Publications by authors named "Matthias Saar"

45 Publications

Robotic Salvage Lymph Node Dissection in Recurrent Prostate Cancer: Lessons Learned from 68 Cases and Implications for Future Clinical Management.

J Urol 2021 Feb 22:101097JU0000000000001697. Epub 2021 Feb 22.

Department of Urology, Saarland University, Homburg/Saar, Germany.

Purpose: Salvage lymph node dissection is a rescue treatment for patients with nodal recurrence after radical prostatectomy. Very limited data are available on robotic salvage lymph node dissection. Our purpose was to investigate perioperative and oncological outcomes of robotic salvage lymph node dissection in a large monocentric series.

Materials And Methods: Perioperative data, complications within 30 days after surgery and oncological outcomes as assessed by histology, prostate specific antigen changes, prostate specific antigen nadir after salvage lymph node dissection, and time to further therapy were analyzed. To identify predictive factors for oncological outcome, Kaplan-Meier and Cox-regression analyses were performed. For cases with a mismatch between preoperative positron emission tomography/computed tomography and the number of histologically positive lymph nodes, prostate specific membrane antigen immunohistochemistry was performed on removed lymph nodes.

Results: A total of 68 patients underwent robotic salvage lymph node dissection with a median operation time of 126 minutes, a blood loss of 50 ml, and a length of stay of 4 days. No major complications (>Clavien 3) occurred. Median followup was 12.1 months. Median time to further therapy was 12.4 months, 37% of patients experienced complete biochemical response (prostate specific antigen <0.2 ng/ml) and 11% reached an undetectable prostate specific antigen, which was maintained for >1 year in 3 cases. Lower preoperative prostate specific antigen, longer time between radical prostatectomy and salvage lymph node dissection, preoperative prostate specific membrane antigen positron emission tomography/computed tomography and complete biochemical response after salvage lymph node dissection were significant predictors of longer therapy-free survival (all p <0.005). Prostate specific membrane antigen immunohistochemistry revealed that prostate specific membrane antigen positron emission tomography/computed tomography tends to miss small lymph node metastases <5 mm.

Conclusions: Robotic salvage lymph node dissection is a feasible approach with low perioperative morbidity and delays further systemic therapy in most patients. Prostate specific membrane antigen positron emission tomography/computed tomography detection is mostly limited to tumor foci >5 mm.
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http://dx.doi.org/10.1097/JU.0000000000001697DOI Listing
February 2021

Can local treatment prolong the sensitivity of metastatic prostate cancer to androgen deprivation or even prevent castration resistance?

World J Urol 2021 Jan 27. Epub 2021 Jan 27.

Department of Urology and Pediatric Urology, Saarland University, Homburg/Saar, Germany.

Purpose: A number of observational clinical studies suggest that prior primary tumor treatment favorably influences the course of metastatic prostate cancer (PCa), but its mechanisms of action are still speculative. Here, we describe the long-lasting sensitivity to various forms of androgen deprivation in patients after radical prostatectomy (RP) for locally advanced PCa as one potential mechanism.

Methods: A consecutive series of 115 radical prostatectomies after inductive therapy for T4 prostate cancer was re-analyzed, and long-term survival, as well as recurrence patterns and responses to different forms of hormonal manipulation, were assessed.

Results: The estimated biochemical response-free, PCa-specific, and overall survival rates after 200 months were 20%, 65%, and 47% with a median overall survival of 156 months. The majority of patients, although not cured of locally advanced PCa (84/115), showed long-term survival after RP. PCa-specific and overall survival rates of these 84 patients with biochemical recurrence were 61% and 44% at 150 months. Long-term sensitivity to ADT was found to be the main reason for the favorable tumor-specific survival in spite of biochemical recurrence.

Conclusions: Sensitivity to primary or secondary hormonal manipulation was the main reason for the long-term survival of patients who had not been cured by surgery only. The results suggest that treatment of the primary tumor-bearing prostate delays castration-resistant PCa and enhances the effect of hormonal therapies in a previously unknown manner. The underlying cellular and molecular mechanisms need to be explored in more detailed analyses, which could profoundly impact treatment concepts of locally advanced and metastatic PCa.
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http://dx.doi.org/10.1007/s00345-020-03568-3DOI Listing
January 2021

[When a urological emergency indicates an internal medical crisis : Priapism as the first clinical manifestation of leukemia].

Urologe A 2021 Jan;60(1):67-70

Klinik für Urologie und Kinderurologie, Universität des Saarlandes, Kirrberger Straße, Gebäude 6, 66424, Homburg/Saar, Deutschland.

Priapism as a sign of a severe hematological disease is a rare event, which has to be considered as both a urological and a hematological emergency that requires immediate treatment. This article describes a clinical case of priapism as the first clinical manifestation of a hitherto undiagnosed chronic myeloid leukemia (CML) and discusses the results of a literature review on this topic.
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http://dx.doi.org/10.1007/s00120-020-01326-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819961PMC
January 2021

Open versus robot-assisted partial nephrectomy: A longitudinal comparison of 880 patients over 10 years.

Int J Med Robot 2021 Feb 21;17(1):1-8. Epub 2020 Sep 21.

Department of Urology and Pediatric Urology, Saarland University, Homburg/Saar, Germany.

Background: Most comparisons between robot-assisted partial nephrectomy (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 centre (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 favoured RAPN, even for more complex tumours.

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.
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http://dx.doi.org/10.1002/rcs.2167DOI Listing
February 2021

[The first 50 robot-assisted donor nephrectomies : Lessons learned].

Urologe A 2020 Dec;59(12):1512-1518

Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Kirrberger Straße 100, 66421, Homburg/Saar, Deutschland.

Background: Minimally invasive donor nephrectomy (DN) is considered the gold standard, but the role of robot-assisted surgery is still controversial.

Objectives: The first 50 robot-assisted DN (RDN) of a urologic transplant department in Germany were retrospectively analyzed.

Materials And Methods: Patient characteristics as well as intra- and postoperative surgical parameters were obtained. The kidney function of the donor was assessed within 5 years of follow-up. Predictors of postoperative kidney function at discharge and 1 year after RDN were estimated by multivariate regression analysis.

