National prospective study on the use of local haemostatic agents during partial nephrectomy.

OBJECTIVE: To assess the use of local haemostatic agents (HAs) in a prospective multicentre large series of partial nephrectomies (PNs). PATIENTS AND METHODS: Prospective National Observational Registry on the Practices of Haemostasis in Partial Nephrectomy (NEPHRON): the study was conducted in 54 French urological centres from 1 June to 31 December 2010. In all, 570 consecutive patients undergoing a PN were enrolled in this study in a prospective manner. The data was collected prospectively via an electronic case-report form: five different sheets were included for preoperative, perioperative, postoperative and follow-up data respectively. Information related to haemostasis was analysed. RESULTS: The median patient age was 60 years and the mean (range) tumour size was 3.68 (0.19-15) cm. An HA was primarily used in 71.4% of patients, with a statistically significant difference among surgical approaches (P = 0.024). In 91.8% of cases, a single use of a HA was sufficient for achieving haemostasis. The HA was used either alone (13.9%) or in association with sutures (80.3%). One or more additional haemostatic action(s) was needed in 12.3% of the cases. When comparing patients who received a HA with those who did not receive a HA, there was no statistical difference between the groups for tumour size (P = 0.542), collecting system drainage (P = 0.538), hospital stay (P = 0.508), operation time (P = 0.169), blood loss (P = 0.387) or transfusion rate (P = 0.713). CONCLUSION: HAs are widely used by urologists during PN. Progress is needed for standardising HA application, especially for the timing of application. For the time being, the role of the HA in nephron-sparing surgery is still to be evaluated.

Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma.

OBJECTIVE: Our objective was to evaluate the levels of miR-210 in tumor and serum samples of conventional renal cell cancer (cRCC) patients to explore whether circulating miR-210 in serum can be used as a biomarker for the detection of cRCC. METHODS: The paired samples from primary cRCC tumors and adjacent non-tumoral renal parenchyma were collected from 32 patients with cRCC. Serum samples were obtained from 68 patients with a cRCC before surgery, 10 samples after one week of surgery, and 42 healthy individuals were included in this study. Real-time PCR was used to measure the microRNA level. The expression of miRNAs was normalized using the dCT method. Expression levels of miR-210 were compared using the Mann-Whitney U test or Wilcoxon test. Diagnostic performance of serum miR-210 level was calculated by using the receiver operating characteristic (ROC) curve. RESULTS: The average miR-210 level was higher in primary cRCC tissues than in normal tissue (p=0.004). For serum samples, the average level of miR-210 was significantly higher in cRCC patients than in controls (p<0.001). The serum miR-210 level yielded an AUC (the areas under the ROC curve) of 0.874 with a sensitivity of 81.0% and a specificity of 79.4%. Furthermore, the average serum level of miR-210 was significantly decreased in the patients one week after the operation (p=0.001). CONCLUSION: Serum mi-210 may have a potential as a novel noninvasive biomarker for the detection of cRCC.

Renal cell carcinoma (RCC) arising in native kidneys of dialyzed and transplant patients: are they different entities?

