Nephron-sparing surgery for renal tumors measuring more than 7 cm: morbidity, and functional and oncological outcomes.

BACKGROUND: The purpose of this study was to evaluate morbidity, functional, and oncological outcomes after NSS in renal tumors > 7 cm. MATERIALS AND METHODS: We retrospectively analyzed data from 168 patients with tumors > 7 cm who were treated using NSS between 1998 and 2012. RESULTS: Imperative and elective indications accounted for 76 (45.2%) and 92 (54.8%) patients, respectively. Major perioperative complications and renal function deterioration occurred in 33 (19.6%) and 51 patients (30.4%), respectively. In multivariate analysis, age older than 60 years (P = .001; hazard ratio [HR], 5) and tumor malignancy (P = .014; HR, 6.7) were prognostic factors for renal function deterioration whereas imperative indication was a risk factor for major postoperative complications (P = .0019; HR, 2.7). In 126 (75%) patients with malignant tumors, after a median follow-up of 30 months (range, 1-254 months), 25 patients (20.2%) died. In multivariate analysis, imperative indication (P = .023; HR, 4.2), positive surgical margin (P = .021; HR, 3.3), and Fuhrman grade > II (P = .013; HR, 3.7) were prognostic indicators for cancer-free survival (CFS). Imperative indication (P = .04; HR, 8.5) and Fuhrman grade > II (P = .04; HR, 3.9) were predictive factors of cancer-specific survival (CSS). In case of elective indication, positive surgical margin, local recurrence, and cancer-related death occurred in 4 (7.6%), 1 (1.1%), and 1 (1.1%) cases, respectively. For elective indication, 5-year estimates of CFS, CSS, and overall survival rates were: 85.7%, 98%, and 93.9%, respectively. CONCLUSION: In this selected population, imperative vs. elective indication status seems to play a critical role in oncologic outcomes. Oncologic results for elective indications are close to those reported with radical nephrectomy.

Treatment of neurogenic stress urinary incontinence using an adjustable continence device: 4-year followup.

PURPOSE: We evaluated the long-term safety and efficacy of an adjustable continence device (ACT® or ProACT™) in male and female patients with neurogenic stress urinary incontinence. MATERIALS AND METHODS: Data on patients consecutively treated with implantation of an adjustable continence device due to neurogenic stress urinary incontinence were reviewed from the start of our experience to the current 4-year followup. RESULTS: We reviewed data on 13 male and 24 female patients with neurogenic stress urinary incontinence due to different forms of pelvic nerve or spinal cord lesions. Mean ± SD age at implantation was 46.2 ± 17.4 years. Of the patients 92% performed clean intermittent self-catheterization. The device was implanted bilaterally using general and local anesthesia in 16.2% and 83.8% of cases, respectively. From before implantation to 48-month followup the mean number of urinary incontinence episodes decreased from 6.1 ± 2.4 to 2.8 ± 3.1 and the mean number of pads used per 24 hours decreased from 4.2 ± 2.7 to 2.2 ± 2.2. Of the patients 54.5% indicated more than 50% improvement of stress urinary incontinence symptoms after 48 months, of whom 38.9% indicated complete continence. Adverse events included erosion/migration, device infection or failure, implantation site pain, bladder stone formation and difficult clean intermittent self-catheterization. CONCLUSIONS: Implantation of the ProACT/ACT device in patients with neurogenic stress urinary incontinence is minimally invasive and safe. It can significantly improve neurogenic stress urinary incontinence in the long term. Thus, it might be a reasonable option for patients who are not willing, not suitable or not yet ready for more invasive surgery, such as artificial urinary sphincter or fascial suspension sling placement.

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.

Identification of a novel biomarker signature associated with risk for bone metastasis in patients with renal cell carcinoma.

