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.

Trends in the use of partial nephrectomy for cT1 renal tumors: Analysis of a 10-yr European multicenter dataset.

AIM: Although extensively addressed in US registries, the utilization rate of Partial Nephrectomy has been poorly addressed in European settings. Our aim is to evaluate the impact of hospital volume on the use of PN for cT1 renal tumors. METHODS: 2526 patients with cT1N0M0 renal tumors treated with either PN or radical nephrectomy at 10 European centres in the last decade were included in the analysis. Joinpoint regression analysis was used to identify significant changes over time in linear slope of the trend for each center. The correlation between yearly caseload and the slopes was assessed with the non-parametric Spearman test. Coincident pairwise tests and regression analyses were used to generate and compare the trends of high-volume (HV), mid-volume (MV) and low-volume (LV) groups. RESULTS: Yearly caseload was significantly associated with increased use of PN (R = 0.69, p = 0.028). The utilization rate of PN was stable at LV centres (p = 0.67, p = 0.7, p = 0.76, for cT1, cT1a, and cT1b tumors, respectively), while increased significantly at MV (p = 0.002, 0.0005 and 0.007, respectively) and HV centers (all p < 0.0001). Regression analysis confirmed the trends for HV and MV as significantly different from those observed in LV centres (all p ≤ 0.002) and highlighted significant differences also between MV and HV centres (all p ≤ 0.03). CONCLUSIONS: We confirmed the association between caseload and the use of PN for cT1 tumors. Our findings suggest that a minimum caseload might turn the tide also in LV centres while a selective referral to HV centers for cT1b tumors should be considered.

Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database.

BACKGROUND: Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients. METHODS: The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index. RESULTS: During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%). CONCLUSION: Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5-year-recurrence rate of almost 40%.

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.

Testicular synthesis and vitamin D action.

CONTEXT: The vitamin D system has pleiotropic effects not only in bone metabolism. Its role in testicular steroidogenesis is new and deserves intensive research. OBJECTIVE: We hypothesize that vitamin D, especially 1,25 dihydroxyvitamin D3 [1,25(OH)2D3 (calcitriol)] induces male steroidogenesis and intend to identify its impact on genes and pathways in testicular androgen regulation. METHODS: Human adult primary testicular cells were isolated, treated with 1,25(OH)2D3, and their gene expression levels profiled by microarray analysis. Highly regulated genes were confirmed by real-time quantitative PCR. In addition, the effects of 1,25(OH)2D3 in combination with LH and IGF-I on the gene expression level of androgens were assessed. T levels in the culture media were determined by a high-resolution ELISA. The expression of vitamin D receptor was confirmed at baseline and after 1,25(OH)2D3 stimulation using immunocytochemistry. RESULTS: Microarrays depicted 63 genes significantly regulated by 1,25(OH)2D3, including genes related to male androgen and vitamin D metabolism, mainly triggered by the vitamin D receptor/retinoid X receptor activation. 1,25(OH)2D3 led to significant changes in the expression profiles of reproductive genes and significantly increased T synthesis in human testicular cell cultures. CONCLUSIONS: Data from our human primary testicular cell culture model suggest that vitamin D plays a major role in male steroidogenesis in vitro.

Validation of the pretreatment derived neutrophil-lymphocyte ratio as a prognostic factor in a European cohort of patients with upper tract urothelial carcinoma.

BACKGROUND: The value of a combined index of neutrophil and white cell counts, named derived neutrophil-lymphocyte ratio (dNLR), has recently been proposed as a prognosticator of survival in various cancer types. We investigated the prognostic role of the dNLR in a large European cohort of patients with upper tract urothelial carcinoma (UTUC). METHODS: Data from 171 non-metastatic UTUC patients, operated between 1990 and 2012 at a single tertiary academic centre, were evaluated retrospectively. Cancer-specific- (CSS) as well as overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the dNLR, multivariate proportional Cox-regression models were applied. Additionally, the influence of the dNLR on the predictive accuracy of the multivariate model was further determined by Harrell's concordance index (c-index). RESULTS: The median follow-up period was 31 months. An increased dNLR was statistically significantly associated with shorter CSS (log-rank P=0.004), as well as with shorter OS (log-rank P=0.002). Multivariate analysis identified dNLR as an independent predictor for CSS (hazard ratio, HR=1.16, 95% confidence interval, CI=1.01-1.35, P=0.045), as well as for OS (HR=1.21, 95% CI=1.09-1.34, P<0.001). The estimated c-index of the multivariate model for OS was 0.68 without dNLR and 0.73 when dNLR was added. CONCLUSIONS: Patients with a high pretreatment dNLR could be predicted to show subsequently higher cancer-specific- as well as overall mortality after surgery for UTUC compared with those with a low pretreatment dNLR. Thus, this combined index should be considered as a potential prognostic biomarker in future.

