Critical analysis of a simplified Fuhrman grading scheme for prediction of cancer specific mortality in patients with clear cell renal cell carcinoma--Impact on prognosis.

INTRODUCTION AND OBJECTIVES: The traditional 4-tiered Fuhrman grading system (FGS) is widely accepted as histopathological classification for clear cell renal cell carcinoma (ccRCC) and has shown prognostic value. As intra- and inter-observer agreement are sub-optimal, simplified 2- or 3-tiered FGSs have been proposed. We aimed to validate these simplified 2- or 3-tiered FGSs for prediction of cancer-specific mortality (CSM) in a large study population from 2 European tertiary care centers. METHODS: We identified and followed-up 2415 patients with ccRCC who underwent radical or partial nephrectomy in 2 European tertiary care centers. Univariable and multivariable analyses and prognostic accuracy analyses were performed to evaluate the ability of several simplified FGSs (i.e. grades I + II vs., grades III + IV, grades I + II vs. grade III and grade IV) to predict CSM. RESULTS: Independent predictor status in multivariate analyses was proved for the simplified 2-tiered FGS (high-grade vs. low-grade), for the simplified 3-tiered FGS (grades I + II vs. grade III and grade IV) as well as for the traditional 4-tiered FGS. The prognostic accuracy of multivariable models of 77% was identical for all tested models. Prognostic accuracy of the model without FG was 75%. CONCLUSIONS: A simplified 2- or 3-tiered FGS could predict CSM as accurate as the traditional 4-tiered FGS in a large European study population. Application of new simplified 2- or 3-tiered FGS may reduce inter-observer-variability and facilitate clinical practice without compromising the ability to predict CSM in ccRCC patients after radical or partial nephrectomy.

[Urethral reconstruction using buccal mucosa transplants]. / Harnröhrenrekonstruktion unter Verwendung von Mundschleimhauttransplantaten.

Buccal mucosa is the ideal material for urethral reconstruction because it is easy to harvest, is accustomed to permanent moisture and can be used at any location in the urethra. Stricture length and local conditions of the urethra have to be considered to decide which technique is required to reconstruct the urethra. Open urethroplasty with buccal mucosa has a success rate over 85% and should be used after unsuccessful internal urethrotomy and primarily in longer strictures.

[Upper tract urothelial carcinoma. An update on clinical and pathological prognostic factors]. / Das Urothelkarzinom des oberen Harntraktes. Ein Update über klinische und pathologische prognostische Faktoren.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon but potentially lethal disease. Accurate risk stratification remains a challenge owing to the difficulty of clinical staging. Identification of risk factors may lead to individualized treatment and patient counselling and holds the potential to improve outcome. A non-systematic PubMed/Medline literature research was performed to identify and summarize clinical and pathological risk factors and urine-based markers which are associated with clinical outcome. Although knowledge of potential prognostic factors has improved over the last 5 years the overall evidence on UTUC risk factors remains limited and prospective, randomized trials are still missing. Radical nephroureterectomy is currently standard treatment for high-grade and muscle invasive UTUC. Several clinical and pathological factors (e.g. stage, grade, age, hydronephrosis, lymphovascular invasion, tumor necrosis and architecture, delay between diagnosis and surgery) were identified to be associated with outcome. Urinary cytology and fluorescence in-situ hybridization are the most commonly used urinary markers. Prospective randomized controlled trials are urgently needed to identify new risk factors and assess the efficacy. The incorporation of such prognosticators into multivariable prediction models may help to guide decision-making with regard to type of treatment, performance of lymphadenectomy and consideration of neoadjuvant or adjuvant systemic therapy.

Transcription alterations of members of the ubiquitin-proteasome network in prostate carcinoma.

The purpose of this work was to investigate the role of the ubiquitin-proteasome network (UPN) in prostate cancer (PCA) and to elicit potential markers for this disease. The UPN represents a key factor in the maintenance of cellular homoeostasis as a result of its fundamental function in the regulation of intracellular protein degradation. Members of this network have a role in the biology of haematological and solid tumours. Tumour cells and normal epithelial cells from 22 prostatectomy specimens were isolated by laser microdissection. Prostate biopsy samples from healthy individuals served for technical calibration and as controls. Transcript levels of eight selected genes with E3 ubiquitin ligase activity (labelling target proteins for proteasome degradation) and two genes belonging to the proteasome-multienzyme complex itself were analysed by quantitative real-time RT-PCR. The proteasome genes PSMC4 and PSMB5 and the E3 ubiquitin ligase NEDD4L were significantly and coherently upregulated in PCA cells compared with the corresponding adjacent normal prostate tissue. Transcription of the E3 ubiquitin ligase SMURF2 was significantly higher in organ-confined tumours (pT2) compared with non-organ-confined cancers (pT3). The results indicate a role for PSMC4 and PSMB5 and the E3 ubiquitin ligase NEDD4L in prostate tumourigenesis, whereas SMURF2 downregulation could be associated with clinical progression. NEDD4L and SMURF2 both target transforming growth factor (TGF)-ß for degradation. This reflects the pleiotropic role of the TGF-ß signalling pathway acting as a tumour suppressor in normal and pre-cancerous cells, but having oncogenic properties in progressing cancer. Further studies have to elucidate whether these alterations could represent clinically relevant PCA-diagnostic and progression markers.

[Technical aspects of nerve sparing during retropubic prostatectomy]. / Aspects techniques de la préservation nerveuse au cours de la prostatectomie rétropubienne.

Retropubic radical prostatectomy is the most commonly used therapeutic option for the treatment of clinically localized prostate cancer. An ongoing stage migration towards organ-confined cancers allows performing a nerve-sparing procedure in a growing number of patients. Key elements for achieving convincing functional results are a sphincter preserving Ligation of the distal part of Santorini's plexus and the subtle preparation of the neurovascular bundle. This article gives a detailed description of the operative technique. Furthermore, a strategy for patient selection and tumour selection for the indication of nerve-sparing radical prostatectomy (NSRP) is suggested.

[Selection criteria for the expected management of localised prostate cancer]. / Selektionskriterien zum abwartenden Management des lokalisierten Prostatakarzinoms.

Prostate cancer harbours the possibility of overtreatment more than any other malignant disease. Due to its slow growth, expected management is an established therapeutic option in newly diagnosed carcinomas. Improved diagnostic methods and the widespread use of PSA lead to earlier diagnosis of cancers that would not adversely affect the life expectancy of the patient, even when they were left untreated. Several statistical models have been published to identify such insignificant cancers; however, all such nomograms suffer from limited sensitivity and specificity. For the indication of expected management, comorbidity and life expectancy must be considered using risk scores and life tables. In general, expected management is a suitable option for elderly patients with low grade cancers. Young patients and those with intermediate or high-grade cancers are most likely to benefit from active local treatment.

[Fast-track surgery in radical retropubic prostatectomy. First experiences with a comprehensive program to enhance postoperative convalescence]. / Radikale retropubische "Fast-track-Prostatektomie". Erste Erfahrungen mit einem interdisziplinären, multimodalen Behandlungskonzept zur Beschleunigung der postoperativen Rehabilitation.

Fast-track surgery is a comprehensive program for the optimization of perioperative care in elective surgery reducing potential postoperative complications and speeding up convalescence. Recent data from randomized colon resection trials emphasize that fast-track surgery is possible in most major operations. Our initial results in radical retropubic prostatectomy fast-track surgery have been encouraging. Fast-track surgery in major urological operations needs validation using randomized trials.