Kidney transplantation in prostate cancer patients after local therapy with curative intent: a systematic review.

PURPOSE: It is still unclear whether kidney transplantation can be safely performed in patients with prostate cancer after local therapy with curative intent. METHODS: The protocol was registered in PROSPERO. We systematically searched Google, MEDLINE, the Cochrane Library, and the ICTRP for studies, official standards, clinical practice guidelines and organ transplant laws. Two review authors independently examined the full-text reports and identified relevant studies and one review author extracted the data. We assessed the overall certainty of the evidence for each outcome according to the GRADE approach. RESULTS: We identified 1346 references through electronic database searching and finally included 6 references for official standards, clinical practice guidelines, and organ transplant laws, and 6 references for retrospective studies with very low certainty of evidence. We identified no prospective or ongoing studies and reported all results narratively. CONCLUSION: We recommend that decisions on kidney transplantation in patients with prostate cancer after local therapy with curative intent should be made on a case-by-case basis. It is indispensable to consult with health care professionals or specialists at transplant centers to obtain individualized information regarding the waiting time requirements for renal transplantation in prostate cancer patients after local therapy with curative intent. No recommendation can be made regarding the waiting times after prostate cancer therapy with curative intent.

[Biobanks, translational research and medical informatics]. / Biobanken, translationale Forschung und Medizininformatik.

When we think of medical research, one intuitively associates it with the analysis of study data collected for a specific research question or with the secondary use of patient data from routine care. However, these are not the only sources for answering scientific questions. Especially for translational research, tissue and liquid samples such as blood, DNA or other body fluids provide essential insights into disease pathogenesis, development of new therapies and treatment decisions. Access to these biomedical materials is provided by so-called biobanks. By collecting, characterizing, documenting and, if necessary, processing human biospecimens in accordance with high quality standards, they can support research of the causes of diseases, early diagnosis and the targeted treatment of diseases, or make a significant contribution to the investigation of common diseases.

Consensus on definition and severity grading of lymphatic complications after kidney transplantation.

BACKGROUND: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy. METHODS: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres. RESULTS: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention. CONCLUSION: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.

ANTECEDENTES: La incidencia de complicaciones linfáticas tras el trasplante renal (post-kidney-transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen. RESULTADOS: En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica. CONCLUSIÓN: Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.

Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

Timing of androgen deprivation monotherapy and combined treatments in castration-sensitive and castration-resistant prostate cancer: a narrative review.

PURPOSE: Standard androgen deprivation therapy (ADT) can be initiated early at the time of diagnosis in asymptomatic castration-sensitive advanced prostate cancer. This definition has recently been expanded to also include an early combined treatment with standard ADT and new antihormonal drugs. We aimed to present the best available evidence for the timing of initiation of ADT monotherapy and combined treatments in castration-sensitive/-resistant prostate cancer. METHODS: For this narrative review, we searched Cochrane reviews in the Cochrane Library, systematic reviews and randomized controlled trials in MEDLINE, phase III and ongoing trials in ClinicalTrials.gov and screened the reference lists to extract articles of interest. One author screened the references which were finally included after assessing their relevance through discussion with other experts in the field. RESULTS: The identified references were grouped by medication (standard ADT, androgen biosynthesis inhibitor, androgen receptor antagonists or combined therapies) and tumor stage (castration sensitive or resistant). The evidence was narratively summarized and discussed in the context of the current therapeutic landscape. CONCLUSIONS: Early standard ADT can reduce symptoms of disease progression and may extend progression-free and overall survival. The patient should be well informed about the higher rates of treatment-related side effects. Deferring standard ADT might be indicated only for well-informed or unfit patients. Early standard ADT is increasingly combined with new antihormonal drugs in castration-sensitive metastatic prostate cancer to gain additional survival and quality of life benefits. Combined treatment at the time of development of castration-resistant disease is well established.

Prognostic models for predicting overall survival in metastatic castration-resistant prostate cancer: a systematic review.