[Postoperative prognosis of chromophobic renal cell carcinoma: comparative analysis of the multinational CORONA database]. / Die postoperative Prognose des chromophoben Nierenzellkarzinoms : Eine vergleichende Analyse anhand der multinationalen CORONA-Datenbank.

BACKGROUND: The chromophobe subtype represents the third most common histological subtype of renal cell carcinoma (chRCC). Due to the rarity of this subtype only one publication regarding the specific analysis of clinical and histopathological criteria as well as survival analysis of more than 200 patients with chRCC is known to date. MATERIALS AND METHODS: A total of 6,234 RCC patients from 11 centres who were treated by (partial) nephrectomy are contained in the database of this multinational study. Of the patients 259 were diagnosed with chRCC (4.2 %) and thus formed the study group for this retrospective investigation. These subjects were compared to 4,994 patients with a clear cell subtype (80.1 %) with respect to clinical and histopathological criteria. The independent influence of the chromophobe subtype regarding tumor-specific survival and overall survival was determined using analysis by Cox proportional hazards regression models. The median follow-up was 59 months (interquartile range 29-106 months). RESULTS: The chRCC patients were significantly younger (60 vs. 63.2 years, p < 0.001), more often female (50 vs. 41 %, p = 0.005) and showed simultaneous distant metastases to a lesser extent (3.5 vs. 7.1 %, p = 0.023) compared to patients with a clear cell subtype. Despite a comparable median tumor size a ≥ pT3 tumor stage was diagnosed in only 24.7 % of the patients compared to of 30.5 % in patients with a clear cell subtype (p = 0.047). In addition to the clinical criteria of age, sex and distant metastases, the histological variables pTN stage, grade and tumor size showed a significant influence on tumor-specific and overall survival. However, in the multivariable Cox regression analysis no independent effect on tumor-specific mortality (HR 0.88, p = 0.515) and overall mortality (HR 1.00, p = 0.998) due to the histological subtype was found (c-index 0.86 and 0.77, respectively). CONCLUSIONS: Patients with chRCC and clear cell RCC differ significantly concerning the distribution of clinical and histopathological criteria. Patients with chRCC present with less advanced tumors which leads to better tumor-specific survival rates in general; however, this advantage could not be verified after adjustment for the established risk factors.

Body mass index has no impact on sperm quality but on reproductive hormones levels.

The influence of overweight and obesity on sperm quality and reproductive hormone levels is under discussion. The aim of the present retrospective study was to evaluate the influence of body mass index (BMI) on sperm quality and reproductive hormones. We analysed semen samples and serum levels of FSH, LH, T and PRL of a total of 2110 men attending our andrology unit from 1994 to 2010 due to infertility work-up. Patients were stratified according to their BMI in four groups. Main outcome measures were sperm motility, morphology and concentration. Serum levels of FSH, LH, T and PRL were evaluated as well. No statistically significant difference was found for sperm quality and BMI between patients categorised according to the four BMI levels. T (P < 0.001) and LH (P = 0.006) significantly differed between the four groups. In multivariable analysis, BMI did not have significantly independent influence on all assessed sperm quality parameters, whereas BMI significantly influenced hormone values for LH (P = 0.001), T (P = <0.001) and PRL (P = 0.044). We therefore conclude that BMI has no significant impact on sperm quality parameters. However, serum levels of LH, T and PRL were significantly influenced by BMI.