Results: RDN has an excellent surgical outcome with low complication rates, short warm (WIT) and cold ischemia time (CIT), little blood loss, and short patient stay. The side of donor nephrectomy does not affect surgical outcome. After RDN, 50% of donors suffer from mild to moderate renal insufficiency without further consequences, as their kidney function does not further decrease. Preoperative eGFR (estimated glomerular filtration rate) and donor age at surgery are the best predictors of postoperative kidney function after RDN.

Conclusions: Robot-assisted donor nephrectomy is an excellent alternative to other minimally invasive approaches rendering solid surgical results possible right from the start.
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http://dx.doi.org/10.1007/s00120-020-01302-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721693PMC
December 2020

Cancer-associated fibroblasts stimulate primary tumor growth and metastatic spread in an orthotopic prostate cancer xenograft model.

Sci Rep 2020 07 28;10(1):12575. Epub 2020 Jul 28.

Department of Urology and Pediatric Urology, Saarland University, Kirrberger Straße 100, Gebäude 6, 66424, Homburg/Saar, Germany.

The unique microenvironment of the prostate plays a crucial role in the development and progression of prostate cancer (PCa). We examined the effects of cancer-associated fibroblasts (CAFs) on PCa progression using patient-derived fibroblast primary cultures in a representative orthotopic xenograft model. Primary cultures of CAFs, non-cancer-associated fibroblasts (NCAFs) and benign prostate hyperplasia-associated fibroblasts (BPHFs) were generated from patient-derived tissue specimens. These fibroblasts were coinjected together with cancer cells (LuCaP136 spheroids or LNCaP cells) in orthotopic PCa xenografts to investigate their effects on local and systemic tumor progression. Primary tumor growth as well as metastatic spread to lymph nodes and lungs were significantly stimulated by CAF coinjection in LuCaP136 xenografts. When NCAFs or BPHFs were coinjected, tumor progression was similar to injection of tumor cells alone. In LNCaP xenografts, all three fibroblast types significantly stimulated primary tumor progression compared to injection of LNCaP cells alone. CAF coinjection further increased the frequency of lymph node and lung metastases. This is the first study using an orthotopic spheroid culture xenograft model to demonstrate a stimulatory effect of patient-derived CAFs on PCa progression. The established experimental setup will provide a valuable tool to further unravel the interacting mechanisms between PCa cells and their microenvironment.
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http://dx.doi.org/10.1038/s41598-020-69424-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387494PMC
July 2020

Three Different Learning Curves Have an Independent Impact on Perioperative Outcomes After Robotic Partial Nephrectomy: A Comparative Analysis.

Ann Surg Oncol 2021 Feb 24;28(2):1254-1261. Epub 2020 Jul 24.

Department of Urology and Pediatric Urology, Saarland University, Homburg/Saar, Germany.

Background: Robot-assisted partial nephrectomy (RAPN) has become widely accepted, but its different underlying types of learning curves have not been comparatively analyzed to date. This study aimed to determine and compare the impact that the learning curve of the department, the console surgeon, and the bedside assistant as well as patient-related factors has on the perioperative outcomes of RAPN.

Methods: The study retrospectively analyzed 500 consecutive transperitoneal RAPNs (2007-2018) performed in a tertiary referral center by 7 surgeons and 37 bedside assistants. Patient characteristics and surgical data were obtained. Experience (EXP) was defined as the current number of RAPNs performed by the department, the surgeon, and the assistant. As the primary outcome, the impact of EXP and patient-related factors on perioperative outcomes were analyzed and compared. As the secondary outcome, a cutoff between "experienced" and "inexperienced" was defined. Correlation and regression analysis, receiver operating characteristic curve analysis, Fisher's exact test, and the Mann-Whitney U test were performed, with p values lower than 0.05 denoting significance.

Results: The EXP of the department, the surgeon, and the assistant each has a major influence on perioperative outcome in RAPN irrespective of patient-related factors. Perioperative outcomes improve significantly with EXP greater than 100 for the department, EXP greater than 35 for the surgeon, and EXP greater than 15 for the assistant.

Conclusions: The perioperative results of RAPN are influenced by three different types of learning curves including those for the surgical department, the console surgeon, and the assistant. The influence of the bedside assistant clearly has been underestimated to date because it has a significant impact on the perioperative outcomes of RAPN.
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http://dx.doi.org/10.1245/s10434-020-08856-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801306PMC
February 2021

ASO Author Reflection: Learning Curves in Robotic Partial Nephrectomy-Not Only the Surgeon Counts.

Ann Surg Oncol 2020 Dec 22;27(Suppl 3):840-841. Epub 2020 Jul 22.

Department of Urology and Pediatric Urology, Saarland University, Homburg/Saar, Germany.

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http://dx.doi.org/10.1245/s10434-020-08866-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677156PMC
December 2020

Current Role of Multiparametric MRI and MRI Targeted Biopsies for Prostate Cancer Diagnosis in Germany: A Nationwide Survey.

Urol Int 2020 8;104(9-10):731-740. Epub 2020 Jul 8.

Department of Urology and Pediatric Urology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Introduction: Multiparametric MRI (mpMRI) and MRI targeted biopsies (MRtb) are a new standard in prostate cancer (PCa) screening and diagnosis. Guidelines already include this approach for patients at risk. We aimed to gather information from German urologists about their knowledge, routine use, and attitude toward mpMRI and consecutive biopsy methods.

Materials And Methods: An anonymous online questionnaire was sent via Survey Monkey to the members of the German Society of Urology (DGU). Statistical analyses were performed using SPSS version 25.0.

Results: 496 members with a median age of 48.6 years (±11.7) participated in the survey. The majority rated mpMRI of the prostate as a very useful diagnostic tool (72.7%). MRtb of the prostate was considered as very advantageous (71.5%). MpMRI was used by 95.9%, and 83.2% also recommended MRtb predominantly in clinical institutions. For targeted biopsy, MRI-ultrasound fusion biopsy was clearly favored (75.8%). MpMRI was mostly used in patients with previously negative biopsy (90.9%) and in patients under active surveillance (60.9%). Arguments against the use of prostate mpMRI are costs (84.9%) and/or lack of sufficient radiological infrastructure (17.4%).

