Retrieved but not transplanted kidneys: how to limit the losses? A retrospective national study.

Despite the organ shortage, a significant number of deceased donor kidneys are retrieved but not transplanted (RNTK). This study aims to describe and analyze the main causes of potential grafts discard and to propose adequate solutions. We collected data from the Cristal database of the French Biomedicine Agency about RNTK over one year. Expert opinion was taken from urologists with extensive expertise in renal transplantation. They retrospectively analyzed each record to assess the appropriateness of each graft refusal and subsequent kidney discard. Of 252 kidneys were retrieved but not transplanted in France over one year. The main reasons for discard were vascular abnormalities in 43.7% (n = 110), suspicion of malignant tumor in 18.7% (n = 47), and severe histological lesions on preimplantation biopsy in 12.3% (n = 31). The reason for kidney refusal was undetermined in 4.8% (n = 12). Iatrogenic lesions were responsible for 26.2% (n = 66). Overall, 46.0% (n = 16) and 25.0% (n = 63) of the grafts were, respectively, properly and improperly denied, and the analysis was not possible in 29.0% (n = 73). In total, 36.9% of RNTK could have been transplanted. Reduction of iatrogenic lesions, improvement of microsurgical repair skills, and proper histological examination are necessary to reduce the number of RNTK. A prospective study applying the proposed principles is undoubtedly essential to complete this work.

Association of genetic variation of the six gene prognostic model for castration-resistant prostate cancer with survival.

BACKGROUND: We previously identified a blood RNA transcript-based model consisting of six immune or inflammatory response genes (ABL2, SEMA4D, ITGAL, C1QA, TIMP1, and CDKN1A) that was prognostic for survival in cohorts of men with castration-resistant prostate cancer (CRPC). We investigated whether inherited variation in these six genes was associated with overall survival (OS) in men with CRPC. METHODS: The test cohort comprised 600 patients diagnosed with CRPC between 1996 and 2011 at Dana-Farber Cancer Institute. Genotyping of 66 tagging single nucleotide polymorphisms (SNPs) spanning the six genes was performed on blood derived DNAs. For the top four SNPs (P < 0.05), validation was conducted in an independent cohort of 223 men diagnosed with CRPC between 2000 and 2014. Multivariable Cox regression adjusting for known prognostic factors estimated hazard ratios (HR) and 95% confidence intervals (CI) of the association of genetic variants with OS. RESULTS: Two thirds of patients in both cohorts had metastases at CRPC diagnosis. Median OS from CRPC diagnosis was 3.6 (95%CI 3.3-4.0) years in the test cohort and 4.6 (95%CI 3.8-5.2) years in the validation cohort. Fifty-nine SNPs in Hardy-Weinberg equilibrium were analyzed. The major alleles of rs1318056 and rs1490311 in ABL2, and the minor alleles of rs2073917 and rs3764322 in ITGAL were associated with increased risk of death in the test cohort (adjusted-HRs 1.27-1.39; adjusted-p <0.05; false discovery rate <0.35). In the validation cohort, a similar association with OS was observed for rs1318056 in ABL2 (adjusted-HR 1.44; 95%CI 0.89-2.34) and rs2073917 in ITGAL (adjusted-HR 1.41; 95%CI 0.82-2.42). The associations did not reach statistical significance most likely due to the small sample size of the validation cohort (adjusted-p = 0.142 and 0.209, respectively). Additional eQTL analysis indicated that minor alleles of rs1318056 and rs1490311 in ABL2 are associated with a lower ABL2 expression in blood. CONCLUSIONS: These findings corroborate our initial work on the RNA expression of genes involved in immunity and inflammation from blood and clinical outcome and suggest that germline polymorphisms in ABL2 and ITGAL may be associated with the risk of death in men with CRPC. Further studies are needed to validate these findings and to explore their functional mechanisms.

Preoperative nomogram to predict the likelihood of complications after radical nephroureterectomy.