When renal cell carcinoma (RCC) metastasizes to bone (a frequent site of systemic spread of this cancer) it becomes highly resistant to radiation therapy and chemotherapy. A better understanding of the biology of bone metastasis in RCC may permit to identify biomarkers for early detection of subclinical disease and better stratification of patients prior to treatment. We therefore investigated in this study, using a multiplex real-time RT-PCR assay, the expression of a panel of 16 biomarkers involved in angiogenesis and tumor invasion; the panel was applied to primary tumors and normal tissues obtained from clear-cell RCC patients with and without bone metastases. We identified a novel combination of biomarkers associated with the risk of bone metastasis. Among the transcripts of the genes studied, VEGFR-1, VEGFR-2, HIF-1alpha, uPA , and PA I-1 overexpression in tumor tissues was significantly associated with the presence of bone metastasis (p=0.02, p=0.02, p<0.0001, p=0.04, and p=0.03, respectively). No differences were found in the expression of these transcripts in the corresponding normal tissues. This preliminary study provides a promising tool that may help in the management of RCC patients with bone metastasis. Indeed, these predictive markers could be useful to identify subclinical disease, improve staging, and guide treatment decisions.

Soluble isoforms of vascular endothelial growth factor are predictors of response to sunitinib in metastatic renal cell carcinomas.

BACKGROUND: Angiogenesis is the target of several agents in the treatment of malignancies, including renal cell carcinoma (RCC). There is a real need for surrogate biomarkers that can predict selection of patients who may benefit from antiangiogenic therapies, prediction of disease outcome and which may improve the knowledge regarding mechanism of action of these treatments. Tyrosine kinase inhibitors (TKI) have proven efficacy in metastatic RCC (mRCC). However, the molecular mechanisms underlying the clinical response to these drugs remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: The present study aimed to identify molecular biomarkers associated with the response to sunitinib, a Tyrosine kinase inhibitor. To evaluate this relationship, primary tumors from 23 metastatic RCC patients treated by sunitinib were analyzed for a panel of 16 biomarkers involved in tumor pathways targeted by sunitinib, using real-time quantitative reverse-transcriptase PCR. Nine of the 23 patients (39%) responded to sunitinib. Among transcripts analyzed, only the levels of vascular endothelial growth factor (VEGF) soluble isoforms (VEGF(121) and VEGF(165)) were associated with the response to sunitinib (P = 0.04 for both). Furthermore, the ratio of VEGF soluble isoforms (VEGF(121)/VEGF(165)) was significantly associated with prognosis (P = 0.02). CONCLUSIONS: This preliminary study provides a promising tool that might help in the management of metastatic RCC, and could be extended to other tumors treated by TKI.

Extended biopsy protocol decreases prostate cancer incidence and risk of aggressive disease on repeated biopsies compared with initial standard procedure.

OBJECTIVES: To compare prostate cancer detection rates in repeated biopsy depending on the number of cores at initial biopsy. METHODS: Out of 3,000 consecutive patients, 534 underwent repeat extended biopsies. At first procedure, 345 patients had undergone standard biopsies (10-15 cores; SBx) whereas 189 other patients had already had a 21-core extended protocol (ExtBx). Clinicobiological and pathological parameters were compared between 2 groups. RESULTS: The prostate cancer detection rate was significantly higher in the SBx group (37%) compared with the ExtBx group (16.8%, p < 0.001). Mean PSA level, mean percent free PSA and mean prostate volume were equivalent in both groups. Thirty-eight percent of cancers detected in the SBx group were graded Gleason 7 or more, compared with 19.3% in the ExtBx group (p = 0.018). Mean percent of core invasion was 25.3% in the SBx group compared to 15.9% in the ExtBx group (p = 0.004). CONCLUSIONS: A full evaluation of all prostate zones using ExtBx seems to be necessary to decrease the risk of undetected prostate cancer on repeated biopsies. For patients who had at their first biopsy an ExtBx, the risk of prostate cancer on the repeated biopsies and the risk of aggressive cancer were lower compared to standard biopsies.

