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Background and objective: Kidney transplant recipients (KTRs) have an increased risk of developing genitourinary cancers, including prostate cancer (PCa), which is expected to become more prevalent due to an aging KTR population. Thus, knowledge of surgical outcomes, including treatment of PCa, within this unique cohort is required. Methods: Data of 62 KTRs undergoing radical prostatectomy (RP) between 2006 and 2023 at nine urologic transplant centers were analyzed. Complications were assessed using the Clavien-Dindo classification. Perioperative outcomes were evaluated, and a follow-up was conducted. Overall survival (OS), biochemical recurrence–free survival (BRFS), and death-censored graft survival were determined via the Kaplan-Meier method and log-rank testing. Key findings and limitations: Overall, 50 open radical retropubic RPs and 12 robot-assisted RPs (RARPs) were included. The intraoperative blood loss was lower after RARP, but operative time was longer. Of the patients, 50% experienced no postoperative complication, and grade ≥3 complications were observed in 14.5%. There was no graft loss related to RP. A histopathologic analysis revealed pN1 in 8.1% and positive surgical margins in 25.8% of the cases. At a median follow-up of 48.5 mo, the median OS was 128 (95% confidence interval [CI] 71.2–184.8) mo, BRFS was 106 (95% CI 55.8; 156.2) mo, and graft survival was 127 (95% CI 66.7–187.3) mo. Limitations include the retrospective design, and variations between groups and centers. Conclusions and clinical implications: Our findings support RP as a feasible and safe treatment option for localized PCa in KTRs with acceptable oncologic outcome. Special care is required in screening and awareness for the risk of understaging. Patient summary: This study analyzed the safety and effectiveness of two prostate cancer surgery methods—open and robot-assisted surgery—in the special group of kidney transplant recipients. Both surgical methods were performed safely with acceptable oncologic outcomes; however, sample size was too small to draw definite conclusions between the two operative methods.

Abstract Exposure to nanoparticles (NPs) is frequently associated with adverse cardiovascular effects. In contrast, NPs in nanomedicine hold great promise for precise lung‐specific drug delivery, especially considering the extensive pulmonary capillary network that facilitates interactions with bloodstream‐suspended particles. Therefore, exact knowledge about effects of engineered NPs within the pulmonary microcirculation are instrumental for future application of this technology in patients. To unravel the real‐time dynamics of intravenously delivered NPs and their effects in the pulmonary microvasculature, we employed intravital microscopy of the mouse lung. Only PEG‐amine‐QDs, but not carboxyl‐QDs triggered rapid neutrophil recruitment in microvessels and their subsequent recruitment to the alveolar space and was linked to cellular degranulation, TNF‐α, and DAMP release into the circulation, particularly eATP. Stimulation of the ATP‐gated receptor P2X7R induced expression of E‐selectin on microvascular endothelium thereby mediating the neutrophilic immune response. Leukocyte integrins LFA‐1 and MAC‐1 facilitated adhesion and decelerated neutrophil crawling on the vascular surface. In summary, this study unravels the complex cascade of neutrophil recruitment during NP‐induced sterile inflammation. Thereby we demonstrate novel adverse effects for NPs in the pulmonary microcirculation and provide critical insights for optimizing NP‐based drug delivery and therapeutic intervention strategies, to ensure their efficacy and safety in clinical applications.

Abstract In this study, we aimed to establish a technique for intraprostatic implantation of prostate cancer (PCa) spheroids and to identify the impact of three-dimensional organization of PCa cells on tumor progression and metastasis in a representative in vivo model. 40,000 LNCaP cells were implanted into the prostate of immunodeficient SCID mice either as single cells (n = 8) or as preformed 3D spheroids (n = 8). For a follow up of 20 weeks, tumor growth was monitored by serum PSA and high-resolution 3D ultrasonography. Eventually, animals were sacrificed and autopsied. The organ dissects were analyzed for the presence of metastases by histology (H&E) and immunohistochemistry (AMACR, AR, Ki-67, CK5, CK8, E-Cadherin, Vimentin). Solid intraprostatic tumors developed in 50% of mice after spheroid implantation and in 50% of mice after implantation of a single cells. Primary tumors of LNCaP spheroids evolved earlier, exhibiting a shorter tumor doubling time whilst developing larger tumor volumes, which was reflected by a higher immunohistochemical expression of Ki-67 and AR, too. Spheroid tumors established lung and lymph node metastases in 75% of mice, in contrast to 50% of mice after single cell implantation. Our technique enables a variety of studies regarding the influence of the tumor microenvironment on PCa progression.

