Trends in kidney transplantation and living donor nephrectomy in Germany: a total population analysis from 2006 to 2021.

PURPOSE: To analyze recent trends of surgical access routes, length of hospital stay (LOS), and mortality in kidney transplantation (KT) and living donor nephrectomy (LDN) in Germany. MATERIALS AND METHODS: We studied the nationwide German hospital billing database and the German hospital quality reports from 2006 to 2021. RESULTS: There were a total of 35.898 KTs. In total, 9044 (25%) were living donor transplantations, while 26.854 (75%) were transplantations after donation after brain death (DBD). The share of open LDN decreased from 82% in 2006 to 22% in 2020 (- 4%/year; p < 0.001). The share of laparoscopic LDN increased from 18% in 2006 to 70% in 2020 (+ 3%/year; p < 0.001). The share of robotic LDN increased from 0% in 2006 to 8% in 2020 (+ 0.6%/year; p < 0.001). Robotic-assisted KT increased from 5 cases in 2016 to 13 procedures in 2019 (p = 0.2). LOS was shorter after living donor KT, i.e., 18 ± 12.1 days versus 21 ± 19.6 days for DBD renal transplantation (p < 0.001). Moreover, LOS differed for open versus laparoscopic versus robotic LDN (9 ± 3.1 vs. 8 ± 2.9 vs. 6 ± 2.6; p = 0.031). The overall in-hospital mortality was 0.16% (n = 5) after LDN, 0.47% (n = 42) after living donor KT and 1.8% (n = 475) after DBD KT. CONCLUSIONS: There is an increasing trend toward minimal-invasive LDN in recent years. Overall, in-hospital mortality was low after KT. However, 5 deceased healthy donors after LKD caution that the risks of this procedure should also be taken very seriously.

Development and outcomes of surgical and urological kidney transplantation programs in Germany: a total population analysis from 2006 to 2021.

PURPOSE: Kidney transplantation (KT) is the most frequently performed organ transplantation. In Germany, KT is performed in urology and surgery departments with unknown consequences of this parallel structure. The aim of the study was to compare the development and outcome of KT in urology and surgery departments. METHODS: On an institutional level, we analyzed the annual caseload from 2006 to 2021 with the reimbursement. INFO tool based on hospitals' quality reports (Reimbursement Institute, Hürth, Germany). For outcome comparison we extracted raw data from the transplantation centers' quality reports (Deutsche Stiftung Organtransplantation, DSO). RESULTS: A total of 23,599 cases (17,781 deceased donor and 5,818 living donor KTs) were included. The total number of KTs decreased from 1851 in 2006 to 1701 in 2021 (- 8%; p = 0.12). The total number of urological KTs decreased from 592 cases in 2006 to 395 cases in 2021 (- 33.3%; p = 0.01). Further analysis revealed no significant differences between intra- and postoperative complications and graft quality at one year for deceased donor KTs (DDKT) although differences in immediate renal function and graft quality at discharge could be observed. There were no significant differences in immediate renal function and graft quality at discharge for living donor KTs (LDKT) between the specialties. CONCLUSION: KTs performed in urology departments declined between 2006 and 2021. Nevertheless, intra- and postoperative complications as well as long-term function did not differ between surgical and urological KT programs. Hence, an interdisciplinary approach, especially considering the upcoming challenges in KT as, e.g., robot-assisted surgery seems reasonable.

Enhancing Human Papillomavirus Vaccination Rates through Better Knowledge? Insights from a Survey among German Medical Students.

