Prognostic value of CXCR4 expression in patients with clear cell renal cell carcinoma.

INTRODUCTION: The expression of CXCR4 is implicated in the metastatic dissemination of different cancers. The information on its prognostic value has been very limited in clear cell renal cell carcinoma (ccRCC). Our objective was to explore the prognostic value of CXCR4 in ccRCC. MATERIALS AND METHODS: 104 patients with a ccRCC were studied. There were 69 men and 35 women with an average age of 64.5 years old (range: 34-86 years). The CXCR4 expression was evaluated by immunohistochemistry. The follow-up varied from 12 to 184 months with a mean of 79.5 months. Kaplan-Meier with a log rank test was performed to compare overall survival and cancer-specific survival after surgery. Univariate and multivariate analyses were performed according to the Cox regression model. RESULTS: CXCR4 expression was found in 68/104 (65.4%) of tumor samples. CXCR4 expression was located in the nucleus in 55/68 (80.8%) cases while cytoplasm or membrane location was found in 13/68 (19.2%) cases. High expression was found in 25/68 (36.8%) cases. During follow-up, 39 patients died, of which 26 died of cancer. Kaplan-Meier analysis revealed that a high expression of CXCR4 was associated with a reduced overall survival (p=0.017) and cancer-specific survival (p=0.022). Univariate analysis indicated that a high expression of CXCR4 was a significant factor for a poorer overall survival (p=0.020) and cancer-specific survival (p=0.027). By multivariate analysis, a high expression of CXCR4 appeared to be an independent factor of overall survival (p=0.024) and cancer-specific survival (p=0.028). CONCLUSION: This study suggested that a high CXCR4 expression was correlated with a worse outcome for ccRCC patients.

First clinical experience in urologic surgery with a novel robotic lightweight laparoscope holder.

PURPOSE: To report the feasibility and the safety of a surgeon-controlled robotic endoscope holder in laparoscopic surgery. PATIENTS AND METHODS: From March 2010 to September 2010, 20 patients were enrolled prospectively to undergo a laparoscopic procedure using an innovative robotic endoscope holder. Two surgeons performed six adrenalectomies, four sacrocolpopexies, five pyeloplasties, four radical prostatectomies, and one radical nephrectomy. Demographic data, overall setup time, operative time, number of assistants needed were reviewed. Surgeon satisfaction regarding the ergonomics was assessed using a 10-point scale. Postoperative clinical outcomes were reviewed at day 1 and 1 month postoperatively. RESULTS: The per-protocol analysis was performed on 17 patients for whom the robot was effectively used for surgery. Median age was 63 years; 10 (59%) patients were female. Median body mass index was 26.8. Surgical procedures were completed with the robot in 12 (71%) cases. Median number of surgical assistant was 0. Overall setup time with the robot was 19 minutes; operative time was 130 minutes during which the robot was used 71% of the time. Mean hospital stay was 6.94 ± 2.3 days. Median score regarding the easiness of use was 7. Median pain level was 1.5/10 at day 1 and 0 at 1 month postoperatively. Open conversion was needed in one (6%) case, and four minor complications occurred in two (12%) patients. CONCLUSION: This use of this novel robotic laparoscope holder is safe, feasible, and provides good comfort to the surgeon.

Prognostic value of serum CA9 in patients with metastatic clear cell renal cell carcinoma under targeted therapy.