Conclusion: Our data illustrate the meanwhile high acceptance and clinical use of the prostate mpMRI and MRtb in Germany.
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http://dx.doi.org/10.1159/000508755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592851PMC
July 2020

Should We Perform Old-for-Old Kidney Transplantation during the COVID-19 Pandemic? The Risk for Post-Operative Intensive Stay.

J Clin Med 2020 Jun 12;9(6). Epub 2020 Jun 12.

Department of Urology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humbold-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.

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.
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http://dx.doi.org/10.3390/jcm9061835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356807PMC
June 2020

Robot-Assisted versus Laparoscopic Donor Nephrectomy: A Comparison of 250 Cases.

J Clin Med 2020 May 26;9(6). Epub 2020 May 26.

Department of Urology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humbold-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.

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.
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http://dx.doi.org/10.3390/jcm9061610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355615PMC
May 2020

Response and outcome of liver metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing Lu-PSMA-617 radioligand therapy.

Eur J Nucl Med Mol Imaging 2021 Jan 6;48(1):103-112. Epub 2020 May 6.

Department of Nuclear Medicine, Saarland University, Homburg, Germany.

Purpose: Little is known about the efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) against liver metastases of metastatic castration-resistant prostate cancer (mCRPC). We retrospectively analyzed efficacy-related outcomes of Lu-PSMA-617 RLT in this setting and potential predictors of those outcomes.

Methods: Twenty-eight consecutive mCRPC patients with liver metastases given Lu-PSMA-617 RLT were analyzed retrospectively. Their planned regimen was 4-6 cycles at 6 ± 2-week intervals; the mean activity/cycle was 6.5 ± 0.5 GBq. Hepatic response was determined by modified positron emission tomography response criteria in solid tumors; association of such response with overall survival (OS) was tested, as were relationships of the selected patient, disease, and treatment characteristics with hepatic progression-free survival (PFS) and OS. Survival analyses used Kaplan-Meier curves, log-rank test at p < 0.05 significance, and Cox proportional-hazards modeling.

Results: Median (minimum-maximum) follow-up was 37.5 (2.3-50.6) months. In liver metastases, complete or partial response was observed in 6 patients (21%) each, and stable disease in 1 (4%), for hepatic disease control in 46%. Overall, median (95% confidence interval) PFS was 5.7 (2.2-9.2) months, and OS, 11.7 (3.0-20.4) months. Patients with hepatic disease control did not reach the median OS, while those with hepatic progressive disease had median OS (95% confidence interval) of 6.4 (1.6-11.1) months. In multivariate analysis, hepatic disease control by Lu-PSMA-617 RLT was significantly independently associated with OS, as was a prostate-specific antigen decline of ≥ 50% after 2 RLT cycles, and good baseline performance status (Eastern Cooperative Oncology Group 0-1). Hepatic tumor burden (≤ 25% vs. > 25% of liver volume) had no apparent relationship with hepatic tumor response, PFS, or OS.

Conclusion: Lu-PSMA-617 RLT frequently controlled liver metastases, resulting in long PFS and significantly improved OS. Hepatic tumor burden appeared to lack any relationship with treatment efficacy, supporting Lu-PSMA-617 RLT of late-stage/end-stage mCRPC with liver metastases.
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http://dx.doi.org/10.1007/s00259-020-04828-5DOI Listing
January 2021

A comparative propensity score-matched analysis of perioperative outcomes of intracorporeal vs extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

BJU Int 2020 08 16;126(2):265-272. Epub 2020 May 16.

Roswell Park Cancer Institute, Buffalo, NY, USA.

Objective: To compare the perioperative outcomes of intracorporeal (ICUD) vs extracorporeal urinary diversion (ECUD) after robot-assisted radical cystectomy (RARC).

Patients And Methods: We retrospectively reviewed the prospectively maintained International Robotic Cystectomy Consortium (IRCC) database. A total of 972 patients from 28 institutions who underwent RARC were included. Propensity score matching was used to match patients based on age, gender, body mass index (BMI), American Society of Anesthesiologists Score (ASA) score, Charlson Comorbidity Index (CCI) score, prior radiation and abdominal surgery, receipt of neoadjuvant chemotherapy, and clinical staging. Matched cohorts were compared. Multivariate stepwise logistic and linear regression models were fit to evaluate variables associated with receiving ICUD, operating time, 90-day high-grade complications (Clavien-Dindo Classification Grade ≥III), and 90-day readmissions after RARC.

Results: Utilisation of ICUD increased from 0% in 2005 to 95% in 2018. The ICUD patients had more overall complications (66% vs 58%, P = 0.01) and readmissions (27% vs 17%, P = 0.01), but not high-grade complications (21% vs 24%, P = 0.22). A more recent RC era and ileal conduit diversion were associated with receiving an ICUD. Higher BMI, ASA score ≥3, and receiving a neobladder were associated with longer operating times. Shorter operating time was associated with male gender, older age, ICUD, and centres with a larger annual average RC volume. Longer intensive care unit stay was associated with 90-day high-grade complications. Higher CCI score, prior radiation therapy, neoadjuvant chemotherapy, and ICUD were associated with a higher risk of 90-day readmissions.

Conclusions: Utilisation of ICUD has increased over the past decade. ICUD was associated with more overall complications and readmissions compared to ECUD, but not high-grade complications.
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http://dx.doi.org/10.1111/bju.15083DOI Listing
August 2020

miR-22 Regulates Invasion, Gene Expression and Predicts Overall Survival in Patients with Clear Cell Renal Cell Carcinoma.

Kidney Cancer 2019 Aug 7;3(2):119-132. Epub 2019 Aug 7.

Department of Urology, School of Medicine, Stanford University, Stanford, California, USA.

Background: Clear cell renal cell carcinoma (ccRCC) is molecularly diverse and distinct molecular subtypes show different clinical outcomes. MicroRNAs (miRNAs) are essential components of gene regulatory networks and play a crucial role in progression of many cancer types including ccRCC.

