Prognostic significance of Fuhrman grade and age for cancer-specific and overall survival in patients with papillary renal cell carcinoma: results of an international multi-institutional study on 2189 patients.

PURPOSE: Because the prognostic impact of the clinical and pathological features on cancer-specific survival (CSS) and overall survival (OS) in patients with papillary renal cell carcinoma (papRCC) is still controversial, we want to assess the impact of clinicopathological features, including Fuhrman grade and age, on survival in surgically treated papRCC patients in a large multi-institutional series. METHODS: We established a comprehensive multi-institutional database of surgically treated papRCC patients. Histopathological data collected from 2189 patients with papRCC after radical nephrectomy or nephron-sparing surgery were pooled from 18 centres in Europe and North America. OS and CSS probabilities were estimated using the Kaplan-Meier method. Multivariable competing risks analyses were used to assess the impact of Fuhrman grade (FG1-FG4) and age groups (<50 years, 50-75 years, >75 years) on cancer-specific mortality (CSM). RESULTS: CSS and OS rates for patients were 89 and 81% at 3 years, 86 and 75% at 5 years and 78 and 41% at 10 years after surgery, respectively. CSM differed significantly between FG 3 (hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.17-8.22; p < 0.001) and FG 4 (HR 8.93, 95% CI 4.25-18.79; p < 0.001) in comparison to FG 1. CSM was significantly worse in patients aged >75 (HR 2.85, 95% CI 2.06-3.95; p < 0.001) compared to <50 years. CONCLUSIONS: FG is a strong prognostic factor for CSS in papRCC patients. In addition, patients older than 75 have worse CSM than patients younger than 50 years. These findings should be considered for clinical decision making.

[Genitourinary malignancies and rheumatoid arthritis]. / Urologische Malignome und rheumatoide Arthritis.

Genitourinary neoplasms are relatively common and the frequency increases with age. Due to demographic changes more patients with inflammatory rheumatic diseases will have concomitant genitourinary tumors or they will develop them under antirheumatic therapy. In such cases, disease-modifying antirheumatic drugs (DMARD) and immunosuppressive therapy have to be carefully balanced on an individual basis. Based on the limited evidence available large increases in the risks from conventional and/or biological DMARDs for patients with genitourinary malignancies appear to be unlikely for most situations. In addition to these more common situations paraneoplastic symptoms in the musculoskeletal system can occur due to genitourinary malignancies. Moreover, novel drugs with immunostimulating activity for some genitourinary tumors may provoke autoimmune symptoms and thus present new challenges for interdisciplinary cooperation between rheumatologists and uro-oncologists. In this review, the diagnostic procedures, therapies and follow-up of cancers in the field of urology are delineated according to the current German and European guidelines. We describe the core issues that both urologists and rheumatologists should bear in mind. Direct communication, routine exchange and involvement of rheumatologists in interdisciplinary tumor boards should improve future treatment quality of our joint patients.

[Metastatic castration-resistant prostate cancer : Clinical data, new treatment options and therapy monitoring]. / Metastasiertes kastrationsresistentes Prostatakarzinom : Aktuelle Daten, neue Therapieoptionen und strukturiertes Therapiemonitoring.

Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient. Furthermore, predictive markers to facilitate the selection of patients for a specific therapy or sequence of therapies remain an unmet need. However, with the recently discovered androgen receptor splice variant V7, which mediates (cross)resistance to or between abiraterone and enzalutamide, the first such marker has been identified. It is critical to monitor the response to treatments at prespecified intervals in order to optimize treatment sequencing so that the patient does not miss a valuable therapeutic window to receive alternative treatment that may prolong his life along with good symptom control and preservation of quality of life.

[Syndrome of persisting mullerian duct with first manifestation in an adult]. / Syndrom des persistierenden Müller-Ganges mit Erstmanifestation beim Erwachsenen.

INTRODUCTION: We report on a 22-year-old male patient who presented with an intrapelvic tumor. CASE REPORT: CT and MRI showed a left pelvic abscess, which was drained. After regression of the abscess, we removed the causative tubular structure surgically, revealing a rudimentary genital structure with parts of the Mullerian and Wolffian ducts. CONCLUSIONS: This case report demonstrates an abscess formation as complication of a previously asymptomatic rudimentary genital structure, which was associated with further abnormalities, such as left testicular agenesia, perineoscrotal hypospadias and transverse testicular ectopia.