AIM: Carbonic anhydrase 9 (CA9) has been found to be one of most powerful biomarkers for clear-cell renal cell carcinoma (RCC). The serum CA9 is detectable. The aim of this study was to evaluate the potential prognostic role of serum CA9 in patients with metastatic clear-cell RCC patients under targeted therapy. PATIENTS AND METHODS: Serum samples came from the randomized phase 2 TORAVA trial. All patients received a targeted therapy (arm A designed as experimental group: temsirolimus and bevacizumab combination; arm B: sunitinib; arm C: interferon-alfa and bevacizumab). Seventy cases of metastatic clear-cell RCC were analyzed. There were 49 males and 21 females. The age ranged from 33.5 to 79.1 years with a median of 61.2 years. Serum samples were collected before treatment. Serum CA9 was quantified by enzyme-linked immunosorbent assay (ELISA). The correlation of the serum CA9 levels with the clinical parameters, treatment response and overall survival was analyzed. Overall survival estimates were calculated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Serum concentrations of CA9 ranged between 0 and 897.3 pg/ml, with an average of 94.4±176.6 pg/ml. There was no association between serum CA9 and clinical parameters such as Eastern Cooperative Oncology Group (ECOG) Performance Status (p=0.367) or Motzer classification (p=0.431). The serum CA9 levels were lower in the response group (64.7±104.7 pg/ml) than the no-response group (108.2±203.8 pg/ml), but the difference was not statisticlly significant (p=0.366). For the patient group overall, the Kaplan-Meier survival curve showed that high serum CA9 levels were significantly associated with shorter overall survival (hazard ratio=2.65, 95% confidence interval=1.19-5.92, log-rank test p=0.0136). For the major group of patients treated with temsirolimus and bevacizumab, the Kaplan-Meier survival curve showed that high serum CA9 levels were significantly associated with shorter overall survival (p=0.0006). CONCLUSION: Serum CA9 levels may be of clinical interest to predict the outcome for patients under targeted therapy for metastatic clear-cell RCC. CA9 may be used to select patients with metastatic clear cell RCC for clinical trials.

Combination of core biopsy and fine-needle aspiration increases diagnostic rate for small solid renal tumors.

AIM: Our aim was to evaluate the performance of combination of fine-needle aspiration (FNA) and core biopsy (CB) as a method for the diagnosis of small solid renal tumors. PATIENTS AND METHODS: Ninety patients with a radiologically detected small solid renal tumor (≤ 4 cm) underwent a biopsy. Patient underwent FNA (FNA group, n=32) or CB (CB group, n=30) or combination of both FNA and CB (combination group, n=28). The diagnostic rate and accuracy of both techniques were assessed. RESULTS: The diagnostic rate of the combination group (92.9%) was superior to that of the FNA group (62.5%) and CB group (76.7%) (p=0.006, and p=0.147, respectively). In the combination group, 11 CBs were diagnostic with 13 nondiagnostic FNAs, while 4 FNAs were diagnostic with 6 nondiagnostic CBs. For tumors ≤ 2 cm, the combination of FNA and CB significantly increased the diagnostic rate, compared with FNA alone (p=0.033) and CB alone (p=0.044). The accuracy for FNA, CB and the combination of FNA and CB was 88%, 100% and 100%, respectively. CONCLUSION: The combination of FNA and CB increased the diagnostic rate of renal biopsy for the small solid renal tumors.

Transversal European survey on testosterone deficiency diagnosis.

BACKGROUND: Despite being one of the relevant public health threats among ageing men, testosterone deficiency syndrome (TDS) is under-recognized and under-diagnosed. OBJECTIVE: To assess current clinical practices of European physicians regarding diagnosis and management of TDS compared with current guidelines. METHODS: Postal survey conducted June-November 2008 in France, Germany, Italy and Spain among urologists, endocrinologists and general practitioners to collect information regarding knowledge of TDS. RESULTS: Among 801 respondents, the majority of endocrinologists and urologists had received training on TDS, either initially or as part of continuous medical education. TDS was recognized by 86.5% of physicians as a true clinical entity, and estimated the prevalence at 10-15% of the male population; 73.5% considered that symptoms and a low level of testosterone were required for diagnosis. Treatment preferences were quarterly intramuscular injections (26.3% of physicians), percutaneous gels (23.9%), matrix patch (21.2%), semi-monthly injections (15.4%) and oral therapy (13.4%). Adverse effects of testosterone replacement therapy, such as benign prostatic hyperplasia and prostate cancer, were a concern for physicians. CONCLUSIONS: TDS management appeared to be close to that recommended in international guidelines. Signs and symptoms of testosterone deficiency were fairly well known, but some diagnostic and treatment variations were observed.

