Plasmablastic Lymphoma: A Review of Clinicopathologic Features and Differential Diagnosis.

Plasmablastic lymphoma (PBL) is a challenging diagnosis given its rarity and lack of expression of markers that are usually used by pathologists in establishing hematopoietic lineage. However, knowledge of the characteristic clinical setting, sites of involvement, and morphologic features of plasmablastic lymphoma can aid in the correct diagnosis of a suspected large cell lymphoma that is negative for B-cell- and T-cell-specific antigens. Herein, we review the clinical and pathologic features of plasmablastic lymphoma with an emphasis on the differential diagnosis of hematolymphoid neoplasms with immunoblastic morphology and/or evidence of plasmacytic differentiation by immunophenotype.

Use of hydroxyethyl starch in leukocytapheresis procedures does not increase renal toxicity.

Background: Hydroxyethyl starch (HES) is reportedly associated with an increased risk of renal failure and death when used for fluid resuscitation in critically ill patients. HES can be used during therapeutic leukocytapheresis (TL) procedures to enhance cell separation. The purpose of this study was to evaluate the occurrence of adverse events associated with HES during TL procedures.

B-cell Non-Hodgkin Lymphomas with Plasmacytic Differentiation.

B-cell non-Hodgkin lymphomas with plasmacytic differentiation are a diverse group of entities with extremely variable morphologic features. Diagnostic challenges can arise in differentiating lymphoplasmacytic lymphoma from marginal zone lymphoma and other low-grade B-cell lymphomas. In addition, plasmablastic lymphomas can be difficult to distinguish from diffuse large B-cell lymphoma or other high-grade lymphomas.

Langerhans Cell Histiocytosis: A Clinicopathologic Review and Molecular Pathogenetic Update.

Langerhans cell histiocytosis (LCH) comprises a wide spectrum of clinical disorders that have in common a proliferation of Langerhans-type cells with characteristic morphologic, immunophenotypic, and ultrastructural features. In part because of the diverse clinical manifestations of LCH, there has long been controversy over whether LCH is best considered a reactive process or a neoplasm. Herein, we discuss the clinical and pathologic features of LCH, including recent advances in the understanding of the molecular pathogenesis of this disease that support its categorization as a neoplasm.

Tumor-associated macrophages are a useful biomarker to predict recurrence after surgical resection of nonfunctional pancreatic neuroendocrine tumors.

Objective: Patients with nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) have poorer survival than those with functional PNETs. Our objective was to identify risk factors for recurrence after resection to better define surveillance parameters to improve long-term outcomes.

Methods: A retrospective analysis was performed for NF-PNET patients who underwent resection at the University of Michigan from 1995 to 2012.

Piloting a stress management and mindfulness program for undergraduate nursing students: student feedback and lessons learned.

Background: Widespread reports of high stress levels and mental health problems among university student populations indicate the use of interventions to facilitate stress reduction and support student resilience and wellbeing. There is growing evidence that regular mindfulness practice may confer positive health benefits and reduced stress levels.

Objectives: The aim of this pilot project was to explore the impact of a seven-week stress management and mindfulness program as a learning support and stress reduction method for nursing and midwifery students.

Circulating proteins as potential biomarkers of sunitinib and interferon-α efficacy in treatment-naïve patients with metastatic renal cell carcinoma.

Purpose: We investigated potential biomarkers of efficacy in a phase III trial of sunitinib versus interferon-alpha (IFN-α), first-line in metastatic renal cell carcinoma (mRCC), by analyzing plasma levels of vascular endothelial growth factor (VEGF)-A, VEGF-C, soluble VEGF receptor-3 (sVEGFR-3) and interleukin (IL)-8.

Methods: Seven hundred and fifty mRCC patients were randomized to oral sunitinib 50 mg/day in repeated cycles of a 4-week on/2-week off schedule or IFN-α 9 million units subcutaneously thrice weekly. Plasma samples collected from a subset of 63 patients on days 1 and 28 of cycles 1-4 and at end of treatment were analyzed by ELISA.

Soluble KIT correlates with clinical outcome in patients with metastatic breast cancer treated with sunitinib.

Background: Sunitinib inhibits vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors, and stem cell factor receptor (KIT). The ability of soluble (s)KIT, VEGF-A, sVEGFR-2, and sVEGFR-3 to predict clinical outcome was analyzed in 61 patients with previously treated metastatic breast cancer (MBC) in a phase II study of sunitinib monotherapy (ClinicalTrials.gov NCT00078000).

Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure.

Purpose: To analyze final long-term survival and clinical outcomes from the randomized phase III study of sunitinib in gastrointestinal stromal tumor patients after imatinib failure; to assess correlative angiogenesis biomarkers with patient outcomes.