Abstract Weibel Palade bodies (WPB) are lysosome‐related secretory organelles of endothelial cells. Commonly known for their main cargo, the platelet and leukocyte receptors von‐Willebrand factor (VWF) and P‐selectin, WPB play a crucial role in hemostasis and inflammation. Here, the authors identify the glycerophosphodiester phosphodiesterase domain‐containing protein 5 (GDPD5) as a WPB cargo protein and show that GDPD5 is transported to WPB following uptake from the plasma membrane via an unique endocytic transport route. GDPD5 cleaves GPI‐anchored, plasma membrane‐resident proteins within their GPI‐motif, thereby regulating their local activity. The authors identify a novel target of GDPD5 , the complement regulator CD59, and show that it is released from the endothelial surface by GDPD5 following WPB exocytosis. This results in increased deposition of complement components and can enhance local inflammatory and thrombogenic responses. Thus, stimulus‐induced WPB exocytosis can modify the endothelial cell surface by GDPD5‐mediated selective release of a subset of GPI‐anchored proteins.

Background: Conversion in partial nephrectomy to radical nephrectomy occurs in 1-5%. This analysis assessed predictors for conversions in robot-assisted partial nephrectomies., Methods: Two thousand five hundred forty-nine patients at eight robotic centers for robot-assisted partial nephrectomy were retrospectively analyzed. Intervention was performed by 25 surgeons with varying expertise. Conversion was defined as change from robot-assisted partial nephrectomy to open partial, open radical or robot-assisted radical nephrectomy. Comparative analyses between converted and non-converted cases and within subgroups as well as multivariate regression analyses for predictors for conversion were performed., Results: Eighty-eight (3.5%) conversions were documented (17% open nephrectomy, 53% open partial nephrectomy, 30% robot-assisted nephrectomy). In case of conversion, patients were significantly older (P<0.001) with a higher Body Mass Index (BMI; P=0.029), larger tumor size (P<0.001), multiple tumors (P<0.001) and higher PADUA scores (P<0.001). Converting surgeons had a significantly lower experience in RAPN (median EXP 64 vs. 29, P<0.001). The main reasons to convert were unfavorable anatomic features (69%). Radical nephrectomy occurred more frequently in tumors with higher PADUA Score (P<0.001). Experienced surgeons in open renal surgery performed more often open partial nephrectomy in case of open conversion (P<0.001). Patients' age, BMI, surgeon's expertise, number of tumors, tumor size and PADUA Score were independent predictors for conversion (P<0.001). Limitations are the retrospective study design and short-term follow-up., Conclusions: Conversions in robot-assisted partial nephrectomy are predominantly determined by patient- and tumor-related factors, but also surgical experience. Intensified surgical training might reduce the risk of conversions with an increased chance for nephron-sparing surgery in converted cases.

Background: Robot-assisted partial nephrectomy (RAPN) is increasingly performed in challenging tumor constellations like multiple renal masses., Methods: The objective was to investigate influencing factors on postoperative renal function (PRF) after ipsilateral robot-assisted partial nephrectomy of multiple tumors (iRAPN-MT). In this retrospective multicenter study, perioperative data of 132 trans- or retroperitoneal iRAPN-MT for ≥ two tumors were analyzed focusing on influencing factors on PRF and acute kidney injury including RIFLE and trifecta criteria. The impact of patient-, surgery- and tumor-related factors was investigated via uni- and multivariate regression analyses., Results: The majority of patients had two renal masses, with three or more lesions in 19%. Median operative time was 175 minutes. Eighty-five percent of the tumors were dissected on-clamp with a median cumulative warm ischemia time (WITsum) of 15 minutes. Trifecta criteria were fulfilled in 57%. In regression analyses, WITsum, BMI and preoperative eGFR had an impact on eGFR loss before discharge (median -11.6 mL/min). BMI and Charlson Comorbidity Index were independent predictors for the lowest RIFLE stage during hospitalization., Conclusions: iRAPN-MT for multiple ipsilateral renal masses is feasible with good trifecta rates. While mostly unmodifiable patient-associated parameters were independent predictors on PRF impairment, WITsum was identified as a surgery-related independent parameter.