CA9 as a molecular marker for differential diagnosis of cystic renal tumors.

OBJECTIVE: CA9 is proven to be a powerful marker for clear cell renal cell carcinoma. The studies on CA9 have been limited to solid renal cell carcinomas (RCC). We have conducted a study of CA9 expression in renal cystic tumors. The purpose of the present study was to extend the utility of CA9 for cystic renal tumors. MATERIALS AND METHODS: Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to detect CA9 expression in cystic renal tumors. Forty-three cystic renal tumors (22 benign and 21 malignant) were included for the immunohistochemical staining. Thirty-six patients with a cystic renal mass (20 malignant and 16 benign cystic tumors) were studied to measure CA9 level in the fluid by ELISA. Sixteen cysts (9 malignant and 7 benign cysts) were subjected both to immunohistochemistry and CA9 measurement in the fluid. RESULTS: Using immunohistochemical staining, all the benign cystic renal tumors including the 18 simple cyst and 4 benign multilocular cystic nephromas did not express CA9. All 13 cystic clear cell RCC were scored as strong staining for CA9. For 8 multilocular clear cell RCC, 7 were scored as strong staining for CA9 and the other one was negative. There was a significant difference in positive percentage (P < 0.001) between the 2 groups of malignant and benign cysts. For the 16 benign cysts, the mean concentration of CA9 in the fluid of cyst was 162 ± 133 pg/ml (median: 0 pg/ml; range: 0-2140 pg/ml). For the 20 malignant renal cystic tumors, the mean concentration of CA9 in the fluid of cyst was 2043 ± 62 pg/ml (median: 2,140 pg/ml; range: 1,112-2,140 pg/ml). There was a significant difference in mean concentration of CA9 between the two groups of malignant and benign cysts (P < 0.001). The presence or absence of CA9 expression measured by immunohistochemistry and ELISA test was concordant in 14 out of 16 cases (88%). CONCLUSIONS: Malignant cystic renal tumors expressed strongly CA9 while the benign renal cysts did not express CA9. CA9 can be detected in the fluid of malignant cystic renal tumors. CA9 is a promising molecular marker to differentiate the malignant cystic renal tumors from the benign cysts.

Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE: Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS: Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION: All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS: Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS: The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS: RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.

Carbonic anhydrase 9 in clear cell renal cell carcinoma: a marker for diagnosis, prognosis and treatment.

Carbonic anhydrase 9 (CA9) is a transmembrane member of the carbonic anhydrase family. It catalyses the reversible hydration of carbon dioxide into bicarbonate and a proton, thus enabling tumour cells to maintain a neutral pH despite an acidic microenvironment. CA9 is not expressed in healthy renal tissue but is expressed in most clear cell renal cell carcinomas (CCRCC) through HIF-1α accumulation driven by hypoxia and inactivation of the VHL gene. CA9 expression can be detected in the tumour by immunohistochemistry (IHC), in blood and tissue by ELISA assay and RT-PCR. It has a 100% diagnostic specificity in solid renal tumours, while ELISA assays on aspiration fluids may help in atypical cysts. Blood-based assays, ELISA for CA9 antigen and RT-PCR for CA9 mRNA are promising for the prognosis and follow-up of localised CCRCC. In metastatic disease, high CA9 expression by IHC was reported to be a powerful prognostic marker with better survival and sensitivity to IL-2, but this is still debated. Almost no data are currently available on the association of CA9 expression and outcome to targeted drugs. The prognostic value of CA9 in CCRCC could be explained by the frequent VHL gene inactivation driving an early activation of the HIF pathway. The poorer prognosis associated with low CA9 expressing tumours could be due to the simultaneous overexpression of EGFR contributing to the activation of AkT and mTOR pathways. Targeting CA9 by inhibitors, radioimmunotherapy, monoclonal antibodies or vaccination is promising and offers new avenues for clinical research.