Experimental Design: Blinded sunitinib or placebo was given daily on a 4-week-on/2-week-off treatment schedule. Placebo-assigned patients could cross over to sunitinib at disease progression/study unblinding.

Mechanism-related circulating proteins as biomarkers for clinical outcome in patients with unresectable hepatocellular carcinoma receiving sunitinib.

Background: Several proteins that promote angiogenesis are overexpressed in hepatocellular carcinoma (HCC) and have been implicated in disease pathogenesis. Sunitinib has antiangiogenic activity and is an oral multitargeted inhibitor of vascular endothelial growth factor receptors (VEGFRs)-1, -2, and -3, platelet-derived growth factor receptors (PDGFRs)-α and -β, stem-cell factor receptor (KIT), and other tyrosine kinases. In a phase II study of sunitinib in advanced HCC, we evaluated the plasma pharmacodynamics of five proteins related to the mechanism of action of sunitinib and explored potential correlations with clinical outcome.

Phase I/II trial of sunitinib plus gefitinib in patients with metastatic renal cell carcinoma.

Objectives: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors with proven clinical benefit in patients with metastatic renal cell carcinoma (RCC). This phase I/II study investigated sunitinib in combination with an epidermal growth factor receptor inhibitor, gefitinib, in patients with metastatic RCC.

Methods: In phase I, patients received sunitinib 37.

Circulating levels of soluble KIT serve as a biomarker for clinical outcome in gastrointestinal stromal tumor patients receiving sunitinib following imatinib failure.

Purpose: To evaluate changes in circulating levels of soluble KIT (sKIT) extracellular domain as a potential biomarker for clinical outcome in gastrointestinal stromal tumor patients treated with the multitargeted tyrosine kinase inhibitor sunitinib following imatinib failure in a previously reported phase III study.

Experimental Design: Patients received sunitinib 50 mg/d (n = 243) or placebo (n = 118) daily in 6-week cycles (4 weeks on, 2 weeks off treatment). Plasma sKIT levels were sampled every 2 weeks in cycle 1 and on days 1 and 28 of subsequent cycles; analyzed by ELISA; and evaluated using Prentice criteria, Cox proportional hazards models, and proportion of treatment effect (PTE) analysis.

Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study.

Background: Hepatocellular carcinoma (HCC) tumour spread is partly dependent on neoangiogenesis. In this open-label, multicentre, phase II trial done in Europe and Asia, sunitinib, a multitargeted tyrosine-kinase inhibitor with anti-angiogenic properties, was assessed in patients with advanced unresectable HCC.

Methods: Between February and July, 2006, eligible patients were enrolled and treated with repeated cycles of oral sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off treatment).

Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma.

Purpose: To assess the safety and efficacy of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma (mRCC) and explore biomarkers for sunitinib response.

Patients And Methods: Patients with mRCC and disease progression after bevacizumab-based therapy received oral sunitinib 50 mg once daily in 6-week cycles on a 4/2 schedule (4 weeks with treatment followed by 2 weeks without treatment) in a phase II multicenter study. The primary end point was objective response rate (ORR).

Synthesis and structure-activity relationship of small-molecule malonyl coenzyme A decarboxylase inhibitors.

The discovery and structure-activity relationship of first-generation small-molecule malonyl-CoA decarboxylase (MCD; CoA = coenzyme A) inhibitors are reported. We demonstrated that MCD inhibitors increased malonyl-CoA concentration in the isolated working rat hearts. Malonyl-CoA is a potent, endogenous, and allosteric inhibitor of carnitine palmitoyltransferase-I (CPT-I), a key enzyme for mitochondrial fatty acid oxidation.

Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation.

Abnormally high rates of fatty acid oxidation and low rates of glucose oxidation are important contributors to the severity of ischemic heart disease. Malonyl coenzyme A (CoA) regulates fatty acid oxidation by inhibiting mitochondrial uptake of fatty acids. Malonyl CoA decarboxylase (MCD) is involved in the decarboxylation of malonyl CoA to acetyl CoA.

Partial inhibition of fatty acid oxidation increases regional contractile power and efficiency during demand-induced ischemia.

Objective: Clinical trials in patients with stable angina show that drugs that partially inhibit myocardial fatty acid oxidation reduce the symptoms of demand-induced ischemia, presumably by reducing lactate production and improving regional systolic function. We tested the hypothesis that partial inhibition of fatty acid oxidation with oxfenicine (a carnitine palmitoyl transferase-I inhibitor) reduces lactate production and increases regional myocardial power during demand-induced ischemia.

Methods: Demand-induced ischemia was produced in anesthetized open-chest swine by reducing flow by 20% in the left anterior descending coronary artery and increasing heart rate and contractility with dobutamine (15 microg kg(-1) min(-1) i.