Objective: Identify prognostic miRNAs and determine the role of miR-22 in ccRCC.

Methods: Hierarchical clustering was done in R using gene expression profiles of over 450 ccRCC cases in The Cancer Genome Atlas (TCGA). Kaplan-Meier analysis was performed to identify prognostic miRNAs in the TCGA dataset. RNA-Seq was performed to identify miR-22 target genes in primary ccRCC cells and Matrigel invasion assay was performed to assess the effects of miR-22 overexpression on cell invasion.

Results: Hierarchical clustering analysis using 2,621 prognostic genes previously identified by our group demonstrated that ccRCC patients with longer overall survival expressed lower levels of genes promoting proliferation or immune responses, while better maintaining gene expression associated with cortical differentiation and cell adhesion. Targets of 26 miRNAs were significantly enriched in the 2,621 prognostic genes and these miRNAs were prognostic by themselves. MiR-22 was associated with poor overall survival in the TCGA dataset. Overexpression of miR-22 promoted invasion of primary ccRCC cells and modulated transcriptional programs implicated in cancer progression including DNA repair, cell proliferation and invasion.

Conclusions: Our results suggest that ccRCCs with differential clinical outcomes have distinct transcriptomes for which miRNAs could serve as master regulators. MiR-22, as a master regulator, promotes ccRCC progression at least in part by enhancing cell invasion.
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http://dx.doi.org/10.3233/KCA-190051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839454PMC
August 2019

Ac-PSMA-617/Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience.

Eur J Nucl Med Mol Imaging 2020 03 22;47(3):721-728. Epub 2019 Nov 22.

Department of Nuclear Medicine, Saarland University, 66421, Homburg, Germany.

Purpose: Up to 30% of patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) never respond or develop resistance to Lu-labeled PSMA-targeted radioligand monotherapy. Single-agent PSMA-targeted radioligand therapy (PRLT) with the alpha-emitter Ac showed promise against mCRPC but may cause severe and/or persistent xerostomia, which may substantially impair patients' quality-of-life. We hypothesized that when Lu-PSMA ligand alone is ineffective, tandem therapy with low-activity Ac-PSMA ligand plus full activity of the beta emitter may enhance efficacy while minimizing xerostomia severity.

Methods: We retrospectively analyzed pilot experience with 1 course of Ac-PSMA-617/Lu-PSMA-617 tandem therapy in our first 20 patients with mCRPC receiving this intervention after insufficiently responding to Lu-PSMA-617 monotherapy. This cohort had late-stage/end-stage disease with high baseline prostate-specific antigen (PSA) concentration (median 215 ng/mL), heavy pre-treatment (abiraterone and/or enzalutamide, and Lu-PRLT [median cumulative activity, 26.3 GBq] in 20/20 patients, 100%; docetaxel and/or cabazitaxel in 13/20 patients, 65%), and frequent Eastern Cooperative Oncology Group performance status of 2 (8/20 patients, 40%).

Results: Median (minimum-maximum) administered activities were Ac-PSMA-617, 5.3 (1.5-7.9) MBq, and Lu-PSMA-617, 6.9 (5.0-11.6) GBq. Significant responders to tandem therapy received Lu-PSMA-617 monotherapy as maintenance (median [minimum-maximum]: 1 [0-5] cycle). After a median (minimum-maximum) 22 (14-63) weeks' follow-up, 13/20 patients (65%) had as best biochemical response a PSA decline > 50%. Median (95% confidence interval) progression-free survival was 19 (12-26) weeks, and overall survival was 48 (4-92) weeks post-tandem therapy administration. Xerostomia was reported as grade 1 (very mild) in 8/20 patients (40%), grade 2 (mild) in 5/20 (25%), and grade 3/4 in 0/20.

Conclusions: Our results suggest that a single course of tandem therapy with low-activity Ac-PSMA-617/full-activity Lu-PSMA-617 may safely enhance response to PRLT in men with late-stage/end-stage mCRPC while minimizing xerostomia severity. Formal study of this combination is warranted.
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http://dx.doi.org/10.1007/s00259-019-04612-0DOI Listing
March 2020

Patient-derived, three-dimensional spheroid cultures provide a versatile translational model for the study of organ-confined prostate cancer.

J Cancer Res Clin Oncol 2019 Mar 24;145(3):551-559. Epub 2018 Nov 24.

Department of Urology, Saarland University, Homburg, Saar, Germany.

Purpose: To generate and characterize 3D spheroid suspension cultures from radical prostatectomy (RP) specimens as a versatile model system for organ-confined prostate cancer (PCa).

Methods: Cancerous tissue samples from RP specimens were excised by a uropathologist. Preparation of 3D spheroids was done by mechanical disintegration and limited enzymatic digestion followed by serial filtration through 100 μm- and 40 μm-cell strainers. Thereafter, spheroids were cultured in a modified stem cell medium and characterized by a live/dead assay, whole-spheroid immunohistochemistry (IHC; CK5, CK8, AMACR, PSA, Ki67, AR, αSMA, Vimentin, E-Cadherin) and PSA-measurements in culture medium. Furthermore, their response to pharmaceutical treatment with docetaxel, bicalutamide, enzalutamide and abiraterone was tested.

Results: 173 RP cases were included. The median preoperative PSA-level was 16.12 ng/ml [range 0.99;345], the median Gleason score was 7b [6;10]. 64 cases were excluded due to low tumor content in frozen sections (43) or to insufficient spheroid formation (21). In the remaining 109 cases, spheroids formed successfully and stayed viable for up to several months. IHC analysis revealed AR-, CK8-, and AMACR-positivity in nearly all cases, while CK5-positive cells were detectable only occasionally as were α-SMA and Vimentin. E-Cadherin was positive in most cases. Furthermore, spheroids proved to be amenable to cryopreservation. While abiraterone had no effect and docetaxel only a moderate effect, spheroid viability was markedly reduced upon bicalutamide and enzalutamide treatment.

Conclusions: Multicellular 3D spheroids can be generated from patient-derived RP tissue samples and serve as an innovative in vitro model of organ-confined PCa.
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http://dx.doi.org/10.1007/s00432-018-2803-5DOI Listing
March 2019

Human Papillomavirus-Associated Invasive Condylomas in a Man with Immunosuppressive Comorbidities.

