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ZusammenfassungDie Jahrtausendwende ging in Bezug auf das Thema weibliche Inkontinenz mit vielen wesentlichen Änderungen einher, der Begriff Stressinkontinenz wurde von Belastungsinkontinenz abgelöst, die Integraltheorie von Petros u. Ulmsten sowie das Hammock-Modell von DeLancey erweiterten das Verständnis der weiblichen Inkontinenz, das TVT (Tension-free vaginal tape) setzte sich in kurzer Zeit weltumspannend als Therapiestandard durch. Die vielversprechend gestartete Stammzelltherapie wird trotz inzwischen vorliegender klinischer Studien kontrovers beurteilt. Etablierte Therapieverfahren sind zunächst die konservative Therapie mit gezieltem Beckenbodentraining, minimal-invasive Verfahren wie die suburethrale Injektion, klassische Operationsverfahren wie die Faszienzügelplastik und die Kolposuspension mit ihren Modifikationen sowie die alloplastischen suburethralen Bänder (TVT, TOT [Transobturator tape], SIS [Single incision sling]), entweder spannungsfrei oder adjustierbar. Die Operationsmethoden liefern auch im Langzeitverlauf insgesamt gute Ergebnisse bei geringerer Morbidität der Bandverfahren. In Anbetracht der weltweiten Zulassungsbeschränkungen alloplastischer Bänder sollten die urogynäkologische Expertise in klassischen Operationstechniken aufrechterhalten werden und neue Entwicklungen den IDEAL (Innovation, Development, Exploration, Assessment, Long-term study)-Empfehlungen folgen.

To investigate the synergistic effect of glycolysis inhibition on therapy answer to tyrosine kinase inhibitors in renal carcinoma. Primary cell cultures from 33 renal tumors including clear cell RCC (ccRCC), papillary RCC and the rare subtype chromophobe RCC as well as two metastases of ccRCC were obtained and cultivated. The patient-derived cells were verified by immunohistochemistry. CcRCC cells were further examined by exon sequencing of the von Hippel–Lindau gene (VHL) and by RNA-sequencing. Next, cell cultures of all subtypes of RCC were exposed to increasing doses of various tyrosine kinase inhibitors (axitinib, cabozantinib and pazopanib) and the glycolysis inhibitor 2-deoxy-d-glucose, alone or combined. CellTiter-Glo® Luminescence assay and Crystal Violet staining were used to assess the inhibition of glycolysis and the viability of the cultured primary cells. The cells expressed characteristic tissue markers and, in case of ccRCC cultures, the VHL status of the tumor they derived from. An upregulation of HK1, PFKP and SLC2A1 was observed, while components of the respiratory chain were downregulated, confirming a metabolic shift towards aerobic glycolysis. The tumors displayed variable individual responses for the therapeutics. All subtypes of RCC were susceptible to cabozantinib treatment indicated by decreased proliferation. Adding 2-deoxy-d-glucose to tyrosine kinase inhibitors decreased ATP production and increased the susceptibility of ccRCC to pazopanib treatment. This study presents a valuable tool to cultivate even uncommon and rare renal cancer subtypes and allows testing of targeted therapies as a personalized approach as well as testing new therapies such as glycolysis inhibition in an in vitro model.

Classical and molecular cytogenetic methods were applied to study the karyotypes of one species of Hipposideridae and three taxa of the Rhinolophidae subgenus Aquias from Malaysian Borneo. Except for four chromosomal pairs with autapomorphic arm combinations, the karyotype of Coelops robinsoni was found to be similar to the closely related Aselliscus stoliczkanus. From the three Rhinolophus taxa studied, only R. trifoliatus was found to share the karyotype with conspecifics from Peninsular Malaysia. In contrast, the karyotype of R. luctus foetidus from Sarawak, Borneo differed in the composition of the Y-autosomal translocation products from the closely related R. morio from Peninsular Malaysia, formerly also a subspecies of R. luctus. Therefore, elevation to specific rank is suggested for R. l. foetidus. Examination of the chromosomal set of male R. sedulus specimens from Borneo with 2n = 45 and a Neo-X1X2Y sex chromosome system revealed extreme differences to the karyotype of specimens from Peninsular Malaysia with 2n = 28, to date also classified as R. sedulus. Therefore, with Sarawak, Borneo, as the type locality for R. sedulus, the taxon from Peninsular Malaysia is here described as a new species.

