First-Line Immune Combination Therapies for Nonclear Cell Versus Clear Cell Metastatic Renal Cell Carcinoma: Real-World Multicenter Data From Germany.

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.

Tumor promoting effect of spheroids in an orthotopic prostate cancer mouse model.

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.

Radiomics and machine learning for renal tumor subtype assessment using multiphase computed tomography in a multicenter setting.

OBJECTIVES: To distinguish histological subtypes of renal tumors using radiomic features and machine learning (ML) based on multiphase computed tomography (CT). MATERIAL AND METHODS: Patients who underwent surgical treatment for renal tumors at two tertiary centers from 2012 to 2022 were included retrospectively. Preoperative arterial (corticomedullary) and venous (nephrogenic) phase CT scans from these centers, as well as from external imaging facilities, were manually segmented, and standardized radiomic features were extracted. Following preprocessing and addressing the class imbalance, a ML algorithm based on extreme gradient boosting trees (XGB) was employed to predict renal tumor subtypes using 10-fold cross-validation. The evaluation was conducted using the multiclass area under the receiver operating characteristic curve (AUC). Algorithms were trained on data from one center and independently tested on data from the other center. RESULTS: The training cohort comprised n = 297 patients (64.3% clear cell renal cell cancer [RCC], 13.5% papillary renal cell carcinoma (pRCC), 7.4% chromophobe RCC, 9.4% oncocytomas, and 5.4% angiomyolipomas (AML)), and the testing cohort n = 121 patients (56.2%/16.5%/3.3%/21.5%/2.5%). The XGB algorithm demonstrated a diagnostic performance of AUC = 0.81/0.64/0.8 for venous/arterial/combined contrast phase CT in the training cohort, and AUC = 0.75/0.67/0.75 in the independent testing cohort. In pairwise comparisons, the lowest diagnostic accuracy was evident for the identification of oncocytomas (AUC = 0.57-0.69), and the highest for the identification of AMLs (AUC = 0.9-0.94) CONCLUSION: Radiomic feature analyses can distinguish renal tumor subtypes on routinely acquired CTs, with oncocytomas being the hardest subtype to identify. CLINICAL RELEVANCE STATEMENT: Radiomic feature analyses yield robust results for renal tumor assessment on routine CTs. Although radiologists routinely rely on arterial phase CT for renal tumor assessment and operative planning, radiomic features derived from arterial phase did not improve the accuracy of renal tumor subtype identification in our cohort.

Multicenter evaluation of complex urinary diversion for renal transplantation: outcomes of complex surgical solutions.

PURPOSE: An abnormal lower urinary tract poses significant challenges for transplant surgeons. Besides the ureteral anastomosis to an ileal conduit, there are diverse complex reconstructive solutions. Due to its rarity, standardization and teaching of complex urinary diversion is extremely difficult. METHODS: The indications and outcomes of complex urinary diversions after kidney transplantation (KT) were retrospectively investigated at eight urologic transplant centers including a current follow-up. RESULTS: Of 37 patients with 21 (56%) males, vesicoureteral reflux (24%), spina bifida (22%), and glomerulonephritis (12%) were the most common causes of terminal renal failure. In 30 (81%) patients, urinary diversion was performed before KT, at a median of 107.5 (range, 10; 545) months before. Transplantations were held at a median patient age of 43 (10; 68) years, including six (16%) living donations. Urinary diversion was modified during 12 (32%) transplantations. After KT, the ileal conduit was the most common incontinent urinary diversion in 25 (67%) patients; a Mainz pouch I and bladder augmentation were the most frequent continent diversions (each n = 3). At a median follow-up of 120 months (range 0; 444), 12 (32%) patients had a graft failure with a 5-year graft survival of 79% (95%CI 61; 90). The median overall survival was 227 months (168; 286) and the 5-year overall survival 89% (69.3; 96.4). CONCLUSION: The mid-term kidney transplant function with complex urinary diversion appears to be comparable to transplants with regular urinary diversions. Hence, complex urinary diversion should always be considered as a surgical option, even during transplantation, if necessary.

[Robot-assisted kidney transplantation-what is new?] / Aktuelles zur robotischen Nierentransplantation ­ quo vadis?

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.

Old for young kidney transplantation: a responsible option for our patients to reduce waiting time?