Urol Int 2019 21;102(2):238-242. Epub 2018 Aug 21.

Department of Urology and Pediatric Urology, Saarland University, Homburg, Germany.

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.
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http://dx.doi.org/10.1159/000491098DOI Listing
July 2019

Robotic salvage lymph node dissection for nodal-only recurrences after radical prostatectomy: Perioperative and early oncological outcomes.

Surg Oncol 2018 Jun 24;27(2):138-145. Epub 2018 Feb 24.

Department of Urology, Saarland University, Kirrberger Straße 100, Building 6, Homburg/Saar, Germany. Electronic address:

Background: Salvage lymph node dissection (sLND) - performed open or minimally-invasive - is a treatment modality that can be offered to patients with nodal recurrence after radical prostatectomy (RP), especially in times where modern imaging methods like choline- or PSMA-PET/CT are available. Yet, there are only very limited data on the safety and oncological effectiveness of robotic sLND.

Methods: We retrospectively identified patients who underwent robotic sLND at our institution between 2013 and 2017 for nodal recurrence after RP, which had been diagnosed either by F-choline- or Ga-PSMA-PET/CT. We analyzed perioperative data and early oncological outcomes with a focus on the comparison of patients with preoperative choline- vs. those with preoperative PSMA-PET/CT.

Results: We identified 36 patients who underwent robotic sLND at a median time of 45.3 months [range 3.1;228.6] after RP, with nodal recurrences detected in 25 patients by PSMA- and in 11 by choline-PET/CT. Median preoperative PSA, operation time and blood loss were 1.98 ng/ml [range 0.09;35.15], 129.5 min [range 65;202] and 50 ml [range 0;400], respectively. No high-grade complications occurred. A median number of 6.5 [range 1;25] lymph nodes were removed with a median of 1 [range 0;9] tumor-occupied node. None of the patients received any adjuvant treatment. Median postoperative PSA-change was -57% [range -100; +58] in the PSMA- and +10% [range -91; +95] in the choline-group (p = 0.015). 44% of patients in the PSMA- and 18% of patients in the choline-group experienced complete biochemical response (cBCR; PSA <0.2 ng/ml). Median time from sLND to the initiation of further therapy was 12 months [range 2;21.5] in the PSMA-group and 4.7 months [range 2.2;18.9] in the choline-group (p = 0.001).

Conclusions: This is the hitherto largest series on robotic sLND for nodal recurrence after RP. Robotic sLND is a feasible therapeutic option with low morbidity, which can at least delay the initiation of further therapy - in some patients up to several years. However, the extend of sLND has to be standardized and randomized trials are needed to finally define the oncological effectiveness of this approach.
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http://dx.doi.org/10.1016/j.suronc.2018.02.010DOI Listing
June 2018

Radical prostatectomy in T4 prostate cancer after inductive androgen deprivation: results of a single-institution series with long-term follow-up.

BJU Int 2019 01 7;123(1):58-64. Epub 2018 Jun 7.

Department of Urology and Pediatric Urology, Saarland University, Homburg/Saar, Germany.

Objectives: To determine the outcomes of complete surgical resection of T4 prostate cancer after inductive androgen-deprivation therapy (ADT), as inductive ADT and subsequent radical prostatectomy (RP) is not recommended by any guideline yet.

Patients And Methods: A monocentric RP database was queried for patients initially diagnosed with T4 prostate cancer, considered primarily as inoperable because of a fixed mass defined by rectal examination in combination with high PSA level and/or large foci of biopsy confirmed undifferentiated prostate cancer. Treatment consisted of primary ADT until PSA nadir with consecutive RP. Patients underwent retropubic RP (RRP) or robot-assisted laparoscopic RP (RALP) after inductive ADT until achievement of the PSA nadir, which is in general reached after 6-7 months. The intraoperative course and complications were analysed. Finally, Kaplan-Meier estimates were calculated for overall survival (OS) and prostate cancer-specific survival (PCSS).

Results: We retrospectively identified 116 patients treated between 2000 and 2014. At diagnosis, the median (range) PSA level was 37.6 (2.44-284) ng/mL. The preoperative median (range) PSA after inductive ADT was 0.73 (0.01-34) ng/mL. Thereafter, patients underwent RRP or, since 2006, RALP. The median (95% confidence interval) OS was 156 (118.9-193.1) months. The PCSS at 150 months was 82%.

Conclusions: Surgical therapy of primarily inoperable prostate cancer is feasible and safe after inductive ADT. The OS of this cohort seems comparable with results described for patients with primary operable high-risk prostate cancer.
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http://dx.doi.org/10.1111/bju.14393DOI Listing
January 2019

A novel mouse model of human prostate cancer to study intraprostatic tumor growth and the development of lymph node metastases.

Prostate 2018 06 24;78(9):664-675. Epub 2018 Mar 24.

Department of Urology, Saarland University, Homburg/Saar, Germany.

Background: In this study, we aimed to establish a versatile in vivo model of prostate cancer, which adequately mimics intraprostatic tumor growth, and the natural routes of metastatic spread. In addition, we analyzed the capability of high-resolution ultrasonography (hrUS), in vivo micro-CT (μCT), and 9.4T MRI to monitor tumor growth and the development of lymph node metastases.

Methods: A total of 5 × 10 VCaP cells or 5 × 10 cells of LuCaP136- or LuCaP147 spheroids were injected into the prostate of male CB17-SCID mice (n = 8 for each cell type). During 12 weeks of follow-up, orthotopic tumor growth, and metastatic spread were monitored by repetitive serum-PSA measurements and imaging studies including hrUS, μCT, and 9.4T MRI. At autopsy, primary tumors and metastases were harvested and examined by histology and immunohistochemistry (CK5, CK8, AMACR, AR, Ki67, ERG, and PSA). From imaging results and PSA-measurements, tumor volume doubling time, tumor-specific growth rate, and PSA-density were calculated.

