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Pieper C.C.,University of Bonn | Meyer C.,University of Bonn | Vollmar B.,University of Rostock | Hauenstein K.,University of Rostock | And 2 more authors.
CardioVascular and Interventional Radiology | Year: 2015

Background: This study aimed to evaluate the embolic properties, time to reperfusion, and histologic changes in temporary embolization of liver tissue with degradable starch microspheres (DSM) in a swine model.Methods: In four adult minipigs, DSMs were injected into the right or left hepatic artery on the lobar level until complete stasis of the blood flow was detectable angiographically. The time required to complete angiographically determined reperfusion was noted. The animals were killed 3 h after complete reperfusion, and samples were taken from the liver. Histologic examinations of the embolized liver parenchyma and untreated tissue were performed.Results: Hepatic arterial embolization using DSMs was technically successful in all cases, with complete blood flow stasis shown by control angiography. A single vial of DSMs (450 mg/7.5 ml) was sufficient to embolize a whole liver lobe in all cases. Angiography showed complete reconstitution of hepatic arterial perfusion after a mean time to reperfusion of 32 ± 6.1 min (range, 26–39 min). Hematoxylin and eosin staining showed no histologically detectable differences between untreated tissue and parenchyma embolized with DSMs except for mild sinusoidal congestion in one case. Indirect in situ DNA nick end labeling staining (TUNEL) showed only single positive hepatocytes, indicating apoptosis.Conclusion: Temporary embolization of the hepatic artery using DSMs is feasible with complete reperfusion after 30 min in pigs. Even after complete arterial blood flow stasis, no extensive tissue damage to the embolized liver parenchyma was observed at histologic examinations in this short-term study. © 2014, Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Source

Mai E.K.,University of Heidelberg | Benner A.,German Cancer Research Center | Bertsch U.,University of Heidelberg | Brossart P.,University of Bonn | And 14 more authors.
British Journal of Haematology | Year: 2016

The prospective, randomized phase III trial GMMG-HD2 aimed at demonstrating non-inferiority of single (Arm A) versus tandem (Arm B) high-dose melphalan followed by autologous transplantation (HDM/ASCT) with regard to 2-year event-free survival (EFS) in newly-diagnosed multiple myeloma (MM) and included 358 evaluable patients [Intention-to-treat population, (ITT), single/tandem HDM/ASCT: n = 177/181]. After a median follow-up of more than 11 years, non-inferiority of single versus tandem HDM/ASCT was demonstrated using the planned non-inferiority threshold of 15% of the 2-year EFS rate. Neither EFS (P = 0·53) nor overall survival (OS) (P = 0·33) differences were observed in the ITT population. In the tandem arm, 26% (n = 47/181) of patients refused a second HDM/ASCT due to non-medical reasons. A per-protocol (PP) analysis, including patients who received the intervention (single/tandem HDM/ASCT: n = 156/93) and patients who did not receive a second HDM/ASCT due to medical reasons (12%, n = 22/181), did not yield differences in EFS (P = 0·61) or OS (P = 0·16). In the ITT and PP set of the tandem arm, the rates of complete responses increased from first to second HDM/ASCT (both P = 0·04). Ten-year OS for the entire ITT was 34% (95% confidence interval: 29-40%). OS after first relapse was significantly shortened in the tandem arm (P = 0·04). In this study single HDM/ASCT was non-inferior to tandem HDM/ASCT in MM. © 2016 John Wiley & Sons Ltd. Source

Hauser S.,Universitatsklinikum Bonn | Kogej M.,Universitatsklinikum Bonn | Fechner G.,Universitatsklinikum Bonn | Von Pezold J.,Katholische Kliniken Oberberg | And 4 more authors.
Anticancer Research | Year: 2013