INTRODUCTION: Vaccination against human papillomavirus (HPV) significantly reduces the risk for malignant diseases like cervix, anal, or penile cancer. However, although vaccination rates are rising, they are still too low mirroring a lack of disease awareness in the community. This study aims to evaluate knowledge about HPV vaccination as well as the vaccination rate among German medical students. MATERIAL AND METHODS: Medical students were surveyed during a German medical students' sports event. The self-designed survey on HPV vaccination consisted of 24 items. The data collection was anonymous. RESULTS: Among 974 participating medical students 64.9% (632) were women, 335 (34.4%) were male and 7 (0.7%) were nonbinary. Mean age was 23.1 ± 2.7 (± standard deviation; range 18-35) years. Respondents had studied mean 6.6 ± 3.3 (1-16) semesters and 39.4% (383) had completed medical education in urology. 613 (64%) respondents reported that HPV had been discussed during their studies. 7.6% (74) had never heard of HPV. In a multivariate model female gender, the knowledge about HPV, and having worked on the topic were significantly associated with being HPV-vaccinated. Older students were vaccinated less likely. CONCLUSIONS: Better knowledge and having worked on the topic of HPV were associated with a higher vaccination rate. However, even in this highly selected group the knowledge about HPV vaccination was low. Consequently, more information and awareness campaigns on HPV vaccination are needed in Germany to increase vaccination rates.

Adoption of Lutetium-177 PSMA radioligand therapy for metastatic castration resistant prostate cancer: a total population analysis in Germany from 2016 to 2020.

PURPOSE: This study is to investigate the adoption and current trends of Lutetium-177 PSMA RLT for mCRPC in Germany. METHODS: We analyzed data from the reimbursement.INFO tool based on German hospitals' quality reports for Lutetium-177 PSMA RLT from 2016 to 2020 and from the nationwide German hospital billing database (Destatis) for general therapy with open radionuclides in combination with prostate cancer from 2006 to 2020. For validation of these billing data, we included the 177Lu-PSMA RLT cycles from two participating institutions from 2016 to 2020. For detection of trends over time we applied linear regression models. RESULTS: General therapy with open radionuclides increased from 2006 to 2020. We identified a total of 12,553 177Lu-PSMA RLT cycles. The number of 177Lu-PSMA RLTs steadily increased from a total of 1026 therapies in 2016 to 3328 therapies in 2020 (+ 576 RLT/year; p < 0.005). In 2016, 25 departments of nuclear medicine offered this treatment, which increased to 44 nuclear medicine departments in 2020. In 2016, 16% of nuclear medicine departments (4/25) performed more than 100 177Lu-PSMA RLTs, which increased to 36% (16/44) in 2020 (p < 0.005). In 2016, 88% (22/25) of 177Lu-PSMA RLTs were performed at a university hospital, which decreased to 70% (31/44) in 2020. The proportion of patients older than 65 years receiving 177Lu-PSMA RLT increased from 78% in 2016 to 81% in 2020. CONCLUSION: Treatment of mCRPC with 177Lu-PSMA RLT has been rapidly increasing in Germany in the recent years providing an additional therapy option. This development is remarkable, because of outstanding formal EMA approval.

Successful management of 30 kg Gigantic para-testicular liposarcoma.

We report the successful management of a paratesticular liposarcoma, which, to the best of our knowledge, is the largest known of its type. A 62-year-old male presented with a painless, gradually progressive left testicular "giant" mass measuring 60 × 40 cm, weighing 30 kg and growing over a period of three 3 years. Additionally, a 5 × 5 cm trophic ulcer could be seen at the bottom of the scrotum. The ultrasound of the left testis revealed the testis having been completely replaced with a cystic and solid tumour. Preoperative serum testicular tumour markers (STM) were within normal limits. The markers included Alpha Feto Protein, Beta Human Chorionic Gonadotropin and Lactose Dehydrogenase. A left sided high inguino-scrotal approach with a huge skin resection including the trophic ulcer with complete removal of the tumour and a primary complex closure of the wound was performed. The post-operative period was uneventful, and histopathology revealed a dedifferentiated liposarcoma. We believe social taboo and fear of disfigurement impart a sense of shame in patients which led to the delayed presentation in a hospital in the index patient. The absence of metastases even with a protracted course is surprising.

Focal Therapy for Renal Cancer: Comparative Trends in the USA and Germany from 2006 to 2020 and Analysis of the German Health Care Landscape.

