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ZusammenfassungSeit der Erstbeschreibung Roboter-assistierter Nierentumoroperationen im Jahr 2001 sind 20 Jahre vergangen, das Verfahren wird aber immer noch nicht flächendeckend in jeder deutschen urologischen Klinik angeboten. Insofern stellt sich die Frage, ob Roboter-assistierte Nierentumoreingriffe heutzutage als Standard angesehen werden können.Bis heute liegen für die Roboter-assistierte radikale Nephrektomie keine randomisiert-kontrollierten Studien zum Vergleich mit dem offenen oder laparoskopischen Vorgehen vor. Dennoch zeigt sich, dass gegenüber der offenen Nephrektomie sowohl Laparoskopie als auch Robotik insgesamt bessere perioperative Ergebnisse bei vergleichbarem onkologischen Outcome ermöglichen. Im direkten Vergleich beider minimal-invasiver Techniken gibt es keine eindeutigen Unterschiede, und insofern keinen Zusatznutzen für den Roboter, zumal die Operation robotisch meist teurer ist. Die Ausweitung der chirurgischen Indikationsstellung und erste Studien zur Roboter-assistierten Entfernung lokal weit fortgeschrittener Nierenzellkarzinome mit Level III bis IV Tumorthromben in der Vena cava deuten aber an, dass die robotische Nephrektomie insbesondere bei hoch komplexen Operationen dem laparoskopischen Zugang überlegen sein kann.Auch bezüglich der Roboter-assistierten Nierenteilresektion liegen bis heute keine prospektiv-randomisierten Studien vor. Trotzdem ließ sich bei robotisch wie auch laparoskopisch durchgeführten Nierenteilresektionen binnen weniger Jahre bei ausreichender Erfahrung des Operateurs eine geringere Morbidität gegenüber der offenen Operation feststellen. Im direkten Vergleich von robotischer und laparoskopischer Nierenteilresektion gibt es bisher keinen Konsens. Es zeichnet sich aber die Tendenz ab, dass Roboter-assistierte Eingriffe zusätzliche Vorteile haben, vor allem bei komplexen, endophytischen Tumoren. Dennoch sind bei Vergleichen der verschiedenen Operationsverfahren viele Einflussfaktoren zu berücksichtigen, zu denen insbesondere patienten- und tumorspezifische Faktoren, aber auch die Erfahrung von Operateur, Bed-Side Assistent und die jährliche Klinikfallzahl zählen.Insofern haben sich Roboter-assistierte Nierentumoroperationen bis heute zu einem sicheren Verfahren mit guten operativen Ergebnissen entwickelt und stellen einen etablierten Standard dar. Die perioperativen Ergebnisse sind denen der offenen Operation überlegen, das onkologische Outcome ist vergleichbar. Auch wenn robotische Eingriffe insbesondere aufgrund der hohen Anschaffungskosten häufig teurer sind als laparoskopische, haben sie das Potential, bei komplexen Operationen bessere Ergebnisse zu erzielen. Durch das Auslaufen des Patentschutzes, Eintreten neuer Hersteller und die Entwicklung neuer Technologien wird der Markt robotischer Chirurgie zukünftig wahrscheinlich starken Veränderungen unterliegen und die Kosten werden voraussichtlich sinken.

Radical nephroureterectomy is the gold standard of treatment for high-risk non-metastatic urothelial carcinoma of the upper urinary tract. However, the optimal surgical approach remains a controversial debate. This study compared the perioperative and oncological outcomes of open and robot-assisted radical nephroureterectomies.131 consecutive radical nephroureterectomies (66 robot-assisted nephroureterectomies vs. 65 open nephroureterectomies) for urothelial carcinoma of the upper urinary tract at a single tertiary referral center were included from 2009 to 2019. The perioperative and oncological outcomes were compared between both surgical approaches, including logistic regression analysis, propensity score matching, Kaplan Meier analyses, and Cox regression models.Overall, robot-assisted surgery had less blood loss (150 ml vs. 250, p = 0.004) and less positive surgical margins (1.5% vs. 15.4%, p = 0.004) at a comparable operating time (robotic 188min vs. 178). Any grade complications were more frequent after open surgery (40.9% vs. 63.1%, p = 0.011), and the length of stay was shorter after robotic nephroureterectomy (9 days vs. 12, p 0.001). These differences remained significant in the propensity score matched analysis, except for the complication rates, which were still lower for the robotic approach, but no longer significant. At a median follow-up of 30.9 months (range 1.4-129.5), neither the progression-free survival (PFS, 2-year: robotic 66.7% vs. open 55.3%), nor the overall survival differed significantly (OS, 2-year: robotic 76.2% vs. open 68.4%). In the Cox regression, the surgical approach did not impact the PFS or OS. Lymph node metastases (HR 3.32, p = 0.008) had the strongest impact on the PFS besides patient age (HR 1.51 per 10 years, p = 0.025) and prior cystectomy (HR 2.42, p = 0.026) in the multivariate analysis.Robot-assisted radical nephroureterectomy had significant perioperative advantages at comparable oncological outcomes compared to open surgery for the treatment of urothelial carcinoma of the upper urinary tract at a high volume center, experienced in robotic surgery.