The prostate cancer gene 3 (PCA3) urine test in men with previous negative biopsies: does free-to-total prostate-specific antigen ratio influence the performance of the PCA3 score in predicting positive biopsies?

OBJECTIVE: to determine the performance characteristics of the prostate cancer gene 3 (PCA3) score on the outcome of biopsy relative to different ranges of free-to-total prostate-specific antigen (PSA) ratio (f/tPSA) in men with a previous negative biopsy and a PSA level of 2.5-10 ng/mL, as urine tests like PCA3 are currently under investigation in order to improve prostate cancer diagnosis and to decrease the rate of unnecessary rebiopsies. PATIENTS AND METHODS: data from the previous prospective European multicentre study were reviewed. Only patients with a PSA level of 2.5-10 ng/mL were included in the present study. In all, 301 patients had complete data. The diagnostic accuracy of the PCA3 score for predicting a positive biopsy outcome was studied using sensitivity, specificity, negative and positive predictive values. The PCA3 performance was evaluated relative to three different subgroups of f/tPSA, as follows: >20% (group 1), 10-20% (group 2) and <10% (group 3). RESULTS: the prostate cancer detection rates were 18.8%, 23.9% and 34.8% in groups 1, 2 and 3, respectively. The area under the receiver operating characteristic curve of the PCA3 score, total PSA and f/tPSA was 0.688, 0.553 and 0.571, respectively. The percentage of men with positive biopsies was 30.6%, 37.0% and 44.4% in those with a PCA3 score of >30, vs 10.3%, 15.5% and 28.6% when the PCA3 score was <30, in groups 1, 2 and 3, respectively. The difference was significant only in groups 1 and 2. In men with a f/tPSA of ≤ 10% the difference in detection rates relative to the PCA3 score was not statistically significant regardless of which PCA3 threshold was used. A high PCA3 score was significantly associated with age, clinical T2 stage and positive biopsy (P < 0.001, 0.013 and <0.001, respectively). In bivariate analysis accounting for the PCA3 score and the f/tPSA, a PCA3 score of >30 was a significant independent predictor of positive biopsies (odds ratio 3.01; 95% confidence interval 1.74-5.23; P < 0.001). CONCLUSIONS: PCA3 remained a better predictor of prostate cancer than f/tPSA. In men with a f/tPSA of >10%, the use of the PCA3 score was highly correlated with the risk of having cancer on re-biopsy, and could prevent unnecessary prostate biopsies if the value is low.

Targeted therapies in metastatic renal cancer in 2009.

The development of targeted molecules in renal carcinogenesis changed the therapeutic approaches of treatment for metastatic clear cell renal cell carcinoma. Four available drugs are currently available, i.e. bevacizumab, sunitinib, sorafenib and temsirolimus, but other molecules and combined therapy are under investigation. In this review we assess published reports of these targeted therapies and discuss the novel promising molecules targeting vascular endothelial growth factor and its receptors, the mammalian target of rapamycin and epithelial growth factor cascade.

Prostate cancer detection rate in patients with repeated extended 21-sample needle biopsy.