High plasma fibrinogen level represents an independent negative prognostic factor regarding cancer-specific, metastasis-free, as well as overall survival in a European cohort of non-metastatic renal cell carcinoma patients.

BACKGROUND: In recent years, plasma fibrinogen has been ascribed an important role in the pathophysiology of tumour cell invasion and metastases. A relatively small-scale study has indicated that plasma fibrinogen levels may serve as a prognostic factor for predicting clinical outcomes in non-metastatic renal cell carcinoma (RCC) patients. METHODS: Data from 994 consecutive non-metastatic RCC patients, operated between 2000 and 2010 at a single, tertiary academic centre, were evaluated. Analyses of plasma fibrinogen levels were performed one day before the surgical interventions. Patients were categorised using a cut-off value of 466 mg dl⁻¹ according to a calculation by receiver-operating curve analysis. Cancer-specific (CSS), metastasis-free (MFS), as well as overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, a multivariable Cox regression model was performed for all three different endpoints. RESULTS: High plasma fibrinogen levels were associated with various well-established prognostic factors, including age, advanced tumour stage, tumour grade and histologic tumour necrosis (all P<0.05). Furthermore, in multivariable analysis, a high plasma fibrinogen level was statistically significantly associated with a poor outcome for patients' CSS (hazard ratio (HR): 2.47, 95% confidence interval (CI): 1.49-4.11, P<0.001), MFS (HR: 2.15, 95% CI: 1.44-3.22, P<0.001) and OS (HR: 2.48, 95% CI: 1.80-3.40, P<0.001). CONCLUSION: A high plasma fibrinogen level seems to represent a strong and independent negative prognostic factor regarding CSS, MFS and OS in non-metastatic RCC patients. Thus, this easily determinable laboratory value should be considered as an additional prognostic factor for RCC patients' individual risk assessment.

Validation of the pre-treatment neutrophil-lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Several studies suggest a negative impact of increased NLR for patient's survival in different types of cancer. However, previous findings from small-scale studies revealed conflicting results about its prognostic significance with regard to different clinical end points in non-metastatic renal cell carcinoma (RCC) patients. Therefore, the aim of our study was the validation of the prognostic significance of NLR in a large cohort of RCC patients. METHODS: Data from 678 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 at a single centre, were evaluated retrospectively. Cancer-specific, metastasis-free, as well as overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of NLR, multivariate Cox regression models were applied for all three different end points. Influence of the NLR on the predictive accuracy of the Leibovich prognosis score was determined by Harrell's concordance index. RESULTS: Multivariate analysis identified increased NLR as an independent prognostic factor for overall (hazard ratio (HR)=1.59, 95% confidence interval (CI)=1.10-2.31, P=0.014), but not for cancer-specific (HR=1.59, 95% CI=0.84-2.99, P=0.148), nor for metastasis-free survival (HR=1.39, 95% CI=0.85-2.28, P=0.184). The estimated concordance index was 0.79 using the Leibovich risk score and 0.81 when NLR was added. CONCLUSION: Regarding patients' OS, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. Adding the NLR to well-established prognostic models such as the Leibovich prognosis score might improve their predictive ability.

Preoperative pregabalin administration significantly reduces postoperative opioid consumption and mechanical hyperalgesia after transperitoneal nephrectomy.