Predictive factors for ipsilateral recurrence after nephron-sparing surgery in renal cell carcinoma.

BACKGROUND: Ipsilateral recurrence after nephron-sparing surgery (NSS) is rare, and little is known about its specific determinants. OBJECTIVE: To determine clinical or pathologic features associated with ipsilateral recurrence after NSS performed for renal cell carcinoma (RCC). DESIGN, SETTING, AND PARTICIPANTS: We analysed 809 NSS procedures performed at eight academic institutions for sporadic RCCs retrospectively. MEASUREMENTS: Age, gender, indication, tumour bilaterality, tumour size, tumour location, TNM stage, Fuhrman grade, histologic subtype, and presence of positive surgical margins (PSMs) were assessed as predictors for recurrence in univariate and multivariate analysis by using a Cox proportional hazards regression model. RESULTS AND LIMITATIONS: Among 809 NSS procedures with a median follow-up of 27 (1-252) mo, 26 ipsilateral recurrences (3.2%) occurred at a median time of 27 (14.5-38.2) mo. In univariate analysis, the following variables were significantly associated with recurrence: pT3a stage (p=0.0489), imperative indication (p<0.01), tumour bilaterality (p<0.01), tumour size >4cm (p<0.01), Fuhrman grade III or IV (p=0.0185), and PSM (p<0.01). In multivariate analysis, tumour bilaterality, tumour size >4cm, and presence of PSM remained independent predictive factors for RCC ipsilateral recurrence. Hazard ratios (HR) were 6.31, 4.57, and 11.5 for tumour bilaterality, tumour size >4cm, and PSM status, respectively. The main limitations of this study included its retrospective nature and a short follow-up. CONCLUSIONS: RCC ipsilateral recurrence risk after NSS is significantly associated with tumour size >4cm, tumour bilaterality (synchronous or asynchronous), and PSM. Careful follow-up should be advised in patients presenting with such characteristics.

Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery.

BACKGROUND: The occurrence of positive surgical margins (PSMs) after partial nephrectomy (PN) is rare, and little is known about their natural history. OBJECTIVE: To identify predictive factors of cancer recurrence and related death in patients having a PSM following PN. DESIGN, SETTING, AND PARTICIPANTS: Some 111 patients with a PSM were identified from a multicentre retrospective survey and were compared with 664 negative surgical margin (NSM) patients. A second cohort of NSM patients was created by matching NSM to PSM for indication, tumour size, and tumour grade. MEASUREMENTS: PSM and NSM patients were compared using student t tests and chi-square tests on independent samples. A Cox proportional hazards regression model was used to test the independent effects of clinical and pathologic variables on survival. RESULTS AND LIMITATIONS: Mean age at diagnosis was 61+/-12.5 yr. Mean tumour size was 3.5+/-2 cm. Imperative indications accounted for 39% (43 of 111) of the cases. Some 18 patients (16%) underwent a second surgery (partial or total nephrectomy). With a mean follow-up of 37 mo, 11 patients (10%) had recurrences and 12 patients (11%) died, including 6 patients (5.4%) who died of cancer progression. Some 91% (10 of 11) of the patients who had recurrences and 83% of the patients (10 of 12) who died belonged to the group with imperative surgical indications. Rates of recurrence-free survival, of cancer-specific survival, and of overall survival were the same among NSM patients and PSM patients. The multivariable Cox model showed that the two variables that could predict recurrence were the indication (p=0.017) and tumour location (p=0.02). No other variable, including PSM status, had any effect on recurrence. None of the studied parameters had any effect on the rate of cancer-specific survival. CONCLUSIONS: PSM status occurs more frequently in cases in which surgery is imperative and is associated with an increased risk of recurrence, but PSM status does not appear to influence cancer-specific survival. Additional follow-up is needed.

Tissue compartment analysis for biomarker discovery by gene expression profiling.