PURPOSE: Prognostic models are developed to estimate the probability of the occurrence of future outcomes incorporating multiple variables. We aimed to identify and summarize existing multivariable prognostic models developed for predicting overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: The protocol was prospectively registered (CRD42017064448). We systematically searched Medline and reference lists up to May 2018 and included experimental and observational studies, which developed and/or internally validated prognostic models for mCRPC patients and were further externally validated or updated. The outcome of interest was overall survival. Two authors independently performed literature screening and quality assessment. RESULTS: We included 12 studies that developed models including 8750 patients aged 42-95 years. Models included 4-11 predictor variables, mostly hemoglobin, baseline PSA, alkaline phosphatase, performance status, and lactate dehydrogenase. Very few incorporated Gleason score. Two models included predictors related to docetaxel and mitoxantrone treatments. Model performance after internal validation showed similar discrimination power ranging from 0.62 to 0.73. Overall survival models were mainly constructed as nomograms or risk groups/score. Two models obtained an overall judgment of low risk of bias. CONCLUSIONS: Most models were not suitable for clinical use due to methodological shortcomings and lack of external validation. Further external validation and/or model updating is required to increase prognostic accuracy and clinical applicability prior to their incorporation in clinical practice as a useful tool in patient management.

[Renal transplantation in urinary diversions]. / Nierentransplantation in Harnableitungen.

Renal transplantations in augmented bladders or urinary diversions are rare, accounting for only 1-2% of all renal transplantations. In most cases a dysfunctional lower urinary tract is the cause of end-stage renal disease in these patients; therefore recovery of the lower urinary tract is mandatory for long-term graft survival. Usually, urinary diversion is timed several months prior to renal transplantation. Beside renal transplantations into an ileum conduit, renal transplantations in continent urinary diversions have become increasingly popular. The most frequent complications are bacteriuria and urinary tract infections, which usually do not lead to graft loss when treated correctly with antibiotics. Long-term outcome of renal transplantations in urinary diversions is comparable to transplantations in healthy native bladders.

[Treatment of benign prostatic hyperplasia in geriatric patients-use and limitations of existing guidelines]. / Therapie des benignen Prostatasyndroms beim geriatrischen Patienten ­ Anwendung und Limitation medizinischer Leitlinien.

The demographic developments of western society and the resulting increase in the number of very old patients in urology represents a challenge for the design of clinical studies and, consequently, recommendations of guidelines. While in internal medicine there is already a subspecialization with a focus on the treatment of elderly and multimorbid patients, in urology there is hardly any subspecialization into the problems of geriatric patients. Thus, using a case study as an example, the treatment decisions for benign prostatic hyperplasia (BPH) in geriatric patients are discussed. In addition the available evidence from the literature and guidelines are presented in order to assiste in daily management of geriatric patients with lower urinary tract symptoms and to critically discuss potential fields of application and limitations of the existing guidelines. In this context, we also examine the challenges when choosing a drug therapy and in deciding which of the many surgical options should be used.

Megaprepuce: presentation of a modified surgical technique with excellent cosmetic and functional results.

OBJECTIVE: Congenital megaprepuce is a malformation consisting of a great redundancy of the inner preputial skin over a penis with normal shaft and glans and is combined with a severe phimosis. Patients suffer from difficulties in voiding because the urine is trapped in the large dome-shaped megaprepuce. We describe a modification of the surgical technique of reconstructing a megaprepuce initially presented by Leao et al. PATIENTS AND METHODS: We retrospectively reviewed 7 patients aged 6-53 months (mean age 17 months, 6 were younger than 18 months) who underwent congenital megaprepuce repair between 02/2014 and 05/2018 in our institution. All these otherwise healthy children suffering from difficulties in voiding and reporting genital ballooning during micturition and urinary retention were referred to our hospital. In all cases, parents needed to express the trapped urine. Four of these patients additionally showed a glanular hypospadias, another one a distal penile hypospadias. In addition to the repair of the megaprepuce, six patients needed correction of a penile curvature, five of whom needed correction of the chordee and one a corporoplasty (Schröder-Essed). The patient showing the distal penile hypospadias additionally underwent hypospadias repair. During the follow-up, we evaluated the cosmetic result and complications such as secondary concealed penis, difficulties in voiding, urinary retention, and urinary infections. RESULTS: Mean follow-up was 18 months. All patients following surgery showed normal voiding without urinary retention or urinary infections and good cosmetic results resembling a circumcised penis in appearance without reconcealment. No intraoperative complications occurred. One patient had a scrotal hematoma postoperatively. Mild transient edema of the penis was seen in all patients, which disappeared spontaneously within one week after surgery. CONCLUSION: Our surgical approach is a safe and relatively simple procedure with a low rate of complications, good cosmetic results, and functional outcome. Whether the hypospadias associated with ventral curvature was a coincidence or part of the disease pattern remains unclear but will probably be the object of further investigations.

