[Devil with angel wings - when vitamin A saves lives]. / Teufel mit Engelsflügeln ­ wenn Vitamin A Leben rettet.

ANAMNESIS AND CLINICAL EXAMINATION: A 40-year-old male patient presented to our emergency department with a new onset of hemorrhagic diathesis. Clinically, there were marked bleeding stigmata with extensive ecchymosis in the thigh area and oral mucosal hemorrhage with otherwise general well-being. DIAGNOSTICS: The coagulation diagnostics performed were consistent with the picture of disseminated intravascular consumption coagulopathy. Microscopic blood count also revealed 74% morphologically atypical promyelocytes. DIAGNOSIS, THERAPY, AND CLINICAL COURSE: Bone marrow investigation confirmed the diagnosis of a microgranular variant of acute promyelocytic leukemia. In addition to coagulation optimization, therapy with all-trans retinoic acid (ATRA) was initiated immediately. Subsequently, arsenic trioxide (ATO) and the anthracycline idarubicin were added. No severe complications occurred in the following course of treatment. Moreover, the patient is currently in complete remission regarding acute promyelocytes leukemia. CONCLUSIONS: Acute promyelocytic leukemia accounts for approximately 10-15% of all acute myeloid leukemias. Often, association with marked coagulation abnormalities due to disseminated intravascular consumption coagulopathy, which is present at diagnosis, APL becomes fatal if untreated. Rapid therapy initiation with ATRA and coagulation optimization, initiated as soon as the diagnosis is suspected, are crucial for prognosis.

Pediatric lung transplantation: supply and demand.

PURPOSE OF REVIEW: Lung transplantation has become an accepted therapy in infants, children, and adolescents suffering from end-stage lung diseases, an impaired quality of life and reduced life expectancy. The aim of this review is to highlight specific aspects of pediatric lung transplantation and to give an update on recent findings. RECENT FINDINGS: Currently, over 100 lung transplant procedures are performed in children annually worldwide. Long-term success is limited by availability of donor organs and waitlist mortality pretransplant, and an increased infection risk because of immunosuppression, and most importantly late complications, such as chronic lung allograft dysfunction, medication nonadherence, and transition intricacies. SUMMARY: Specific aspects of pediatric lung transplantation will be reviewed and an update on most recent developments in the management of pediatric lung transplant recipients given.

Implication of vascular endothelial growth factor A and C in revealing diagnostic lymphangiogenic markers in node-positive bladder cancer.

Several lymphangiogenic factors, such as vascular endothelial growth factors (VEGFs), have been found to drive the development of lymphatic metastasis in bladder cancer (BCa).Here, we have analyzed the gene expression of lymphangiogenic factors in tissue specimens from 12 non-muscle invasive bladder cancers (NMIBC) and 11 muscle invasive bladder cancers (MIBC), considering tumor and tumor-adjacent normal bladder areas obtained from the same organs. We then compared the results observed in patients with those obtained after treating human primary bladder microvascular endothelial cells (MEC) with either direct stimulation with VEGF-A or VEGF-C or by co-culturing (trans-well assay) MEC with bladder cancer cell lines varying in VEGF-A and VEGF-C production based on tumor grade.The genes of three markers of lymphatic endothelial commitment and development (PDPN, LYVE-1 and SLP-76) were significantly overexpressed in tissues of MIBC patients showing positive lymphovascular invasion (LVI+), lymph node metastasis (Ln+) and tumor progression. Their expression was also significantly enhanced either after direct stimulation of MEC by VEGF-A and VEGF-C or in the trans-well assay with each bladder cancer cell line.SLP-76 showed the highest gene expression. Both VEGF-A and VEGF-C also enhanced the expression of SLP-76 protein in MEC. However, a correlation between increase of SLP-76 gene expression and the ability of MEC to migrate could only be seen after induction by VEGF-C.The significant expression of SLP-76 in LVI+/Ln+ progressive MIBC and its overexpression in MEC after VEGF-A and VEGF-C stimulation suggest the need to develop this regulator of developmental lymphangiogenesis as a diagnostic tool in BCa.

High VEGF-D and Low MMP-2 Serum Levels Predict Nodal-Positive Disease in Invasive Bladder Cancer.

BACKGROUND: To investigate stromal variables including angiogenesis, lymphangiogenesis, and matrix metalloproteinase (MMP) in the serum of patients with urothelial carcinoma of the bladder (UCB) and to evaluate their association with histopathological characteristics and clinical outcome. MATERIAL AND METHODS: Protein levels of vascular endothelial growth factors-A, -C, -D (VEGF-A/-C/-D), their receptors- VEGF-R2 and -R3 (VEGF-R2/-R3), and matrix metalloproteinases 2, -3, and -7 (MMP-2, MMP-3, MMP-7) were quantified in the blood serum samples of 71 patients with UCB before radical cystectomy (RC). Samples of patients with non-invasive UCB or no history of UCB were investigated as controls (n=20). Protein levels in the serum were measured using a flow cytometric cytokine assay. RESULTS: A positive association for VEGF-D (p<0.001) and an inverse association for MMP-2 (p=0.017) were observed in patients with positive lymph node (LN) status at the time of RC. VEGF-A (p<0.001), VEGF-C (p<0.001), MMP-2 (p<0.001), and MMP-7 (p=0.005) serum levels were different in serum of patients with invasive UCB compared with non-invasive UCB or healthy individuals. None of the serum markers were associated with disease progression. CONCLUSIONS: High VEGF-D and low MMP-2 serum levels predict LN metastasis in patients with UCB at the time of RC. VEGF-A, VEGF-C, MMP-2, and MMP-7 serum levels varied significantly between invasive and non-invasive disease as well as in comparison with healthy individuals. Clinical implementation of these marker serum measurements may be valuable to select high-risk patients with more invasive or nodal-positive disease.