PURPOSE: The Eurotransplant Senior program allocating grafts from donors ≥ 65 years to recipients aged ≥ 65 years has proven good results within the last 20 years. However, "old" grafts are also allocated to younger recipients < 65 years, and this outcome of "old for young" kidney transplantations (KT) still lacks detailed investigations. METHODS: All "old for young" KT performed at four tertiary referral centers were retrospectively compared including a recent follow-up, stratifying for "old for young" (donor ≥ 65 years to recipient < 65 years) vs. "very old for young" KT (donor ≥ 70 years to recipient < 65 years). RESULTS: Overall, 99 patients were included with 56 (56.6%) "old for young" and 43 (43.4%) "very old for young" KT. The median waiting time did not differ (60.7 vs. 45.8 months, respectively) at comparable living donation rates (57.1% vs. 44.2%) as well as intra- and postoperative results. At a median follow-up of 44 months (range 1; 133), the 3-year graft survival of 91% vs. 87% did not significantly vary. In subgroup analyses assessing living donation or donation after brain death (DBD) KT only, the graft survival was significantly longer for "old for young" KT within the living donation subgroup. In multivariate Cox regression analyses, the presence of panel-reactive antibodies was the only significant impact factor on graft survival (HR 8.32, p = 0.001). CONCLUSION: This analysis clearly demonstrates the effectiveness of the "old for young" approach, enabling favorable perioperative results as well as comparable data of graft- and overall survival, while reducing waiting time for eligible patients.

Early CRP kinetics to predict long-term efficacy of first-line immune-checkpoint inhibition combination therapies in metastatic renal cell carcinoma: an updated multicentre real-world experience applying different CRP kinetics definitions.

Objectives: Although biomarkers predicting therapy response in first-line metastatic renal carcinoma (mRCC) therapy remain to be defined, C-reactive protein (CRP) kinetics have recently been associated with immunotherapy (IO) response. Here, we aimed to assess the predictive and prognostic power of two contemporary CRP kinetics definitions in a large, real-world first-line mRCC cohort. Methods: Metastatic renal carcinoma patients treated with IO-based first-line therapy within 5 years were retrospectively included in this multicentre study. According to Fukuda et al., patients were defined as 'CRP flare-responder', 'CRP responder' and 'non-CRP responder'; according to Ishihara et al., patients were defined as 'normal', 'normalised' and 'non-normalised' based on their early CRP kinetics. Patient and tumor characteristics were compared, and treatment outcome was measured by overall (OS) and progression-free survival (PFS), including multivariable Cox regression analyses. Results: Out of 316 mRCC patients, 227 (72%) were assigned to CRP groups according to Fukuda. Both CRP flare- (HR [Hazard ratio]: 0.59) and CRP responders (HR: 0.52) had a longer PFS, but not OS, than non-CRP responders. According to Ishihara, 276 (87%) patients were assigned to the respective groups, and both normal and normalised patients had a significantly longer PFS and OS, compared with non-normalised group. Conclusion: Different early CRP kinetics may predict therapy response in first-line mRCC therapy in a large real-world cohort. However, further research regarding the optimal timing and frequency of measurement is needed.

Last Resort from Nursing Shortage? Comparative Cost Analysis of Open vs. Robot-Assisted Partial Nephrectomies with a Focus on the Costs of Nursing Care.

Despite perioperative advantages, robot-assisted surgery is associated with high costs. However, the lower morbidity of robotic surgery could lead to a lower nursing workload and cost savings. In this comparative cost analysis of open retroperitoneal versus robot-assisted transperitoneal partial nephrectomies (PN), these possible cost savings, including other cost factors, were quantified. Therefore, patient, tumor characteristics, and surgical results of all PN within two years at a tertiary referral center were retrospectively analyzed. The nursing effort was quantified by the local nursing staff regulation and INPULS® intensive care and performance-recording system. Out of 259 procedures, 76.4% were performed robotically. After propensity score matching, the median total nursing time (2407.8 vs. 1126.8 min, p < 0.001) and daily nursing effort (245.7 vs. 222.6 min, p = 0.025) were significantly lower after robotic surgery. This resulted in mean savings of EUR 186.48 in nursing costs per robotic case, in addition to savings of EUR 61.76 due to less frequent administrations of erythrocyte concentrates. These savings did not amortize the higher material costs for the robotic system, causing additional expenses of EUR 1311.98 per case. To conclude, the nursing effort after a robotic partial nephrectomy was significantly lower compared to open surgery; however, this previously unnoticed savings mechanism alone could not amortize the overall increased costs.

