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Squamous penile cancer displays a rare human papillomavirus (HPV)–associated tumor entity. Investigations on the molecular pathogenesis of HPV-driven penile cancer are impaired by the rareness of clinical specimens and, in particular, are missing relevant cell culture models. Here, we identified in HPV-positive penile cancer cell lines that HPV16 oncoproteins control TP63 expression by modulating critical regulators, while integration into the TP63 open reading frame facilitates oncogene expression. The resulting feed-forward loop leads to elevated p63 levels that in turn enhance the release of the neutrophil-recruiting chemokine CXCL8. Remarkably, elevated CXCL8 amounts lead to the increased surface exposition of the Fc receptor of human IgA antibodies, FcαRI, on neutrophils and correlated with a higher susceptibility to antibody-dependent neutrophil-mediated cytotoxicity (ADCC) using an EGFR-specific IgA2 antibody. IHC staining of tissue microarrays proved that elevated expression of p63 together with neutrophil infiltration were significantly more frequent in HPV-positive penile cancer displaying a higher tumor grade. In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.

Highlights • Elevated expression of Wnt pathway associated factors in HPV-positive penile cancer cells. • lacking nuclear beta-catenin translocation indicated an actively abrogated Wnt signaling. • elevated expression of the Wnt antagonist DKK1 in HPV-positive penile cancer cells. • DKK1-driven autocrine Wnt pathway inhibition in penile cancer cells. • DKK1+ penile cancers are with a higher frequency HPV+, less differentiated and grow more aggressively., Penile squamous cell cancer (PSCC) is the most frequent penile malignant disease. Infections with human papillomaviruses (HPV) are a major etiologic driver of PSCC. However, the molecular details of the underlying carcinogenesis are understudied because of rare clinical specimens and missing cell lines. Here, we investigated if the expression of high-risk HPV16 oncogenes causes an augmentation of the Wnt pathway using unique HPV-positive penile cancer (PeCa) cell lines in monolayer and organotypic 3D raft cultures as well as tissue micro arrays containing clinical tissue specimens. The HPV oncoproteins enhanced the expression of Leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and the HPV-positive PeCa cells expressed a signature of Wnt target and stemness-associated genes. However, the notable lack of nuclear β-catenin in vitro and in situ raised the question if the enhanced expression of Wnt pathway factors is tantamount to an active Wnt signaling. Subsequent TOP-flash reporter assays revealed Wnt signaling as absent and not inducible by respective Wnt ligands in PeCa cell lines. The HPV-positive PeCa cells and especially HPV-positive PeCa specimens of the tumor core expressed the Wnt antagonist and negative feedback-regulator Dickkopf1 (DKK1). Subsequent neutralization experiments using PeCa cell line-conditioned media demonstrated that DKK1 is capable to impair ligand-induced Wnt signaling. While gene expression analyses suggested an augmented and active canonical Wnt pathway, the respective signaling was inhibited due to the endogenous expression of the antagonist DKK1. Subsequent TMA stainings indicated Dkk1 as linked with HPV-positivity and metastatic disease progression in PeCa suggesting potential as a prognostic marker.

Squamous penile cancer displays a rare human papillomavirus (HPV)–associated tumor entity. Investigations on the molecular pathogenesis of HPV-driven penile cancer are impaired by the rareness of clinical specimens and, in particular, are missing relevant cell culture models. Here, we identified in HPV-positive penile cancer cell lines that HPV16 oncoproteins control TP63 expression by modulating critical regulators, while integration into the TP63 open reading frame facilitates oncogene expression. The resulting feed-forward loop leads to elevated p63 levels that in turn enhance the release of the neutrophil-recruiting chemokine CXCL8. Remarkably, elevated CXCL8 amounts lead to the increased surface exposition of the Fc receptor of human IgA antibodies, FcαRI, on neutrophils and correlated with a higher susceptibility to antibody-dependent neutrophil-mediated cytotoxicity (ADCC) using an EGFR-specific IgA2 antibody. IHC staining of tissue microarrays proved that elevated expression of p63 together with neutrophil infiltration were significantly more frequent in HPV-positive penile cancer displaying a higher tumor grade. In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.

Objective To investigate the effect of perioperative complications involving artificial urinary sphincter (AUS) implantation on rates of explantation and continence as well as health-related quality of life (HRQOL). Materials and methods Inclusion criteria encompassed non-neurogenic, moderate-to-severe stress urinary incontinence (SUI) post radical prostatectomy and primary implantation of an AUS performed by a high-volume surgeon (>100 previous implantations). Reporting complications followed the validated Clavien-Dindo scale and Martin criteria. HRQOL was assessed by the validated IQOL score, continence by the validated ICIQ-SF score. Statistical analysis included Chi (2) test, Mann-Whitney-U test, and multivariate regression models (p