The impact of combined direct normal irradiation nowcasts on revenues of two different concentrating solar power plant technologies under a time-of-delivery tariff is investigated. The applied tariff scheme offers considerably increased remuneration during evening hours with maximum energy demand and is similar to that used in South Africa for some concentrating solar power (CSP) plants already. The ideal forecast derived from ground-based observations was used to quantify the maximum economic advantage of using any forecasting scheme - and is estimated around 4 % for parabolic trough power plants and as around 8 % for solar tower power plants. This implies a maximum impact of up to 2.2 Mio and 5.3 Mio EUR of additional revenues per year for a typical 110 MW solar trough or solar tower power plant, respectively. The investigated nowcast strategy merges several satellite and numerical weather prediction based nowcasts together with a smart persistence approach in order to generate a best-of nowcast for now- and forecast time horizons up to 9 hours and in the 15 min temporal resolution required for the electricity market participation. The results for the combined nowcast are evaluated with respect to daily power plant operating principles and focusing on a power plant specific forecast verification strategy. The combined nowcast is therefore compared with ECMWF IFS based forecasts and with an optimized ground observation driven persistence approach in two representative locations around the Mediterranean area. The study investigates the impact both with respect to annual energy yield and economic annual revenues of CSP plants. It is found that in our study period 2010 and 2013 to 2015 the merged nowcast strategy adds 0.8 to 4.4 % in additional revenues per year compared to the ECMWF IFS day ahead forecast, which is a typical example of nowadays routinely available forecasts in the power plant's control room. This implies additional revenues of about 450 to 2900 kEUR per year when adding a nowcasting scheme to the solar production forecast tool already in operation at some power plants.

Background The APLNR (apelin receptor) has been shown to be an essential gene for cancer immunotherapy, with deficiency in APLNR leading to immunotherapy failure. The aim of this study is to investigate the expression of APLN (apelin) and APLNR in patients with renal cell carcinoma (RCC), and its association with clinicopathological parameters and survival. Methods Three well-characterised patient cohorts with RCC were used: Study cohort 1 (clear-cell RCC; APLN/APLNR mRNA expression; n = 166); TCGA validation cohort (clear-cell RCC; APLN/APLNR mRNA expression; n = 481); Study cohort 2 (all RCC subtypes; APLNR protein expression/immunohistochemistry; n = 300). Associations between mRNA/protein expression and clinicopathological variables/patients’ survival were tested statistically. Results While APLN showed only very weak association with tumour histological grade (TCGA cohort), APLNR/mRNA protein expression correlate significantly with ccRCC aggressiveness. APLNR is expressed in tumour vasculature and tumour cells at different levels, and these expression levels associate with tumour aggressiveness in opposing directions. APLNR expression was negatively correlated with PD-L1 expression by tumour cells in a subset of patients with ccRCC. APLNR expression in either compartment is an independent prognostic factor for survival of patients with ccRCC. Conclusion The APLNR/APLN-system appears to play an important role in ccRCC, warranting further clinical investigation.

Lebensbedrohliche Blutungen aus portosystemischen Varizen sind eine gefurchtete Komplikation der portalen Hypertension. Insbesondere Varizen in untypischen Lokalisationen – sog. ektope Varizen – stellen fur Diagnose und Therapie eine Herausforderung dar. In der vorliegenden Arbeit wird der Fall eines Patienten mit Leberzirrhose und rezidivierenden Blutungen aus einem Ileumconduit nachgezeichnet, die aus einer peristomalen Varikosis resultierten. Deren verzogerte Diagnosestellung fuhrte zu einer vitalitatsgefahrdenden Hamorrhagie, die erfolgreich mittels interventionell-radiologischer Varizenembolisation und Anlage eines TIPS (transjugularer intrahepatischer portosystemischer Shunt) unter Kontrolle gebracht werden konnte.