Impact of Surgical Experience Before Robot-assisted Partial Nephrectomy on Surgical Outcomes: A Multicenter Analysis of 2500 Patients.

Background: Robot-assisted partial nephrectomy (RAPN) is a challenging procedure that is influenced by a multitude of factors. Objective: To assess the impact of prior surgical experience on perioperative outcomes in RAPN. Design setting and participants: In this retrospective multicenter study, results for 2548 RAPNs performed by 25 surgeons at eight robotic referral centers were analyzed. Perioperative data for all consecutive RAPNs from the start of each individual surgeon's experience were collected, as well as the number of prior open or laparoscopic kidney surgeries, pelvic surgeries (open, laparoscopic, robotic), and other robotic interventions. Intervention: Transperitoneal or retroperitoneal RAPN. Outcome measurements and statistical analysis: The impact of prior surgical experience on operative time, warm ischemia time (WIT), major complications, and margin, ischemia, complication (MIC) score (negative surgical margins, WIT ≤20 min, no major complications) was assessed via univariate and multivariable regression analyses accounting for age, gender, body mass index (BMI), American Society of Anesthesiologists score, PADUA score, and RAPN experience. Results and limitations: BMI, PADUA score, and surgical experience in RAPN had a strong impact on perioperative outcomes. A plateau effect for the learning curve was not observed. Prior laparoscopic kidney surgery significantly reduced the operative time (p < 0.001) and WIT (p < 0.001) and improved the MIC rate (p = 0.022). A greater number of prior robotic pelvic interventions decreased WIT (p = 0.011) and the rate of major complications (p < 0.001) and increased the MIC rate (p = 0.011), while prior experience in open kidney surgery did not. One limitation is the short-term follow-up. Conclusions: Mastering of RAPN is an ongoing learning process. However, prior experience in laparoscopic kidney and robot-assisted pelvic surgery seems to improve perioperative outcomes for surgeons when starting with RAPN, while experience in open surgery might not be crucial. Patient summary: In this multicenter analysis, we found that a high degree of experience in keyhole kidney surgery and robot-assisted pelvic surgery helps surgeons in achieving good initial outcomes when starting robot-assisted kidney surgery.

Optimal Selection of Patients with Genitourinary Cancers for Anti-PD1/PD-L1 Treatment with a Focus on Urothelial and Renal Cell Carcinoma.

Despite the recent approval of numerous immune checkpoint inhibitors (ICIs) for the treatment of genitourinary tumors, predictive biomarkers are still lacking. Different approaches are necessary, as the only approved biomarker for urothelial carcinoma (UC), namely PD-L1 immunostaining, has questionable predictive value. By contrast, tumor-infiltrating cells have been associated with therapy response in both UC and renal cell carcinoma. Tumor-derived gene signatures can further identify patients with pre-existing adaptive immunity. Whereas tumor mutation burden, DNA repair defects, and microsatellite instability are of some predictive value, the utility of single gene mutations has not yet been proved. As ICIs mainly target tumor metastases, analysis of primary tumors appears to be suboptimal. Circulating biomarkers reflecting tumor and systemic alterations in a more complex and dynamic manner are of great potential. The most promising approach is an analysis of complex tumor composition with concomitant consideration of the host immune status, which is also influenced by the gut microbiome. PATIENT SUMMARY: Immunotherapy is one of the treatment options for cancers of the urinary tract and kidney. We review the methods for measuring biomarkers that may predict which patients are most likely to respond to this treatment.

C-reactive protein flare predicts response to anti-PD-(L)1 immune checkpoint blockade in metastatic urothelial carcinoma.