[Metastatic castration-resistant prostate cancer: position paper for structured therapy monitoring]. / Metastasiertes kastrationsresistentes Prostatakarzinom: Positionspapier für ein strukturiertes Therapiemonitoring.

This position paper is intended to help to structure and to standardize therapy monitoring in patients with metastatic castration-resistant prostate cancer (mCRPC). With the treatment options available today, patients with metastatic disease can often maintain good quality of life and stable disease for several years. It is crucial that once a therapy becomes insufficiently effective that it be replaced in a timely manner by a new treatment option. From a prognostic point of view, it is important that patients receive as many as possible and in the ideal case all currently available treatment options.

[Prostate cancer. Current and practice-relevant news from urology in 2011]. / Prostatakarzinom. Aktuelles und praxisrelevantes in der Urologie 2011.

The effect of 5α reductase inhibitors in prostate cancer has been extensively investigated. The studies determined that finasteride and also dutasteride reduced the risk of prostate cancer; however, particularly high-grade cancer was not reduced and may possibly even have been increased. This is appropriately reflected in the S3 guideline on prostate cancer. New data on early recognition show that after longer term observation prostate cancer-specific mortality can be more effectively reduced by screening than was initially shown by the original data from the ERSPC study. Active surveillance is becoming more important for the therapy of early prostate cancer. Other new publications have shown good results for patients who underwent surgery for high risk prostate cancer. For metastasized prostate cancer new immunotherapeutic, chemotherapeutic and hormonal options are now available or will soon be approved.

Internalized SP-A and lipid are differentially resecreted by type II pneumocytes.

Biochemical and morphological assays were developed to study surfactant protein A (SP-A) and lipid resecretion kinetics by isolated type II cells in vitro. After a 10-min uptake period with SP-A (3 microg/10(6) cells) in combination with liposomes (60 microg/10(6) cells), the cells were allowed to resecrete. After 5 min of resecretion, only 21.7 +/- 4.6% of the internalized SP-A remained intracellularly compared with 54 +/- 2.9% of the lipids. Extracellular SP-A present during the resecretion period partially inhibited resecretion (SP-A, 36% at 5 min; lipid, approximately 16% at 5 min). Lipid resecretion was also dependent on the SP-A concentration present during the uptake period. Although, as shown by confocal laser scanning microscopy, after a 10-min uptake period at 37 degrees C, most of the fluorescein isothiocyanate-labeled SP-A and rhodamine-phosphatidylethanolamine-labeled lipids colocalized within the cells, after an additional 10 min of resecretion, both the strength of the fluorescence signals and the extent of colocalization had markedly decreased. These data indicate that internalized lipid and SP-A can be resecreted rapidly by type II cells, likely via different pathways.

Surfactant protein A and lipid are internalized via the coated-pit pathway by type II pneumocytes.

Surfactant protein (SP) A and SP-A-mediated lipid uptake by isolated type II cells were investigated with biochemical and morphological methods. Inhibition of coated-pit function by potassium depletion severely reduced both SP-A and SP-A-mediated lipid internalization. Lipid uptake in the absence of SP-A was not affected. With confocal laser scanning microscopy and immunoelectron microscopy, SP-A and lipid predominantly (60%) colocalized in intracellular vesicles carrying early endosomal markers (EEA1) 5 min after endocytosis but were negative for the late endosomal or lysosomal marker LAMP-1. As estimated by subcellular fractionation, at this time point, 23% of the internalized SP-A and 45% of internalized lipid were localized within light (<0.38 M sucrose) fractions, which contain lamellar bodies and are positive for EEA1. The remaining label was predominantly found within EEA1-positive and plasma membrane-containing subfractions (> or = 1 M sucrose). We suggest that in isolated type II cells in vitro, SP-A and lipid are taken up together via the coated-pit pathway and that at early time points, both components reside in the same early endosomal compartment.