Preoperative anemia and allogeneic blood transfusions (ABTs) may affect outcomes in cancer surgery. The prevalence of anemia, the use of ABTs, the risks of transfusions, lengths of stay and mortality of oncological patients undergoing radical cystectomy were investigated in three University Hospitals in Germany.Hospital records of 220 consecutive patients undergoing radical cystectomy from 2010 to 2012 were retrospectively analyzed for independent risk factors of ABT and unfavorable outcomes (readmission, increased length of stay (LOS) or death) using multivariate regression analysis.Preoperative anemia was present in 40%. 70% of patients received blood transfusions. Low preoperative and intraoperative nadir hemoglobin levels were associated with receipt of ABT (OR 1.33, P = 0.04 and OR 2.94, P 0.001 respectively). Transfusion of ten or more red blood cell units (RBCs) during the entire hospital stay was a predictor of an increased LOS (P 0.001) and death (OR 52, 95%CI [5.9, 461.3], P 0.001), compared to non-transfused patients. Preoperative ABT and ASA scores were associated with ≥10RBCs.Anemic patients undergoing radical cystectomy had a high risk to receive ABTs. Preoperative transfusions and transfusion of ≥10RBCs during the entire hospital stay may increase patient`s mortality. Prospective, randomized controlled studies have to follow this study.

How does asexual reproduction influence genome evolution? Although is it clear that genomic structural variation is common and important in natural populations, we know very little about how one of the most fundamental of eukaryotic traits—mode of genomic inheritance—influences genome structure. We address this question with the New Zealand freshwater snail Potamopyrgus antipodarum, which features multiple separately derived obligately asexual lineages that coexist and compete with otherwise similar sexual lineages. We used whole-genome sequencing reads from a diverse set of sexual and asexual individuals to analyze genomic abundance of a critically important gene family, rDNA (the genes encoding rRNAs), that is notable for dynamic and variable copy number. Our genomic survey of rDNA in P. antipodarum revealed two striking results. First, the core histone and 5S rRNA genes occur between tandem copies of the 18S–5.8S–28S gene cluster, a unique architecture for these crucial gene families. Second, asexual P. antipodarum harbor dramatically more rDNA–histone copies than sexuals, which we validated through molecular and cytogenetic analysis. The repeated expansion of this genomic region in asexual P. antipodarum lineages following distinct transitions to asexuality represents a dramatic genome structural change associated with asexual reproduction—with potential functional consequences related to the loss of sexual reproduction.

SummaryComparing the molecular and cellular properties among primates is crucial to better understand human evolution and biology. However, it is difficult or ethically even impossible to collect matched tissues from many primates, especially during development. An alternative is to model different cell types and their development using induced pluripotent stem cells (iPSCs). These can be generated from many tissue sources, but non-invasive sampling would decisively broaden the spectrum of non-human primates that can be investigated. Here, we report the generation of primate iPSCs from urine samples. We first validate and optimize the procedure using human urine samples and show that Sendai virus transduction of reprogramming factors into urinary cells efficiently generates integration-free iPSCs, which maintain their pluripotency under feeder-free culture conditions. We demonstrate that this method is also applicable to gorilla and orangutan urinary cells isolated from a non-sterile zoo floor. We characterize the urinary cells, iPSCs and derived neural progenitor cells using karyotyping, immunohistochemistry, differentiation assays and RNA-sequencing. We show that the urine-derived human iPSCs are indistinguishable from well characterized PBMC-derived human iPSCs and that the gorilla and orangutan iPSCs are well comparable to the human iPSCs. In summary, this study introduces a novel and efficient approach to generate iPSCs non-invasively from primate urine. This will allow to extend the zoo of species available for a comparative approach to molecular and cellular phenotypes.Graphical AbstractWorkflow overview for establishing iPSCs from primate urine(A) We established the protocol for human urine based on a previous description (Zhou 2012). We tested volume, storage and culture conditions for primary cells and compared reprogramming by overexpression of OCT3/4, SOX2, KLF4 and MYC (OSKM) via lipofection of episomal vectors and via transduction of a sendai virus derived vector (SeV). (B) We used the the protocol established in humans and adapted it for unsterile floor-collected samples from non-human primates by adding Normocure to the first passages of primary cell culture and reprogrammed visually healthy and uncontaminated cultures using SeV. (C) Pluripotency of established cultures was verified by marker expression, differentiation capacity and cell type classification using RNA sequencing.

