The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions

<p>Abstract</p> <p>Background</p> <p>To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions.</p> <p>Methods</p> <p>78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF), smooth muscle actin (SMA) and CD34, while microvessel density (MVD) was counted using the anti-CD31 antibody.</p> <p>Results</p> <p>VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma.</p> <p>Conclusion</p> <p>Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma.</p

Endoscopic Vacuum Therapy for Iatrogenic Rectal Perforation

Serious iatrogenic bowel injuries during screening colonoscopy are rare events. If a perforation is detected during colonoscopy, endoscopic therapy can be attempted depending on the size and type as well as local endoscopic experience. We report the case of a 54-year-old female patient who was treated by endoscopic vacuum therapy (EVT) for a rectal perforation she had suffered during an outpatient screening colonoscopy. Two hours after the complication, an emergency endoscopy was performed. A perforation of the lower third of the rectum with a longitudinal diameter of 4 cm and a depth of 2.5 cm was detected. Due to the deep defect and the suspected increased risk of abscess formation after mechanical perforation closure with endoclips, we decided to perform EVT. The therapy was performed over a total period of 7 days. The patient was symptom free at all times. On the 2nd and 5th day, the endoscopic findings were re-evaluated and the inserted endosponges were changed. The sponge was adjusted to the wound conditions at each check and its length was gradually shortened. The endoscopic findings improved steadily. The EVT was completed after 7 days with the result of complete wound closure. The inflammatory parameters dropped continuously from day 1. On day 8, the patient could be discharged from inpatient treatment. No complications occurred in the post-inpatient course. This case is an example of successful EVT after iatrogenic rectal perforation. EVT should be considered for iatrogenic rectal perforation when signs of systemic inflammation are present and primary mechanical wound closure appears critical due to the depth of the defect and the presumed risk of abscess formation

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor Levels Reflect Renal Function in Newly Diagnosed Patients with Multiple Myeloma Treated with Bortezomib-Based Induction

(1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney disease in different disease settings. The aim of this study was to investigate a possible link between suPAR circulating levels and renal impairment (RI) in newly diagnosed patients with symptomatic multiple myeloma (NDMM) before and after frontline therapy with bortezomib-based regimens. (2) Methods: We studied 47 NDMM patients (57% males, median age 69.5 years) before the administration of anti-myeloma treatment and at best response to bortezomib-based therapy. suPAR was measured in the serum of all patients and of 24 healthy matched controls, using an immuno-enzymatic assay (ViroGates, Denmark). (3) Results: suPAR levels were elevated in NDMM patients at diagnosis compared to healthy individuals (p &lt; 0.001). suPAR levels strongly correlated with disease stage (p-ANOVA &lt; 0.001). suPAR levels both at diagnosis and at best response negatively correlated with estimated glomerular filtration rate (eGFR) values (p &lt; 0.001). Interestingly, no significance changes in suPAR levels were observed at best response compared to baseline values (p = 0.31) among 18 responding patients with baseline eGFR &lt; 50 mL/min/1.73 m(2). (4) Conclusions: SuPAR levels reflect renal function in NDMM patients treated with bortezomib-based induction. Responders may have elevated circulating suPAR levels, possibly reflecting persistent kidney damage, despite their renal response

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor Levels Reflect Renal Function in Newly Diagnosed Patients with Multiple Myeloma Treated with Bortezomib-Based Induction

(1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney disease in different disease settings. The aim of this study was to investigate a possible link between suPAR circulating levels and renal impairment (RI) in newly diagnosed patients with symptomatic multiple myeloma (NDMM) before and after frontline therapy with bortezomib-based regimens. (2) Methods: We studied 47 NDMM patients (57% males, median age 69.5 years) before the administration of anti-myeloma treatment and at best response to bortezomib-based therapy. suPAR was measured in the serum of all patients and of 24 healthy matched controls, using an immuno-enzymatic assay (ViroGates, Denmark). (3) Results: suPAR levels were elevated in NDMM patients at diagnosis compared to healthy individuals (p &lt; 0.001). suPAR levels strongly correlated with disease stage (p-ANOVA &lt; 0.001). suPAR levels both at diagnosis and at best response negatively correlated with estimated glomerular filtration rate (eGFR) values (p &lt; 0.001). Interestingly, no significance changes in suPAR levels were observed at best response compared to baseline values (p = 0.31) among 18 responding patients with baseline eGFR &lt; 50 mL/min/1.73 m(2). (4) Conclusions: SuPAR levels reflect renal function in NDMM patients treated with bortezomib-based induction. Responders may have elevated circulating suPAR levels, possibly reflecting persistent kidney damage, despite their renal response