BACKGROUND: Prevalence of prostate cancer (PCa) after a negative first extended prostate needle biopsy protocol is unknown. OBJECTIVE: To evaluate the prevalence of significant PCa in patients who have had a negative first extended prostate biopsy protocol. DESIGN, SETTING, AND PARTICIPANTS: Between March 2001 and May 2007, 2500 consecutive patients underwent an extended protocol of 21 biopsies. Of 953 patients who had a negative first extended prostate biopsy procedure, 231 patients underwent a second or more set of 21-core biopsies. Indications for repeated biopsies were persistently elevated prostate-specific antigen (PSA), PSA increase during the follow-up, or prior prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation (ASAP). INTERVENTION: All participants underwent at least two extended prostate needle biopsy protocols. MEASUREMENTS: Clinical and pathologic factors (age, PSA, PSA doubling time, PIN, ASAP, digital rectal exam [DRE]) were analyzed for their ability to predict positive biopsy, and tumour parameters were assessed in patients undergoing radical prostatectomy. RESULTS AND LIMITATIONS: Second, third, and fourth extended 21-sample biopsy procedures yielded a diagnosis of PCa in 18%, 17%, and 14% of patients respectively. Patients with prior PIN had 16% risk of prostate cancer; patients with ASAP had a 42% risk. The mean number of positive cores was 2.19. Prostate volume and PSA density were statistically significant predictors of positive biopsy (p<0.05). For the 43 patients who underwent radical prostatectomy, pathologic findings revealed mean Gleason score of 6.7 (6-8), pT2a-c in 72%, pT3a in16%, and pT4 in 7%. Mean cancer volume was 1.15 cc and 85.2% of tumours were clinically significant (tumour volume > 0.5 cc, Gleason > or = 7 and/or pT3). CONCLUSIONS: Negative first extended biopsies should not reassure a patient of not having PCa. However, prostate cancers detected after two or more sets of extended procedures, appear to be localized (intracapsular disease) and well-differentiated prostate cancers, although they are still clinically significant.

Endoscopic management of pancreatic fistula after distal pancreatectomy and enucleation.

BACKGROUND: Preoperative endoscopic pancreatic sphincterotomy (EPS) has been proposed to prevent postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) or enucleation (EN). The use of EPS as a curative treatment for POPF has been scarcely reported. We reported 10 consecutive patients who were successfully treated by EPS for a prolonged POPF. STUDY DESIGN: Ten patients underwent EPS for prolonged POPF (median duration = 40 days, range 20-114; median daily output = 80 mL, range 50-250) after 6 DPs, 2 ENs, and 2 medial pancreatectomies. RESULTS: EPS was performed in all patients, with stent insertion in 4. No patient developed a specific complication because of EPS. POPF healed within a median delay of 4 days (range 1-12). One patient underwent a repeated endoscopy to treat stent malposition. The median delay of discharge after EPS was 13 days (range 8-15). With a 20-month median follow up, 1 patient developed early transient POPF recurrence because of spontaneous stent migration. CONCLUSIONS: EPS is indicated for prolonged POPF after DP or EN because it is highly feasible, shortens healing, and is well tolerated.

Analysis of complications from 600 retroperitoneoscopic procedures of the upper urinary tract during the last 10 years.

INTRODUCTION: The aim of this study is to review 10 years experience of retroperitoneoscopy procedures. METHODS: A total of 600 patients treated between 1995 and 2007 by retroperitoneoscopy (nephrectomy, partial and total nephrectomy, adrenalectomy, pyeloplasty, renal cyst, calyceal diverticulectomy) were reviewed for per, peri and postoperative complications including patients in the learning curve. RESULTS: The mean blood loss was 159 mL. Conversion to open surgery was required in 28 patients (4.6%) primarily due to technical problems during dissection (elective). There were 32 (5.3%) surgical complications, including bleeding or hematomas in 12 cases and 2 of them required reintervention, urinomas in 8 which were treated by installation of a ureteral drainage (JJ stent). Wound or deep abscesses happened in four, urinary fistula in one and pancreatic fistula in another. Evisceration (hernias) was seen in three patients. Intestinal injury occurred in two. The complication rate depended on the difficulty of the procedure and learning curve of the surgeon. A total of 28 patients (4.6%) presented medical postoperative complications (hyperthermias, deep venous thrombosis, pyelonephritis, pulmonary superinfections, pulmonary atelectasia and transient vascular ischemic accident). Mean postoperative hospital stay was 6.2 days (ranged from 2 to 20). CONCLUSION: Retroperitoneoscopy can be the technique of choice for accessing and carrying out all the surgery of the upper urinary tract respecting the principles of oncological surgery. After experience with 600 cases during the last 10 years the technique has become safe, simplified, reproducible and effective although not easy. Most complications are minor and easily managed.