Aims To comparatively analyse outcomes after ARGUS classic and ArgusT adjustable male sling implantation in a real-world setting. Methods Inclusion criteria encompassed: non-neurogenic, moderate-to-severe stress urinary incontinence (≥2 pads), implantation of an ARGUS classic or ArgusT male sling between 2010 and 2012 in a high-volume center (>150 previous implantations). Functional outcomes were assessed using daily pad usage, 24-hour pad testing, and International Consultation on Incontinence (ICIQ-SF) questionnaires. Continence was defined as zero pads per 24 hours. Complications were graded using Clavien-Dindo scale. For multivariate analysis, binary logistic regression models were used (P Results A total of 106 patients (n = 74 [ARGUS classic], n = 32 [ArgusT]) from four centers were eligible. Median follow-up was 44.0 months (24-64). Patient cohorts were well-balanced. We observed a statistical trend in favor of ARGUS classic regarding postoperative urine loss based on standardized 24-hour pad test (71 ± 162 g [ARGUS classic] vs 160 ± 180 g [ArgusT]); P = .066]. Dry rates were 33.3% (ARGUS classic) and 11.8% (ArgusT, P = .114). In multivariable analysis, ArgusT male sling could not be confirmed as an independent predictor of decreased success (OR, 0.587; 95% CI; 0.166-2.076, P = .408). There were no Clavien IV and V complications. Inguinal pain was significantly higher after ArgusT implantation (P = .033). Explantation rates were higher for ArgusT compared to ARGUS classic (14.0 vs 23.3%; P = .371). Longer device survival for the ARGUS classic male sling was observed in Kaplan-Meier analysis (P = .198). Conclusions In the largest comparative analysis of ARGUS classic and ArgusT male sling with the longest follow-up to date, we observed low continence rates with superior functional outcomes and decreased explantation rates after ARGUS classic implantation.

Zusammenfassung Hintergrund Die roboterassistierte Prostataadenomenukleation (RAPAE) ist ein minimal-invasives Verfahren zur operativen Behandlung der Prostatahyperplasie mit Volumina >80 cm3. An der vorliegenden Analyse wurde retrospektiv die postoperative (postop.) Morbidität der RAPAE gegenüber der offenen Prostataadenomenukleation (PAE) anhand der Clavien-Dindo-Klassifikation sowie hämatologischer Parameter untersucht. Patienten und Methoden In die retrospektive Analyse wurden 78 Patienten multizentrisch eingeschlossen, wovon jeweils die Hälfte eine RAPAE und eine PAE erhielten. Folgende Parameter wurden zwischen beiden Gruppen untersucht: Alter, PSA-Wert, Prostatavolumen, ASA-Score, Krankenhausaufenthaltsdauer, Operationsdauer, Hb-Wert Abfall am 1. Tag und innerhalb der ersten 5 postop. Tage, CRP-Peak innerhalb der ersten 5 postop. Tage und die Transfusionsrate. Ergebnisse Im Vergleich der RAPAE zur PAE zeigten sich keine Unterschiede im Alter, PSA-Wert, ASA-Score und Volumina. Die RAPAE-Gruppe hatte eine erhöhte Operationsdauer (178 vs. 110 min.; p =p =p =p =0,01) und Blutkonservenmenge pro Patient (0,1 vs. 1,3; p =0,01), einen niedrigeren Clavien-Dindo Score (0,44 vs. 1,23; p =0,003) und niedrigere CRP-Werte (52 vs. 104 mg/l; p =p = Schlussfolgerung Aufgrund der minimal-invasiven Operationstechnik ist die RAPAE ein sicheres Verfahren mit weniger Blutverlust, Transfusionsrate und geringeren Komplikationen im Vergleich zur PAE. Im PAE-Kollektiv traten häufiger Komplikationen aufgrund von Blutungen auf. Dies hatte eine verlängerte Liegezeit und einen deutlich erhöhten Transfusionsbedarf zur Folge.

Objective: To analyze decision-making in patients with male urinary incontinence (SUI) in centers of expertise. The artificial urinary sphincter (AUS) remains the gold standard for male patients with moderate to severe SUI but adjustable male slings are a minimally invasive treatment option with good results, hence without a high level of evidence regarding the optimal patient selection. Materials and Methods: In total, 220 patients (88 AUS; 132 adjustable slings) were investigated from the DOMINO database that underwent surgery between 2010 and 2012 in 5 urological departments that offer adjustable sling systems as well as AUS systems for patients with moderate to severe urinary incontinence. For statistical analysis, the Mann-Whitney U test was used to identify differences between both groups. Results: Patients selected for an adjustable male sling were less likely to have a neurological disease (5.3 vs. 9.1%; p = 0.030), a prior urethral stricture (22.7 vs. 50.0%; p = 0.001), a prior incontinence surgery (24.4 vs. 45.5%; p = 0.01), or a prior radiation therapy (26.5 vs. 40.1%; p = 0.001). The severity of preoperative incontinence was higher in patients selected for an AUS with a mean pad usage per day of 7.60 versus 5.80 (p < 0.001). Mean postoperative pad usage and patients’ subjective perception were comparable in both groups. Conclusion: In centers offering both options, the decision-making is mainly based upon presence of radiation therapy and previous failed incontinence surgery. Despite the more complex patient cohort selected for an AUS implantation with a possible impact on the postoperative outcome, the functional results seem to be comparable indicating a proper preoperative patient assessment and selection in this cohort.