Background The vesicle fusion protein Dysferlin (DYSF) is mainly known as a membrane repair protein in muscle cells. Mutations of DYSF lead to muscular dystrophies and cardiomyopathies. In contrast to other members of the Ferlin protein family, few is known about its role in cancer. Our study was designed to investigate the expression and functional properties of DYSF in ccRCC and its association with clinicopathological parameters and survival. Material and methods TCGA cohort: mRNA expression data of DYSF were extracted from TCGA for patients with ccRCC (n = 603; ccRCC n = 522, benign n = 81). Study cohort: mRNA expression of DYSF in ccRCC was determined using qPCR (n = 126; ccRCC n = 82, benign n = 44). Immunohistochemical staining against DYSF was performed on tissue microarrays to validate protein expression (n = 172; ccRCC n = 142, benign n = 30). Correlations between mRNA/protein expression and clinicopathological data were statistically tested. Following siRNA-mediated knockdown of DYSF in ccRCC cell line ACHN, cell migration, invasion and proliferation were investigated. Results Both DYSF mRNA and protein expression are significantly up-regulated in ccRCC tissue. DYSF mRNA expression decreased during tumor progression: lower expression levels were measured in higher stage/grade and metastatic ccRCC with independent prognostic significance for overall and cancer-specific survival. In contrast, protein expression correlated positively with pathological parameters. Overexpression showed tendency toward poor survival. Accordingly, knockdown of DYSF suppressed migration and invasion of ccRCC cells. Conclusion DYSF mRNA and protein expression are opposingly involved in tumor progression of ccRCC. DYSF could be used as a prognostic biomarker to predict survival of patients with ccRCC.

PIWI-interacting RNAs (piRNAs) have been suggested to serve as biomarkers in cancer. In this study, we validated the expression profile of two piRNAs derived from mitochondria, piR-34536 and piR-51810, in tissue and serum of a cohort of clear cell renal cell carcinoma (ccRCC) patients. Tissue and serum samples of patients with ccRCC were collected prospectively in our biobank. Total RNA was isolated from 118 ccRCC tissues, 75 normal renal tissues as well as 30 serum samples from patients with ccRCC, and 15 serum samples from patients with non-malignant diseases. The expression of piRNAs was determined using quantitative real-time PCR. Both piR-34536 and piR-51810 were downregulated in ccRCC compared to non-malignant renal tissue. Decreased tissue piRNA levels were significant and independent predictors of shortened progression-free, cancer-specific and overall survival of ccRCC patients. The piRNA levels in serum did not differ in ccRCC patients and control subjects. The expression of piR-34536 and piR-51810 in ccRCC tissues may be used as prognostic biomarkers in ccRCC.

Zusammenfassung Hintergrund Die Arbeitsgruppe um Kälble stellte 2008 das „Serosa lined and tapered ileum“ („Fulda-Nippel“) als neuen Kontinenzmechanismus des modifizierten MAINZ-Pouch-I vor. In Anlehnung an das Prinzip von Abol-Enein wird ein getapertes Ileumsegment in einen seroserösen Tunnel aus einem zweiten „U“-förmigen Ileumsegment eingebettet. Bei dieser Technik werden Kontinenzmechanismus und Augmentation miteinander kombiniert. Sie kann in allen Pouchformen und auch als kontinente Vesikostomie genutzt werden. Patienten und Methoden In der urologischen Klinik des Universitätsklinikums Bonn wurde diese Technik seit 2008 in bisher 21 Fällen bei unterschiedlichen Indikationen verwendet. In der ersten Analyse von 2011 konnte der Nippel bereits durch geringe Frühkomplikationsraten überzeugen. Ziel dieser Studie ist die Re-Evaluation der Technik insbesondere im Hinblick auf Stenose- und Inkontinenzraten im Langzeitverlauf. Ergebnisse Bei einer mittleren Nachbeobachtungszeit von 37 Monaten traten Stomastenosen in 33 % der Fälle auf. Eine Inkontinenz des Nippels wurde bei 21 % (n = 4) der Patienten beobachtet. Bei zwei der Patienten war die Ursache der Inkontinenz das komplette Ausgleiten des Nippels aus der seroserösen Einbettung. Schlussfolgerung In der Langzeitanalyse zeigen sich ähnliche Stenose- und Inkontinenzraten im Vergleich zu den zwei etabliertesten Techniken, dem Appendixnippel und dem Ileuminvaginationsnippel. Trotz Limitation aufgrund der kleinen Fallzahl ist der Fulda-Nippel zumindest als eine adäquate „Zweitlinientechnik“ bei Versagen der initialen Methode anzusehen. Als Vesikostomie bietet der Fulda-Nippel den Vorteil, Augmentation und Kontinenzmechanismus elegant miteinander zu vereinen und sollte hier auch als Primärtechnik Verwendung finden.

