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To evaluate the effectiveness and safety profile of the tyrosine kinase inhibitor Axitinib for patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting. Adult patients from the German non-interventional post-approval multicenter STAR-TOR registry with a/mRCC (NCT00700258) were included if treated with Axitinib in second line or beyond. Overall survival (OS), progression-free survival (PFS) and adverse events were evaluated across subgroups using descriptive statistics and survival analyses. Between November 2012 and December 2020, 75 study sites recruited 210 patients treated with Axitinib (69,6% male; median age 69 years; median Karnofsky Index 80%). Clear cell RCC was the most frequent histological subtype (81.0%). Axitinib was administered as second-line in 51.4%, third-line in 24.8%, and fourth-line treatment and beyond in 23.8% of the patients, respectively. MSKCC score was 15.0% favorable, 33.6% intermediate, and 51.3% poor risk. Median PFS was 5.6 months, and median OS 18.3 months. Patients with lactate dehydrogenase (LDH) levels > 300U/l had a nominally significantly shorter OS than patients with LDH≤300U/l (8.2 vs. 19.0 months, p = 0.008). Drug related adverse and serious adverse events were reported in 56.7% and 17.6% of the patients, respectively (most common adverse event: gastrointestinal disorders; 37.6%). This real-world study confirms the clinical relevance of Axitinib in the second-line and beyond setting for a/mRCC with OS and PFS reported in concordance with pivotal trials, while demonstrating a favorable safety profile. A high LDH serum level could be a negative predictive marker for Axitinib effectiveness, which can aid in clinical decision making.

Hintergrund: Elektive skrotale Eingriffe sind mit einer hohen Rate an postoperativen Komplikationen verbunden. Eine besondere Empfehlung zur postoperativen Versorgung gibt es nicht. Ziel der Arbeit: Wir untersuchten den Einfluss einer stützenden Herrenunterhose auf postoperative Komplikationen und Lebensqualität. Material und Methoden: Von 07/2020 bis 11/2021 wurden Patienten vor elektiver skrotaler Operation in die Interventionsgruppe „stützende Herrenunterhose“ oder die Kontrollgruppe randomisiert. Neben Basischarakteristika der Patienten wurden intraoperative und postoperative Befunde erfasst. Der primäre Endpunkt umfasste postoperative Komplikationen. Sekundäre Endpunkte waren verlängerter Krankenhausaufenthalt, ungeplante Wiedervorstellungen/-aufnahmen, gesteigerter Analgetikabedarf und die gesundheitsbezogene Lebensqualität, welche mittels EQ5D-Fragebogen präoperativ, am 1. Tag und 4 Wochen postoperativ erfasst wurde. Ergebnisse: Daten von 50 Patienten konnten ausgewertet werden. Das mittlere Alter betrug 46,7 Jahre (Standardabweichung [SD] 18,6). Am häufigsten wurden inguinale Hodenfreilegungen mit/ohne Ablatio testis (52 %), Hydrozelenresektionen (22 %) oder Varikozelenligaturen (14 %) durchgeführt. Die mittlere Operationsdauer betrug 62,8 (SD 35,2) min, die stationäre Verweildauer 2,6 (SD 1,2) Tage. 20 % der Patienten erlitten eine postoperative Komplikation. Die Art des Eingriffs korrelierte signifikant mit dem Auftreten von postoperativen Komplikationen (p= 0,01), ungeplanter ambulanter Wiedervorstellung (p= 0,001) und Wiederaufnahme (p= 0,04). Hinsichtlich biometrischer und perioperativer Daten zeigten sich keine signifikanten Unterschiede zwischen Interventionsgruppe (n= 27) und Kontrollgruppe (n= 23). Schlussfolgerung: Nach elektiven skrotalen Eingriffen tritt eine nicht zu vernachlässigende Anzahl an Komplikationen auf. Das Auftreten von Komplikationen beeinflusst den subjektiven Gesundheitszustand noch 4 Wochen nach der Operation. Die postoperative Versorgung mit einer stützenden Unterhose scheint keinen Einfluss auf die postoperative Komplikationsrate zu haben, jedoch beeinflusst sie die Lebensqualität bei Patienten mit skrotalem Zugang positiv.

BackgroundNoise in the operating room (OR) is a stressor with far-reaching negative consequences. The Silent Operating Theatre Optimisation System (SOTOS) suppresses the noise level in the OR and improves the communication of the OR-staff. This study investigates whether SOTOS has a positive impact on the OR-staff’s perceived stress, exhaustion, activity and concentration.MethodsData were collected in a quasi-experimental study design of 32 radical prostatectomies using the da Vinci robotic-assisted system. Sixteen randomly chosen surgeries were carried out with SOTOS and 16 without. A total of 34 OR-staff-members took part, each 32 surgeries involving five planned OR-staff-members. Two points of measurement, before and after each surgery, were carried out, with a final sample of n=143 repeated measurements data. Before and after surgery, OR-staff-members completed a concentration test and a questionnaire concerning their perceived stress, exhaustion and activity levels.ResultsThe OR-staff felt significantly less stressed, less exhausted and more active during and after surgery when operating with SOTOS. Especially the primary surgeons, assisting surgeons and circulating nurses profited from SOTOS. SOTOS did not reveal a significant impact on the OR-staff’s concentration in this study.ConclusionFor urological surgeries using the da Vinci system SOTOS constitutes a technical resource which significantly reduces perceived noise stress and exhaustion and improves the activity of primary surgeons, assisting surgeons and circulating nurses. These efficiencies likely lead to positive changes in their health and job satisfaction and are hence beneficial to the patient safety and hospital resources.