INTRODUCTION: The aim of the study was to investigate trends of FT for in-patient treatment of renal RCC in the USA and Germany. METHODS: We analyzed the SEER database for the USA and the nationwide German hospital billing database each from 2006 to 2019 for a RCC diagnosis in combination with FT, radical nephrectomy, and partial nephrectomy. FT was defined as radiofrequency ablation (RFA) or cryotherapy. Linear regression analysis was performed to detect changes over time. RESULTS: For the USA, we included 7,318 FT cases. The share of FT increased from 2.4% in 2006 to 6.4% in 2019 (p < 0.001). For Germany, we identified 2,920 FT cases. The share of FT increased from 0.7% in 2006 to 2.0% in 2019 (p < 0.001). The number of RFAs in the USA steadily increased by 227% from a total of 93 in 2006 to 304 in 2019 while the number of cryotherapies in the USA steadily increased by 289% from a total of 127 in 2006 to 494 in 2019 (p < 0.001). The number of RFAs in Germany increased by 344% from a total of 59 in 2006 to 262 in 2019 (p < 0.001) while the number of cryotherapies steadily increased by 43% from a total of 54 in 2006 to 77 in 2019 (p < 0.001). In Germany, RFA is significantly more performed than cryotherapy while in the USA cryotherapy is more frequently applied. CONCLUSION: We observed a constant increase of FT in the USA and Germany for RCC in-patient treatment with a higher share in the USA.

Alternative- and focal therapy trends for prostate cancer: a total population analysis of in-patient treatments in Germany from 2006 to 2019.

PURPOSE: Focal therapy (FT) offers an alternative approach for prostate cancer (PCa) treatment in selected patients. However, little is known on its actual establishment in health care reality. PATIENTS AND METHODS: We defined FT as high-intensity focused ultrasound (HIFU), hyperthermia ablation, cryotherapy, transurethral ultrasound ablation (TULSA) or vascular-targeted photodynamic therapy (VTP) TOOKAD®. We analyzed the nationwide German hospital billing database for a PCa diagnosis in combination with FT. For analyses on the hospital level, we used the reimbursement.INFO tool based on hospitals' quality reports. The study period was 2006 to 2019. RESULTS: We identified 23,677 cases of FT from 2006 to 2019. Considering all PCa cases with surgery, radiotherapy or FT, the share of FT was stable at 4%. The annual caseload of FT increased to a maximum of 2653 cases in 2008 (p < 0.001) and then decreased to 1182 cases in 2014 (p < 0.001). Since 2015, the cases of FT remained on a plateau around 1400 cases per year. The share of HIFU was stable at 92-96% from 2006 to 2017 and decreased thereafter to 75% in 2019 (p = 0.015). In 2019, VTP-TOOKAD® increased to 11.5% and TULSA to 6%. In 2006, 21% (62/299) of urological departments performed FT and 20 departments reached > 20 FT procedures. In 2019, 16% (58/368) of urological departments performed FT and 7 departments reached > 20 FT. In 2019, 25 urological departments offered FT other than HIFU: 5 centers hyperthermia ablation, 11 centers VTP TOOKAD®, 3 centers cryotherapy, 6 centers TULSA. CONCLUSION: The FT development in Germany followed the Gartner hype cycle. While HIFU treatment is the most commonly performed FT, the share of newer FT modalities such as VTP-TOOKAD® and TULSA is remarkably increasing.

Decision Regret and Quality of Life after Focal Therapy with Vascular-Targeted Photodynamic Therapy (TOOKAD®) for Localized Prostate Cancer.

PURPOSE: The aim of the study was to assess quality of life (QoL), decision involvement, and decisional regret after treatment with vascular-targeted photodynamic therapy (VTP) (TOOKAD®) for unilateral low-risk prostate cancer. METHODS: Validated questionnaires (EORTC QLQ-C30 and QLQ-PR25) capturing QoL post-treatment, involvement in decision-making (Control Preferences Scale) and decision regret (Decisional Regret Scale), were given to patients at the 12-month visit after undergoing VTP at our institution between May 2018 and February 2021. RESULTS: Out of 44 patients, 36 patients were included in this study and 31 (86.1%) responded to the questionnaires. Mean overall health score capturing QoL at 12 months was 79.3 (standard deviation: ±18.1). 70.9% of the patients (n = 22) had no decision regret, and 67.8% of men (n = 21) had an active role in decision-making. In control biopsy at 12 months post-treatment, 19.4% of patients (n = 7) presented with local recurrence and progression to higher Gleason score (GS) was found in 13.8% of patients (n = 5). Patients (n = 3) presenting with tumor recurrence or progression to higher GS in control biopsy showed a significantly higher level of decision regret (p < 0.009). CONCLUSION: Only 9.7% of men (n = 3) felt a strong emotion of regret at 12 months after VTP. Level of decision regret was significantly higher in patients with local recurrence or tumor progression detected in control biopsy. QoL was stable after VTP.