Objective: The artificial urinary sphincter (AUS) is the surgical gold standard after previously failed surgical treatment for male urinary stress incontinence. The evidence for a male sling as salvage treatment is poor, but there is a proportion of patients that refuse implantation of an AUS or have a relative contraindication. The goal of our retrospective study was an analysis of outcome and complications of patients with a secondary sling after previously failed surgery for stress urinary incontinence (SUI). Materials and Methods: Data on 186 patients who had a prior incontinence surgery were extracted from the DOMINO database. 139 patients (74.7%) received an AUS and 41 patients (22.0%) who had received a secondary sling system between 2010 and 2012 after previously failed surgery for male urinary incontinence could be identified and were further analyzed. Results: Eight patients (19.5%) received a secondary repositioning sling and 33 patients (80.5%) received a secondary adjustable sling system. A prior surgery for urethral stricture was performed in 4 patients (9.8%). No major intraoperative complications were reported. A simultaneous explantation was performed in 12 patients (29.3%). The mean number of pad reductions was 4.93 (p = 0.026). No intraoperative complications and no postoperative surgical revisions were reported. The mean follow-up of the patient cohort with a secondary sling was 16 months. Conclusion: We provide the largest cohort of male patients up to date with a secondary sling after primary failure of surgery for male SUI. Although the procedure is a rarely performed surgery and without a high level of evidence, a secondary adjustable male sling system might be a feasible option in selected patients with acceptable complication rates, whereas a valuable outcome regarding continence rates cannot be sufficiently supplied by our data.

Purpose The aim was to study the correlation between cuff size and outcome after implantation of an AMS 800 artificial urinary sphincter. Methods A total of 473 male patients with an AMS 800 sphincter implanted between 2012 and 2014 were analyzed in a retrospective multicenter cohort study performed as part of the Central European Debates on Male Incontinence (DOMINO) Project. Results Single cuffs were implanted in 54.5% and double cuffs in 45.5% of the patients. The cuffs used had a median circumference of 4.5 cm. Within a median follow of 18 months, urethral erosion occurred in 12.8% of the cases and was associated significantly more often with small cuff sizes (P

Background: Due to the risks of hematological side effects resp. clinical aggravation, not all patients with metastasized castration resistant prostate cancer (mCRPC) and bone metastases should undergo all six cycles of radium-223-dichloride therapy. A parameter helping us to assess the chances of successful therapy management as well as the risk of hematological side effects is needed. The aim of this study is to analyze “Bone Marrow Scintigraphy” (BMS) as a prognostic factor. Methods: 106 patients were included in our single-center study. 93 patients underwent BMS with 492-667 MBq Tc-99m Scintimun® prior to therapy. The “Uptake Ratio” (UR) was calculated by positioning “regions of interest” (ROI) around the sacroiliac region, the sternum and the background areas. We calculated an UR threshold value by means of a “Receiver-Operating-Characteristics” (ROC) curve. The UR and the “Bone Scan Index” (BSI), which is automatically gained by bone scintigraphy, were related and compared to other measured parameters (lab parameters, androgen deprivation therapy (ADT)). Statistics software IBM® SPSS® Statistics (Version 24.0) was employed to identify prognostic factors by univariate und multivariate analyzes.Results: The sacroiliac area-to-background technique proved helpful in combination with the calculated threshold UR=8 for quantitative assessment of a BMS. Radium-223-dichloride treatment showed significantly lower hematological toxicity at UR>8 (p=0.001). More precisely subdivided, there was a significant effect on to the number of erythrocytes (p=0.018), leucocytes (p=0.030) und neutrophil granulocytes (p=0.031). Significant prognostic factors influencing the “Overall survival” (OS) were the bone marrow (BM) distribution pattern (p=0.039) and the calculated UR (p=0.027). Conclusion: An UR value of 8 can be used for an approximation in prognostic assessment of risks and chances of this therapy. A combination of a qualitative and a quantitative evaluation of pre-therapeutic BMS could help to minimize therapy drop-outs and an avoidable exposure to radium-223-dichloride-therapy as well as other potential radio-nuclide therapies.

AIM To analyze the influence of implantation volume of artificial sphincters (AMS 800) on outcome in a large central European multicenter cohort study. METHODS As part of the DOMINO (Debates on Male Incontinence) project, the surgical procedures and outcomes were retrospectively analyzed in a total of 473 patients who received an artificial sphincter (AMS 800) between 2010 and 2012. Clinics that implanted at least 10 AMS 800 per year were defined as high-volume centers. RESULTS Sixteen centers had a mean rate of 9.54 AMS 800/y of which five clinics were identified as high-volume centers. They implanted significantly more double cuffs (55% vs 12.1%; P

Das Peniskarzinom stellt in der klinischen Praxis eine Seltenheit dar. Es werden globale Unterschiede in der Inzidenz des Peniskarzinoms, gesellschaftliche Einflussfaktoren sowie Risikofaktoren beschrieben. In diesem Beitrag erfolgt eine Auswertung der epidemiologischen Literatur, die Diskussion der einzelnen Risikofaktoren sowie die Erorterung praventiver Masnahmen. Es besteht ein deutlicher Unterschied in der Inzidenz des Peniskarzinoms im Vergleich industrialisierter Lander mit sog. Schwellen- und Entwicklungslandern. Ein Zusammenhang zwischen einer Phimose sowie erfolgter Zirkumzision in Bezug auf die Entstehung des Peniskarzinoms konnte mehrfach nachgewiesen werden. Zudem besteht eine Assoziation mit chronisch inflammatorischen Erkrankungen als auch einer HPV-Infektion (humane Papillomaviren). Praventive Masnahmen sind vor dem Hintergrund der Seltenheit der Erkrankung gerade in Bezug auf die Durchfuhrung einer Zirkumzision kritisch zu betrachten. Die regelmasige klinische Untersuchung des Genitals ist sinnvoller Bestandteil einer Fruherkennungsmasnahme.