BACKGROUND: Preoperative administration of pregabalin is proposed as a promising way of enhancing postoperative pain control. Whereas a few studies have investigated the effect of pregabalin on postoperative opioid consumption, no study has focused on the influence on postoperative hyperalgesia. In this randomized, triple-blinded, placebo-controlled study, we aimed to demonstrate that a single, preoperative dose of pregabalin reduces postoperative opioid consumption, mechanical hyperalgesia, and pain sensitivity. METHODS: Patients undergoing elective transperitoneal nephrectomy received 300 mg pregabalin or placebo 1 h before anaesthesia. After operation, patients received piritramide via a patient-controlled analgesia device. Pain levels and side-effects were documented. The area of hyperalgesia for punctuate mechanical stimuli around the incision was measured 48 h after the operation with a hand-held von Frey filament. Mechanical pain threshold was tested before and 48 h after surgery with von Frey filaments with increasing diameters. RESULTS: In each group, 13 patients were recruited. Total piritramide consumption [77 (16) vs 52 (16) mg, P=0.0004] and the normalized area of hyperalgesia [143 (87) vs 84 (54) cm(2), P=0.0497] were significantly decreased in the pregabalin group. There were no significant differences in mechanical pain threshold levels [1.20 (0.56) log(g) vs 1.05 (0.58) log(g), P=0.6738]. No case of severe sedation was reported in both groups. No other side-effects were observed. CONCLUSIONS: Our study has shown that preoperative administration of 300 mg pregabalin in patients undergoing transperitoneal nephrectomy reduces postoperative opioid consumption and decreases the area of mechanical hyperalgesia.

Guía clínica para el diagnóstico y tratamiento de los carcinomas de las células uroteliales de las vías urinarias superiores: actualización de 2011 / European Guidelines for the Diagnosis and Management of Upper Urinary Tract Urothelial Cell Carcinomas: 2011 Update

Contexto: El Grupo de Guías Clínicas sobre el carcinoma de células uroteliales de las vías urinarias superiores (CCU-VUS) de La Asociación Europea de Urología (EAU) ha elaborado una nueva guía clínica para ayudar a los médicos a evaluar el tratamiento del CCU-VUS basado en los datos científicos, y a incorporar las presentes recomendaciones a la práctica clínica diaria. Objetivo: Este documento ofrece una breve visión general de la guía clínica de la EAU sobre el CCU-VUS como una ayuda para los médicos en su práctica diaria. Adquisición de datos científicos: Las recomendaciones proporcionadas en la guía actual se basan en una meticulosa revisión de las guías y documentos sobre CCU-VUS disponibles, identificados mediante una búsqueda sistemática en Medline. Los datos sobre neoplasias uroteliales malignas y CCU-VUS en la literatura se buscaron mediante Medline con las siguientes palabras clave: cáncer del tracto urinario, carcinomas uroteliales, tracto urinario superior, carcinoma, células de transición, pelvis renal, uréter, cáncer vesical, quimioterapia, nefroureterectomía, tratamiento adyuvante, tratamiento neoadyuvante, recidiva, factores de riesgo y supervivencia. Un equipo de expertos sopesó las referencias Síntesis de los datos científicos: Hay una falta de datos en la literatura actual para proporcionar recomendaciones consistentes, debido a la rareza de la enfermedad. Una serie de recientes estudios multicéntricos ya están disponibles, mientras que las publicaciones anteriores se basaban solo en poblaciones limitadas. Sin embargo, la mayoría de estos estudios han sido análisis retrospectivos. Se recomienda la clasificación TNM2009. Se hacen recomendaciones para el diagnóstico, así como para el tratamiento radical y conservador; también se tratan los factores pronósticos. Se proporcionan recomendaciones para el seguimiento del paciente después de diferentes opciones terapéuticas. Conclusiones: Esta guía contiene información para el diagnóstico y tratamiento de los pacientes individuales de acuerdo a un enfoque estándar actual. Al determinar el régimen de tratamiento óptimo, los médicos deben tener en cuenta las características clínicas específicas de cada paciente con respecto a la función renal, incluyendo comorbilidades médicas, localización del tumor, grado y estadio y el estado de los marcadores moleculares (AU)

Context: The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice. Objective: This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice. Evidence acquisition: The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched sing Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references. Evidence synthesis: There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options. Conclusions: These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient’s specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status (AU)

[European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. European Association of Urology Guideline Group for urothelial cell carcinoma of the upper urinary tract]. / Guía clínica para el diagnóstico y tratamiento de los carcinomas de las células uroteliales de las vías urinarias superiores: actualización de 2011.

CONTEXT: The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice. OBJECTIVE: This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references. EVIDENCE SYNTHESIS: There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options. CONCLUSIONS: These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient's specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status.

Collecting system invasion and Fuhrman grade but not tumor size facilitate prognostic stratification of patients with pT2 renal cell carcinoma.