Chimerism in humans is defined as the presence of two genetically different cell lines within the same organism. It is usually an acquired condition that is restricted to certain tissues and can be explained by therapeutic interventions such as blood transfusion or the transplantation of allogenic hematopoietic cells. Implications of such patients for forensic DNA testing have been described in the literature. In some rare cases, true inherited chimerism is observed. This so called tetragametic chimerism occurs via the fertilization of the two ova by two spermatozoa, followed by the fusion of early embryos and the development of an organism with intermingled cell lines. Such examples have been found in mice and other mammalian species including humans. We describe a phenotypically normal woman in whom tetragametic chimerism (46,XX/46,XX) was unexpectedly identified by STR typing during routine DNA profiling. Cytogenetic analysis proved to be a valuable tool for both independent confirmation and direct visualization of the two coexisting cell lines.

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

This study aimed to investigate the prognostic value of a quantitative, detailed, yet practical analysis of perineural invasion in radical prostatectomy specimens in a high-risk prostate cancer cohort. A total of 114 patients with prostate cancer who underwent radical prostatectomy between 2000 and 2013 were analysed. Using S100 protein immunohistochemistry assisted in the detection of nerves. In the area of closest proximity of the tumour to the dorso-lateral margins, nerves were counted and the infiltration of nerves was categorised (0-3). Category 0 was nerves without immediate tumour-cell-contact. All nerves being fully surrounded by tumour (classical perineural carcinosis) were categorised group 3. Two further categories discriminated between nerves that were touched either by carcinoma cells below 50% of the circumference (category 1) or above (category 2). Perineural carcinosis (Pn1) was seen in 61.4% of cases and correlated positively with ISUP grades, pT categories and presence of intraductal carcinoma but failed significance on Kaplan-Meier analysis. A more quantitative analysis of percentual perineural involvement did demonstrate significant survival differences: cases with less than one Pn1-positive nerve in 5 high power fields had longer survival times. Incomplete perineural involvement (category 1-2) did not have a prognostic value, endorsing the current definition of perineural carcinosis as full circumferential encasement of a nerve by tumour cells. A quantitative analysis of the percentage of nerves positive for perineural invasion has a higher prognostic value than the classical dichotomous statement on the mere presence of perineural invasion.

Background Noncoding RNAs play an important role in human carcinogenesis. YRNAs, a novel class of noncoding RNAs, have been identified as biomarkers in breast cancer patients. Objective To test the hypothesis that YRNA expression is dysregulated in clear cell renal cell carcinoma (ccRCC). Design, setting, and participants We first measured the expression of all known YRNAs (hY1, hY3, hY4, and hY5) in a screening cohort (30 ccRCC and 15 normal renal tissues). Subsequently, hY3 and hY4 were validated in an independent cohort (88 ccRCC and 59 normal renal tissues). Finally, hY3 and hY4 levels in serum samples from 30 ccRCC and 15 control individuals were measured. YRNAs were detected using quantitative real-time polymerase chain reaction. Outcome measurements and statistical analysis Relative expression values were analyzed using the Mann-Whitney-U test and Kaplan Meier estimates. Results and limitations Expression of hY3 and hY4 was increased in ccRCC samples compared with normal renal tissue, whereas hY1 and hY5 levels were similar. Expression levels of hY4 correlated with ccRCC stage and the presence of lymph node metastases. Neither hY3 nor hY4 were circulating at different levels in ccRCC patients and control individuals. Conclusions The expression of hY3 and hY4 is altered in ccRCC and associated with advanced disease. Patient summary In this report we studied the expression of noncoding YRNA in clear cell renal cell carcinoma tissue. We observed increased hY3 and hY4 expression levels in cancer tissues. However, expression levels were not different in the serum of patients with cancer or benign disease.

