[Lymph node metastatic penile cancer: a challenge in uro-oncology-guideline-conform treatment]. / Das lymphonodulär metastasierte Peniskarzinom: eine uroonkologische Herausforderung ­ die leitlinienorientierte Therapie.

Penile squamous cell carcinoma is a rare, highly aggressive cancer of older men. The metastatic stage has significant therapeutic and prognostic features. Treatment of penile cancer is significantly influenced by the operation, in which an R0 situation must be achieved to ensure a realistic chance of cure. Other local therapeutic procedures such as radiotherapy are often of secondary importance. Neoadjuvant and adjuvant chemotherapy are relevant components of multimodal therapy. Post-therapeutically, patients require lifelong, risk-adapted follow-up care.

[Conventional grading vs. molecular grading : Decision aids for clinical routine]. / Konventionelles vs. molekulares Grading : Entscheidungshilfen für den klinischen Alltag.

Conventional histopathological grading of a cancer is of utmost importance for the management and prognosis of the patient. Histopathological grading is predominantly a function of the differentiation and proliferation of tumor cells, the amount of necrosis present and the pattern of invasion. In addition, the molecular set-up of a given cancer which can be determined to some degree by immunohistochemistry or by methods analyzing genetic and epigenetic alterations can be used in some instances to improve the information gained by conventional histopathologic grading. Indeed, this latter option implies the promise of individualized tumor therapy. While this promise is on the horizon, the clinical implications for penile cancer are not yet transferable to individualized penile cancer treatment.

[Penile cancer : Diagnosis and treatment]. / Peniskarzinom : Diagnose und Therapie.

The incidence of penile cancer in central Europe and North America is low, and patients often present at a late stage of the disease. The diagnosis can very often be made by visual examination of the primary tumor. Its morphology, size, and location as well as the inguinal lymph nodes are of clinical interest. The removal of (micro)metastatic lymph nodes is decisive for the prognosis. These cannot be diagnosed clinically or by imaging with sufficient reliability, which makes invasive lymph node staging necessary. Penile cancer can only be cured by surgery in patients with localized cancer and early stage regional lymph node metastasis. The primary tumor, including metastatic lymph nodes, must be completely excised as early as possible. If indicated, organ preservation must be performed with strict adherence of safety margins. Optimal lymph node management is crucial for long-term survival.

Paclitaxel-coated stents to prevent hyperplastic proliferation of ureteral tissue: from in vitro to in vivo.

Ureteric stents have become an indispensable tool in the armamentarium of every urologist. However, they carry their own morbidity resulting mostly from infectious or abacterial fouling and biofilm formation, and/or urothelial hyperplastic reaction. All of these may interact and lead to clinical complications. Many different stent designs and coatings have been proposed. In this study, we focused on the effect of paclitaxel-coated stents on hyperplastic proliferation of ureteral tissue, using as example anastomotic strictures after ureteroureterostomy in a rat model. Human urothelial cells (SV-HUC-1) were used to determine paclitaxel dosages in vitro. Polyurethane stents were coated with a paclitaxel containing biodegradable polymer and studied in a ureteroureterostomy rat model. 48 male 9-week-old Sprague-Dawley rats underwent either sham surgery (n = 16) or ureteroureterostomy with sutured anastomosis, and consecutive stenting with either a paclitaxel-coated or an uncoated stent (16 per group), respectively. The animals received daily intraperitoneal injections of 5-bromo-2-deoxyuridine (20 mg/ml, 100 mg/kg body weight) during the first eight postoperative days, and were sacrificed on day 28. Healing of the ureteral anastomosis and proliferation of urothelial cells was examined histologically and immunohistochemically. In vitro, a concentration of 10 ng/mm2 paclitaxel can be considered as non-toxic, while still exerting an anti-proliferative effect on urothelial cells. Histologically, typical wound healing processes were seen at the site of the ureteral anastomosis in vivo. Proliferation of urothelial cells was significantly lower in animals with paclitaxel-coated stents compared to those with uncoated stents (LI 41.27 vs. 51.58, p < 0.001). Our results indicate that stenting of ureteral anastomoses with paclitaxel-coated stents can reduce hyperplastic proliferation of ureteral tissue. Paclitaxel-coated stents thus might be able to prevent not only scar-induced postoperative stenosis after reconstructive surgery, but also hyperplastic urothelial reaction in non-anastomotic stent patients as part of their inflammatory response to the foreign material.