[Patient events in German urology: trend towards hybrid formats?] / Patientenveranstaltungen in der deutschen Urologie: Trend zu Hybridformaten?

BACKGROUND: Patient events are an important tool to respond to the increasing need of the public for health information. Through the "patient forum", the German Society of Urology (DGU) is committed to patient information and public relations at its annual congresses. The goal of the study was to evaluate the events from 2017-2019 and to compare them with the first digital patient forum in 2020. MATERIALS AND METHODS: Using a two-page standardized questionnaire, we surveyed the visitors of the presence patient forums (presence group = P) of the three annual congresses of the DGU 2017-2019 as well as the users of the digital event 2020 (online group = O). RESULTS: We obtained 71 records for 2017-2019 and 18 for 2020. The median age of visitors was 64 years (range 30-89). Males were 66% (P) vs. 83% (O) of participants (p = 0.005). The offer was rated overall as good to very good by both groups, i.e., 1.6 (P) vs. 1.6 (O; p = 0.7) on a scale from 1 to 6 with 1 being the highest rating. In line with the lower interaction in the digital format, the possibility to ask questions was rated worse with 1.5 (P) vs. 2.8 (O; p = 0.003). When asked about the desired future event format, two-thirds of the users of the digital patient forum were in favor of a hybrid event on-site and online. CONCLUSION: Patient events are suitable means of communication for the public and are rated well by visitors. In particular, interaction with experts is highly valued. Face-to-face formats are associated with a high logistical effort and high costs, and their reach is limited. In the future, hybrid formats could be a reasonable alternative, as they combine the advantages of online and face-to-face formats.

Trends in the use of testicular prostheses in Germany: a total population analysis from 2006-2021.

INTRODUCTION: Testicular tumors are the most common malignancies in young adults and their incidence is growing. The implantation of a testicular prosthesis, for example, during orchiectomy is a standard procedure but its frequency in Germany is unknown. This study aims to analyze trends of testicular prosthesis implantation in recent years in Germany. MATERIAL AND METHODS: The nationwide German hospital billing database and the German hospital quality reports from 2006 to 2021 were studied. RESULTS: A total of 12,753 surgical procedures with implantation of testicular prosthesis and 1,244 procedures with testicular prosthesis explantation were included. Testicular prosthesis implantation increased in total from 699 cases in 2006 to 870 cases in 2020 (+11.4 cases/year; p < 0.001). The share of implantation of testicular prosthesis due to testicular tumor decreased from 72.6% in 2006 to 67.5% in 2020 (p < 0.001). The share of implantation due to gender affirming surgery increased from 6.8% in 2006 to 23.3% in 2020 (p < 0.001). The share of implantation due to testicular atrophy decreased from 11.4% in 2006 to 3.4% in 2020 (p < 0.001). Simultaneous implantation of testicular prosthesis during orchiectomy for testicular cancer increased from 7.8% in 2006 to 11.4% in 2020 (p < 0.001). In 2006, 146 hospitals (85%) performed < 5 testicular prosthesis implantation, while 20 hospitals (12%) performed 5-15 implantation procedures and 6 hospitals (3%) performed > 15 testicular implantation surgeries. In 2021, 115 hospitals (72%) performed < 5 testicular prosthesis implantation, while 39 hospitals (25%) performed 5-15 implantation procedures and 5 hospitals (3%) performed > 15 testicular implantation surgeries. CONCLUSION: This study shows that implantation of testicular prostheses is steadily increasing. Explantation rates are low. Besides testicular cancer transgender surgeries were the main driver for increasing case numbers in recent years.

[Development of circumcision rates in Germany since the approval of ritual circumcision : A population-based analysis from 2013 to 2018]. / Entwicklung der Zirkumzisionszahlen in Deutschland seit Billigung der rituellen Beschneidung : Eine bevölkerungsbezogene Analyse von 2013 bis 2018.