UNLABELLED: What's known on the subject? and What does the study add? Patients with end-stage renal disease (ESRD) have an increased risk of developing RCC in their native kidneys. The prevalence of RCC is 3-4% in cases of ESRD in dialyzed and/or transplanted patients, which corresponds to a rate 100-times higher than that in the general population. This is the first study, to our knowledge, comparing the characteristics of kidney cancer in the ESRD population according to their dialysis or transplantation status at the time of diagnosis. The differences in stage and survival we observed may be due to differences in surveillance strategies between transplanted and not transplanted patients, nevertheless, the differences in pathological subtypes suggest they could also be due to differences in the tumorigenesis process. OBJECTIVE: • To compare clinical, pathological and outcome features of renal cell carcinomas (RCCs) arising in patients with chronic renal failure (CRF) with or without renal transplantation. PATIENTS AND METHODS: • In all, 24 French University Departments of Urology and Kidney Transplantation participated in this retrospective study comparing RCCs arising in patients with CRF according to their dialysis or transplantation status at the time of diagnosis. • Information about age, sex, symptoms, duration of CRF, mode and duration of dialysis, renal transplantation, tumour staging and grading, histological subtype and outcome were recorded in a unique database. • Qualitative and quantitative variables were compared by using chi-square and Student statistical analysis. Survival was assessed by Kaplan-Meier and Cox methods. RESULTS: • Data on 303 RCC cases diagnosed between 1985 and 2009 were identified in 206 men (76.3%) and 64 women (23.7%). • Transplanted and not transplanted patients accounted for 213 (70.3%) and 90 cases (29.7%), respectively. • In transplant recipients, RCC was diagnosed at a younger age [mean (sd) 53 (11) vs 61 (14) years, P < 0.001), the mean tumour size was smaller [3.4 (2.3) vs 4.2 (3.1) cm, P= 0.02), pT1a stage (75 vs 60%, P= 0.009) and papillary histological subtype (44 vs 22%, P < 0.001) were more frequent than in their dialysis-only counterparts. • Nodal (1 vs 6%, P= 0.03) and distant metastases rates (0 vs 5%, P < 0.001) were significantly increased in patients who had not had a transplant. However, Fürhman grading, symptoms, tumour multifocality or bilaterality, presence of acquired cystic kidney disease, were not significantly different between the groups. • Estimated 5-year survival rates were 97% and 77% for transplanted and not transplanted patients, respectively (P < 0.001). In univariate analysis, presence of symptoms (P= 0.008), poor performance status (P= 0.04), large tumour size, advanced TNM stage (P < 0.001), high Führman grade (P= 0.005) and absence of transplantation (P < 0.001) were all adverse prognostic factors. In multivariate analysis, only T stage remained an independent predictor for cancer-related death (P < 0.001). CONCLUSION: • RCC arising in native kidneys of transplant patients seems to exhibit many favourable clinical, pathological and outcome features compared with those diagnosed in dialysis-only patients. Further research is needed to determine whether it is due to particular molecular pathways or to biases in relation to mode of diagnosis.

Factors impacting survival in patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy.

INTRODUCTION: This study aims to assess the influence of different prognostic factors on survival of upper tract urothelial carcinoma (UTUC) managed by nephroureterectomy and to investigate whether these factors have an independent prognostic significance. MATERIALS AND METHODS: A retrospective review of institutional databases from two teaching hospitals identified 269 consecutive patients with UTUC managed with nephroureterctomy between 1985 and 2005. Mean follow up was 80.6 months (median 70.3 months). Follow up was completed until January 2009. Tumor location and other clinicopathological variables were analyzed regarding survival. Data accrued included age, gender, tumor characteristics (pT stage, grade, lymph node status), tumor location, use of chemotherapy and period of diagnosis. Tumor location was divided into two groups (renal pelvis and ureter) based on the location of the tumor. RESULTS: Five year and 10 year overall survival estimates for this cohort were 71.3% and 40.0% respectively. According to tumor location, survival was 73.6% and 47.0% for the renal pelvis versus 67.8% and 32.3% for the ureter, respectively (log rank test: p = 0.027). In multivariate analysis, among the clinicopathological variables, T stage was the most significant prognostic factor (p < 0.001). Nodal involvement (p = 0,005), high grade (p < 0.001), first period of diagnosis (p < 0.001) and ureteral tumor location (p = 0.003) were significantly associated with lower survival rates. Prognosis of UTUC improved over time: survival was significantly better during the last period of diagnosis (2001-2005) (p < 0.002). CONCLUSIONS: Tumor location and diagnostic period should be considered as an independent prognostic factor for upper tract transitional cell carcinoma.

Kidney Graft Urothelial Carcinoma: Results From a Multicentric Retrospective National Study.

OBJECTIVE: To calculate the incidence of renal graft urothelial carcinoma in renal transplant recipients in a national large retrospective cohort and to analyze circumstances of diagnosis, treatment and outcome. MATERIAL AND METHODS: We conducted a national retrospective, multicenter study. Thirty two transplant centers were asked to report its cases of kidney graft tumors and the number of kidney transplantations performed since the beginning of their transplantation activity. RESULTS: Between January 1988 and December 2018, 56,806 patients were transplanted in the 32 centers participating in this study. Among this cohort, 107 renal graft tumors (excluding lymphoma) were diagnosed among them 11 renal transplant recipients were diagnosed with an urothelial carcinoma in the kidney graft. The calculated incidence was 0.019%. The median patient age at the time of diagnosis was 56.7 years (49.8-60.9) and 51.4 years (47-55.7) at the time of transplantation. The median time between transplantation and diagnosis was 66.6 months (14.3-97). Before treatment, 3 patients had graft tumor biopsies revealing urothelial carcinomas, 3 patients had endoscopic retrograde uretero-pyelography showing lacunary images. Two patients had a diagnostic flexible ureteroscopy with biopsies. Total nephrectomy was performed in all cases. CONCLUSION: Even though occurring in the context of immune suppression, most of these tumors seemed to have a relatively good prognosis. With regards to functional outcomes histological diagnosis should always be sought for before radical treatment of these tumors. Treatment should be a transplant nephrectomy including all the ureter with a bladder cuff to ensure optimal carcinologic control.