ZusammenfassungEin gemischt epithelial-stromaler Tumor der Niere ist selten. Histologisch tritt er in einem Komplex aus Epithel und Stroma auf und enthält zystische und solide Areale. Prädisponiert sind vor allem perimenopausale Frauen mit Anwendung einer Hormonersatztherapie. Typische Symptome sind Hämaturie, Flankenschmerz und ein tastbarer Unterbauchtumor, wobei immer mehr Autoren über inzidentelle Tumoren berichten. So auch in unserem Fallbericht. Wir berichten über den ersten publizierten Fall in Deutschland: eine 60-jährige Patientin mit einem gemischt epithelial-stromalen Tumor der rechten Niere. Der Tumor wurde mittels laparoskopischer Nephrektomie entfernt.

BACKGROUND: Fixed and adjustable male slings for the treatment of male urinary stress incontinence became increasingly popular during the last decade. Although fixed slings are recommended for the treatment of mild to moderate stress urinary incontinence, there is still a lack of evidence regarding the precise indication for an adjustable male sling. Furthermore, there is still no evidence that one type of male sling is superior to another. However, both, adjustable and fixed slings, are commonly utilized in daily clinical practice. This current investigation aims to evaluate the differences between fixed and adjustable male slings regarding indications, complication rates and functional outcome in the treatment of male stress urinary incontinence in current clinical practice. METHODS: A total of 294 patients with a fixed and 176 patients with an adjustable male sling were evaluated in a multicenter single arm cohort trial. Data collection was performed retrospectively according the medical record. Functional outcome was prospectively analyzed by standardized, validated questionnaires. Descriptive statistics was performed to present patient characteristics, complication rates and functional outcome. A chi2-test for categorical and independent t-test for continuous variables was performed to identify heterogeneity between the groups and to correlate preoperative characteristics with the outcome. A P value

Hintergrund: Die haufigste Krebserkrankung bei Mannern ist das Prostatakarzinom. D’Amico et al. (1998) haben eine Klassifikationsmethodik entwickelt, um sowohl die Aggressivitat des Wachstums als auch das Risiko der Metastasierung einschatzen zu konnen. Die Klassifikation basiert auf den Parametern PSA-Wert, Gleason-Score (GS) und Tumorausdehnung (T). Daraus ergeben sich Low-Risk-, Intermediate-Risk- und High-Risk-Patienten. Wir beobachteten im Rahmen einer groseren heuristischen Untersuchung zum Thema „Bedeutung und Notwendigkeit der pelvinen Lymphadenektomie bei Low-Risk Prostatakarzinompatienten“ u. a. das Zusammenspiel der Parameter (PSA, GS, T) mit dem Auftreten von Lymphknotenmetastasen bei Low-Risk-Patienten, bei denen im Rahmen der radikalen Prostatektomie eine Lymphadenektomie durchgefuhrt wurde. Patienten/Material und Methoden: Aufgrund der komplizierten bzw. dunnen Datenlage – bei keinem der „echten“ (d. h. bestatigten) (Low-Risk=LR) LR-Patienten wurden Metastasen gefunden – definierten wir einen Ubergangs-bereich zwischen Low-Risk und Intermediate-Risk (Korridor=K) angelehnt an D’Amico: PSA ≤ 10 ng/ml und GS≤7a (K: 7a) und T1a–T2c (K: T2b, T2c): Das Kollektiv setzt sich aus 288 Patienten (60 Low-Risk (LR), 228 Korridor (K)) zusammen. Wir analysierten Anzahl und Haufigkeit der Lymphknoten und Metastasen. Zudem untersuchten wir das Kollektiv hinsichtlich eines postoperativen GS-Upgrades. Die Ergebnisse basieren auf heuristischen Methoden. Ergebnisse: Die Datenlage im Ubergangsbereich, d. h. im Korridorbereich und dem verifizierten Low-Risk Bereich stellt sich ausgesprochen kompliziert dar: Insgesamt wurden bei den den 288 Patienten 3 743 Lymphknoten entnommen (Mittelwert: 13) davon waren lediglich 7 Lymphknoten metastasiert und diese stammten von 5 K-Patienten. Die Anzahl der insgesamt entfernten Lymphknoten bei diesen 5 Patienten liegt in einem kleinen Intervall [23,32], im Durchschnitt wurden ihnen 26 Lymphknoten entfernt. Ein postoperatives GS-Upgrade wurde bei 20,14% aller Patienten festgestellt. Schlussfolgerung: Ein postoperatives GS-Upgrade bei jedem funften Patienten zeigt, dass ein nicht unerhebliches praoperatives Undergrading vorliegt, was dazu fuhren kann, dass Patienten nicht adaquat therapiert werden. Die Offnung der D’Amico Klassifikation ware ein Weg, die Gefahr des Undergradings zu minimieren. In diesem Zusammenhang kann eine pelvine Lymphadenektomie zumindest bei Patienten aus dem Korridor nicht abgelehnt werden.