Results: All 24 mice developed orthotopic tumors. The tumor growth could be reliably monitored by a combination of hrUS, μCT, MRI, and serum-PSA measurements. In most animals, lymph node metastases could be detected after 12 weeks, which could also be well visualized by hrUS, and MRI. Immunohistochemistry showed positive signals for CK8, AMACR, and AR in all xenograft types. CK5 was negative in VCaP- and focally positive in LuCaP136- and LuCaP147-xenografts. ERG was positive in VCaP- and negative in LuCaP136- and LuCaP147-xenografts. Tumor volume doubling times and tumor-specific growth rates were 21.2 days and 3.9 %/day for VCaP-, 27.6 days and 3.1 %/day for LuCaP136- and 16.2 days and 4.5 %/day for LuCaP147-xenografts, respectively. PSA-densities were 433.9 ng/mL per milliliter tumor for VCaP-, 6.5 ng/mL per milliliter tumor for LuCaP136-, and 11.2 ng/mL per milliliter tumor for LuCaP147-xenografts.

Conclusions: By using different monolayer and 3D spheroid cell cultures in an orthotopic xenograft model, we established an innovative, versatile in vivo model of prostate cancer, which enables the study of both intraprostatic tumor growth as well as metastatic spread to regional lymph nodes. HrUS and MRI are feasible tools to monitor tumor growth and the development of lymph node metastases while these cannot be visualized by μCT.
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http://dx.doi.org/10.1002/pros.23508DOI Listing
June 2018

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI.

Sci Rep 2017 10 27;7(1):14249. Epub 2017 Oct 27.

Department of Urology, Saarland University, Homburg/Saar, Germany.

In this study, we aimed to comparatively evaluate high-resolution 3D ultrasonography (hrUS), in-vivo micro-CT (μCT) and 9.4T MRI for the monitoring of tumor growth in an orthotopic renal cell carcinoma (RCC) xenograft model since there is a lack of validated, non-invasive imaging tools for this purpose. 1 × 10 Caki-2 RCC cells were implanted under the renal capsule of 16 immunodeficient mice. Local and systemic tumor growth were monitored by regular hrUS, μCT and MRI examinations. Cells engrafted in all mice and gave rise to exponentially growing, solid tumors. All imaging techniques allowed to detect orthotopic tumors and to precisely calculate their volumes. While tumors appeared homogenously radiolucent in μCT, hrUS and MRI allowed for a better visualization of intratumoral structures and surrounding soft tissue. Examination time was the shortest for hrUS, followed by μCT and MRI. Tumor volumes determined by hrUS, μCT and MRI showed a very good correlation with each other and with caliper measurements at autopsy. 10 animals developed pulmonary metastases being well detectable by μCT and MRI. In conclusion, each technique has specific strengths and weaknesses, so the one(s) best suitable for a specific experiment may be chosen individually.
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http://dx.doi.org/10.1038/s41598-017-14759-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660163PMC
October 2017

Development of a patient and institutional-based model for estimation of operative times for robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

BJU Int 2017 11 16;120(5):695-701. Epub 2017 Jul 16.

Roswell Park Cancer Institute, Buffalo, NY, USA.

Objectives: To design a methodology to predict operative times for robot-assisted radical cystectomy (RARC) based on variation in institutional, patient, and disease characteristics to help in operating room scheduling and quality control.

Patients And Methods: The model included preoperative variables and therefore can be used for prediction of surgical times: institutional volume, age, gender, body mass index, American Society of Anesthesiologists score, history of prior surgery and radiation, clinical stage, neoadjuvant chemotherapy, type, technique of diversion, and the extent of lymph node dissection. A conditional inference tree method was used to fit a binary decision tree predicting operative time. Permutation tests were performed to determine the variables having the strongest association with surgical time. The data were split at the value of this variable resulting in the largest difference in means for the surgical time across the split. This process was repeated recursively on the resultant data sets until the permutation tests showed no significant association with operative time.

Results: In all, 2 134 procedures were included. The variable most strongly associated with surgical time was type of diversion, with ileal conduits being 70 min shorter (P < 0.001). Amongst patients who received neobladders, the type of lymph node dissection was also strongly associated with surgical time. Amongst ileal conduit patients, institutional surgeon volume (>66 RARCs) was important, with those with a higher volume being 55 min shorter (P < 0.001). The regression tree output was in the form of box plots that show the median and ranges of surgical times according to the patient, disease, and institutional characteristics.

Conclusion: We developed a method to estimate operative times for RARC based on patient, disease, and institutional metrics that can help operating room scheduling for RARC.
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http://dx.doi.org/10.1111/bju.13934DOI Listing
November 2017

Segmental Testicular Infarction: Case Series and Literature Review of a Rare Diagnosis in Men with Acute Testicular Pain.

Urol Int 2018 24;101(1):114-116. Epub 2017 Mar 24.

Department of Urology, Saarland University Medical Center, Homburg/Saar, Germany.

The incidence of segmental testicular infarction (STI) is very low. Such a disorder most often affects young men. The most common symptom is sudden testicular pain. We report 6 cases of men diagnosed with STI. Clinical examination, blood test, urine analysis, and ultrasound examination with colour Doppler were performed. Furthermore, tissue sonoelastography or MRI was performed in selected patients. All men underwent surgical exploration. In all but one man, the affected testis was preserved. Although STI is a rare condition, it should be taken into account if testicular pain prior to suspicious ultrasound imaging occurs. To be aware of this benign testicular pathology and its clinical and imaging features is important to avoid unnecessary orchiectomies in young patients.
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http://dx.doi.org/10.1159/000464411DOI Listing
January 2019

Early Oncologic Failure after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

J Urol 2017 06 18;197(6):1427-1436. Epub 2016 Dec 18.

Roswell Park Cancer Institute, Buffalo, New York. Electronic address:

Purpose: We sought to investigate the prevalence and variables associated with early oncologic failure.