Prostate cancer in renal transplant recipients.

BACKGROUND: We conducted a retrospective multi-centre study to determine the characteristics of prostate cancer in renal transplant recipients (RTR) and to analyse the relation with immunosuppressive maintenance therapies. METHODS: Patients from 19 French transplant centres diagnosed with prostate cancer at least 1 year after kidney transplantation were included in this study. Data regarding demographics, kidney transplantation, prostate cancer and immunosuppressive treatment were analysed. RESULTS: Sixty-two patients met the eligibility criteria for this study. Thirty-eight patients (61.3%) received calcineurin inhibitors (CNI) and azathioprine (AZA) with or without steroids, twenty received CNI with or without steroids (32.2%) and four received CNI and mycophenolate mofetil (6.5%). Patients with CNI and AZA immunosuppressive therapy presented more high-stage cancer (T3 and T4) when compared to patients receiving CNI alone (47.5% versus 15%, respectively, P = 0.03). A non-significant increase in lymph node invasion was found in patients receiving CNI and AZA compared to patients receiving CNI alone (21% versus 5%, P = 0.16). In the multivariate analysis, the immunosuppressive regimen with CNI and AZA was the only independent risk factor for locally advanced disease (P = 0.007). CONCLUSION: Our results showed that RTR are at risk for early occurrence and for locally advanced prostate cancer, especially when they received a CNI and AZA maintenance immunosuppressive therapy.

[Effects of tacrolimus vs cyclosporin-A on bone metabolism after kidney transplantation: a cross-sectional study in 28 patients]. / Comparaison des effets de la ciclosporine-A et du tacrolimus sur le métabolisme osseux des patients transplantés rénaux: une étude transversale chez 28 patients.

BACKGROUND: Controversy exists about the effects of calcineurin inhibitors on bone metabolism. We decided to compare the effects of CyA vs FK506 on bone metabolism of kidney recipients. PATIENTS AND METHODS: From 94 patients grafted at the University Hospital of Nice between 1996 and 1999 treated either by CyA (N=49) or by FK506 (N=45), we selected 14 pairs (18 M, 10F), matched for gender, BMI, time lapsed since transplantation and gonadal status in females. Patients with>1 transplantation or>1 rejection episode were excluded. Cumulative dose of steroids was recorded. Bone mineral density (BMD) was mesured at heel and forearm, as well as serum concentration of calcium, phosphate, parathyroid hormone (PTH), vitamin D metabolites, C-telopeptide (CTX), creatinine, estradiol as well as Bone Alkaline Phosphatase (BAP) activity. RESULTS: Despite the matching, time on hemodialysis was longer in FK506 group. Cumulative dose of steroids was similar between groups. There was no difference between groups in BMD and biochemical parameters except for estradiol serum levels which were dramatically lower in FK506 than in CsA (P=0,02) and for a trend (p=0,08) for BAP and CTX to be higher in FK506 than in CsA. CONCLUSIONS: BMD is not lower in FK506- than in CsA-treated patients although exposure to hyperparathyroidism was longer and estradiol levels were lower in the FK506 than in the CsA group. These data suggest that FK506 may have a favorable bone effect to compensate for these deleterious factors. This hypothesis remains to be tested in longitudinal studies.

Long-term results of transperitoneal laparoscopic fenestration in the treatment of simple renal cysts.

The aim of this paper was to assess long-term results of transperitoneal laparoscopic fenestration in the treatment of symptomatic simple renal cysts. Fifteen consecutive patients (7 men, 8 women), with a mean age of 51 years (range, 36-79 years), underwent transperitoneal fenestration of simple renal cysts (SRC) at our institution from 1994 to 2001. Data were collected by reviewing patients' clinical files, conducting telephone interviews regarding symptoms, and followup renal ultrasonography (US). There were 15 symptomatic cysts (10 parenchymal, 5 peripelvic) ranging in diameter from 3.5 to 20 cm (mean, 8 cm). All patients had lumbar pain and in four (26.6%) the collecting system was compressed by the cysts. Fenestration was carried out laparoscopically in all patients. There was no mortality and no postoperative complications were recorded. No malignancies were detected at final histopathology. Mean length of stay was 2.5 days. All patients were available for long-term followup. At a mean of 60 months (range, 22-93 months) from surgery, three patients (20%) complained of slight discomfort in the lumbar area not requiring any analgesic. No recurrence of the cysts was seen on US. Two asymptomatic patients (13.3%) developed additional cysts originating from sites different than the one operated on. Laparoscopic fenestration of SRC is safe and effective in the long term to relieve patients from symptoms.