[Molecular tumor board penile cancer-a challenge]. / Molekulares Tumorboard Peniskarzinom ­ eine Herausforderung.

Due to its low incidence there is only very limited data concerning molecular markers in penile cancer. Recent studies show potential prognostic markers for lymph node metastasis, survival and response to chemotherapy or targeted therapy. Nevertheless the number of patients in the studies is very limited. Therefor clear recommendations for clinical decisions remain very weak. Patients with metastatic disease should be treated in clinical trials with translational biomarker research to improve the molecular tumor board in the future.

[Compulsory organ donation-a controversial topic]. / Verpflichtung zur Organspende ­ ein kontroverses Thema.

The number of organ donations in Germany has continuously fallen in recent years. The proposed Transplantation Act stipulates that every German citizen is considered an organ donor if he/she has not objected during his/her lifetime. This proposal has received wide approval, but also much criticism. The German Society for Urology, the German Society for Surgery, the German Society for Nephrology and the German Transplantation Society have all spoken out in press releases in favor of the introduction of an opt out (presumed consent) solution. The German Bundestag will decide on the proposed bill in autumn.

[Renal cell carcinoma diagnosis and prognosis within the context of the WHO classification 2016]. / Histopathologische Diagnose und Prognose des Nierenzellkarzinoms im Kontext der WHO-Klassifikation 2016.

BACKGROUND: Histological classification of renal cell carcinoma (RCC) has become more and more important for clinical management, but relatively few is known regarding the swiftness with which the 2016 World Health Organization (WHO) classification of RCC was adopted in the daily routine diagnostics. AIM: To retrospectively review the histological diagnosis of RCC within the context of 2016 WHO classification followed by survival analysis. MATERIAL AND METHODS: Retrospective register based analysis of RCC diagnosis between 1998 and 2017 and survival analysis. RESULTS: 1440 RCC cases were registered between 1998 and 1917. According to 2016 WHO classification, 77.7% clear cell RCC and 22.3% non-clear cell RCC were diagnosed. A total of 37 rare subtypes were recorded, among those 1% MiT family translocation RCC, 0.35% acquired cystic disease-associated RCC, 0.35% multilocular cystic renal neoplasm of low malignant potential, 0.35% collecting duct carcinoma, 0.3% mucinous tubular and spindle cell carcinoma, 0.1% clear cell papillary RCC and 0.1% RCC with (angio)leiomyomatous stroma. Cox regression analysis showed significant different overall survival and progression-free survival between the histological subtypes. DISCUSSION: The complexity of the 2016 WHO classification of RCC put high demands on histopathological diagnostics. At University Medicine Center Rostock morphological distinct RCC entities have been mostly diagnosed by conventional means via hematoxillin and eosin stained slides, but beyond immunohistochemistry additionally molecular techniques were established. The histologic subtyping of RCC according to 2016 WHO classification has prognostic significance and might have predictive significance for unique therapeutic approaches.

[Local treatment of penile cancer]. / Lokale Therapie beim Peniskarzinom.

In recent decades, the local treatment of penile cancer has focused primary on the removal of the primary tumor. Due to the significant psycho-oncological effects of treating the primary tumor, the guidelines on penile cancer now contain a clear recommendation for preserving the target organ and prior to each surgical procedure histological examination should be performed to confirm the penile cancer. For more advanced tumors, reconstructive plastic surgery should also be considered. The treatment of the primary tumor should be based on the stage and the local extent and size of the tumor. The aim of this article is to highlight current standards in the local treatment of penile cancer.