INTRODUCTION: The religious and cultural circumcision of male infants in Germany is controversially discussed. After the passing of the religious circumcision bill in 2012, an increase of infant circumcisions without medical indication was feared. The aim of this study was to analyze the development of the circumcision case numbers. MATERIALS AND METHODS: We used the research database of the German Institute for Applied Health Research with a representative anonymous sample of 4.9 million insured persons to estimate the annual circumcision numbers in Germany from 2013-2018. We stratified the data according to age (< 18 vs. ≥ 18 years). The number of male adolescents in the study period was taken from the database of the German Federal Statistical Office. RESULTS: In the study period, 673,819 circumcisions were performed. From 2014, there was a significant decrease in the number of cases across all age groups (p = 0.049). Thereby, circumcisions in minors significantly increased (p = 0.002) and procedures in adults significantly decreased (p = 0.01) during the entire study period. The number of male minors increased by 4% from 6,709,137 (2013) to 6,992,943 (2018). The corresponding population-based number increased from 7.5 circumcisions per 1000 minors in 2013 to 8 in 2018 (p = 0.037). CONCLUSIONS: After the passage of the circumcision bill in 2012, there was a significant increase of circumcisions in the age group of < 18 years in Germany. A major limitation of our study is that presumably many ritual circumcisions might not be provided within the health care system.

[Outpatient before inpatient treatment?-Reality of care and economic analysis for minor urological interventions in Germany between 2013 and 2018]. / Ambulant vor stationär? ­ Versorgungswirklichkeit und ökonomische Analyse von kleinen urologischen Eingriffen in Deutschland von 2013 bis 2018.

BACKGROUND: Although outpatient provision of services is economically desirable, many minor urological interventions in Germany are currently carried out on an inpatient basis. The aim of our study is to investigate whether the current health policy framework contributes to more outpatient treatment. MATERIALS AND METHODS: We used a sample of 4.9 million anonymous, insured persons representative according to age and region provided by the Institute for Applied Health Research (InGef GmbH). We report extrapolations for the number of outpatient and inpatient services throughout Germany between 2013 and 2018. In addition, we performed an economic analysis for two selected interventions. RESULTS: During the study period, the total number of prostate biopsies declined from 184,573 to 174,558 cases. The share of outpatient biopsies declined continuously by 0.9% per year from 81% to 76% (p < 0.001). For botulinum toxin injection into the bladder, the total increased from 15,630 to 26,824 cases. The share of outpatient treatments increased by 2.7% per year from 3% to 19% (p = 0.01). For the other examined interventions (insertion of suprapubic urinary catheters, the insertion, removal, and changing of ureteral stents, cystoscopies and urethral dilatation), there were no significant changes in the share of outpatient procedures. CONCLUSIONS: The significant increase of outpatient botulinum toxin injections shows the successful control effect through adapted remuneration options. A shift to the inpatient sector was observed for prostate biopsies. This may be due to higher hygienic standards and technical requirements for MRI fusion.

Targeted Quantification of Carbon Metabolites Identifies Metabolic Progression Markers and an Undiagnosed Case of SDH-Deficient Clear Cell Renal Cell Carcinoma in a German Cohort.

Renal cell carcinoma (RCC) is among the 10 most common cancer entities and can be categorised into distinct subtypes by differential expression of Krebs cycle genes. We investigated the predictive value of several targeted metabolites with regards to tumour stages and patient survival in an unselected cohort of 420 RCCs. Unsupervised hierarchical clustering of metabolite ratios identified two main clusters separated by α-ketoglutarate (α-KG) levels and sub-clusters with differential levels of the oncometabolite 2-hydroxyglutarate (2HG). Sub-clusters characterised by high 2HG were enriched in higher tumour stages, suggesting metabolite profiles might be suitable predictors of tumour stage or survival. Bootstrap forest models based on single metabolite signatures showed that lactate, 2HG, citrate, aspartate, asparagine, and glutamine better predicted the cancer-specific survival (CSS) of clear cell RCC patients, whereas succinate and α-ketoglutarate were better CSS predictors for papillary RCC patients. Additionally, this assay identifies rare cases of tumours with SDHx mutations, which are caused predominantly by germline mutations and which predispose to development of different neoplasms. Hence, analysis of selected metabolites should be further evaluated for potential utility in liquid biopsies, which can be obtained using less invasive methods and potentially facilitate disease monitoring for both patients and caregivers.