The international guidelines recommend sentinel lymph node biopsy (SLNB) for lymph node staging in penile cancer with non-palpable inguinal lymph nodes (LN) but it is not recommended with palpable inguinal LN. The aim of this study was to evaluate the reliability and morbidity of SLNB in combination with an ultrasound-guided resection of suspect inguinal LNs as a new multimodal, minimally invasive staging approach in these patients. We performed SLNB in 26 penile cancer patients with 42 palpable inguinal LNs. Prior to the combined staging procedures the patients underwent an ultrasound examination of the groins as well as planar lymphatic drainage scintigraphy and SPECT/CT scans. During the surgical procedure, the radioactive-labelled sentinel lymph nodes and, in addition, sonographically suspect LNs, were resected under ultrasound guidance. Follow-up screening was done by ultrasound examination of the groins according to the guidelines of the European Association of Urology. Nineteen groins of 42 preoperatively palpable inguinal findings were histologically tumor-positive. SLNB alone showed lymphogenic metastases in 14 groins. Sonography revealed five further metastatic groins, which would not have been detected during SLNB due to a tumor-related blockage of lymphatic drainage or a so-called re-routing of the tracer. During follow-up, none of the 28 groins with tumor-negative LN status showed any LN recurrence in this combined investigation technique. The median follow-up period was 46 (24 to 92) months. Morbidity of this procedure was low at 4.76 % in relation to the number of groins resp. 7.69 % in relation to the number of patients. The results show that this combined procedure is a reliable multimodal diagnostic approach for treatment of penile cancer patients with palpable inguinal LNs. It is associated with low morbidity rates. SLNB alone would lead to a significantly higher false-negative rate in these patients. The encouraging results of this work can extend the range of indications for nuclear medicine in the form of SLNB using radioactive tracers in this patient group.

Purpose Sentinel lymph node biopsy (SLNB) has been described as a minimally invasive method for lymph node staging in patients with a penile carcinoma and nonpalpable inguinal nodes in national and international guidelines of involved professional societies. However, this method is rarely used. The aim of this study was to validate reliability and morbidity of this method and to discuss radiation exposure of persons involved. Methods Twenty-eight patients with histologically negative sentinel lymph nodes in 47 groins with nonpalpable inguinal lymph nodes were included in this study (17 T1(a/b)-, 8 T2- and 3 T3-stages). We recorded prospectively all cases of lymph node recurrence and complications in patients with initially nonpalpable inguinal lymph nodes and histologically negative sentinel lymph nodes. False-negative findings and morbidity were calculated as qualitative criteria. Inguinal regions with palpable lymph nodes and/or evidence of metastases were not considered in accordance with the guidelines. Results During a median follow-up of 68 (4-131) months, we observed one case of bilateral lymph node recurrence and one case of prolonged inguinal lymphorrhea, which could be managed conservatively. Per inguinal region, false-negative rate was 4.25%, and morbidity rate was 2.12%; seen per patient, the rates were both 3.57%. Conclusions Sentinel lymph node biopsy under use of radioactive tracers is a reliable method of lymph node staging in patients with penile carcinoma and nonpalpable inguinal lymph nodes. The methodical complexity is justified by high reliability and low radiation exposure for both patient and medical staff and low morbidity rates.

Background Salvage extended pelvic lymph node dissection (salvage ePLND) in patients with prostate cancer (PCa) biochemical recurrence is an alternative to the commonly used androgen deprivation therapy (ADT) and/or chemotherapy. Small patient number, insufficient accuracy of contemporary imaging methods for lymph node relapse diagnostics, and the lack of prospective data present limiting factors for a wider application of salvage ePLND. The purpose of this publication is to review German and European data and studies on the subject of salvage ePLND and to discuss future perspectives. Materials and methods We analyzed available studies up to October 2014 from Medline with the keywords "salvage lymph node dissection prostate cancer". Results A total of 51 publications since 1984 (up to October 2014) meeting the search criteria were found. Ten of these were studies that analyzed the results of salvage ePLND. Of these 10 studies, 6 originated from German clinics. Furthermore, among these 51 publications, there were 2 clinical case reports (1 from Germany) and 3 reviews (none from Germany). Conclusions The available data show insufficient evidence-based validity. There have been no prospective studies and just one multicenter study. However, single-center retrospective studies have shown promising results. Salvage ePLND leads to biochemical remission, freedom from clinical recurrence, and probably also to renewed response to ADT in patients with castration-resistant PCa. Multicenter prospective studies should be conducted in Germany (where most of the available studies have been performed). The selection of patients should be analyzed in order to identify clear selection criteria for salvage ePLND.

Background The incidence of penile cancer in Europe lies in the range of 0.9 to 2.1 cases per 100 000 persons per year. Carcinogenesis is associated with human papilloma virus (HPV) infection and with chronic inflammation. Methods This review is based on publications (2010-2017) retrieved by a selective search in PubMed and EMBASE and on the guidelines of the European Association of Urology, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence (NICE). Results 95% of cases of penile cancer are accounted for by squamous cell carcinoma, whose numerous subtypes have different clinical courses. Chronic preputial inflammation due to phimosis or lichen sclerosus is often associated with penile cancer. Circumcision lowers the risk of penile cancer (hazard ratio: 0.33). Maximally organ-preserving surgery with safety margins of no more than a few millimeters is the current therapeutic standard, because a local recurrence, if it arises, can still be treated locally with curative intent. Local radiotherapy can be performed in early stages. Lymphogenic metastasis must be treated with radical lymphadenectomy and adjuvant chemotherapy. Patients with clinically unremarkable inguinal lymph nodes nonetheless need invasive lymph node staging because of the high rate of lymphogenic micrometastasis. Conclusion Penile cancer is curable in all early stages with the appropriate treatment, but its prognosis depends crucially on the proper management of the regional (i.e., inguinal) lymph nodes. In many countries, the treatment of this rare disease entity has been centralized.