[Penile cancer: diagnosis and staging]. / Peniskarzinom: Diagnose und Staging.

Penile cancer is often an obvious visual diagnosis but histologic verification should be obtained prior to treatment. The clinical examination should determine the tumor stage and whether it has infiltrated the cavernous bodies and/or the urethra and it should adequately assess the inguinal lymph nodes. Preoperative imaging of the lesion is only indicated in equivocal cases. Curative treatment requires the complete removal of the primary tumor and all metastatic lymph nodes. Lymph node management is the key prognostic factor in the treatment of penile cancer. No imagining technique such as the ultrasound, CT, MRI or PET/CT is able to adequately detect micrometastatic lymph nodes. Therefore, invasive (inguinal) lymph node diagnosis is indicated for all tumour stages from pT1G2. Over 90% of penile cancer cases can be cured with early diagnosis and adequate treatment if routine self-examination and physical examinations are regularly performed.

[Lymph-node-positive penile cancer : Management and systemic therapy]. / Lymphknotenpositives Peniskarzinom : Management und systemische Therapie.

Cancer-specific survival in men with penile cancer depends foremost on regional lymphatic metastasis and its extent. Patients with limited inguinal lymph node metastases have a 5-year survival of up to 80%. However, those with pelvic lymph node metastases and/or systemic disease have a 5-year survival prognosis of only 0-33%. In any case, in patients with regional lymph node metastases multimodal treatment with complete lymphadenectomy and adjuvant chemotherapy is indicated.

[Psychosocial effects in patients with penile cancer : A systematic review]. / Psychosoziale Auswirkungen bei Patienten mit Peniskarzinom : Ein systematischer Überblick.

BACKGROUND: Psychological stress of patients with penile cancer arises from the cancer diagnosis itself and the treatment consequences. In addition, there is cancer-specific distress. There is the chance of cure in localized stages and in those with limited regional lymph node metastases but this requires surgery and often adjuvant chemotherapy. This systematic review gives a summary of the existing literature to date. MATERIALS AND METHODS: A critical database search using Medline was made in Ovid from 1946 to 2017, in the Cochrane Central Register of Controlled Trials (CENTRAL) and in the Web of Science from 1900 to 2017. This was complemented by a search of the World Health Organization's International Clinical Trials Registry Platform Search Portal and ClinicalTrials.gov. The reference lists of the included studies were manually searched for additional references. RESULTS: Selected studies (n = 10) addressed the psychosocial effects of penile cancer treatment on quality of life and sexual function. Due to the heterogeneity of the study designs only a narrative description of the results was possible. Defects or mutilation due to penile cancer cause psychological distress in a significant number of patients. Organ-sparing interventions have a positive impact on quality of life and sexual function. CONCLUSION: The external genitals are a focus of sexual identity. Mutilating treatment causes significant distress but organ-sparing treatment and reconstruction positively influence quality of life.

[Management of penile cancer patients: new aspects of a rare tumour entity]. / Das Management von Patienten mit Peniskarzinom ­ Neue Aspekte in der Therapie einer seltenen Tumorentität.

Over the past few decades, some principles in the treatment of penile cancer have changed fundamentally. While 15 years ago a negative surgical margin of at least 2 cm was considered mandatory, organ-sparing surgery permitting minimal negative surgical margins has a high priority nowadays. The current treatment principle requires as much organ preservation as possible and as much radicality as necessary. The implementation of organ-sparing and reconstructive surgical techniques has improved the quality of life of surviving patients. However, oncological and functional outcomes are still unsatisfactory. Alongside with adequate local treatment of the primary tumour, a consistent management of inguinal lymph nodes is of fundamental prognostic significance. In particular, clinically inconspicuous inguinal lymph nodes staged T1b and upwards need a surgical approach. Sentinel node biopsy, minimally-invasive surgical techniques and modified inguinal lymphadenectomy have reduced morbidity compared to conventional inguinal lymph node dissection. Multimodal treatment with surgery and chemotherapy is required in all patients with lymph node-positive disease; neoadjuvant chemotherapy has been established for patients with locally advanced lymph node disease, and adjuvant treatment after radical inguinal lymphadenectomy for lymph node-positive disease. An increasing understanding of the underlying tumour biology, in particular the role of the human papilloma virus (HPV) and epidermal growth factor receptor (EGFR) status, has led to a new pathological classification and may further enhance treatment options. This review summarises current aspects in the therapeutic management of penile cancer.

