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Ziel der retrospektiven Studie war die Evaluation der Diagnostik (Dx) und des postop Outcomes der Penisfraktur (PF). Wir führten eine Aktenstudie der Patienten durch, die sich konsekutiv zwischen 1995 und 2008 mit V.a. eine PF vorstellten. Durch eine Nachsorge wurden Langzeitkomplikationen (LK) sowie die Scores des IIEF-5 und des IPSS retrospektiv vor sowie nach PF ermittelt. Bei 79,4% der 34 Patienten (Median 38,5 Jahre) bestätigte sich die PF, die sich in 76,5% während dem Koitus ereignete. Die Magnetresonanztomographie (MRT) zeigte sich dem Cavernosogramm überlegen. Von 25 operierten PF waren 16% beidseitig und 28% von einer Urethraläsion begleitet. Nur 30,8% der 13 Patienten mit verfügbarer Nachsorge haben postop keine LK und 38,5% eine normale erektile Funktion. 3 von 4 operativ versorgten Urethraläsionen bedingten eine Miktionsstörung. MRT ist in der Dx der PF notwendig, die Häufigkeit postop auftretender LK wird unterschätzt., The aim of the study was to evaluate the diagnostic methods and the postoperative outcome of the penile fracture (pf). We assessed a follow-up of those patients, who frequented our center between 1995 and 2008 with clinical symptoms of a pf. By an follow-up we studied the complications as well as the scores of IIEF-5 and IPSS before and after pf. In 79,4% of the 34 patients (mean 38,5 years) the investigations confirmed the diagnosis, 76,5% of the pf happened during sexual intercourse. The imaging by MRI showed better value than the cavernosography. 16% of the operated 25 pf were bilateral and 28% associated with urethral lesion. Only 30,8% of the 13 patients, where we aquired a follow-up had no complications and 38,5% a normal erectile function. 3 of the 4 operated urethral lesions caused voiding problems. MRI should be assessed in the diagnostic of the pf, the prevalence of postoperative complicated is underestimated.

Expression of epidermal growth factor receptor (EGER) may be of prognostic value in renal cell cancer (RCC). Gene amplification of EGER was investigated in a cohort of 315 patients with advanced RCC from a previously reported randomised study. Using fluorescent in situ hybridisation, only 2 patients (0.6%) had gene amplification; therefore gene amplification is of no prognostic value in RCC.

Udgivelsesdato: 2010-Mar, Expression of epidermal growth factor receptor (EGFR) may be of prognostic value in renal cell cancer (RCC). Gene amplification of EGFR was investigated in a cohort of 315 patients with advanced RCC from a previously reported randomised study. Using fluorescent in situ hybridisation, only 2 patients (0.6%) had gene amplification; therefore gene amplification is of no prognostic value in RCC.

Purpose Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2. Patients and Methods Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy-stratified by Karnofsky performance status and number of metastatic sites-were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses. Results Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT (hazard ratio [HR] = 0.94; P = .60), and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT (HR = 0.88; P = .29). In a biomarker analysis of patients with EGFR-overexpressed tumors (3+ by immunohistochemistry [IHC]; n = 241) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT (HR = 0.76; P = .06), and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT (HR = 0.69; P = .02). These results were confirmed by Cox regression analysis. No unexpected toxicities were observed; the most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhea (40%). Conclusion Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC.

Ziel dieser Arbeit war es, anhand einer retrospektiven Analyse sowie einer Nachuntersuchung und Befragung mittels standardisierten Interviews aller Patienten mit Fournier'scher Gangrän an unserer Universitätsklinik von 1996-2006 das Krankheitsbild dieser Sonderform der nekrotisierenden Fasziitis mit Fokus im Urogenitalbereich bzgl. klinischer Erscheinung, Diagnostik, Therapie und Verlauf zu charakterisieren. An Hand unserer Daten haben wir unser Vorgehen in einem diagnostischen und therapeutischen Algorithmus festgehalten. Der Schwerpunkt der Therapie liegt in rascher und radikaler chirurgischer Sanierung, aggressiver intensivmedizinischer Behandlung, konsequenter Harnableitung und individueller Indikation zur passageren Stuhlableitung. Nach verzögerter plastisch-chirurgischer Versorgung der entstandenen Defekte waren alle untersuchten Patienten mit dem ästhetischen und funktionellen Ergebnis subjektiv zufrieden., Aim of our study was to characterize clinical presentation, management and course of the disease and patients quality of life after plastic-surgical treatment of Fournier´s gangrene, a special form of necrotising fasziitis. The study was performed analysing patients charts from 1996 to 2006 and also performing a follow up visit including a standardised questionaire. Employing these data we summarised our diagnostic and therapeutical procedures in an algorithm with focus on rapid and radical surgical treatment, comprehensive intensive care treatment and urinary and individual stool diversion. After delayed plastic surgical coverage all patients were satisfied with the esthetic and functional result.