Materials And Methods: We retrospectively reviewed the IRCC (International Radical Cystectomy Consortium) database of patients who underwent robot-assisted radical cystectomy since 2003. The final cohort comprised a total of 1,894 patients from 23 institutions in 11 countries. Early oncologic failure was defined as any disease relapse within 3 months of robot-assisted radical cystectomy. All institutions were surveyed for the pneumoperitoneum pressure used, breach of oncologic surgical principles, and techniques of specimen and lymph node removal. A multivariate model was fit to evaluate predictors of early oncologic failure. The Kaplan-Meier method was applied to depict disease specific and overall survival, and Cox proportional regression analysis was used to evaluate predictors of disease specific and overall survival.

Results: A total of 305 patients (22%) experienced disease relapse, which was distant in 220 (16%), local recurrence in 154 (11%), peritoneal carcinomatosis in 17 (1%) and port site recurrence in 5 (0.4%). Early oncologic failure developed in 71 patients (5%) at a total of 10 institutions. The incidence of early oncologic failure decreased from 10% in 2006 to 6% in 2015. On multivariate analysis the presence of any complication (OR 2.87, 95% CI 1.38-5.96, p = 0.004), pT3 or greater disease (OR 3.73, 95% CI 2.00-6.97, p <0.001) and nodal involvement (OR 2.14, 95% CI 1.21-3.80, p = 0.008) was a significant predictor of early oncologic failure. Patients with early oncologic failure demonstrated worse disease specific and overall survival (23% and 13%, respectively) at 1 and 3 years compared to patients who experienced later or no recurrences (log rank p <0.001).

Conclusions: The incidence of early oncologic failure following robot-assisted radical cystectomy has decreased with time. Disease related rather than technical related factors have a major role in early oncologic failure after robot-assisted radical cystectomy.
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http://dx.doi.org/10.1016/j.juro.2016.12.048DOI Listing
June 2017

Robot-assisted vs open adrenalectomy: evaluation of cost-effectiveness and peri-operative outcome.

BJU Int 2016 Dec 10;118(6):952-957. Epub 2016 Jun 10.

Department of Urology and Paediatric Urology, Saarland University Medical Centre, Homburg, Germany.

Objectives: To compare robot-assisted laparoscopic adrenalectomy (RALA) and open adrenalectomy (OA) with regard to intra-operative complications, peri-operative outcome and cost effectiveness.

Subjects And Methods: Functional and statistical data from patients who underwent OA or RALA between 2001 and 2015 were prospectively recorded including intra- and postoperative outcomes. Data on per-day costs from current census reports (€540/day and €1 145/day for normal and intermediate care [IMC]) were also used to evaluate treatment costs. Additional costs for RALA were assumed at €2288 as reported in the current literature. Patients were matched by American Society of Anesthesiologists score, age, side of surgery and gender for comparison of OA and RALA. A total of 28 matched pairs were analysed with regard to patient characteristics, peri-operative outcomes and cost-effectiveness. Statistical significance of outcome variables was determined using Student's t-test and Pearson's chi-squared test.

Results: As a result of the matching process, patient groups did not differ in their main characteristics. Length of hospital stay was shorter for RALA than for OA (11.1 ± 4.8 vs 6.8 ± 1.2 days; P < 0.01) as was IMC treatment (2.3 ± 1.7 vs 1.2 ± 0.4 days; P < 0.01). The mean operating time was longer for RALA (128.5 ± 46.5 vs 102.2 ± 44.5 min; P = 0.03), but the last 10 RALA procedures (mean: 97.1 ± 35.2 min) were similar to OA. The rate of complications was similar in the two groups. Estimated costs were €8 627.5 for OA and €7 334 for RALA.

Conclusions: The study showed that RALA was safe and cost-effective compared with OA. Increasing experience leads to similar operating times, putting high-volume centres at an advantage.
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http://dx.doi.org/10.1111/bju.13529DOI Listing
December 2016

Spheroid culture of LuCaP 136 patient-derived xenograft enables versatile preclinical models of prostate cancer.

Clin Exp Metastasis 2016 Apr 12;33(4):325-37. Epub 2016 Feb 12.

Department of Urology, Stanford University School of Medicine, Stanford, CA, 94305, USA.

LuCaP serially transplantable patient-derived xenografts (PDXs) are valuable preclinical models of locally advanced or metastatic prostate cancer. Using spheroid culture methodology, we recently established cell lines from several LuCaP PDXs. Here, we characterized in depth the features of xenografts derived from LuCaP 136 spheroid cultures and found faithful retention of the phenotype of the original PDX. In vitro culture enabled luciferase transfection into LuCaP 136 spheroids, facilitating in vivo imaging. We showed that LuCaP 136 spheroids formed intratibial, orthotopic, and subcutaneous tumors when re-introduced into mice. Intratibial tumors responded to castration and were highly osteosclerotic. LuCaP 136 is a realistic in vitro-in vivo preclinical model of a subtype of bone metastatic prostate cancer.
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http://dx.doi.org/10.1007/s10585-016-9781-2DOI Listing
April 2016

Organ-Preserving Surgical Treatment of a Horseshoe Kidney Occupied by a Large Renal Cell Carcinoma with Extensive Venous Invasion: A Case Report.

Urol Int 2018 11;100(2):245-247. Epub 2016 Feb 11.

Department of Urology, Saarland University Medical Center, Homburg/Saar, Germany.

The horseshoe kidney is one of the most common congenital disorders affecting the urogenital system. Following a fusion of the lower kidney poles, which in turn lead to the formation of an isthmus, this anatomical variation is accompanied by other characteristic properties like an incomplete ascension, ventral rotation of the pelvices as well as atypical vascular supply. Even though renal carcinoids and Wilms tumors are more common in horseshoe kidneys, the incidence of renal cell carcinomas seems to be unaffected. Here we report the case of a locally advanced renal cell carcinoma with extensive venous invasion occurring in a horseshoe kidney and its complex surgical management. The whole primary tumor as well as a majority of venous tumor thrombi could be removed by a combination of 2/3 nephrectomy and cavotomy with thrombectomy. During 1 year of follow-up, the patient neither suffered from a tumor relapse, nor did he require renal replacement therapy. Thus, we conclude that even in cases of RCC where advanced disease is associated with complex anatomical situations, organ-preserving surgical treatment should be pursued to achieve excellent functional and oncological results.
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http://dx.doi.org/10.1159/000443671DOI Listing
September 2018

Quality of Preoperative Biopsy Is a Risk Factor for Positive Surgical Margins in Organ-Confined Prostate Cancer Treated with Nerve-Sparing Robot-Assisted Radical Prostatectomy.