To study the expression of YRNAs (Ro-associated Y), a novel class of non-coding RNAs, in prostate cancer (PCA) patients. The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival PCA (prostate adenocarcinoma, n = 56), normal (n = 36) and benign prostatic hyperplasia (BPH; n = 28) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for biochemical recurrence-free survival were analysed. All YRNAs were significantly downregulated in PCA tissue compared to normal tissue (all YRNAs) and to BPH tissue (RNY4 and RNY5; RNY1 and RNY3 as trend). Among tumor ISUP grade groups, the most prominent differences in the expression were evident between groups 1 and 2 (RNY1, RNY3 und RNY4; all p

In various malignancies RNA fragments are dysregulated. Our study was designed to determine the expression of 4, 5'-tRNA halves in the tissue and serum of patients with clear cell renal cell carcinoma.Tissue and serum samples of patients with clear cell renal cell carcinoma and nonmalignant disease were collected prospectively in our biobank. We isolated total RNA from 95 clear cell renal cell carcinomas and 50 normal renal tissues as well as serum RNA from 27 patients with clear cell renal cell carcinoma and 13 with nonmalignant urological disease. To specifically determine the expression of 5'-tRNA halves we dephosphorylated and ligated an adaptor nucleotide to the 3' end of the tRNA halves. The expression levels of 4, 5'-tRNA halves (5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC, 5'-tRNA-Leu-CAG and 5'-tRNA-Lys-TTT) were then measured by TaqMan® based quantitative reverse transcription-polymerase chain reaction.All studied 5'-tRNA halves were down-regulated in clear cell renal cell carcinoma tissues, indicating a potential role as a tumor suppressor. Furthermore, we noted decreased expression of 5'-tRNA halves in patients with adverse clinicopathological parameters. All 5'-tRNA halves were expressed at lower levels in nonorgan confined clear cell renal cell carcinoma. The 5'-tRNA-Lys-TTT halves inversely correlated with ISUP (International Society of Urological Pathology) grade. In patients with clear cell renal cell carcinoma 5'-tRNA-Arg-CCT, 5'-tRNA-Glu-CTC and 5'-tRNA-Lys-TTT halves circulated at lower levels than in control subjects, indicating relevance as noninvasive biomarkers.In patients with clear cell renal cell carcinoma 5'-tRNA halves have potential as diagnostic and prognostic biomarkers. The 5'-tRNA halves may act in a tumor suppressive manner, which requires further research to confirm.

Mitochondrial dysfunction is common in cancer and the mitochondrial electron transport chain is often affected in carcinogenesis. To date, little is known about the expression of the ATP synthase subunits in clear cell renal cell carcinoma (ccRCC). The NextBio database was used to determine an expression profile of the ATP synthase subunits based on published microarray studies. We observed down-regulation of 23 out of 29 subunits of the ATP synthase. Differential expression was validated exemplarily for 12 genes (ATP5A1, ATP5B, ATPAF1, ATP5C1, ATP5D, ATP5O, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5I, ATP5S; screening cohort ccRCC n = 18 and normal renal tissue n = 10) using real-time PCR. Additional eight genes (ATP5A1, ATP5B, ATPAF1, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5S) were internally validated within an enlarged cohort (ccRCC n = 74; normal renal tissue n = 36). Furthermore, down-regulation of ATP5A1, ATPAF1, ATP5G1/G2/G3 was confirmed on the protein level using Western Blot and immunohistochemistry. We observed that altered expression of ATPAF1 and ATP5G1/G2/G3 was correlated with overall survival in patients with ccRCC. In conclusion, down-regulation of many ATP Synthase subunits occurs in ccRCC and is the basis for the reduced activity of the mitochondrial electron chain. Alteration of the expression of ATP5A1, ATPAF1, and ATP5G1/G2/G3 is characteristic for ccRCC and may be prognostic for ccRCC patients' outcome.

Introduction Mitochondrial dysfunction is common in cancer, and the mitochondrial electron transport chain is often affected in carcinogenesis. So far, little is known about the expression of the mitochondrial complex I (NADH:ubiquinone oxidoreductase) subunits in clear-cell renal-cell carcinoma (ccRCC). Materials and Methods An expression profile of the mitochondrial complex I subunits was determined using the NextBio database. Subsequently, the expression of selected subunits was experimentally validated on mRNA (quantitative real-time polymerase chain reaction) and protein (Western blot analysis, immunohistochemistry) level. Results We observed that 7 subunits of the complex I were down-regulated in at least 3 microarray studies. Deregulated mRNA expression was confirmed for NDUFA3 , NDUFA , NDUFB1 , NDUFB9 , NDUFS1 , NDUFS8 , and NDUFV1. Low NDUFS1 mRNA expression was a significant and independent adverse predictor of a shorter overall survival in our mRNA cohort and the ccRCC cohort of The Cancer Genome Atlas project. NDUFS1 expression was furthermore analyzed on the protein level, and a distinct down-regulation was observed in ccRCC as well as in the chromophobe and the sarcomatoid subtype compared to normal renal tissue. Conclusion Expression alterations occur in only a few subunits of the mitochondrial complex I subunits in ccRCC, and altered mRNA and protein expression levels of NDUFS1 may be useful to distinguish between renal-cell carcinoma and normal renal tissue.