PURPOSE: Robust biomarkers to predict response to immune checkpoint blockade (ICB) in metastatic urothelial carcinoma (mUC) are still in demand. Recently, early C-reactive protein (CRP) kinetics and especially the novel CRP flare-response phenomenon has been associated with immunotherapy response. METHODS: We conducted a multicentre observational study comprising 154 patients with mUC treated with ICB to evaluate the predictive value of a previously described on-treatment CRP kinetics: CRP flare responders (at least doubling of baseline CRP within the first month after initiation of ICB followed by a decline below baseline within three months), CRP responders (decline in baseline CRP by ≥ 30% within three months without a prior flare) and the remaining patients as CRP non-responders. CRP kinetics groups were correlated with baseline parameters, PD-L1 status, progression-free survival (PFS) and overall survival (OS). RESULTS: Objective response was observed in 57.1% of CRP responders, 45.8% of CRP flare responders and 17.9% of CRP non-responders (P < 0.001). CRP flare response was associated with prolonged PFS and OS (P < 0.001). In multivariable Cox regression analysis, CRP flare responders showed a risk reduction of ∼70% for tumour progression and death compared to CRP non-responders. Subgroup analysis of CRP flare responders revealed that patients with a long-flare response (completed flare-response kinetics ≥6 weeks on-treatment) showed even more favourable outcomes following ICB (HR = 0.18, 95%-CI: 0.07-0.48, P < 0.001). CONCLUSION: CRP (flare)response robustly predicts immunotherapy response and outcomes in mUC independent of PD-L1 status. Thus, early on-treatment CRP kinetics is a promising low-cost and easy-to-implement biomarker to optimise therapy monitoring in patients with mUC treated with ICB.

Comparison of First-Line Anti-PD-1-Based Combination Therapies in Metastatic Renal-Cell Carcinoma: Real-World Experiences from a Retrospective, Multi-Institutional Cohort.

INTRODUCTION: The aim of this study was to test for differences in overall (OS) and progression-free survival (PFS) rates and toxicity in first-line immune checkpoint inhibition (IO) combination therapy in metastatic renal-cell carcinoma (mRCC) patients. METHODS: Between November 2017 and April 2021, 104 patients with histologically confirmed mRCC from 6 tertiary referral centers with either IO + IO (nivolumab + ipilimumab, n = 68) or IO + tyrosine kinase inhibitor (TKI) (pembrolizumab + axitinib, n = 36) were included. Kaplan-Meier and Cox regression analyses tested for OS and PFS differences. RESULTS: Of 104 mRCC patients, 68 received IO + IO (65.4%) and 36 IO + TKI (34.6%) therapy, respectively. Median age was 67 years (interquartile range: 57-70.3). Patients receiving IO + TKI were less likely to be poor risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium score (16.7 vs. 30.9%) and presented with lower T-stage, compared to IO + IO treated patients. Median PFS was 9.8 months (CI: 5.3-17.6) versus 12.3 months (CI: 7.7 - not reached) for IO + IO versus IO + TKI treatment, respectively (p = 0.22). Median OS was not reached, survival rates at 12 months being 73.9 versus 90.0% for IO + IO versus IO + TKI patients (p = 0.089). In subgroup analyses of elderly patients (≥70 years, n = 38), IO + TKI treatment resulted in better OS rates at 12 months compared to IO + IO (91.0 vs. 57.0%; p = 0.042). CONCLUSION: IO + IO and IO + TKI as first-line therapies in mRCC patients were both comparable as for the oncological outcome and toxicity.

Primary Tumor Resection Decelerates Disease Progression in an Orthotopic Mouse Model of Metastatic Prostate Cancer.

Radical prostatectomy in oligometastatic prostate cancer is a matter of intense debate. Besides avoiding local complications, it is hypothesized that primary tumor resection may result in better oncological outcomes. The aim of our study was to analyze the effect of primary tumor resection on disease progression in an orthotopic prostate cancer mouse model. First, the optimal time point for primary tumor resection, when metastases have already occurred, but the primary tumor is still resectable, was determined as 8 weeks after inoculation of 5 × 105 LuCaP136 cells. In a second in vivo experiment, 64 mice with metastatic prostate cancer were randomized into two groups, primary tumor resection or sham operation, and disease progression was followed up for 10 weeks. The technique of orthotopic primary tumor resection was successfully established. Compared with the sham operation group, mice with primary tumor resection showed a significantly longer survival (p < 0.001), a significantly slower PSA increase (p < 0.01), and a lower number of lung metastases (p = 0.073). In conclusion, primary tumor resection resulted in slower disease progression and longer survival in an orthotopic mouse model of metastatic prostate cancer. In future studies, this model will be used to unravel the molecular mechanisms of primary tumor/metastasis interaction in prostate cancer.

[Robot-assisted surgery as an elective-fascinating lesson(s)?] / Wahlfach Robotische Chirurgie ­ Faszination Lehre(n)?