[Presurgical assessments]. / Assessments vor Operationen.

For the estimation of perioperative risks and mortality in the context of radical urological tumor surgery in elderly patients, the guidelines meanwhile require the use of geriatric assessments. The aim of this work is therefore to explain frequently used geriatric assessments and to give an overview of their predictive significance in radical urological tumor surgery. Comprehensive geriatric assessments provide a good description of the patient's state of health, but are hardly feasible in clinical routine due to their complexity. It is more reasonable to use screening tools with subsequent targeted examination of high-risk patients. Special tools allow the standardized assessment of functional status, mobility, cognition, mood, nutrition, frailty, comorbidities and polypharmacy and have different prognostic significance. Evidence on the predictive value of assessments prior to radical urological tumor surgery is mainly described for the systematic classification of comorbidities. In cystectomy, the Charlson Comorbidity Index (CCI) and the American Society of Anesthesiologists (ASA) score allow an estimation of the risk of complications and mortality. The focus of assessments prior to prostatectomy is to identify patients with sufficient life expectancy to benefit from radical surgery. CCI and ASA scores as well as the Eastern Co-operative Oncology Group (ECOG) score can help to assess the risk of perioperative complications in kidney tumor surgery.

[Renal transplantation: Opportunities and risks for medical refugees]. / Nierentransplantation: Chancen und Risiken bei medizinischen Flüchtlingen.

BACKGROUND: Families with children and adolescents with end-stage renal disease came to Germany from the former Eastern Bloc countries before the wave of refugees in 2015, in order to enable their children to survive with adequate kidney replacement therapy and in the best case a kidney transplant. METHODS: In a case study, medical records of 4 childen and adolescents were retrospectively analyzed. These patients who fled to Germany for the treatment of terminal renal failure applied for asylum and were successfully transplanted after the usual waiting period. RESULTS: Four of the eight children and adolescents who came to Erlangen for treatment of terminal renal failure between 2003 and 2013 received a functioning kidney transplant (deceased donor kidney) after dialysis therapy was difficult due to lack of compliance to drug and dietary recommendations such as fluid restriction. Since children and adolescents are treated with chronic dialysis only with the aim of kidney transplantation, a living donation was discussed but was not possible for medical reasons. 3 recipients are symptom-free with a functional graft. DISCUSSION: The case study demonstrates that children and adolescents fleeing to Germany due to their end stage renal disease are better integrated after kidney transplantation, have better chances of obtaining a good education and can be expected to live independently with their own income in the future.

Is there evidence for a close connection between side of intravesical tumor location and ipsilateral lymphatic spread in lymph node-positive bladder cancer patients at radical cystectomy? Results of the PROMETRICS 2011 database.

PURPOSE: To evaluate the possible association between bladder tumor location and the laterality of positive lymph nodes (LN) in a prospectively collected multi-institutional radical cystectomy (RC) series. METHODS: The study population included 148 node-positive bladder cancer (BC) patients undergoing RC and pelvic lymph node dissection in 2011 without neoadjuvant chemotherapy and without distant metastasis. Tumor location was classified as right, left or bilateral and compared to the laterality of positive pelvic LN. A logistic regression model was used to identify predictors of ipsilaterality of lymphatic spread. Using multivariate Cox regression analyses (median follow-up: 25 months), the effect of the laterality of positive LN on cancer-specific mortality (CSM) was estimated. RESULTS: Overall, median 18.5 LN [interquartile range (IQR), 11-27] were removed and 3 LN (IQR 1-5) were positive. There was concordance of tumor location and laterality of positive LN in 82% [95% confidence interval (CI), 76-89]. Patients with unilateral tumors (n = 78) harbored exclusively ipsilateral positive LN in 67% (95% CI 56-77). No criteria were found to predict ipsilateral positive LN in patients with unilateral tumors. CSM after 3 years in patients with ipsilateral, contralateral, and bilateral LN metastasis was 41, 67, and 100%, respectively (p = 0.042). However, no significant effect of the laterality of positive pelvic LN on CSM could be confirmed in multivariate analyses. CONCLUSIONS: Our prospective cohort showed a concordance of tumor location and laterality of LN metastasis in BC at RC without any predictive criteria and without any influence on CSM. It is debatable, whether these findings may contribute to a more individualized patient management.