BACKGROUND: Although high throughput technologies for gene profiling are reliable tools, sample/tissue heterogeneity limits their outcomes when applied to identify molecular markers. Indeed, inter-sample differences in cell composition contribute to scatter the data, preventing detection of small but relevant changes in gene expression level. To date, attempts to circumvent this difficulty were based on isolation of the different cell structures constituting biological samples. As an alternate approach, we developed a tissue compartment analysis (TCA) method to assess the cell composition of tissue samples, and applied it to standardize data and to identify biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: TCA is based on the comparison of mRNA expression levels of specific markers of the different constitutive structures in pure isolated structures, on the one hand, and in the whole sample on the other. TCA method was here developed with human kidney samples, as an example of highly heterogeneous organ. It was validated by comparison of the data with those obtained by histo-morphometry. TCA demonstrated the extreme variety of composition of kidney samples, with abundance of specific structures varying from 5 to 95% of the whole sample. TCA permitted to accurately standardize gene expression level amongst >100 kidney biopsies, and to identify otherwise imperceptible molecular disease markers. CONCLUSIONS/SIGNIFICANCE: Because TCA does not require specific preparation of sample, it can be applied to all existing tissue or cDNA libraries or to published data sets, inasmuch specific operational compartments markers are available. In human, where the small size of tissue samples collected in clinical practice accounts for high structural diversity, TCA is well suited for the identification of molecular markers of diseases, and the follow up of identified markers in single patients for diagnosis/prognosis and evaluation of therapy efficiency. In laboratory animals, TCA will interestingly be applied to central nervous system where tissue heterogeneity is a limiting factor.

Conditional survival predictions after nephrectomy for renal cell carcinoma.

PURPOSE: Conditional survival implies that on average long-term cancer survivors have a better prognosis than do newly diagnosed individuals. We explored the effect of conditional survival in renal cell carcinoma. MATERIALS AND METHODS: We studied 3,560 patients with renal cell carcinoma of all stages treated with nephrectomy. We applied conditional survival methodology to a previously reported posttreatment nomogram predicting survival after nephrectomy for patients with renal cell carcinoma stage I to IV. We used the same predictor variables that were integrated in the original multivariable Cox regression models, namely TNM stage, Fuhrman grade, tumor size and symptom classification. To validate the conditional survival nomogram we used an independent cohort of 3,560 patients from 15 institutions. RESULTS: The 5-year survival of patients immediately after nephrectomy was 74.2%, which increased to 80.4%, 85.1%, 90.6% and 89.6% at 1, 2, 5 and 10 years after nephrectomy, respectively. The predicted probabilities varied by as much as 50% when, for example, predictions of renal cell carcinoma specific mortality at 10 years were made after nephrectomy vs 5 years later. Within the external validation cohort the accuracy of the conditional nomogram was 89.5%, 90.5%, 88.5% and 86.7% at 1, 2, 5 and 10 years after nephrectomy. CONCLUSIONS: We developed (2,530) and externally validated (3,560) a conditional nomogram for predicting renal cell carcinoma specific mortality that allows consideration of the length of survivorship. Our tool provides the most realistic prognosis estimates with high accuracy.

Can renal mass biopsy assessment of tumor grade be safely substituted for by a predictive model?

