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.

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.

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.

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.

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.

Neuropilin-2 and its ligand VEGF-C predict treatment response after transurethral resection and radiochemotherapy in bladder cancer patients.

The standard treatment for invasive bladder cancer is radical cystectomy. In selected patients, bladder-sparing therapy can be performed by transurethral resection (TURBT) and radio-chemotherapy (RCT) or radiotherapy (RT). Our published in vitro data suggest that the Neuropilin-2 (NRP2)/VEGF-C axis plays a role in therapy resistance. Therefore, we studied the prognostic impact of NRP2 and VEGF-C in 247 bladder cancer patients (cN0M0) treated with TURBT and RCT (n = 198) or RT (n = 49) and a follow-up time up to 15 years. A tissue microarray was analyzed by immunohistochemistry. NRP2 expression emerged as a prognostic factor in overall survival (OS; HR: 3.42; 95% CI: 1.48 - 7.86; p = 0.004) and was associated with a 3.85-fold increased risk of an early cancer specific death (95% CI: 0.91 - 16.24; p = 0.066) in multivariate analyses. Cancer specific survival (CSS) dropped from 166 months to 85 months when NRP2 was highly expressed (p = 0.037). Patients with high VEGF-C expression have a 2.29-fold increased risk of shorter CSS (95% CI: 1.03-5.35; p = 0.043) in univariate analysis. CSS dropped from 170 months to 88 months in the case of high VEGF-C expression (p = 0.041). Additionally, NRP2 and VEGF-C coexpression is a prognostic marker for OS in multivariate models (HR: 7.54; 95% CI: 1.57-36.23; p = 0.012). Stratification for muscle invasiveness (T1 vs. T2-T4) confirmed the prognostic role of NRP2 and NRP2/VEGF-C co-expression in patients with T2-T4 but also with high risk T1 disease. In conclusion, immunohistochemistry for NRP2 and VEGF-C has been determined to predict therapy outcome in bladder cancer patients prior to TURBT and RCT.

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

PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.

MicroRNA profiles classify papillary renal cell carcinoma subtypes.

BACKGROUND: Besides the conventional clear-cell renal cell carcinoma (ccRCC), papillary RCC (pRCC) is the second most common renal malignancy. Papillary RCCs can further be subdivided into two distinct subtypes. Although a clinical relevance of pRCC subtyping has been shown, little is known about the molecular characteristics of both pRCC subtypes. METHODS: We performed microarray-based microRNA (miRNA) expression profiling of primary ccRCC and pRCC cases. A subset of miRNAs was identified and used to establish a classification model for ccRCC, pRCC types 1 and 2 and normal tissue. Furthermore, we performed gene set enrichment analysis with the predicted miRNA target genes. RESULTS: Only five miRNAs (miR-145, -200c, -210, -502-3p and let-7c) were sufficient to identify the samples with high accuracy. In a collection of 111 tissue samples, 73.9% were classified correctly. An enrichment of miRNA target genes in the family of multidrug-resistance proteins was noted in all tumours. Several components of the Jak-STAT signalling pathway might be targets for miRNAs that define pRCC tumour subtypes. CONCLUSION: MicroRNAs are able to accurately classify RCC samples. Deregulated miRNAs might contribute to the high chemotherapy resistance of RCC. Furthermore, our results indicate that pRCC type 2 tumours could be dependent on oncogenic MYC signalling.

[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.

[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.

[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.

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.

[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.

[Plasmacytoid carcinoma. Five case reports of a rare variant of urothelial carcinoma]. / Das plasmazytoide Urothelkarzinom. 5 Fallberichte einer seltenen Variante des konventionellen Urothelkarzinoms.

Plasmacytoid carcinoma is a rare variant of urothelial carcinoma and is characterised by distinct histopathological and clinical characteristics. The incidence varies between 2.7% and 3.1% of all muscle-invasive urothelial carcinoma. It is an aggressive, high-grade tumor with poor prognosis. Negative E-cadherin expression seems to be important for exact diagnosis. Systemic chemotherapy of plasmacytoid carcinoma could lead to prolonged patient survival.

[ABO-incompatible renal transplantation--why and how?]. / ABO-inkompatible Nierentransplantation--warum und wie?

Early renal transplantation is hampered by a long-standing lack of organ donors, particularly in Germany, which leads to long waiting times for postmortal kidneys. Despite the expansion of donor criteria and the transplantation of marginal organs, the curve for the number of kidney donors has been flattening and is even decreasing. Living donor transplantation may expand the donor pool; however, up to one-third of potential living donors must be excluded because of blood group incompatibility. Recently, new protocols for ABO-incompatible transplantation have made it possible to overcome blood group mismatch in kidney transplantation. Close cooperation between the nephrology and urology departments at the University Clinic of Erlangen has allowed for successful ABO-incompatible transplantation in seven patients, using the Swedish protocol with slight modifications.