PURPOSE: The 7th edition of TNM for renal cell carcinoma introduced a subdivision of pT2 tumors at a 10 cm cutoff. In the present multicenter study the influence of tumor size as well as further clinical and histopathological parameters on cancer specific survival in patients with pT2 tumors was evaluated. MATERIALS AND METHODS: A total of 670 consecutive patients with pT2 tumors (10.4%) of 6,442 surgically treated patients with all tumor stages were pooled (mean followup 71.4 months). Tumors were reclassified according to the current TNM classification, and subdivided in stages pT2a and pT2b. Cancer specific survival was analyzed using the Kaplan-Meier method, and univariable and multivariable analyses were used to assess the influence of several parameters on survival. RESULTS: Tumor size continuously applied and subdivided at 10 cm or alternative cutoffs did not significantly influence cancer specific survival. In addition to N/M stage, Fuhrman grade and collecting system invasion also had an independent influence on survival. Integration of a dichotomous variable subsuming Fuhrman grade and collecting system invasion (grade 3/4 and/or collecting system invasion present vs grade 1/2 and collecting system invasion absent) into multivariate models including established prognostic parameters resulted in improvement of predictive abilities by 11% (HR 2.3, p <0.001) for all pT2 cases and 151% (HR 3.1, p <0.001) for stage pT2N0M0 cases. CONCLUSIONS: Tumor size did not have a significant influence on cancer specific survival in pT2 tumors, neither continuously applied nor based on various cutoff values. To enhance prognostic discrimination, multifactorial staging systems including pathological features should be implemented. The prognostic relevance of the variable subsuming Fuhrman grade and collecting system invasion should be considered for future evaluation.

Patterns of invasion and histological growth as prognostic indicators in urothelial carcinoma of the upper urinary tract.

The biological significance of squamous and glandular differentiation and different patterns of invasion in upper urinary tract urothelial carcinoma is unclear. We reviewed 268 cases of consecutive upper urinary tract carcinomas with respect to the presence of squamous and/or glandular differentiation and different patterns of invasion (nodular, trabecular, and infiltrative) and correlated data with patient outcome. Squamous or glandular differentiation occurred in 47/268 (18%) tumors and its presence correlated with high tumor stage (P<0.001) and grade (P<0.001). Invasive patterns were nodular in 49/227 (22%), trabecular in 95/227 (42%), and infiltrative in 83/227 (37%) tumors. The nodular pattern prevailed in low stage (P<0.001) and low-grade (P<0.001) tumors, whereas the infiltrative pattern prevailed in high stage (P<0.001) and high-grade (P<0.001) tumors. Multivariate analysis proved that tumor stage (P<0.001) and the infiltrative pattern (P<0.001) are independent predictors of metastasis-free survival, whereas tumor grade and squamous and glandular differentiation lacked independent influence on patient outcome. In conclusion, the infiltrative pattern of invasion significantly correlated with advanced disease and poor patient outcome. In contrast, the presence of squamous and/or glandular invasion did not prove independent influence on patient outcome. The pattern of invasion should be commented upon separately in the pathology report.

Interdigitating dendritic cell sarcoma of urinary bladder mimicking large intravesical calculus.

Interdigitating dendritic cell sarcomas are extremely rare neoplasms with an unpredictable clinical course that usually occur in lymph nodes. We report the first adult patient with interdigitating dendritic cell sarcoma involving the bladder. A 71-year-old man presented with lower urinary tract symptoms and gross hematuria. Cystoscopy and transabdominal ultrasonography showed a large hyperechoic intravesical mass. The histologic analysis revealed a spindled cell neoplasm with an immunophenotype consistent with interdigitating dendritic cell sarcoma. Complete resection was achieved, and the patient was well without evidence of tumor 6 years after surgery. Urologists should be aware of this entity, which should be included in the differential diagnosis of bladder tumors.

CD10 is a diagnostic and prognostic marker in renal malignancies.