PURPOSE: Fuhrman grade represents a key determinant of the natural history of small renal masses that represent renal cell carcinoma. We tested whether renal mass biopsy prediction of Fuhrman grade in the nephrectomy specimen could be safely substituted for by an accurate statistical model. To date the best available model has shown poor accuracy (55.6%), which is close to flipping a coin (50%) and clearly inadequate for use in clinical practice. MATERIALS AND METHODS: We identified 1,139 patients with T1aN0M0 renal cell carcinoma treated with partial or radical nephrectomy at 11 participating institutions from 1989 to 2004. This cohort was used in univariate and multivariate logistic regression models predicting high Fuhrman grade (III-IV) at nephrectomy. Predictors included age at diagnosis, gender, tumor size and symptom classification. Multivariate logistic regression coefficients were used to generate a nomogram. RESULTS: The rate of Fuhrman grade III-IV in patients with T1aN0M0 renal cell carcinoma was 12.3%. Stratifying patients with Fuhrman grade III-IV by age, gender, histological subtypes and sample size failed to reveal statistically significant differences. On univariate analysis predicting Fuhrman grade III-IV at nephrectomy only tumor size was a statistically significant predictor (p = 0.05). The most accurate multivariate nomogram for Fuhrman grade III-IV prediction was 58.3% (95% CI 57.8-58.9) accurate. Of all tested predictors only tumor size achieved independent predictor status (p = 0.009). CONCLUSIONS: Our analysis derived in European patients shows that statistical models cannot safely replace renal mass biopsy based prediction of Fuhrman grade III-IV at nephrectomy. Our findings corroborate a report from the United States in which a similar model had 55.6% accuracy. Jointly the studies indicate that statistical models are unreliable and cannot safely be substituted for renal mass biopsy in North American or European patients.

Urinary collecting system invasion is an independent prognostic factor of organ confined renal cell carcinoma.

PURPOSE: We evaluated urinary collecting system invasion as a prognostic parameter of renal cell carcinoma. MATERIALS AND METHODS: A total of 1,124 patients who underwent nephrectomy for a renal tumor at 5 European centers were included in this retrospective study. Several variables were analyzed including urinary collecting system invasion, age, sex, TNM stage, Fuhrman grade, histological subtype, Eastern Cooperative Oncology Group performance status and cancer specific survival. RESULTS: There were 771 males (68.6%) and 353 females (31.4%) in this study, and median age was 61 years (range 14 to 88). Median tumor size was 6 cm (range 1 to 24). Tumors were organ confined and Fuhrman grade was recorded as 1 or 2 in 67.1% and 62.3% of cases, respectively. Symptoms were present at diagnosis, and Eastern Cooperative Oncology Group performance status was 1 or more in 50.3% and 16.1% of the cases, respectively. Median followup was 43 months (range 1 to 299). At the end of followup 246 patients (21.9%) died of cancer. In 132 cases (11.7%) urinary collecting system invasion was noted. Urinary collecting system invasion was associated with symptoms, TNM stage, Fuhrman grade, tumor size (p <0.001) and Eastern Cooperative Oncology Group performance status (p = 0.003), but not with histological subtype (p = 0.7). On univariate analysis TNM stage, Fuhrman grade, symptoms, Eastern Cooperative Oncology Group performance status, tumor size and urinary collecting system invasion (p = 0.0001) were significant predictors of cancer specific survival. Urinary collecting system invasion was an independent prognostic parameter only in the setting of pT1-T2 tumors. When the urinary collecting system was invaded the 5 and 10-year probabilities of survival were 43% and 41%, respectively. CONCLUSIONS: Urinary collecting system invasion appears to be an independent prognostic parameter of organ confined renal cell carcinoma. Our data support the need to integrate this parameter in further TNM revisions.

Baseline renal function, ischaemia time and blood loss predict the rate of renal failure after partial nephrectomy.

OBJECTIVE: To identify independent predictors of renal failure after partial nephrectomy (PN) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Data were available for 166 patients with pathological T1-3 N0M0 RCC treated with PN. Renal failure after PN was defined as a decrease in glomerular filtration rate (GFR) of >25% (RIFLE criteria). The GFR before and after PN was estimated using the Modification of Diet in Renal Disease study group equation. Univariable and multivariable logistic regression models were used to assess a decrease of >25% in GFR from the preoperative level. Candidate predictor variables were age, gender, PN indication (absolute vs relative), preoperative GFR, tumour size, perioperative blood loss, surgery duration and clamping time. RESULTS: After PN, 22 (13.3%) patients had a decrease in GFR of >25%. The perioperative blood loss (P = 0.02), clamping time (P = 0.04) and preoperative GFR (P = 0.002) were independent predictors of a decrease in GFR of >25%. CONCLUSIONS: We identified two important potentially modifiable variables that should be considered in the planning of PN, i.e. the clamping time and blood loss. It is possible that selective referral to experienced surgeons who can perform PN within short surgical and clamping times, and with minimal blood loss, could minimize the rate of renal failure, especially in patients with an underlying renal function impairment.