ZusammenfassungIn den letzten drei Jahrzehnten wurden Nierentumore, basierend auf histopathologischen und molekularen Merkmalen, immer umfassender differenziert. Dies hat inzwischen eine zunehmend größere Bedeutung für die klinische Praxis, da differenzierte Therapieoptionen sowohl für die organbegrenzten als auch für die metastasierten Nierenzelltumore zur Verfügung stehen. Die Kenntnis der molekularen Veränderungen ist Voraussetzung für die Entwicklung, aber auch für die differenzierte Anwendung zielgerichteter systemischer Therapieverfahren. Diese Arbeit gibt einerseits einen Überblick über die molekulare Differenzierung der Nierentumore, andererseits werden molekulare Biomarker zur Diagnose, Prognosebewertung und Therapieentscheidung vorgestellt und kritisch diskutiert.

Zusammenfassung Hintergrund Die minimal-invasive Donornephrektomie (DN) ist inzwischen operativer Standard, bezüglich der Rolle von roboterassistierten Verfahren gibt es bisher keinen Konsens. Fragestellung Die ersten 50 transperitonealen roboterassistierten Donornephrektomien (RDN) einer urologischen Universitätsklinik in Deutschland wurden retrospektiv ausgewertet. Material und Methoden Patientencharakteristika, intra- und postoperative Parameter wurden erfasst und die Nierenfunktion in einem 5‑jährigen Follow-up ausgewertet. Signifikante Prädiktoren für die Nierenfunktion bei Entlassung und ein Jahr postoperativ wurden in einem multivariablen Regressionsmodell bestimmt. Ergebnisse Die RDN hat exzellente Ergebnisse mit niedriger Komplikationsrate, kurzer warmer (WIZ) und kalter Ischämiezeit (KIZ) sowie geringem Blutverlust und kurzer Patientenverweildauer. Die Seite der Nierenentnahme hat hierauf keine Auswirkungen. Nach RDN sind etwa 50 % der Spender formal niereninsuffizient, was aber zumeist ohne Relevanz ist, weil sich die Nierenfunktion der Spender im Follow-up nicht weiter verschlechtert. Die postoperative Nierenfunktion lässt sich bei der RDN mithilfe der präoperativen eGFR (errechnete glomeruläre Filtrationsrate) und dem Spenderalter sehr gut vorhersagen. Schlussfolgerungen Die robotische DN stellt eine sehr gute Alternative zu anderen minimal-invasiven Operationsverfahren dar, die von Beginn an exzellente operative Ergebnisse ermöglicht.