OBJECTIVE Surgical site infection (SSI) is defined as infection at or near surgical incisions within 30 days of an operative procedure and classified either incisional superficial and deep or organ/space. The aim of the study is to report and compare the incidence and management of SSIs after robot-assisted laparoscopic radical prostatectomy (RALP) and retropubic radical prostatectomy (RRP). MATERIAL AND METHODS Within the last 4 years, we identified 285 patients that underwent RRP, n=187 (66%) or RALP, n=98 (34%). We reviewed the frequency, types and way of management of SSI complications. RESULTS A significant difference was found between RALP and RRP (2/98, 2% vs. 27/187, 14.4%; p

Seit mehreren Jahren ist die dynamische Sentinel-Lymphknotenbiopsie (DSNB) fest in den Leitlinien der „European Association of Urology“ (EAU) als minimal-invasive Methode fur das Lymphknotenstaging bei Patienten mit einem Peniskarzinom und nicht-palpablen Lymphknoten verankert. Aufgrund des hohen methodischen Aufwands und der initial unzuverlassigen Ergebnisse wird das Verfahren in Deutschland jedoch selten angewendet. Ziel dieser Untersuchung war es, die Zuverlassigkeit und Morbiditat dieses Verfahrens zu uberprufen. Prospektiv wurden die Anzahl der Lymphknotenrezidive und Komplikationen bei allen Patienten mit initial nicht-palpablen Leistenlymphknoten und histologisch negativen Sentinel-Lymphknoten erfasst. Als Qualitatskriterien wurden die Falsch-negativ- (Prozentsatz der Lymphknotenrezidive von allen negativen Prozeduren) und die Morbiditatsrate berechnet. Leisten mit palpablen Lymphknoten und/oder Metastasennachweis durch die DSNB wurden hier nicht betrachtet. Die Studie umfasst 37 Patienten mit histologisch negativen Sentinel-Lymphknoten in 63 Leisten mit nicht-palpablen Leistenlymphknoten. Es lagen 21 T1(a/b)-, 10 T2- und 6 T3-Stadien vor. Der Differenzierungsgrad war gut in 4, mittelgradig bei 26 und schlecht bei 7 Patienten. Wahrend einer medianen Nachbeobachtungszeit von 52 (1–131) Monaten wurden ein beidseitiges Lymphknotenrezidiv sowie eine konservativ beherrschbare prolongierte Lymphorrhoe bei jeweils einem Patienten beobachtet. Pro Leiste betrugen die Falschnegativrate 3,2 % und die Morbiditatsrate 1,6 %, pro Patient jeweils 2,7 %. Die DSNB ist eine zuverlassige Methode fur das Lymphknotenstaging bei Peniskarzinompatienten mit nicht-palpablen Leistenlymphknoten. Die hohe Zuverlassigkeit rechtfertigt zusammen mit der geringen Morbiditat den hoheren methodischen Aufwand.

Moderne bildgebende Verfahren erweitern das diagnostische Spektrum und die Aussagekraft der Prostatadiagnostik. Mit dem Ziel einer verbesserten Karzinomdetektion wurde der Stellenwert der perinealen HistoScanning™- (HS-)gestutzten Templateprostatabiopsie ermittelt. Bei insgesamt 104 konsekutiven Mannern (Alter 69 Jahre, PSA 9,9 ng/ml) wurde vor einer erweiterten Prostatabiopsie eine HS-Untersuchung durchgefuhrt. Die Patienten erhielten eine gezielte templategestutzte transperineale und transrektale Biopsie der HS positiven Areale, sowie eine systematische transrektale 14-fach-Biopsie (Bx) der Prostata. Die Detektionsrate wurde hinsichtlich Lokalisation, Sensitivitat (Sens), Spezifitat (Spez), pradiktiver Genauigkeit, negativ-pradiktivem Wert (NPV) and positiv-pradiktivem Wert (PPV) analysiert. Ein Karzinom der Prostata zeigten 44 von 104 (42 %) Patienten. Histologisch waren ferner ASAP („atypical small acinar proliferations“) in 3 (2,9 %), HG-PIN („high-grade prostatic intraepithelial neoplasia“) in 16 (15,4 %) und chronische Prostatitis in 74 (71,1 %) Fallen nachweisbar. Die Detektionsrate in HS-positiven Arealen war im Vergleich zur systematischen Bx signifikant erhoht. Die jeweiligen Detektionsraten im Kollektiv waren trotz der entsprechend reduzierten Anzahl von Biopsien untereinander vergleichbar. Sens., Spez., pradiktiver Genauigkeit, NPV und PPV betrugen 37,2, 85,6, 78,6, 88,7 und 30,8 %. HS fuhrt in Kombination mit einer perinealen templategestutzen Biopsie zu einer verbesserten Detektionsrate im Vergleich zur transrektal gesteuerten Biopsie. HS erweitert den Informationsgehalt herkommlicher TRUS-Bildgebung (transrektaler Ultraschall) und verbessert den diagnostischen Stellenwert gezielter Prostatabiospien.