CA9 level in renal cyst fluid: a possible molecular diagnosis of malignant tumours.

AIMS: The preoperative differentiation of malignant renal cystic tumours from benign lesions is critical, and it remains a common diagnostic problem. The aim was to examine if the Carbonic anhydrase 9 (CA9) level in cyst fluid can provide a molecular diagnosis of malignant cyst. METHODS AND RESULTS: Twenty-eight patients with a cystic renal mass were included. Fine-needle aspiration was performed to obtain the fluid. Postoperative pathology confirmed that there were 16 cystic renal cell carcinomas. Twelve benign cystic tumours were used as controls. One hundred microlitres of supernatant of cyst fluid was used to measure the CA9 protein level, which was measured by an enzyme-linked immunosorbent assay technique. CA9 was strongly detected and considered as positive in the cyst fluid of all 16 cystic malignant tumours (>1000 pg/ml), whereas its expression was negative in 11/12 benign cystic tumours (<300 pg/ml). The difference in percentages of positive CA9 between malignant and benign renal cystic tumours was significant (P < 0.001). CONCLUSION: The fluid of malignant cystic renal tumours contains a high level of CA9 protein. The measurement of CA9 level in cyst fluid may be used as a molecular diagnosis for differentiation between malignant and benign renal cystic masses.

Partial versus radical nephrectomy in patients with adverse clinical or pathologic characteristics.

OBJECTIVES: To assess cancer-specific survival of partial nephrectomy (PN) patients with >or= 7-cm lesions or unfavorable pathology (stage T3a or Fuhrman grades III-IV). MATERIAL AND METHODS: At 13 participation centers, 4072 partial or radical nephrectomies (RN) were performed for RCC between 1984 and 2001. Of all procedures, 925 (22.7%) were for tumors > 7 cm, 973 (23.9%) had Fuhrman grades III or IV, and 861 (21.1%) had stage pT3a. None had nodal or distant metastases. Matched (age, gender, tumor size, T stage, histologic subtype, and Fuhrman grade [FG]) survival analyses addressed the effect of nephrectomy type (partial vs radical) on cancer-specific mortality. RESULTS: Partial nephrectomy for tumors > 7 cm was associated with higher mortality than RN (HR = 5.3; P = .025). No significant cancer-specific survival differences were recorded after PN for FG III-IV (HR = 0.7, P = .5) or for pT3a lesions (HR = 2.5, P = .9). CONCLUSIONS: Partial nephrectomy may undermine cancer control in patients with tumors > 7 cm. Conversely, after PN, the same cancer control rates as after RN may be expected in patients with Fuhrman grades III-IV or with pT3a histology.

Stage-specific effect of nodal metastases on survival in patients with non-metastatic renal cell carcinoma.

OBJECTIVE: To quantify the survival disadvantage related to the presence of exclusive nodal metastases (eNM) in patients with otherwise non-metastatic (M0) renal cell carcinoma (RCC). PATIENTS AND METHODS: Data were retrieved from 12 institutional databases and yielded 3507 patients with T1-3N1-2M0 RCC treated with partial or radical nephrectomy. Cox regression analyses relied on T stage, Fuhrman grade and presence of eNM. Data were analysed using univariable, multivariable and stratified analyses. RESULTS: Overall 165 (4.7%) patients had eNM; of 2023 patients of stage T1, 23 (1.1%) had eNM, vs 20 of 448 (4.5%) for T2 and 122 of 993 (12.3%) for T3. In univariable analyses the presence of eNM increased the rate of cancer specific mortality (CSM) by 7.1 times. After adjusting for T stage and Fuhrman grade, in all patients eNM increased the rate of CSM by 3.2 times. In stratified analyses adjusted for Fuhrman grade, the increase in CSM related to the presence of eNM was 28.9, 4.3 and 2.5 times (all P < 0.001) for stages T1, T2 and T3, respectively. CONCLUSIONS: From the prognostic perspective, staging lymphadenectomy appears of most value in patients with T1-2 RCC, but the low prevalence of eNM questions the practical applicability of nodal staging in those patients. Conversely, in patients with T3 RCC, the prevalence and the prognostic impact of eNM might make a staging lymphadenectomy worthwhile.