Das lokal begrenzte Nierenzellkarzinom wird in der urologischen Praxis durch bessere Fruherkennung und hohere Lebenserwartung zunehmend relevant. Die gegenwartige Evidenz neuer Aspekte in der Therapie des lokal begrenzten Nierenzellkarzinoms, insbesondere die Fragen nach dem Organerhalt, Zugangsweg und fokal-ablativen Therapien wurden untersucht. In einer systematischen Literaturrecherche wurden relevante aktuelle Arbeiten aus den Jahren 2018 und 2019 eingeschlossen. Bis heute stehen prospektiv-randomisierte Studien zum Vergleich von Nephrektomie vs. Nierenteilresektion, allen drei operativen Zugangswegen untereinander und zum Vergleich mit fokal-ablativen Verfahren aus. Auch wenn die Nierenteilresektion eine hohere Morbiditat als die Nephrektomie hat, konnten positive Effekte auf das Uberleben nachgewiesen werden. Altere Patienten (>75 Jahre) mit fortgeschrittenen Tumoren schienen bisher nicht von der Nierenteilresektion zu profitieren, wobei minimal-invasive Verfahren in solchen Untersuchungen unterreprasentiert waren. Die minimal-invasive Nierenteilresektion hat gegenuber dem offenen Zugangsweg deutliche Vorteile, wobei das roboterassistierte Vorgehen dem laparoskopischen uberlegen ist. Fokal-ablative Verfahren sind technisch sicher und gut durchfuhrbar, reprasentative Vergleiche zur Nierenteilresektion stehen jedoch aus. Die Nierenteilresektion bleibt der therapeutische Goldstandard beim lokal begrenzten Nierenzellkarzinom und sollte vorzugsweise roboterassistiert durchgefuhrt werden. Fokal-ablative Therapieverfahren konnen in ausgewahlten Fallen eine Alternative darstellen.

ZusammenfassungDie Entdeckung von immer kleineren Tumoren durch den umfassenden Einsatz von bildgebenden Verfahren, die Erweiterung der operativen Techniken und der systemischen Therapieoptionen fordern auch für Nierentumorpatienten eine Individualisierung der Therapie. Essenzielle Voraussetzung ist dabei die Kenntnis der Tumorbiologie, da sie eine differenzierte Diagnostik, individuelle Prognosebewertung und Therapiewahl, basierend auf Biomarkern, und die Entwicklung von neuen Therapiestrategien ermöglicht.Nierenzelltumore werden aktuell in 16 histologische Subtypen unterschieden, die durch spezifische genetische Veränderungen charakterisiert sind. Aufgrund ihrer unterschiedlichen Aggressivität ist die Kenntnis der Subtypen sowohl für die Therapieentscheidung als auch für die Nachsorge wichtig. Molekulare Marker können bei der Differenzialdiagnose eingesetzt werden. Molekulare Signaturen werden zukünftig aber auch wesentlich zur Prognosedifferenzierung innerhalb der Subtypen beitragen, wie für das klarzellige Nierenzellkarzinom bereits gezeigt wurde. Dies wird zur Entwicklung differenzierter Nachsorgeprotokolle und zu einer genaueren Selektion der Patienten für adjuvante Therapien führen. Für metastasierte Patienten stehen immer mehr medikamentöse Therapien zur Verfügung, die zielgerichtet in bestimmte zelluläre Signal- oder Kommunikationswege eingreifen. Auch wenn bisher noch keine validen prädiktiven Biomarker verfügbar sind, liegen vielversprechende Daten zu molekularen Signaturen in Korrelation mit dem Ansprechen auf Tyrosinkinaseinhibitoren oder Checkpointinhibitoren vor, die in Zukunft wesentlich besser als die klinischen Scores eine individuelle Therapiewahl ermöglichen werden.Zur Überführung der vielversprechenden Biomarker in die klinische Praxis sind nun prospektive multizentrische Studien erforderlich. Die Berücksichtigung von bereits vorhandenen Erkenntnissen aus der Tumorbiologie der verschiedenen NZK-Entitäten sowohl bez. der veränderten Signalwege in den Tumorzellen selbst als auch der Rolle des Mikromilieus einschließlich der Immunzellen ist eine essenzielle Voraussetzung für eine weitere Verbesserung von Diagnostik und Therapie.

Background Most comparisons of robot-assisted (RARC) versus open radical cystectomy (ORC) for urothelial carcinoma do not factor the inherent stage selection bias or surgical experience. Methods We compared the perioperative outcomes of 229 RARC and 335 ORC at a single tertiary referral center with propensity score matching and multiple regression models, when controlling for tumor and patient characteristics, surgeon's experience and type of urinary diversion. Results RARC had less major complications (19.8% vs. 34.1%) and ICU admissions (6.6% vs. 19.8%), with lower blood loss (400 vs. 500ml) and transfusion rates. The operating time was longer (336 vs. 286min), but decreased with surgeon's experience. RARC had less PSMs (3% vs. 8.4%) and a higher lymph node count (14 vs. 11). Conclusions In this large single center series comparing RARC with ORC controlling for stage selection bias and surgical experience, RARC proved significantly better outcomes, especially with intracorporeal urinary diversion. This article is protected by copyright. All rights reserved.