Robot-assisted surgery, as a development of laparoscopic surgery, has an increasing field of application. Beside urology, this technique has also been implemented in visceral and thoracic surgery and gynaecology. For the surgeon an enhanced view of the surgical field and a better mobility of the instruments are the most important advantages. Thus, it is possible to work more accurate and prevent inadvertent tissue damage. For the anaesthesiologist several characteristics are of importance. Limited access to the patient as a result of a special positioning requires adequate anaesthetic preparation. For many visceral and thoracic surgical interventions the head and airway of the patient is bedded remote from the anaesthesiologist. Therefore, a standardised order and protection of all i. v.-lines, cables and the ventilation-hose of the (double-lumen) tube is essential. After the roboter is connected to the patient, it is nearly impossible to change or extend patient monitoring. Especially in case of emergency, e. g. respiratory complications or heart failure, a close communication with the surgeon and a team approach are indispensable.

Das Urachus-Karzinom ist selten. Die Diagnosestellung ist haufig ein Zufallsbefund, da das Leitsymptom auch bei einer Reihe von anderen urologischen Erkrankungen vorkommt. So auch in unserem Fallbericht. Wir berichten uber den Fall eines muzinosen Adenokarzinoms des Urachus bei einem 26-jahrigen Patienten. Das Karzinom wurde mittels partieller Zystektomie mit Tumorexzison nach umbilikal entfernt.

Background Sentinel lymph node (SLN) biopsy represents a well-established diagnostic tool for the assessment of lymphatic metastasis. Correct pre- and intraoperative visualization of SLN is of the utmost importance to ensure the safety and feasibility of the procedure. Aim of this study was to evaluate the diagnostic value of preoperative SLN imaging via single photon emission computed tomography/computed tomography (SPECT/CT) and planar scintigraphy in patients with penile carcinoma with nonpalpable inguinal lymph nodes. Materials and methods After peritumoral intradermal tracer injection (150 MBq/4.05 mCi Tc-99m nanocolloid), we acquired planar scintigraphies including indirect body contouring using a twin head gamma camera. Subsequently we acquired SPECT/CT images of the abdomen via a hybrid system. Prospective evaluation of 52 groins in 26 examined patients was done for all image files obtained with both techniques by 2 trained experts in consensual assessment. Results A total of 71 SLNs in 37 groins were identified by means of planar scintigraphy. In these images, no radiolabeled lymph nodes were visualized in 15 out of 52 groins (28.8%). The SPECT/CT images showed a total of 82 SLNs in 42 groins. In 19.2% (10 of the 52 groins), there was no visualization of lymph nodes in SPECT/CT. 8 SLNs in 7 groins that were visualized in the planar technique were found to be false positive by SPECT/CT. In total, 19 SLNs in 16 groins that were overlooked by planar imaging could only be detected by SPECT/CT. In contrast to planar scintigraphy, SPECT/CT imaging enabled clear and precise anatomical localization of SLNs in all 42 groins where radiolabeled SLNs were visible. Even under consideration of all lymphatic drainage regions, statistical evaluation showed a significantly higher number of detected SLNs with SPECT/CT in comparison to the planar technique ( P = 0.0022). Conclusion In these patients SPECT/CT is capable of visualizing SLNs that cannot be detected with planar imaging. The SPECT/CT technique reduces the number of false positive findings from planar SLN imaging and is able to show anatomic SLN localization more precisely. If possible, preoperative SLN imaging should be performed by means of the SPECT/CT technique in patients with this tumor entity.

Introduction: To evaluate the safety and efficacy of the TiLOOP® male sling (pfm medical, Cologne, Germany) used in the treatment for male stress urinary incontinence (SUI). Material and Methods: We retrospectively evaluated a total of 34 patients with a TiLOOP® male sling. Perioperative complication rates were assessed and validated questionnaires were prospectively evaluated to assess quality of life and satisfaction rate. Outcome and complication rates were analysed by using descriptive statistics. Correlation of continence outcome and risk factors was performed with the chi-square test. A p value below 0.05 was considered statistically significant. Results: The majority of patients (70.6%) were diagnosed with mild or moderate male SUI. During surgery, one instance (2.9%) of intraoperative urethral injury was observed. There were no immediate postoperative complications. The mean follow-up time was 44.6 months. An improvement of male SUI was reported by 61.9% of the patients and 38.1% reported no change according the Patient Global Impression of Improvement. The mean perineal pain score was 0.5 according to the international index of pain. Conclusions: The TiLOOP® is a safe treatment option for male SUI in our cohort with a low complication rate. However, the functional outcome of the TiLOOP® was inferior when compared to the outcome of the AdVance® male sling.