Introduction The prevalence of urinary incontinence is increasing. Two major risk factors are overweight and age. We present objective and subjective cure rates of elderly and overweight patients treated with an adjustable single-incision sling system (AJUST™, C.R. BARD, Inc.). Materials and Methods Between 04/2009 and 02/2012 we treated 100 female patients with the single incision sling. Patients were retrospectively evaluated by Stamey degree of incontinence, cough test, pad use, and overall satisfaction. The primary outcomes of the study were objective and subjective cure rates, secondary outcomes were the safety profile of the sling and complications. Results The overall success rate in this population was 84.6% with a mean follow-up of 9.3 months. The average usage of pads per day decreased from 4.9 to 1.6 and was significantly lower in patients with a BMI

Die Standardtherapie des metastasierten Urothelkarzinoms ist die Cisplatin-basierte Polychemotherapie, unter der es jedoch auch bei initial gutem Ansprechen meist zu einem Progress kommt. In den letzten Jahren zeigt sich bei verschiedenen Tumorentitaten der Nutzen von zytoreduktiven oder konsolidierten Operationen mit einem verlangerten Uberleben. Aufgrund der meist kurzen Uberlebenszeiten wurde das metastasierte Urothelkarzinom bislang jedoch nicht als Kandidat fur eine solche multimodale Therapie erachtet. Verschiedene retrospektive Studien zeigen jedoch einen Nutzen operativer Radikaloperationen fur ein selektioniertes Patientengut mit metastasiertem Urothelkarzinom: Sowohl die konsolidative Zystektomie als auch die Metastasektomie nach vorangegangener Chemotherapie kann in einigen Fallen ein Langzeituberleben ermoglichen. Prognostisch relevante Parameter sind dabei neben einem guten Ansprechen auf die Chemotherapie v. a. eine limitierte Metastasierung in regionale Lymphknoten und/oder eine singulare Lungenmetastase.

Background Research shows disparities in cancer outcomes by ethnicity or socio-economic status. Therefore, it is the aim of our study to perform a matched-pair analysis which compares the outcome of German and non-German (in the following described as ‘foreign’) cancer patients being treated at the Center for Integrated Oncology (CIO) Köln Bonn at the University Hospital of Bonn between January 2010 and June 2016. Methods During this time, 6314 well-documented patients received a diagnosis of cancer. Out of these patients, 219 patients with foreign nationality could be matched to German patients based on diagnostic and demographic criteria and were included in the study. All of these 438 patients were well characterized concerning survival data (Overall survival, Progression-free survival and Time to progression) and response to treatment. Results No significant differences regarding the patients’ survival and response rates were seen when all German and foreign patients were compared. A subgroup analysis of German and foreign patients with head and neck cancer revealed a significantly longer progression-free survival for the German patients. Differences in response to treatment could not be found in this subgroup analysis. Conclusions In summary, no major differences in survival and response rates of German and foreign cancer patients were revealed in this study. Nevertheless, the differences in progression-free survival, which could be found in the subgroup analysis of patients with head and neck cancer, should lead to further research, especially evaluating the role of infectious diseases like human papillomavirus (HPV) and Epstein-Barr virus (EBV) on carcinogenesis and disease progression.

OBJECTIVE To analyze the expression of mitochondrial respiratory chain protein subunits in clear cell renal cell carcinoma. METHODS Possible prognostic candidates were determined using The Cancer Genome Atlas database (n = 605). The database provided valid messenger ribonucleic acid expression data for 93 genes encoding for the subunits. Selected subunits were further investigated at the messenger ribonucleic acid and protein level by real-time polymerase chain reaction, western blot and immunohistochemistry with the cohorts of the University Hospital Bonn. RESULTS The Cancer Genome Atlas messenger ribonucleic acid expression data indicated univariate and multivariate prognostic impact for seven subunits (NDUFS8, NDUFS7, COX5B, COX6B1, SDHD, COX15 and COX19). Using real-time polymerase chain reaction, significant downregulation (P