BACKGROUND: Even though robot-assisted operations have evolved to a standard procedure in surgery, they are underrepresented in the curriculum of current medical students. OBJECTIVES: We present our experience and findings in Germany's first elective "Robot-assisted surgery" at a urological department for undergraduate medical students. MATERIALS AND METHODS: Ten undergraduates in their final years were taught the theoretical basics and practical skills in robot-assisted surgery within six lessons each lasting 2 h, including the opportunity to observe a live robot-assisted surgery. The increase of knowledge (ten multiple-choice questions) and skills (exercises Camera 0, Clutch, and Sea Spikes 1) on a robotic simulation device were quantified including an evaluation of the student's perspective. RESULTS: The 10 participants had a significant increase in knowledge and gave at a median of 3.5 additional correct answers in the final assessment (p = 0.011). For two out of three practical exercises, the overall score significantly increased (Camera 0 and Sea Spikes 1, for both p < 0.05), but for the exercise "Clutch", only economy of motion significantly improved (p = 0.028). The elective was evaluated (very) good and the willingness of the participants to become urologists significantly increased (p = 0.007). CONCLUSION: There is a great interest of many undergraduate medical students in robot-assisted surgery. Offering an elective appears to be an excellent format to teach the theoretical background and practical skills in robotic (urologic) surgery. Moreover, such an elective could raise more attention to the field of urology and might attract future colleagues.

C-reactive protein flare-response predicts long-term efficacy to first-line anti-PD-1-based combination therapy in metastatic renal cell carcinoma.

OBJECTIVES: Immune checkpoint blockade (IO) has revolutionised the treatment of metastatic renal cell carcinoma (mRCC). Early C-reactive protein (CRP) kinetics, especially the recently introduced CRP flare-response phenomenon, has shown promising results to predict IO efficacy in mRCC, but has only been studied in second line or later. Here, we aimed to validate the predictive value of early CRP kinetics for 1st-line treatment of mRCC with αPD-1 plus either αCTLA-4 (IO+IO) or tyrosine kinase inhibitor (IO+TKI). METHODS: In this multicentre retrospective study, we investigated the predictive potential of early CRP kinetics during 1st-line IO therapy. Ninety-five patients with mRCC from six tertiary referral centres with either IO+IO (N = 59) or IO+TKI (N = 36) were included. Patients were classified as CRP flare-responders, CRP responders or non-CRP responders as previously described, and their oncological outcome was compared. RESULTS: Our data validate the predictive potential of early CRP kinetics in 1st-line immunotherapy in mRCC. CRP responders, especially CRP flare-responders, had significantly prolonged progression-free survival (PFS) compared with non-CRP responders (median PFS: CRP flare-responder: 19.2 months vs. responders: 16.2 vs. non-CRP responders: 5.6, P < 0.001). In both the IO+IO and IO+TKI subgroups, early CRP kinetics remained significantly associated with improved PFS. CRP flare-response was also associated with long-term response ≥ 12 months. CONCLUSIONS: Early CRP kinetics appears to be a low-cost and easy-to-implement on-treatment biomarker to predict response to 1st-line IO combination therapy. It has potential to optimise therapy monitoring and might represent a new standard of care biomarker for immunotherapy in mRCC.

Organ-Specific Uptake of Extracellular Vesicles Secreted by Urological Cancer Cells.

Extracellular vesicles (EVs) secreted by cancer cells have been shown to take a pivotal part in the process of local and systemic tumor progression by promoting the formation of a supportive local tumor microenvironment and preparing premetastatic niches in distant organ systems. In this study, we analyzed the organ-specific uptake of EVs secreted by urological cancer cells using an innovative in-vivo approach. EVs from benign and malignant prostate, kidney, and bladder cells were isolated using ultracentrifugation, fluorescence-labeled and injected intravenously in immunodeficient mice. After 12 or 24 h, the animals were sacrificed, their organs were harvested and analyzed for the presence of EVs by high-resolution fluorescence microscopy. Across all entities, EVs were taken up fast (12 h > 24 h), and EVs from malignant cells were taken up more efficiently than EVs from benign cells. Though not entirely organ-specific, EVs were incorporated in different amounts, depending on the entity (prostate: lung > liver > brain; kidney: brain > lung > liver; bladder: lung > liver > brain). EV uptake in other organs than lung, liver, brain, and spleen was not observed. Our results suggest a role of EVs in the formation of premetastatic niches and an organotropism in EV uptake, which have to be examined in more detail in further studies.