Background For penile cancer (PC) there are no known molecular predictors of lymphatic spread and/or chemoresistance. Objective To identify functional biomarkers that can predict malignant progression and treatment responsiveness. Design, setting, and participants We used four patient-derived PC cell lines and measured invasion and capillary tube formation, chemoresponsiveness, and mRNA and protein expression. Data were further validated in E2F1 transcription factor knockdown and overexpression experiments. We quantified E2F1 transcript levels in a set of nonmetastatic tumours (NM), metastasised primary tumours (PT), and lymph node metastases (M) from 24 patients. E2F1 immunohistochemistry was performed in another set of 13 PC biopsies. Outcome measurements and statistical analysis Relationships between different parameters were analysed using Student t tests. Transcript levels in patient samples were compared using Mann-Whitney U tests. Significance was set at p Results and limitations In cell lines established from lymph node metastases, E2F1 was more abundantly expressed, pRB was inactivated, and CDK2, CDK4, and cyclins D and E were elevated in comparison to cells from primary PC. Overexpression of E2F1 enhanced migratory capacity and lymphatic endothelial tubule formation, while depletion reduced invasiveness and increased chemosensitivity. VEGFR-3 and VEGF-C and mesenchymal markers were upregulated by high E2F1. E2F1 was clearly upregulated in infiltrative and metastatic primary tumours and metastases (NM vs PT, p p Conclusions E2F1 is a driver of invasion and lymphatic dissemination and promotes chemoresistance. E2F1-related biomarkers might assist in stratifying PC patients for different treatment regimens. Patient summary The availability of penile cancer cell lines allows molecular research on the mechanisms underlying metastasis and chemotherapy. A critical pathway involved in both features has been identified and may lead to better patient stratification for treatment selection.

Numerous surgical procedures are available for the treatment of stress urinary incontinence in women and men. On a par with classical therapy options (e.g. colposuspension and artificial sphincter prosthesis) suburethral tape procedures have become established as the minimally invasive standard of care. Regarding comorbidities and recurrent urinary incontinence, therapeutic procedures should be modified on an individual basis. It is crucial to involve patients in therapeutic decision-making and counseling should be given with respect to all conservative and operative alternatives.

Das Problem der korrekten und erfolgreichen Behandlung einer Hb-relevanten Makrohamaturie bei bekanntem Blasentumor tritt im klinischen Alltag haufiger auf. Besonders schwierig ist es eine valide Therapieoption bei nicht-operablen, alteren Patienten zu identifizieren. Eine mogliche Variante ist die Blasenarterienembolisation. Bedauerlicherweise existieren wenige Publikationen zu diesem Thema, eine umfangreiche Recherche zur Embolisation der Blase ist in der Literatur kaum zu finden. Wir berichten uber eine Harnblasenarterienembolisation bei einem 84-jahrigen Patienten, der eine Hb-relevante, transurethral nicht beherrschbare Makrohamaturie bei Blasenkarzinom zeigte. Nach erfolgter Embolisation entwickelte sich im Verlauf eine massive Nekrose des rechten Musculus glutaeus maximus. Wahrend der anschliesenden Opera­tion wurde die gesamte Muskulatur der Gluteusregion abgetragen und der rechte N. Ischiadicus durchtrennt. Der Patient wurde auf die Intensivstation und anschliesend auf die Palliativstation verlegt. Trotz Ruckbildung der Makrohamaturie ist die Prognose fur den Patienten aufgrund der lebenslanglichen Immobilitat, der grosen Wundflache und der fraglichen Wundheilung ungunstig. Nur wenn keine anderen therapeutischen Masnahmen moglich sind, sollten die vesikalen Arterien embolisiert werden. Dabei ist zu beachten, dass die Embolisation superselektiv und nur von einem erfahrenen Radiologen durchgefuhrt werden darf. Es sollten auf keinen Fall flussige Embolisate verwendet werden. Eine falsch durchgefuhrte Embolisation kann zu einer breiten Nekrose fuhren. Die radiologische Diagnostik hilft, die Grenze der Nekroseregion abzugrenzen. Bei einer groseren Flache der Nekrose ist sehr schonend und mit besonderem Augenmerk auf die Erhaltung des N. Ischiadicus zu operieren.

Die Vereinigung europaischer Urologen empfiehlt in ihren aktuellen Leitlinien fur das Lymphknotenstaging des Peniskarzinoms bei nicht palpablen Leistenlymphknoten die dynamische Lymphknotenbiopsie („dynamic sentinel node biopsy“, DSNB) als diagnostische Methode der ersten Wahl. Ziel dieser Studie war es, die Zuverlassigkeit der DSNB zu uberprufen. Die DSNB wurde zwischen 2004 und 2012 in allen Patienten mit einem invasiven Peniskarzinom und nicht palpablen Leistenlymphknoten angewendet. Als Merkmal der Zuverlassigkeit wurde die Falsch-negativ-Rate bestimmt. Daneben wurden Komplikationen dokumentiert. Die Ergebnisse wurden prospektiv erfasst. Eine DSNB wurde bei insgesamt 29 Patienten mit palpatorisch unauffalligen Leistenlymphknoten durchgefuhrt. Bei 2 Patienten wurden Metastasen mit Hilfe der DSNB nachgewiesen, ein Patient entwickelte einen Lymphknotenbefall nach negativer DSNB. Somit ergibt sich eine Falsch-negativ-Rate von 3,70 %. Die Morbiditatsrate lag bei 3,45 %. Die Sentinel-Lymphknotenbiopsie ist eine zuverlassige diagnostische Methode. Die hohen methodischen wie auch logistischen Anforderungen legen nahe, dass sie nur in ausgewahlten Zentren durchgefuhrt werden sollte.