Simple Summary: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge due to the lack of biomarkers indicating the optimal drug for each patient. This study analyzed blood samples of patients with predominant clear cell mRCC who were treated with the mTOR inhibitor everolimus after failure of one prior tumor therapy. In an exploratory approach, predictive blood biomarkers were searched. We found lower levels of the protein thrombospondin-2 (TSP-2) at the start of the therapy and higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation to be associated with therapy response. Of note, these blood biomarkers had a higher predictive value than baseline patient parameters or risk classifications. Polymorphisms in the mTOR gene appeared to be associated with therapy response, but were not significant. To conclude, it seems feasible to identify patients showing longtime responses to everolimus and possible to increase tumor therapy response rates based on biomarkers for individual therapy selection. Abstract: There is an unmet need for predictive biomarkers in metastatic renal cell carcinoma (mRCC) therapy. The phase IV MARC-2 trial searched for predictive blood biomarkers in patients with predominant clear cell mRCC who benefit from second-line treatment with everolimus. In an exploratory approach, potential biomarkers were assessed employing proteomics, ELISA, and polymorphism analyses. Lower levels of angiogenesis-related protein thrombospondin-2 (TSP-2) at baseline (≤665 parts per billion, ppb) identified therapy responders with longer median progression-free survival (PFS; ≤665 ppb at baseline: 6.9 months vs. 1.8, p = 0.005). Responders had higher lactate dehydrogenase (LDH) levels in serum two weeks after therapy initiation (>27.14 nmol/L), associated with a longer median PFS (3.8 months vs. 2.2, p = 0.013) and improved overall survival (OS; 31.0 months vs. 14.0 months, p < 0.001). Baseline TSP-2 levels had a stronger relation to PFS (HR 0.36, p = 0.008) than baseline patient parameters, including IMDC score. Increased serum LDH levels two weeks after therapy initiation were the best predictor for OS (HR 0.21, p < 0.001). mTOR polymorphisms appeared to be associated with therapy response but were not significant. Hence, we identified TSP-2 and LDH as promising predictive biomarkers for therapy response on everolimus after failure of one VEGF-targeted therapy in patients with clear cell mRCC.

Background Most comparisons between robot-assisted (RAPN) and open partial nephrectomy (OPN) indicate the superiority of RAPN, but the learning curve is often not considered. Methods All consecutive partial nephrectomies from the very first RAPN at a single tertiary referral center (n=818, 500 RAPN vs. 313 OPN) were retrospectively analyzed. Complications, success rates, and surgical outcomes were compared. Inequalities between cohorts and the inherent learning curve were controlled by subgroup comparisons, regression analyses, and propensity score matching. Results Overall, RAPN had fewer complications, less blood loss, and shorter length of stay. However, an inherent learning curve caused higher complications for the first 4 years. Thereafter, perioperative outcomes clearly favored RAPN, even for more complex tumors. Conclusions In one of the largest monocentric cohorts over more than 10 years, RAPN was found to be superior to OPN. However, not all advantages of RAPN are immediate because a learning curve must be passed. This article is protected by copyright. All rights reserved.

Health care systems worldwide have been facing major challenges since the outbreak of the SARS-CoV-2 pandemic. Kidney transplantation (KT) has been tremendously affected due to limited personal protective equipment (PPE) and intensive care unit (ICU) capacities. To provide valid information on risk factors for ICU admission in a high-risk cohort of old kidney recipients from old donors in the Eurotransplant Senior Program (ESP), we retrospectively conducted a bi-centric analysis. Overall, 17 (16.2%) patients out of 105 KTs were admitted to the ICU. They had a lower BMI, and both coronary artery disease (CAD) and hypertensive nephropathy were more frequent. A risk model combining BMI, CAD and hypertensive nephropathy gained a sensitivity of 94.1% and a negative predictive value of 97.8%, rendering it a valuable search test, but with low specificity (51.1%). ICU admission also proved to be an excellent parameter identifying patients at risk for short patient and graft survivals. Patients admitted to the ICU had shorter patient (1-year 57% vs. 90%) and graft (5-year 49% vs. 77%) survival. To conclude, potential kidney recipients with a low BMI, CAD and hypertensive nephropathy should only be transplanted in the ESP in times of SARS-CoV-2 pandemic if the local health situation can provide sufficient ICU capacities.