Background: Cell-free serum DNA levels are increased in patients with cancer, and at least partially, these DNA fragments are derived from cancer cells. A few reports indicated that methylated serum DNA in patients with bladder cancer (BCA) is a useful non-invasive biomarker. The purpose of this prospective multicenter study was to validate earlier studies. Materials and Methods: In total, 227 consecutive participants (non-muscle invasive BCA, n=75; muscle-invasive BCA, n=20; transurethral bladder resection (TURB) without BCA, n=48; benign disease, n=31; healthy individuals, n=53), were recruited for this study. Cell-free serum DNA was isolated and digested with methylationsensitive restriction-enzymes (Bsh1236I, HpaII and HinP1I) to quantify the amount of methylated (TIMP3, APC, RARB, TIG1, GSTP1, p14, p16, PTGS2 and RASSF1A) DNA fragments. Results: The amount of methylated DNA was usually small (<10%), and the methylation frequencies varied for different genes (e.g. frequent: TIMP3; moderate: APC, RARB, TIG1; infrequent: p16, PTGS2, p14, RASSF1A, GSTP1). Methylation levels at each gene site and the number of methylated genes were increased in BCA compared to healthy individuals, but were similar in BCA and patients with non-malignant disease. The number of methylated genes allowed for discrimination (62% sensitivity, 89% specificity) of BCA patients from healthy individuals. DNA hypermethylation was not correlated with advanced stage or grade in patients with BCA. Conclusion: The detection of hypermethylated DNA in serum allows for discrimination of patients with BCA and healthy individuals, but there is no difference between patients with BCA and those with nonmalignant disease, thereby limiting its value as a noninvasive biomarker. Source

Molderings G.J.,University of Bonn | Meis K.,Evangelische Kliniken Bonn | Kolck U.W.,Evangelische Kliniken Bonn | Homann J.,Evangelische Kliniken Bonn | Frieling T.,Medizinische Klinik II
Immunogenetics | Year: 2010

Systemic mast cell activation syndrome is a mast cell disorder characterized by an unregulated increased activation of mast cells leading to a pathologically enhanced release of mediators. Mutations in tyrosine kinase kit which crucially determines mast cell activity have been suggested as a necessary condition for the development of a clinically symptomatic mast cell disease. At the level of mRNA in mast cell progenitor cells of 20 patients with systemic mast cell activation syndrome and of 20 gender- and age-matched healthy volunteers, the tyrosine kinase kit was investigated for genetic alterations by means of RT-PCR and direct sequencing of the amplificates. In mast cells of 13 out of these 20 patients, multiple predominantly novel potential functionally activating point mutations or complex alterations of the mRNA sequence encoding the tyrosine kinase kit were detected. In contrast, in 19 of the 20 healthy subjects, no functionally relevant alterations of c-kit transcripts were detected. The present findings support the idea that the systemic mast cell activation syndrome is a clonal disease most commonly associated with variable activating mutations in the tyrosine kinase kit. © 2010 Springer-Verlag. Source

Hauser S.,University of Bonn | Kogej M.,University of Bonn | Fechner G.,University of Bonn | Von Ruecker A.,University of Bonn | And 6 more authors.
Anticancer Research | Year: 2012

Background/Aim: Cell-free DNA may serve as a biomarker for patients with cancer; we designed our study to determine its potential in patients with bladder cancer (BCA). Materials and Methods: Short β-actin (ACTB)-106 and large ACTB-384 fragments were quantified using real time PCR (RT-PCR); the ratio of ACTB-384/ACTB-106 was defined as DNA integrity. We analyzed the serum from 95 patients with and from 132 without BCA. Results: Patients with BCA had increased ACTB-106 levels and lower DNA integrity compared to patients without cancer. However, patients undergoing transurethral bladder resection (TURB) with histological exclusion of BCA had a similar ACTB-106 level and DNA integrity, as patients with BCA. Cell-free DNA was not correlated with smoker status, pT stage, grade or lymph node metastasis, or DNA integrity. There was a weak inverse correlation of age with DNA integrity in patients with BCA. Conclusion: Analysis of serum cell-free DNA levels and fragmentation patterns are of limited value regarding the identification of patients with BCA. Source

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