Introduction: The aim was to compare treatment outcomes of clear cell metastatic renal cell carcinoma (ccmRCC) versus non-ccmRCC (nccmRCC) patients who received first-line immune combination therapies., Materials and Methods: Within our retrospective multi-institutional consecutive database of eight tertiary-care centers, we identified mRCC patients treated with first-line immune combination therapies between 11/2017 and 12/2022. Using log-rank analysis and multivariable Cox regression, we tested for differences in overall survival (OS) and progression-free survival (PFS) of nccmRCC versus ccmRCC patients. Covariables consisted of age at diagnosis, sex, International Metastatic Renal Cell Carcinoma Database Consortium risk groups, Eastern Cooperative Oncology Group status, and sarcomatoid feature., Results: Of 289 study patients, 39 (13%) patients harbored nccmRCC. Median OS was 37 months versus not reached for ccmRCC versus nccmRCC patients (P = .6). Median PFS was 13 versus 15 months (P = .9). Multivariable Cox regression models did not identify nccmRCC as an independent predictor of higher overall mortality in mRCC patients (hazard ratio [HR]: 1.23; P = .6) or a higher progression rate (HR: 1.0; P = 1.0)., Conclusion: In our real-world multi-institutional study, no differences in OS and PFS between ccmRCC and nccmRCC patients receiving first-line immune combination treatment were observed, even after adjustment for important patient and tumor characteristics. More prospective trials in nccmRCC patients are needed., Competing Interests: Disclosure The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objective: Kidney transplant recipients (KTRs) have an increased risk of developing genitourinary cancers, including prostate cancer (PCa), which is expected to become more prevalent due to an aging KTR population. Thus, knowledge of surgical outcomes, including treatment of PCa, within this unique cohort is required., Methods: Data of 62 KTRs undergoing radical prostatectomy (RP) between 2006 and 2023 at nine urologic transplant centers were analyzed. Complications were assessed using the Clavien-Dindo classification. Perioperative outcomes were evaluated, and a follow-up was conducted. Overall survival (OS), biochemical recurrence-free survival (BRFS), and death-censored graft survival were determined via the Kaplan-Meier method and log-rank testing., Key Findings and Limitations: Overall, 50 open radical retropubic RPs and 12 robot-assisted RPs (RARPs) were included. The intraoperative blood loss was lower after RARP, but operative time was longer. Of the patients, 50% experienced no postoperative complication, and grade ≥3 complications were observed in 14.5%. There was no graft loss related to RP. A histopathologic analysis revealed pN1 in 8.1% and positive surgical margins in 25.8% of the cases. At a median follow-up of 48.5 mo, the median OS was 128 (95% confidence interval [CI] 71.2-184.8) mo, BRFS was 106 (95% CI 55.8; 156.2) mo, and graft survival was 127 (95% CI 66.7-187.3) mo. Limitations include the retrospective design, and variations between groups and centers., Conclusions and Clinical Implications: Our findings support RP as a feasible and safe treatment option for localized PCa in KTRs with acceptable oncologic outcome. Special care is required in screening and awareness for the risk of understaging., Patient Summary: This study analyzed the safety and effectiveness of two prostate cancer surgery methods-open and robot-assisted surgery-in the special group of kidney transplant recipients. Both surgical methods were performed safely with acceptable oncologic outcomes; however, sample size was too small to draw definite conclusions between the two operative methods., (© 2024 The Author(s).)

Background: The first robot-assisted kidney transplantation (RAKT) was conducted in 2010, and the first time in Germany in 2016. As more than 5 years have passed, current evidence, technological developments and the latest (German) experience are presented., Objectives: The current evidence and experience of RAKT was investigated from an international and German perspective., Materials and Methods: In a systemic search, relevant publications were analyzed and compared with the experiences at a German urological transplant department., Results: From an international perspective, RAKT can now be considered a standard procedure at experienced departments, as more than 680 RAKT have been documented in Europe. The functional results are excellent with low complication rates and good mid- to long-term functional outcomes. Although RAKT was initially only performed with living organ donations, it has also been successfully conducted with cadaveric grafts. The surgical technique can be applied in challenging and complex situations, such as for arteriosclerotic recipient vessels or for kidney transplantations in children. Although RAKT is still not widely performed in Germany, the university hospital in Marburg, the third urological department in Germany, has successfully initiated a robotic transplant program., Conclusions: Compared to open kidney transplantation, robot-assisted kidney transplantation enables at least noninferior results. It further appears to translate the well-documented advantages of minimally invasive surgery to kidney transplantation. However, its spread throughout Germany is only slowly increasing, possibly because only a handful of urological departments still perform kidney transplantations., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)