PURPOSE: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2. PATIENTS AND METHODS: Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number of metastatic sites--were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses. RESULTS: Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT (hazard ratio [HR] = 0.94; P = .60), and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT (HR = 0.88; P = .29). In a biomarker analysis of patients with EGFR-overexpressed tumors (3+ by immunohistochemistry [IHC]; n = 241) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT (HR = 0.76; P = .06), and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT (HR = 0.69; P = .02). These results were confirmed by Cox regression analysis. No unexpected toxicities were observed; the most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhea (40%). CONCLUSION: Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC Udgivelsesdato: 2008/5/10

Die Dissertation beschäftigt sich mit den Eigenschaften von Malononitrilamid 715 (MNA 715), einem Inhibitor der Dihydroorotat-Dehydrogenase, als Immunsuppressivum im Modell der heterotopen Herztransplantation in der Maus. MNA 715 wurde in Dosen von 5 bis 30 mg/kg/die für 7 oder 21 Tage appliziert. Das Transplantatüberleben wurde durch Palpation erfaßt, die Transplantate zu unterschiedlichen Zeitpunkten explantiert, konventioneller und immunhistologischer Färbeverfahren und einem RNase Protektion Assay unterzogen. Zu Einschätzung der immunsuppressiven Potenz von MNA 715 wurden die gleichen Experimente mit FK 506 durchgeführt. Es konnte gezeigt werden, daß MNA 715 dem in der Klinik etablierten FK 506 überlegen ist. Zu 30% konnte durch zeitlich limitierte Gabe von MNA 715 Organüberleben von über 100 Tagen erzielt werden. Toleranz konnte jedoch nicht induziert werden., This study deals with the characteristics of the novel immunosuppressive compound malononitrilamide 715 (MNA 715) in a model of heterotopic heart allotransplantation in the mouse. MNA 715 inhibits the dihydroorotate-dehydrogenase. MNA 715 was given in doses ranging from 5 to 30 mg/kg/die for 7 or 21 days. Graft survival was monitored by daily palpation through the recipient´s flank. Grafts were harvested at defined time points following transplantation. Conventional and immunohistology was performed as well as RNase protection assay. In order to assess the immunosuppressive strength of MNA 715 the same experimental procedure was performed using the well established drug FK 506 for comparison. The results showed that MNA 715 is superior to FK 506, in the model used in this study. Application of MNA 715, limited in time, led to long time allograft survival in 30% of the treated mice, although immunological tolerance was not achived.

Die Dissertation beschäftigt sich mit den Eigenschaften von Malononitrilamid 715 (MNA 715), einem Inhibitor der Dihydroorotat-Dehydrogenase, als Immunsuppressivum im Modell der heterotopen Herztransplantation in der Maus. MNA 715 wurde in Dosen von 5 bis 30 mg/kg/die für 7 oder 21 Tage appliziert. Das Transplantatüberleben wurde durch Palpation erfaßt, die Transplantate zu unterschiedlichen Zeitpunkten explantiert, konventioneller und immunhistologischer Färbeverfahren und einem RNase Protektion Assay unterzogen. Zu Einschätzung der immunsuppressiven Potenz von MNA 715 wurden die gleichen Experimente mit FK 506 durchgeführt. Es konnte gezeigt werden, daß MNA 715 dem in der Klinik etablierten FK 506 überlegen ist. Zu 30% konnte durch zeitlich limitierte Gabe von MNA 715 Organüberleben von über 100 Tagen erzielt werden. Toleranz konnte jedoch nicht induziert werden., This study deals with the characteristics of the novel immunosuppressive compound malononitrilamide 715 (MNA 715) in a model of heterotopic heart allotransplantation in the mouse. MNA 715 inhibits the dihydroorotate-dehydrogenase. MNA 715 was given in doses ranging from 5 to 30 mg/kg/die for 7 or 21 days. Graft survival was monitored by daily palpation through the recipient´s flank. Grafts were harvested at defined time points following transplantation. Conventional and immunohistology was performed as well as RNase protection assay. In order to assess the immunosuppressive strength of MNA 715 the same experimental procedure was performed using the well established drug FK 506 for comparison. The results showed that MNA 715 is superior to FK 506, in the model used in this study. Application of MNA 715, limited in time, led to long time allograft survival in 30% of the treated mice, although immunological tolerance was not achived.