Evaluation of polymorphisms in angiogenesis-related genes as predictive and prognostic markers for sunitinib-treated metastatic renal cell carcinoma patients.

PURPOSE: Single nucleotide polymorphisms (SNPs) in angiogenesis-associated genes might play an important role in activity of the tyrosine kinase inhibitor sunitinib and could affect survival of cancer patients treated with this drug. The aim of this retrospective study was to elucidate the role of 10 known SNPs in VEGFA, VEGFR1, VEGFR2 and VEGFR3 as potential prognostic and predictive markers in an independent cohort of patients with metastatic renal cell carcinoma (mRCC). METHODS: DNA from 121 mRCC patients treated with sunitinib was used to analyze SNPs by TaqMan genotyping assays. Disease control rate was evaluated according to RECIST. Adverse effects of sunitinib were registered from medical records. The results of Cox and logistic regression were verified by correction for multiple testing. RESULTS: Kaplan-Meier analysis revealed a reduced progression-free survival in patients with the wild-type (WT) allele of the VEGFA SNP rs699947 compared to variant alleles. Patients with the AA/AC-alleles of the VEGFR1 SNP rs9582036 had an improved median overall survival compared to those with the CC-WT allele what could be confirmed by multivariable Cox proportional hazard regression analyses. No statistically significant associations between the analyzed SNPs and higher risk for adverse effects were observed. CONCLUSIONS: The results of this study suggest that most of the selected SNPs in angiogenesis-related genes are not associated with survival of mRCC patients after sunitinib therapy or with adverse effects. Only the VEGFR1 SNP rs9582036 showed a statistically significant association with overall survival. The potential of SNPs as prognostic and predictive markers for sunitinib-treated mRCC patients should be finally assessed by prospective studies.

Analyses of potential predictive markers and survival data for a response to sunitinib in patients with metastatic renal cell carcinoma.

BACKGROUND: Patients with metastatic clear cell renal cell carcinoma (ccRCC) are frequently treated with tyrosine kinase inhibitors (TKI) such as sunitinib. It inhibits angiogenic pathways by mainly targeting the receptors of VEGF and PDGF. In ccRCC, angiogenesis is characterized by the inactivation of the von Hippel-Lindau gene (VHL) which in turn leads to the induction of HIF1α target genes such as CA9 and VEGF. Furthermore, the angiogenic phenotype of ccRCC is also reflected by endothelial markers (CD31, CD34) or other tumor-promoting factors like Ki67 or survivin. METHODS: Tissue microarrays from primary tumor specimens of 42 patients with metastatic ccRCC under sunitinib therapy were immunohistochemically stained for selected markers related to angiogenesis. The prognostic and predictive potential of theses markers was assessed on the basis of the objective response rate which was evaluated according to the RECIST criteria after 3, 6, 9 months and after last report (12-54 months) of sunitinib treatment. Additionally, VHL copy number and mutation analyses were performed on DNA from cryo-preserved tumor tissues of 20 ccRCC patients. RESULTS: Immunostaining of HIF-1α, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2, pPDGFRα and -ß was significantly associated with the sunitinib response after 6 and 9 months as well as last report under therapy. Furthermore, HIF-1α, CA9, CD34, VEGFR1 and -3 and PDGRFα showed significant associations with progression-free survival (PFS) and overall survival (OS). In multivariate Cox proportional hazards regression analyses high CA9 membrane staining and a response after 9 months were independent prognostic factors for longer OS. Frequently observed copy number loss and mutation of VHL gene lead to altered expression of VHL, HIF-1α, CA9, and VEGF. CONCLUSIONS: Immunoexpression of HIF-1α, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2, pPDGFRα and -ß in the primary tumors of metastatic ccRCC patients might support the prediction of a good response to sunitinib treatment.