Insulin-like growth factor 2 (IGF2) is the predominant IGF in adults and regulates cell growth. In contrast to normal tissues, where IGF2 is imprinted and only expressed from the paternal allele, loss of imprinting (LOI) and biallelic IGF2 expression are observed in many cancers including prostate cancer (PCa). We here studied whether LOI of IGF2 in normal circulating peripheral blood lymphocytes can predict increased PCa risk.We analyzed IGF2 protein levels, IGF2 820G/Agenotype and imprinting status, as well as methylation status of the IGF2 imprinting control region (ICR) in 113 blood samples of patients with a history of radical prostatectomy (RPE) for PCa by ELISA, restriction-fragment length polymorphism, and bisulfite-DNA sequencing. Results were compared to 249 male blood donors with unknown prostate specific antigen (PSA) status.The 820G/Agenotype was enriched in the RPE group and was associated with younger age at cancer diagnosis. LOI in patients was only slightly more frequent than in controls, but IGF2 levels were significantly higher and uncoupled from the imprinting status. Analysis of the IGF2/H19ICR revealed marked hypermethylation.The IGF 820G/Agenotype is associated with PCa diagnosis at younger age. Increased IGF2 in patients with PCa appears to be the result of impaired imprinting in non-neoplastic cells rather than a paracrine tumor product. Uncoupling of IGF2 protein levels from imprinting status (not LOI alone) and hypermethylation of the ICR characterized PCa patients and could have the potential to indicate persons at risk in screening programs.

The plakophilins, members of the armadillo-repeat family, consist of three different proteins (PKP1-3) that are specifically recruited to desmosomal plaques in a highly cell type-specific manner. Using immunofluorescence, immunoelectron microscopy, and immunoblot, we found that all three plakophilins occurred in luminal and basal cells of the pseudostratified prostate epithelium. The analysis of 135 cases of prostatic adenocarcinomas grouped into tumors with low (Gleason score ≤ 6), intermediate (Gleason score 7), and high Gleason score (8 ≤ Gleason score ≤ 10) showed that the expression of PKP1 was reduced or lost in adenocarcinomas with high Gleason scores. The expression of PKP2 was unchanged in all prostatic adenocarcinomas analyzed. In contrast, PKP3 expression was increased in carcinomas with high Gleason scores in comparison with carcinomas with low Gleason scores. In DU 145 cell lines with either overexpression or knockdown of PKP3, both imbalances resulted in fewer desmosomal cell contacts. In addition, overexpression of PKP3 in DU 145 cells led to an augmentation in proliferation rate. Our data imply that both loss of PKP1 and up-regulation of PKP3 expression are biologically important events in prostate cancer and are associated with a more aggressive phenotype.

Intravesical instillation of mitomycin C after a transurethral resection of a bladder tumor constitutes a standard treatment modality in the management of superficial transitional cell carcinoma in the urinary bladder. An immediate instillation of mitomycin C after transurethral resection has been shown to reduce the recurrence rate of superficial transitional cell carcinoma. Intravesical mitomycin C is generally considered to be a safe treatment option, but the past few years have seen the publication of a number of case reports on severe complications following mitomycin C instillation. This article reports on the mode of action, as well as the intravesical effects and current indications for mitomycin C instillation. This review will summarize the oncological benefits of mitomycin C in comparison with other intravesical treatments, such as bacillus Calmette–Guérin, and elucidate the incidence and types of possible complications associated with intravesical mitomycin C chemotherapy.

Due to the lack of specific markers the analysis of lymphatic vessel density (LVD) has been almost impossible in the past. We report the novel specific marker for lymphatic endothelium, lymphatic vessel endothelial hyaluronan receptor (LYVE-1), in prostatic, benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissue. Normal blood vessels were additionally quantified in BPH and PCa.

Background and Purpose: The architecture of the lower renal pole seems to have a considerable influence on caliceal stone clearance after different therapeutic modalities. The published data are partially inconsistent, and publications on reproducibility are completely lacking. The aim of this study was to evaluate the intraobserver and interobserver reproducibility of different measures of lower-calix anatomy.Materials and Methods: We studied the intraobserver and interobserver reproducibility of parameters describing the lower-pole anatomy that are significant for treatment outcome. Forty renal units without urologic disease were analyzed by five independent urologists. Infundibular length (IL), infundibular width (IW), and lower infundibulopelvic angles (LIP) were measured by the Elbahnasy (LIP I), Keeley (LIP II), and Gupta (LIP III and LIP IV) methods. Statistical analysis of each parameter and investigator was performed.Results: All LIP angles showed low interobserver correspondence: correlation coefficients (CC) did not exceed 0.44 (P< 0.05). Even the relatively clearly defined parameters IW and IL achieved CCs of only 0.63 and 0.49, respectively. The intraobserver correlation achieved better results: 0.73 (LIP I), 0.84 (LIP II), 0.73 (LIP III), 0.65 (LIP IV), 0.88 (IL), and 0.82 (IW). With the Elbahnasy method, almost all renal units were classified as favorable for stone persistence after shockwave lithotripsy. With the Keeley and Gupta methods, more than 50% of the kidneys were defined as having low clearance probability.Conclusions: Assessment of the chosen parameters is difficult and shows high interobserver variation. Inexperience in measuring the specific angles and low imaging quality can limit correct evaluation. The large number of kidneys with anatomy inappropriate for clearance of lower-pole stones may explain the poor outcome of shockwave treatment for stones in a lower calix. Prospective studies will determine the clinical value of anatomic assessments.

Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) play a decisive role as prognostic markers in clear-cell renal cell carcinoma (RCC). To date, the role of PD-1/PD-L1 as a prognostic marker in papillary RCC (pRCC) remains scarce.