[Multimodal therapy for bladder sparing with high grade bladder tumors]. / Multimodale Therapien zum Blasenerhalt bei High-grade-Blasentumoren.

The demographic changes of our society, with an increasing number of elderly patients and higher comorbidity, leads to the fact that managing transitional cell carcinoma (TCC) in the elderly is becoming increasingly more important. Thus, the value and indication of conservative or less invasive treatment approaches have to be continuously re-evaluated. The gold standard of treatment for invasive high grade TCC is radical cystectomy with curative intent. However, not each and every patient is suitable for this procedure or the operation is rejected. Thus, alternative treatment options (curative or palliative) including bladder sparing approaches should be offered to this group of patients. These include transurethral resection (TUR-B), open partial cystectomy, chemotherapy (intravesical or systemic), local radiation and minimally invasive interventional therapies alone or in combination. A lower physical and mental burden and, more important, a faster convalescence and the maintenance of the quality of life, are the major aims of these strategies. From an oncologic point of view these concepts have to be viewed with caution, since they may only lead to a temporarily stable disease or the elimination of symptoms. However, long-term follow-up demonstrates that with the correct indication for a multi-modal treatment, a subset of patients with high grade TCC of the bladder may be cured when implementing a bladder sparing approach.

[Urethral duplication: long-term results for a rare urethral anomaly]. / Urethralduplikatur : Langzeitergebnisse einer seltenen Urethralfehlbildung.

INTRODUCTION: Urethral duplication is a rare anomaly that can occur in various forms. Urethral duplication must be diagnosed and adequately treated. Only if clinical complaints develop should surgical management be considered. PATIENTS AND METHODS: The aim of this study was to retrospectively analyze patients with congenital urethral duplication: age at the time of diagnosis, type of urethral duplication, diagnostic and therapeutic measures as well as clinical aftercare were evaluated. RESULTS: This homogeneous and selected cohort included nine male children. The average follow-up was 6.2 years. Seven children were symptomatic (77.7%). We found a double urethra with epispadias in four boys and with hypospadias in three boys and urethral duplication with perineal/anal meatus in one patient and normotopia in another patient. In two children without symptoms, the urethral duplication was an incidental finding during diagnostic work-up for other anomalies. Seven children had additional urological anomalies: one fusiform megalourethra, three urethral valves with hypospadias, and two epispadias. Two children without symptoms were managed conservatively. An open operation joining the urethras was performed in three children, and four boys underwent endoscopic treatment of the urethral duplication. Long-term results revealed normal continence in all of the children. One child exhibited recurrent urinary tract infections and late stricture, which was opened endoscopically in a second session. CONCLUSION: A surgical approach is only indicated in the presence of clinical complaints. There is no surgical gold standard. The decision is ultimately reached on an individual basis depending on the findings and anatomy in view of the rarity and variability of the clinical picture. The functional result is of foremost importance for the urethra that requires reconstruction, but the cosmetic aspect should be respected to the same extent. We present the results of our experience in treating children with this urological condition. At the same time larger (multicenter) studies are needed, which will make it possible to formulate guidelines for this rare anomaly.

[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.

[Optimized standards for prostate biopsy]. / Optimierte Standards der Prostatastanzbiopsie.

As individual risk assessment mainly depends on the correct prediction of the tumor's biological behavior, primary diagnosis plays a key role in the clinical management of prostate cancer patients. Prostate core needle biopsy, as a primary diagnostic tool, should not only confirm clinical suspicion but also supply the urologist with information which is necessary for risk-adapted therapy. The experience and competence of both the urologist and the pathologist are crucial for the quality of prostate core needle biopsy diagnosis. Optimized handling and submission of prostate core needle biopsy specimens by the urologist to the pathologist are of outstanding importance for improving the number of cancer cases detected. Increasing availability of molecular markers leads to the necessity of developing new tissue sampling procedures which allow prostate core needle biopsy specimens to be simultaneously studied histologically and by molecular approaches.

[Wilms' tumor in adults]. / Wilms-Tumor bei Erwachsenen.

BACKGROUND: Wilms' tumor (nephroblastoma) is the most frequent renal tumor in childhood. In contrast nephroblastoma in adults is rare, and the disease used to have a poor prognosis. PATIENTS AND METHODS: Of 1,300 registered patients, a total of 41 patients older than 16 years were enrolled in the pediatric nephroblastoma trial from 1994 to 2005. Median age at diagnosis was 25.4 years (range: 16-62 years). Treatment was given according to the pediatric protocol. RESULTS: The adults had higher local stages, more frequent metastasis, and developed more toxicity due to therapy. Vincristine caused severe neurotoxicity in many cases. The distribution of histological subtypes was similar to the children's. The outcome is better than previously described with an overall survival of 71%. Patients with local stage I and II have an event-free survival of 84%. This is comparable to children's survival rates. CONCLUSION: Adults with nephroblastoma have a very good prognosis if treated according to a pediatric protocol.