiac MR is considered the gold standard in assessing RV function. The purpose of this study is to evaluate the clinical utility of an investigational iterative reconstruction algorithm in the quantitative assessment of RV function. This technique has the potential to improve the clinical utility of CMR in the evaluation of RV pathologies, particularly in patients with dyspnea, by shortening acquisition times without adversely influencing imaging performance. Segmented cine images were acquired on 9 healthy volunteers and 29 patients without documented RV pathologies using conventional GRAPPA acquisition with factor 2 acceleration (GRAPPA 2), a spatio-temporal TSENSE acquisition with factor 4 acceleration (TSENSE 4), and iteratively reconstructed Sparse SENSE acquisition with factor 4 acceleration (IS-SENSE 4). 14 subjects were re-analyzed and intraclass correlation coefficients (ICC) were calculated and Bland-Altman plots generated to assess agreement. Two independent reviewers qualitatively scored images. Comparison of acquisition techniques was performed using univariate analysis of variance (ANOVA). Differences in RV EF, BSA-indexed ESV (ESVi), BSA-indexed EDV (EDVi), and BSA-indexed SV (SVi) were shown to be statistically insignificant via ANOVA testing. R(2) values for linear regression of TSENSE 4 and IS-SENSE 4 versus GRAPPA 2 were 0.34 and 0.72 for RV-EF, and 0.61 and 0.76 for RV-EDVi. ICC values for intraobserver and interobserver quantification yielded excellent agreement, and Bland-Altman plots assessing agreement were generated as well. Qualitative review yielded small, but statistically significant differences in image quality and noise between TSENSE 4 and IS-SENSE 4. All three techniques were rated nearly artifact free. Segmented imaging acquisitions with IS-SENSE reconstruction and an acceleration factor of 4 accurately and reliably quantitates RV systolic function parameters, while maintaining image quality. TSENSE-4 accelerated acquisitions showed poorer correlation to standard imaging, and inferior interobserver and intraobserver agreement. IS-SENSE has the potential to shorten cine acquisition times by 50 %, improving imaging options in patients with intermittent arrhythmias or difficulties with breath holding.