Antagonism of vascular endothelial growth factor results in microvessel attrition and disorganization of wound tissue

Vascular endothelial growth factor (VEGF) is a potent growth factor that is indispensable for the development of blood vessels in the fetus and for wound healing in adults. VEGF likely plays a role in maintaining the blood vessels once they have been formed. It is not clear, however, whether a low tissue VEGF (caused either by disease or by systemic administration of VEGF antagonists) can cause abnormalities in preexisting blood vessels, especially of wound tissue that requires high local levels of VEGF for healing. The present study investigated the effect of VEGF antagonism on blood vessels of foreign-body granulomas (a model of wound-healing tissue). Granulomas were induced by implanting perforated polyvinyl tubes into the subcutaneous tissue of rats and allowed to develop for 14 days, at which time the implanted tubes were completely encapsulated by the subcutaneous tissue. The encapsulated granulomas consisted of 3 distinct histological layers, of which the middle layer was well perfused by a rich supply of microvessels. Morphologically, the granuloma remained "stable" after developing for 14 days. At 1 week, VEGF levels in the granuloma fluid, which is in equilibrium with the interstitial fluid, were 25 times higher than in the plasma. VEGF levels in the granuloma fluid continued to increase for up to 3 weeks, reflecting the high dependence of the wound tissue on ambient VEGF levels. After injection of the VEGF receptor antagonist in the fully formed granuloma, the preexisting blood vessels in the middle layer regressed and underwent apoptosis, accompanied by expansion of the extracellular matrix (predominately collagen I) into areas normally devoid of matrix. We conclude that wound tissue is sensitive to ambient VEGF levels, and that a low VEGF condition resulting from VEGF receptor antagonism can disrupt the healing of wound tissue.     

CT differentiation of enlarged mediastinal lymph node due to anthracosis from metastatic lymphadenopathy: a comparative study proven by endobronchial US-guided transbronchial needle aspiration

PURPOSE

Anthracosis often results in mediastinal nodal enlargement. The aim of this comparative study was to evaluate if it is possible to differentiate endobronchial ultrasound-guided trans-bronchial needle aspiration (EBUS-TBNA) proven anthracotic lymph nodes from malignant lymph node enlargement by means of multislice computed tomography (MSCT).

METHODS

We compared the MSCT findings of 89 enlarged lymph nodes due to anthracosis with 54 malignant lymph nodes (non-small cell lung cancer 75.9%, small cell lung cancer 18.5%, and non-Hodgkin lymphoma 5.6%). The lymph nodes were assessed for density (calcification, fat, and necrosis), shape (oval, round), contrast enhancement, and contour (sharp, ill-defined).

RESULTS

Malignant lymph nodes showed significantly greater axis diameters (P < 0.001). Both anthracotic and malignant nodes were most often oval (86.5% of all malignant nodes vs. 81.5% of all anthracotic nodes, P = 0.420) and showed confluence in a remarkable percentage (28.1% vs. 42.6%, P = 0.075). Anthracotic nodes showed calcifications more often (18% vs. 0%, P < 0.001). Malignant lymph nodes showed a significantly greater short and long axis diameter (P < 0.001), and they had a higher frequency of ill-defined contours (27.8% vs. 2.2%, P < 0.001) and contrast enhancement (27.8% vs. 5.6%, P < 0.001). Nodal necrosis, which appeared in one third of the malignant nodes, was not observed in anthracosis (35.2% vs. 0%, P < 0.001). Confluence of enlarged lymph nodes was seen in malignant lymph nodes (42.6%), as well as in lymph node enlargement due to anthracosis (28.1%, P = 0.075).

CONCLUSION

Our results show that there are significant differences in MSCT findings of malignant enlarged lymph nodes and benign lymph node enlargement due to anthracosis.Anthracosis is characterized by alterations not only of the lung parenchyma and bronchioles but also of the lymphatic system, resulting in chronic lymphadenopathy and nodal enlargement (1). Since finding of enlarged mediastinal lymph nodes on computed tomography (CT) may raise the suspicion of metastasis in patients with a known primary neoplasm (2, 3), and lymph node anthracosis may appear as false positive on positron emission tomography (PET) (4–6), it can confuse clinicians in staging of lung cancer patients.The aim of this comparative study of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and chest CT was to evaluate whether it is possible to differentiate enlarged anthracotic lymph nodes from malignant lymph node enlargement by means of CT. To the best of our knowledge, this study seems to be the first to deal with the differential diagnosis of enlarged anthracotic and malignant lymph nodes in this setting.     

A serum microRNA signature associated with complete remission and progression after autologous stem-cell transplantation in patients with multiple myeloma

We have examined serum microRNA expression in multiple myeloma (MM) patients at diagnosis and at complete response (CR) after autologous stem-cell transplantation (ASCT), in patients with stable monoclonal gammopathy of undetermined significance, and in healthy controls. MicroRNAs were first profiled using TaqMan Human MicroRNA Arrays. Differentially expressed microRNAs were then validated by individual TaqMan MicroRNA assays and correlated with CR and progression-free survival (PFS) after ASCT. Supervised analysis identified a differentially expressed 14-microRNA signature. The differential expression of miR-16 (P = 0.028), miR-17 (P = 0.016), miR-19b (P = 0.009), miR-20a (P = 0.017) and miR-660 (P = 0.048) at diagnosis and CR was then confirmed by individual assays. In addition, high levels of miR-25 were related to the presence of oligoclonal bands (P = 0.002). Longer PFS after ASCT was observed in patients with high levels of miR-19b (6 vs. 1.8 years; P < 0.001) or miR-331 (8.6 vs. 2.9 years; P = 0.001). Low expression of both miR-19b and miR-331 in combination was a marker of shorter PFS (HR 5.3; P = 0.033). We have identified a serum microRNA signature with potential as a diagnostic and prognostic tool in MM.