AIMS: To determine the diagnostic and prognostic value of CD10 immunoreactivity in renal cell carcinomas (RCCs) and transitional cell carcinomas (TCCs). METHODS AND RESULTS: CD10 expression was investigated in primary (n = 180) and metastatic (n = 58) RCCs and upper urinary tract TCCs (n = 53) using a tissue microarray technique. One hundred and fifty-four of 172 (90%) evaluable primary and 48/56 (86%) evaluable metastatic RCCs expressed CD10. Extensive immunoreactivity (positivity of >50% cancer cells) decreased with rising tumour grade in conventional RCCs [G1/G2 72/81 (89%), G3/G4 33/48 (69%); P = 0.009]. Chromophobe RCCs showed a significantly lower overall and extensive immunoreactivity compared with conventional tumours (P < 0.001). In papillary RCCs immunoreactivity of more than 10% of cancer cells for CD10 was seen more often in type 2 (7/8, 88%) compared with type 1 (5/12, 42%; P =0.054) tumours. In conventional RCCs, pure apical membranous staining was associated with low tumour stage (P = 0.003), low grade (P = 0.004) and improved prognosis on univariate analysis (P = 0.031). TCCs were less frequently stained (51%). Extensive staining, however, was associated with high-stage tumours (P = 0.024), high-grade (P = 0.073) tumours, and was associated with shorter disease-free survival in univariate analysis (P = 0.003). CONCLUSIONS: CD10 proved to be an additional marker for renal malignancies with predominantly diagnostic potential.

Are heterogenous results of EGFR immunoreactivity in renal cell carcinoma related to non-standardised criteria for staining evaluation?

AIMS: To assess whether heterogeneity of epidermal growth factor receptor (EGFR) immunoreactivity in renal cell carcinoma (RCC) is related to non-standardised criteria for staining evaluation. METHODS: EGFR expression was investigated in 132 primary and 55 metastatic conventional RCCs using a tissue microarray technique. RESULTS: Overall, membranous and/or cytoplasmic EGFR immunostaining was present in 123 of 132 (93%) primary and 49 of 53 (92%) metastatic RCCs, with extensive immunoreactivity (> 50% of tumour cells) in 110 of 132 (83%) primary tumours and 39 of 53 (73%) metastases. Cytoplasmic staining was associated with high tumour stage and high tumour grade. In addition, strong membranous staining (score 3+) prevailed in high grade RCCs. Cytoplasmic immunostaining was associated with an unfavourable prognosis, whereas overall (cytoplasmic and membranous) immunoreactivity and intensity of membranous staining were not. CONCLUSIONS: Different methods of immunohistochemical evaluation led to different results, strengthening the need for standardisation, especially against a background of rapidly evolving EGFR targeted cancer treatment strategies.

Long-term results of nephron-sparing surgery for renal cell carcinoma in 114 patients: risk factors for progressive disease.

OBJECTIVES: To evaluate risk factors for metastatic disease after nephron-sparing surgery (NSS) for renal cell carcinoma (RCC). PATIENTS AND METHODS: NSS for RCC was used 117 times in 114 patients at our institution; 61 had a normal contralateral kidney and were selected for elective NSS, and in 56 cases (53 patients) the indication for NSS was imperative. Univariate and multiple regression analysis was used to evaluate the risk factors for metastatic disease. RESULTS: After a mean follow-up of 80 months, there was tumour progression in 17 of the 114 patients (15%). In the univariate analysis, the tumour diameter (P = 0.03) and imperative indication (P = 0.009), and in multiple regression analysis only imperative indication, were significant risk factors for metastatic disease (P = 0.016). CONCLUSIONS: Elective NSS for RCC provides excellent long-term results in selected patients, whereas those undergoing NSS imperatively are at a significantly higher risk of metastatic disease and require a close follow-up.

Angiomyolipoma with a caval thrombus.

We report the case of a female patient presenting with flank pain. Abdominal ultrasound revealed a tumor of 8 cm in diameter. After abdominal computerized tomography, the tumor was classified as angiomyolipoma with a tumor thrombus in the inferior vena cava. After nephrectomy, the diagnosis was confirmed histologically. To our knowledge, this is the 11th case of a renal angiomyolipoma extending into the vena cava.