Living kidney donation is the best treatment for end-stage renal disease, however, the best surgical approach for minimally-invasive donor nephrectomy (DN) is still a matter of debate. This bi-centric study aimed to retrospectively compare perioperative outcomes and postoperative kidney function after 257 transperitoneal DNs including 52 robot-assisted (RDN) and 205 laparoscopic DNs (LDN). As primary outcomes, the intraoperative (operating time, warm ischemia time (WIT), major complications) and postoperative (length of stay, complications) results were compared. As secondary outcomes, postoperative kidney and graft function were analyzed including delayed graft function (DGF) rates, and the impact of the surgical approach was assessed. Overall, the type of minimally-invasive donor nephrectomy (RDN vs. LDN) did not affect primary outcomes, especially not operating time and WIT, and major complication and DGF rates were low in both groups. A history of smoking and preoperative kidney function, but not the surgical approach, were predictive for postoperative serum creatinine of the donor and recipient. To conclude, RDN and LDN have equivalent perioperative results in experienced centers. For this reason, not the surgical approach, but rather the graft- (preoperative kidney function) and patient-specific (history of smoking) aspects impacted postoperative kidney function.

Human papilloma virus (HPV) infections are one of the most common sexually transmitted diseases. We present the case of a 77-year-old Caucasian male with enormous genital warts of the penis, scrotum, groins and anus. Lesions were excised by electrosurgery. The histological examination revealed Condylomata gigantea as well as an invasive perianal squamous cell carcinoma. Mucosal “low-risk” HPV type 6 was detected. The patient had a history of an immunosuppressing disease. During the 4-year follow-up, multiple relapses occurred. Thus, particularly in immunosuppressed patients, early prophylactic HPV vaccination seems to be indicated for use in the prevention of HPV-associated mutilating and life-threatening disease. Vaccination should also protect from “low-risk” HPV.

Introduction: Non-coding RNAs (ncRNAs) are important regulators of cellular signaling in tumor-related processes. They can not only be detected in tumor tissues, but also in body fluids. ncRNAs are released into circulation as cell-free RNAs in at least two ways: bound to proteins like Ago2 or packed in extracellular vesicles (EV). Therefore, they have a great potential to serve as biomarkers in liquid biopsies. This review gives an overview of the current knowledge concerning ncRNAs and EVs as putative liquid biomarkers in urological tumor diseases.Areas covered: Literature was searched for ncRNAs including microRNA, long non-coding RNA, small interfering RNA, small nuclear RNA, small nucleolar RNA and PIWI-interacting RNA in blood (serum, plasma) and urine samples from urological tumor (urothelial, kidney, prostate, testicular germ cell, penile cancer) patients.Expert opinion: The data demonstrate an important potential of circulating non-coding RNAs as biomarkers in liquid biopsies for diagnosis and follow-up of patients with urological tumors. To translate these markers into clinical practice, independent and prospective validation, standardization of isolation and quantification techniques are inevitable. Another task is the development of predictive ncRNA biomarkers to overcome problems associated with tumor heterogeneity and to select patients individually for systemic therapies.

Background Antibody-mediated rejection is a leading cause for renal transplant loss. Rodent models are useful to dissect pathomechanisms and to develop treatment strategies. Although used for decades as a model, glomerular histopathological findings of Fischer-344 kidneys transplanted into Lewis rats have never been comprehensively described. Methods Kidneys from Fischer-344 rats were transplanted into Lewis rats as life-sustaining allografts without immunosuppression. Lewis isografts and normal Fischer-344 kidneys served as controls. Grafts were harvested at 9 days, 6 and 26 weeks. Histopathological examination included light microscopy, immunohistochemistry, and morphometry. Findings were compared with 51 human biopsies with transplant glomerulopathy. Results Most glomerular findings in rat allografts resembled human acute and chronic antibody-mediated rejection with glomerulitis, microthrombosis, microaneurysms, glomerular hypertrophy, podocyte loss, glomerular basement membrane splitting, and secondary focal and segmental glomerulosclerosis. In line with previous reports on nonendothelial antigens, glomerular immunoglobulin and C4d deposition was mostly nonendothelial. Only in 26-week allografts, we found mesangial and subendothelial immune complex-type electron-dense deposits. Similar deposits were found in 8 of 51 human biopsies with transplant glomerulopathy after rigorous exclusion of immune complexes of other cause, particularly recurrent glomerulonephritis and hepatitis C. Conclusions Thus, our model closely reflects the glomerular changes of acute antibody-mediated rejection in humans and of a special subset of human transplant glomerulopathy. The significance of alloimmune immune complex-type deposits in human transplants deserves further investigation.