[Efficacy of extracorporeal lithotripsy in acute renal colic: prospective study about 57 consecutive patients]. / Efficacité de la lithotritie extra-corporelle dans la phase aiguë de la colique néphrétique. Etude sur 57 patients consécutifs.

INTRODUCTION: This study was designed to evaluate the efficacy of ESWL in the management of acute renal colic. MATERIAL AND METHOD: From January 2003 to August 2003, 102 patients were hospitalised for renal colic. We treated 57 patients by ESWL using an EDAP LT 02 apparatus. Successful treatment was defined by stone fragmentation on the plain abdominal x-ray at 24 hours associated with resolution of pain after only one ESWL session. RESULTS: The overall complete success rate after only one ESWL session was 49%. Results according to site: UPJ stones: 46% of success, lumbar ureter: 14%, iliac ureter: 33%, pelvic ureter: 66%. According to size: < 5 mm: 57% of success, 6 to 10 mm: 70%, 11 to 15 mm: 27%, > 15 mm: 0%. No difference in success rate was observed according to the cumulative energy delivered or according to the duration of ESWL sessions. CONCLUSION: ESWL can be considered to be a first-line treatment for acute renal colic. Its best indications correspond to pelvic or UPJ stones less than 10 mm in diameter. We believe that it is useless to exceed a duration of 30 min per ESWL session at a frequency of to 2 Hz.

Comparison of UW and Celsior: long-term results in kidney transplantation.

BACKGROUND: The aim of this study was to compare 2 preservation solutions in kidney transplant recipients in the same center during the same period since initiation of the use of High Na+; low K+ solution (Celsior). MATERIAL AND METHODS: From January 1999 to April 2011, 610 consecutive renal transplantations were done in our department with deceased donor kidneys. Data were collected prospectively. Organ procurement was performed in our center for 305 kidneys. We washed and preserved 409 kidneys in UW, and 201 in Celsior solution. RESULTS: Donors criteria were worse in the Celsior group for age, male sex, creatinemia, and cold ischemia. Populations of recipients were comparable. There were no differences at 1 and 12 months in creatinine levels (p=0.9 and 0.8, respectively) and in number of delayed graft functions (DGF) (p=0.8 and relative risk =0.9) between groups. There were no differences in post-transplantation outcomes for all variables. At 5 years, graft survival was 90.4% for UW and 93.5% for Celsior (p=0.44). CONCLUSIONS: Our retrospective study did not succeed in demonstrating superiority of a High Na+; low K+ solution compared to a UW type reference solution. Celsior has the same effectiveness as UW during kidney cold storage.

Vasculitis of the bladder: An extremely rare case report.

INTRODUCTION: Isolated vasculitis of the bladder is extremely rare. The main causes of which are auto-immune diseases and occasionally infections. Corticosteroid therapy plays a central role in treatment in the majority of cases. PRESENTATION OF CASE: We report a case of gross hematuria associated with irritative low urinary tract symptoms (LUTS) and an increase of biological parameters of inflammation. Radiologic studies suspected a pelvic tumor process. We performed a cystoscopy with multiple biopsies. The pathological findings of the chips were in favor of a thrombotic nongranulomatous vasculitis of small and medium caliber. In view of these findings, all systemic diseases and inflammatory diseases such as cryoglobulinemia, the anti-phospholipid syndrome, Crohn's disease were eliminated. The symptoms regressed completely under antibiotics and anticoagulants. DISCUSSION: Our treatment options were based on the extent of the acute phase reaction and the pelvic venous thrombosis. A few similar cases have been reported in the literature, particularly a case of isolated necrotizing vasculitis of the bladder involving small vessels with a mild laboratory acute phase reaction which was treated with corticosteroids and cyclophosphamide. CONCLUSION: It is important to differentiate this rare pathological feature of the bladder from other bladder tumors as the treatment is medical rather than surgical.

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.

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.

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.

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.