[Psychosocial stress in patients with prostate cancer : Experiences by using psychooncological screening questionnaires]. / Psychosoziale Belastungen bei Patienten mit Prostatakarzinom : Erfahrungen im Einsatz mit psychoonkologischen Screeningfragebögen.

BACKGROUND: Prostate cancer is the most common malignancy in men and accounts for most surgical procedures in uro-oncology. Stressful sequelae of radical prostatectomy are incontinence and erectile dysfunction. Hormone ablation and radiation therapy are also known stressors. Mental stress has a low prevalence compared to other tumor entities. It is highly probable that there is an underexpression of verbally reported emotional experiences. Therefore, a low-threshold access to psycho-oncological services and accurate identification of patients with mental comorbidities is important. The aim of this study was to identify the distress level with clarification of the stress in patients with prostate cancer. MATERIALS AND METHODS: Prospective evaluation of prostate cancer patients (n = 81, mean age 69 years) with regard to stress level, stress factors and the need for care using the Distress Thermometer, a standardized ultrashort stress-screening questionnaire. RESULTS: The mean stress level was 4.4 points. In total, 56% of patients indicated a stress level ≥5, i. e. a clinically relevant psychological burden was indicated. Main stressors were sexual problems (35%), reduced mobility (30%), pain (27.5%), tingling paresthesia (26%) and worries (26%). CONCLUSION: The psychological burden of prostate cancer patients is not as high as in other solid organ malignancies. However, some patients have a significantly increased psychosocial stress level. Identifying this subgroup and clarifying the correlation with specific stress and risk factors are important tasks of clinical care.

Stratification of clear cell renal cell carcinoma (ccRCC) genomes by gene-directed copy number alteration (CNA) analysis.

Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

[Surgical treatment of metastatic penile cancer - what is the scientific rationale?] / Operative Therapie von Metastasen beim Peniskarzinom ­ gibt es eine wissenschaftliche Grundlage?

The treatment of metastases of penile cancer is confined to lymphatic metastases. Limited lymph node metastasis in penile cancer can be cured by radical lymph node surgery if complete removal of all lymph nodes of the region is achieved. Adjuvant chemotherapy is recommended. This approach applies to the regional lymph nodes of the inguinal and pelvic regions. Applying this concept to retroperitoneal lymph node metastases may also be reasonable in selected cases. The individual prognosis depends on the extent of lymphatic spread.

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.

[Renal decapsulation for the treatment of anuria : A "forgotten" treatment from the early 20th century]. / Die Dekapsulierung der Niere als Therapie der Anurie : Ein "vergessenes" Therapieverfahren aus dem frühen 20. Jahrhundert.

In the early 20th century, Harrison first performed renal decapsulation in anuric children with scarlet fever and observed improvement in renal function postoperatively. The pathophysiological explanation was seen in intraparenchymal renal pressure due to edema which was improved by surgical decapsulation. The technique of decapsulation was simple excision after incision and blunt dissection of the renal parenchyma. Renal decapsulation then became a procedure commonly used for many indications in inflammatory renal conditions; indications were renal angioneurosis, hydronephrosis, toxic, bacterial and chronic nephritis, renal abscess and even eclampsia. With the beginning of the antibiotic era, renal decapsulation became obsolete and has disappeared from the urological spectrum completely.