Urol Int 2015 18;95(4):465-71. Epub 2015 Nov 18.

Department of Urology, Saarland University Medical Center, Homburg/Saar, Germany.

Purpose: Positive surgical margins (PSM) during robot-assisted radical prostatectomy (RARP) negatively influence patients' prognosis. The aim of our study was to identify risk factors for PSM in patients with organ-confined prostate cancer (PCa).

Methods: A clinical database of all patients that underwent a RARP at our institution was used. Uni- and multivariable logistic regression analyses were conducted on the PSM rates for all patients with organ-confined PCa.

Results: Altogether, 1,600 patients were identified, including 1,085 organ-confined PCa with a PSM rate of 7.8%. On multivariable analysis, bilateral nerve-sparing (OR 3.025, 95% CI 1.587-5.765), surgeon volume <200 cases (OR 1.881, 95% CI 1.120-3.159) and a preoperative PSA >10 ng/ml (OR 3.674, 95% CI 1.379-9.796) remained independent prognostic factors. In a subgroup of patients undergoing a nerve-sparing RARP, the quality of the prostate biopsy (OR 2.398, 95% CI 1.325-4.341) was the sole independent risk factor for a PSM.

Conclusion: An elevated preoperative PSA, surgical experience and a nerve-sparing procedure are all significantly associated with a higher risk for a PSM after RARP. For those undergoing a nerve sparing RARP, an accurate preoperative biopsy with detailed information on the location of positive cores is essential to prevent PSMs.
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http://dx.doi.org/10.1159/000440666DOI Listing
September 2016

da Vinci and Open Radical Prostatectomy: Comparison of Clinical Outcomes and Analysis of Insurance Costs.

Urol Int 2016 9;96(3):287-94. Epub 2015 Jul 9.

Saarland University Medical Center, Department of Urology and Pediatric Urology, Homburg/Saar, Germany.

Purpose: To assess clinical outcomes and reimbursement costs of open and robotic-assisted radical prostatectomies in Germany.

Methods: Perioperative data of 499 open (2003-2006) and 932 (2008-2010) robotic-assisted radical prostatectomies as well as longitudinal reimbursement costs of an anonymized health insurance research database from Germany containing data of patients who underwent robotic-assisted or open radical prostatectomy were retrospectively analysed in a single-centre study.

Results: Significantly better outcomes after robotic-assisted vs. open prostatectomy were observed in regards to positive surgical margins (13.3 vs. 22.4%; p < 0.0001), intraoperative transfusions (0.1 vs. 2.6%; p < 0.0001), hospitalization (8.7 vs. 15.2 days; p < 0.0001) and duration of catheter (6.6 vs. 12.8 days; p < 0.0001). Operating time was significantly longer with robotic-assisted radical prostatectomy when compared to open surgery (184.4 vs. 128.0 min; p < 0.0001), while intraoperative complications showed a similar occurrence between both groups. Significant fewer postoperative complications were observed after robotic-assisted radical prostatectomy (26.5 vs. 42.5%; p < 0.0001) and rate of re-admission was lower for the robotic patients (13.6 vs. 19.4%; p = 0.0050). While insurance costs were higher in the 2 years before radical prostatectomy for the patients who underwent a robotic procedure (4,241.60 vs. 3,410.23 €; p = 0.202), additive costs of care of the year of surgery plus the 2 following years were less for the robotic cohort when compared to the costs incurred by the open group (21,673.71 vs. 24,512.37 €; p = 0.1676).

Conclusions: The observed clinical advantages of robotic-assisted radical prostatectomy seem to result in reduced health insurance cost postoperatively when compared to open surgery. This should be taken into consideration regarding reimbursement and implementation of a clinically superior method.
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http://dx.doi.org/10.1159/000431104DOI Listing
February 2017

Orthotopic tumorgrafts in nude mice: A new method to study human prostate cancer.

Prostate 2015 Oct 12;75(14):1526-37. Epub 2015 Jun 12.

Institute for Clinical and Experimental Surgery, Saarland University, Homburg/Saar, Germany.

Background: In vivo model systems in prostate cancer research that authentically reproduce tumor growth are still sparse. While orthotopic implantation is technically difficult, particularly in the mouse, most models favor subcutaneous tumor growth. This however provides little information about natural tumor growth behavior and tumor stroma interaction. Furthermore, established prostate cancer cell lines grown as in vivo xenografts are not able to reflect the variety of tumor specific growth patterns and growth behavior in men. Primary cell cultures are difficult to handle and an induction of orthotopic tumors has not been successful yet. Therefore, a tumorgraft model using tumor tissue from prostatectomy specimens was developed.

Methods: Balb/c nude mice were used to graft fresh prostate tumor tissue by renal subcapsular and orthotopic implantation. Testosterone propionate was supplemented. Animals were tracked by means of 30 MHz ultrasound to monitor tumor engraftment and growth. Autopsy, histology, PSA measurements as well as immunostaining and PCR for human tissue were performed to confirm orthotopic tumor growth.

Results: Renal subcapsular engraftment was seen in 2 of 3 mice. Orthotopic engraftment was observed in 7 of 11 animals (63.6%) with an overall engraftment of 5 out of 9 patient specimens (55.6%). Ultrasound confirmed the tumor growth over time. Of interest, the tumorgrafts not only retained essential features of the parental tumors, but also stained positive for tumor specific markers such as AR, PSA, and AMACR. Tumor positive animals showed highly elevated serum PSA levels with confirmation of a human specific PCR sequence and a human endothelial cell lining in the tumor vessels.

Conclusions: Standardized implantation of fresh tumor tissue in nude mice prostates generates tumorgrafts with histological properties of organ-confined prostate cancer. These tumorgrafts display a new approach for an optimized in vivo model of prostate cancer and will allow further investigations on specific pathways of tumor initiation and progression as well as therapeutic response.
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http://dx.doi.org/10.1002/pros.23027DOI Listing
October 2015