Does the Side Matter? A Retrospective Cohort Study Comparing Left and Right Pure Laparoscopic Donor Nephrectomies.

OBJECTIVES: Right laparoscopic donor nephrectomy (RLDN) is no longer regarded inferior to left LDN (LLDN). However, this knowledge is based on many studies suffering from inherent learning curves, center-specific imbalances, and different laparoscopic techniques. METHODS: Pure LDNs at a high-volume referral center from 2011 to 2016 were retrospectively analyzed. Patient, graft characteristics, outcomes of LDNs, and corresponding open kidney transplantations were compared between LLDN and RLDN including a follow-up. RESULTS: 160 (78.4%) LLDNs and 44 (21.6%) RLDNs only differed regarding graft characteristics, as more right grafts had multiple veins (34.1 vs. 6.9%, p < 0.001) and worse scintigraphic function (44 vs. 51%, p < 0.001). RLDNs were shorter (201 vs. 220 min, p = 0.032) with longer warm ischemia time (165 vs. 140 s, p < 0.001), but left grafts were transplanted faster (160 vs. 171 min, p = 0.048). Recipients of right kidneys had more postoperative complications (grade 3: 25.6 vs. 11.3%, p = 0.020). At a follow-up of 45 (range 6-79) months, neither the kidney function, nor death-censored graft (5-year: LLDN 89 vs. 92%, p = 0.969) and patient survival (5-year: LLDN 95 vs. 98%, p = 0.747) differed. CONCLUSIONS: Pure LLDN and RLDN can have different outcomes at high-volume centers, especially higher complications for recipients of right grafts. However, long-term function and graft survival are the same irrespective of the chosen side.

[Biomarkers for renal cell tumours]. / Biomarker: der Weg zur individualisierten Therapie bei Nierenzelltumoren.

During the last three decades, renal tumours have become increasingly well differentiated on the basis of their histopathological and molecular features. This subtyping has increasingly impacted clinical practice because more therapeutic options are available in organ-confined and metastatic renal cell tumours. The knowledge of the underlying molecular alterations is essential to develop molecular targeted therapies and to select the most effective systemic therapy for each patient. This manuscript gives an overview of the molecular differentiation on the one hand, and on diagnostic, prognostic and predictive biomarkers on the other hand.

[Robot-assisted surgery for renal cell carcinoma - today a standard?] / Roboter-assistierte Chirurgie des Nierenzellkarzinoms ­ heute ein Standard?

Twenty years have passed since the first reports on robot-assisted kidney tumor surgery in 2001. However, robotic surgery has not spread to all German urologic departments yet. Hence, one has to question whether robot-assisted kidney tumor surgery can be considered a standard today. Until now, no prospective randomized controlled trials have compared robot-assisted radical nephrectomy with the open or laparoscopic approach. Regardless, laparoscopy and robotics both have proven better perioperative and comparable oncological outcomes than with open nephrectomy. In direct comparison, robot-assisted nephrectomy has no additional benefits over the laparoscopic approach and is less cost-effective. However, reports on robot-assisted level III or IV vena cava tumor thrombectomies illustrate that robotic surgery can be superior to the laparoscopic approach in highly complex interventions. Likewise, no prospective randomized controlled trials have analyzed robot-assisted partial nephrectomy yet. When conducted by experienced surgeons, robotic and laparoscopic partial nephrectomies can also have lower morbidity compared to the open approach. No consensus has been reached when directly comparing robotic and laparoscopic partial nephrectomy. However, evidence is increasing that robot-assisted partial nephrectomy can offer additional benefits, especially for the treatment of highly complex endophytic renal tumors. Thereof, head-to-head comparisons are often impacted by patient- and tumor-related factors, as well as the learning curve of the surgeon, bed-side assistant and the annual caseload of the department. Hence, one has to conclude that robot-assisted kidney tumor surgery has evolved into a standard procedure with good results. The perioperative outcomes of robot-assisted surgery are superior to the open technique at a comparable oncological follow-up. Even if robot-assisted interventions are often more expensive than laparoscopic surgery due to higher costs of acquisition, robotics have the potential to gain superior results especially in very complex tumor surgery. Due to expiring patent protections, new manufacturers and the development of new technologies, the market of robotic surgery will most likely undergo significant changes and its costs will probably decrease within the next years.