Prognostic markers for the definition of the individual metastatic risk in renal cell carcinoma are still missing. The aim of our study was to establish a total number of specific aberrations (TNSA) genetic score as a new prognostic test for metastatic risk evaluation. Fluorescence in situ hybridization (FISH) was performed on isolated cell nuclei of 100 ccRCCs (50 M1/50 M0) and 100 FFPE sections (second cohort, 32 M1/68 M0). For each chromosomal region (1q21.3, 7q36.3, 9p21.3p24.1, 20q11.21q13.32) cut-off values were determined by receiver-operator curve (ROC)-curve analysis. TNSA was calculated based on the dichotomized specific CNVs. The prognostic significance of CNVs was proven by Cox and logistic regression. TNSA was the best predictor of metastasis and recurrence free survival in both cohorts. We derived an algorithm for risk stratification by combining TNSA and T-category, which increased the prognostic accuracy to 87% (specificity = 86%, sensitivity = 88%). This model divides patients into two risk groups with significantly different RFS, CSS, and OS (P = 3.8×10-5 , P = 5×10-6 and P = 3.57×10-8 respectively). The genetic risk model was superior to Leibovich score and was able to identify patients with metachronous metastatic spread which were incorrectly classified as "low" or "intermediate risk." We present a new tool for individual risk stratification by combining genetic alterations with clinico-pathologic parameters. Interphase FISH proves to be a dependable method for prognostic evaluation in primary tumor tissue on isolated cell nuclei as well as on FFPE sections. Especially in organ-confined tumors the genetic score seems to be an important tool to identify patients at high risk for metastatic disease.

Gynecomastia is a common incidental finding in males that can be caused by various benign or malignant diseases. In rare cases, it results from Leydig cell tumors, a rare entity accounting for 3% of all testicular neoplasms. Some of them are hormonally active but seldom cause symptomatic endocrine disturbance. Here we report on a 32-year-old male presenting with gynecomastia which he had already been suffering from for two years. Although he had been seen by three other specialists, including a urologist, none of them found the small mass in the upper pole of his right testis. We decided to perform testis-sparing surgery which confirmed the diagnosis of a hormonally active Leydig cell tumor. During follow-up, hormonal status normalized, and gynecomastia began to resolve.

Changes in miRNA expression of glomerular capillaries during antibody-mediated rejection (ABMR) are poorly understood and could contribute to the deleterious inflammation and fibrosis of ABMR via suppression of target genes. A better understanding could lead to novel diagnostic tools and reveal novel therapeutic targets. We explored deregulated miRNAs in an glomeruloendothelial in vitro model of ABMR due to class I human leukocyte antigen (HLA) with and without complement activation. We studied a set of 16 promising candidate miRNAs in microdissected glomeruli a confirmation set of 20 human transplant biopsies (DSA+) compared to 10 matched controls without evidence for ABMR. Twelve out of these 16 glomerulocapillary miRNAs could successfully be confirmed as dysregulated in vivo with 10 upregulated (let-7c-5p, miR-28-3p, miR-30d-5p, miR-99b-5p, miR-125a-5p, miR-195-5p, miR-374b-3p, miR-484, miR-501-3p, miR-520e) and 2 downregulated (miR29b-3p, miR-885-5p) in DSA+ vs. controls. A random forest analysis based on glomerular miRNAs identified 18/20 DSA+ and 8/10 controls correctly. This glomerulocapillary miRNA signature associated with HLA class I-DSA could improve our understanding of ABMR and be useful for diagnostic or therapeutic purposes.