A preoperative prognostic model for patients treated with nephrectomy for renal cell carcinoma.

BACKGROUND: Currently two pretreatment prognostic models with limited accuracy (65-67%) can be used to predict survival in patients with localized renal cell carcinoma (RCC). OBJECTIVE: We set out to develop a more accurate pretreatment model for predicting RCC-specific mortality after nephrectomy for all stages of RCC. DESIGN, SETTING, AND PARTICIPANTS: The data originated from a series of prospectively recorded contemporary cases of patients treated with radical or partial nephrectomy between 1984 and 2006. Model development was performed using data from 2474 patients from five centers and external validation was performed using data from 1972 patients from seven centers. MEASUREMENTS: The probability of RCC-specific mortality was modeled using Cox regression. The significance of the predictors was confirmed using competing risks analyses, which account for mortality from other causes. RESULTS AND LIMITATIONS: Median follow-up in patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the development and validation cohorts, respectively. The freedom from cancer-specific mortality rates in the nomogram development cohort were 75.4% at 5 yr after nephrectomy and 68.3% at 10 yr after nephrectomy. All variables except gender achieved independent predictor status. In the external validation cohort the nomogram predictions were 88.1% accurate at 1 yr, 86.8% accurate at 2 yr, 86.8% accurate at 5 yr, and 84.2% accurate at 10 yr. CONCLUSIONS: Our model substantially exceeds the accuracy of the existing pretreatment models. Consequently, the proposed nomogram-based predictions may be used as benchmark data for pretreatment decision making in patients with various stages of RCC.

Prognostic value of renal vein and inferior vena cava involvement in renal cell carcinoma.

BACKGROUND: The prognostic significance of venous tumor thrombus extension in patients with renal cell carcinoma (RCC) is a matter of many controversies in the current literature. OBJECTIVE: To evaluate the prognostic role of inferior vena cava (IVC) involvement in a large series of pT3b and pT3c RCCs. DESIGN, SETTING, AND PARTICIPANTS: A total of 1192 patients from 13 European institutions underwent a radical nephrectomy for pT3b and pT3c RCC between 1982 and 2003. The patients were evaluated in a retrospective manner. Age, gender, clinical symptoms, Eastern Cooperative Oncology Group (ECOG) performance status, TNM stage, tumor size, adrenal invasion, perinephric fat invasion, histological type, and Fuhrman grade were reviewed. The log-rank and Cox uni- and multivariate regression analyses were used to evaluate prognostic factors for overall survival. MEASUREMENTS: Overall survival and prognostic factors for overall survival in patients with RCC extending to the renal vein (RV) or to the IVC. RESULTS AND LIMITATIONS: The median follow-up was 61.4 mo (56.3-66.5 mo). The mean age was 63.2 yr. The mean tumor size was 8.9 cm. Group 1 (Gr 1) included 933 patients with a renal vein tumor thrombus (78.3%), Group 2 (Gr 2) included 196 patients with a subdiaphragmatic IVC tumor thrombus (16.4%), and Group 3 (Gr 3) included 63 patients with a supradiaphragmatic IVC tumor thrombus (5.3%). Median survival was 52 mo for Gr 1, 25.8 mo for Gr 2, and 18 mo for Gr 3. In univariate analysis, Gr 1 had a significantly better overall survival than Gr 2 (p<0.001) and Gr 3 (p