[Prerequisites, skills and productivity of young academic urologists in Germany]. / Forschungsvoraussetzungen, -skills und -leistungen urologischer Nachwuchswissenschaftler in Deutschland.

BACKGROUND: To safeguard scientific and clinical progress, German urology requires properly trained junior scientists. Before initiating or continuing actions aiming at quality improvement an analysis of the status quo is necessary. OBJECTIVE: To assess the conditions to pursue research, research skills and research output of junior scientists in urology in Germany. MATERIAL UND METHODS: A 16-item online questionnaire was sent to 95 junior scientists in urology within the research network GeSRU Academics. Primary outcomes were the conditions to pursue research in terms of research time, research skills and sources of learning and research output as measured by peer-reviewed publications. Subpopulations were compared with respect to the number of peer-reviewed publications. RESULTS: Out of 78 junior scientists (82% response rate) 45% pursued research exclusively in their leisure time. Self-assessment of research skills varied from good (systematic literature search) to sufficient (grant acquisition). The main source of learning for research skills was self-study, followed by mentor, own department, courses and networks. Of the junior scientists 81% had peer-reviewed publications (median 4). The groups of junior scientists who pursued research (partially) during working hours, who had good skills and whose research skills were supported by a mentor/network had significantly more peer-reviewed publications than their counterparts. CONCLUSION: Junior scientists in urology in Germany lack protected time to pursue research and have varying research skills, which are predominantly acquired by self-study and demonstrate their first research output as peer-reviewed publications.

Micropapillary morphology is an indicator of poor prognosis in patients with urothelial carcinoma treated with transurethral resection and radiochemotherapy.

Purpose of this study was to evaluate prognostic impact of rare variants of urothelial bladder cancer (BC) after treatment with combined radiochemotherapy (RCT). To this end tumour tissue of 238 patients with urothelial carcinoma (UC) treated with transurethral resection of the bladder (TUR-B) and RCT with curative intent was collected. Histomorphological analysis included re-evaluation and semi-quantitative assessment of rare UC subtypes. Additionally, human epidermal growth factor receptor 2 (HER2) chromogenic in situ hybridisation (CISH) was performed in tumours with a micropapillary component exceeding 30 %. Long-term follow-up was available for 200 patients (range 3-282 months). Variant UC histology was found in 45 of 238 tumours, most frequently micropapillary UC (N = 17) including cases with a small fraction of tumour with micropapillary morphology. The mere presence of micropapillary morphology did not affect prognosis. In tumours with extensive (≥30 %) micropapillary morphology (N = 8) Kaplan-Meier analysis revealed significantly worse cancer specific survival (CSS) (P = 0.002) compared to conventional UC (mean survival times 97 months and 229 months, respectively). Univariate Cox regression analysis of cases with ≥30 % micropapillary morphology revealed a hazard ratio of 4.726 (95 % CI 1.629-13.714) for CSS (P = 0.004). CISH revealed HER2 gene amplification in 3/10 tumours with ≥30 % micropapillary component. In conclusion, for BC treated with TUR-B and RCT, the presence of micropapillary morphology in more than 30 % of the tumour is an adverse prognostic factor. Further studies are needed to evaluate a potential benefit of different, especially multimodal treatment strategies for micropapillary UC and also other subtypes of UC. Her2 represents a promising therapeutic target in a subset of micropapillary UC.