OBJECTIVES: To construct a nomogram based on preoperative variables to better predict the likelihood of complications occurring within 30 days of radical nephroureterectomy (RNU). PATIENTS AND METHODS: The charts of 731 patients undergoing RNU at eight academic medical centres between 2002 and 2014 were reviewed. Preoperative clinical, demographic and comorbidity indices were collected. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo scale. Multivariate logistic regression determined the association between preoperative variables and post-RNU complications. A nomogram was created from the reduced multivariate model with internal validation using the bootstrapping technique with 200 repetitions. RESULTS: A total of 408 men and 323 women with a median age of 70 years and a body mass index of 27 kg/m2 were included. A total of 75% of the cohort was white, 18% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, 20% had a Charlson comorbidity index (CCI) score >5 and 50% had baseline chronic kidney disease (CKD) ≥ stage III. Overall, 279 patients (38%) experienced a complication, including 61 events (22%) with Clavien grade ≥ III. A multivariate model identified five variables associated with complications, including patient age, race, ECOG performance status, CKD stage and CCI score. A preoperative nomogram incorporating these risk factors was constructed with an area under curve of 72.2%. CONCLUSIONS: Using standard preoperative variables from this multi-institutional RNU experience, we constructed and validated a nomogram for predicting peri-operative complications after RNU. Such information may permit more accurate risk stratification on an individual cases basis before major surgery.

Influence of statin use on clinicopathological characteristics of localized prostate cancer and outcomes obtained after radical prostatectomy: a single center study.

INTRODUCTION: To assess the impact of statin use on biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP). MATERIALS AND METHODS: Data from all men treated with robot-assisted laparoscopic RP (RALRP) for localized prostate cancer between 2009 and 2014 at our institution were prospectively collected: age, body mass index (BMI), statin-use status, preoperative prostate-specific antigen (PSA) level, clinical T stage, biopsy Gleason score (bGS), D'Amico risk group, pathological T stage, specimen Gleason score (sGS), multifocality, peri neural invasion, positive surgical margins and time to BCR. Univariate and multivariate analysis were performed to test associations between statin use and prognostic factors of prostate cancer and/or BCR. RESULTS: Overall, 591 patients with a median follow up of 42.3 months [25.8-59.9] were included in the current study and split in two cohorts: statin users (n = 156) and statin non-users (n = 435). When comparing statin user and non-users, no significant difference was found in terms of clinical, biochemical and pathological characteristics except for BMI (median 29 versus 26, respectively; p = 0.04). Regarding BCR, there was no significant difference between men using statin versus those not using them (4.5% versus 4.6%, p = 0.65). In univariate analysis, statin use was not significantly correlated to any prognostic factors of prostate cancer recurrence. Furthermore, there was no significant difference in the 5 years biochemical-free survival rates between statin users and non-users (75% versus 73%; p = 0.7). CONCLUSIONS: From the current study, statin daily intake was not significantly associated with any prognostic factors of prostate cancer and with BCR after RARLP.

Malnourishment in bladder cancer and the role of immunonutrition at the time of cystectomy: an overview for urologists.

The 'gold standard' treatment for patients with carcinoma invading the bladder muscle is radical cystectomy (RC). Such patients are known to be at risk of malnutrition because of age and disease factors. Current evidence has established the nutritional and immunological benefits of immune-enhancing nutritional supplements in upper gastrointestinal surgery. There are currently no guidelines for immunonutrition (IM) use in urology and bladder cancer specifically. We carried out a systematic review of the available literature in the MEDLINE/Embase database. We assessed the rates of malnutrition in RC cohorts and analysed the clinical impacts of nutritional deficiency. The impact of immune-enhancing supplements was also investigated in RC cohorts with regard to postoperative outcomes. The prevalence of severe malnutrition was found to be 16-22%. There was a consistent association of malnourished patients with adverse postoperative outcomes in terms of mortality and morbidity. There is a paucity of data regarding IM in urological cohorts. Postoperative IM in RC was not found to have significant benefits beyond early return to a normal diet. There is not enough evidence in malnourished urological study cohorts to establish a consensus on IM. Until there are more well-controlled comparative effective studies or randomized trials, the role of IM should be considered investigational in patients with bladder cancer.

Impact of the length of time between diagnosis and surgical removal of urologic neoplasms on survival.

OBJECTIVE: Our aim was to assess the effect of surgical wait time on the survival of patients with urological neoplasms, including prostate, bladder, penile, and testicular cancers and upper tract tumours (UTUC). MATERIALS AND METHODS: Current, relevant studies were identified from the literature. Keywords used for article retrieval were as follows: delay; surgery; prostate cancer; urothelial carcinoma; renal cell carcinoma; testicular cancer; bladder; renal pelvis; ureter; and survival. RESULTS: Regarding the length of surgical wait time, it does not matter in cases of incidental T1a renal cell carcinomas. In other cases of renal cell carcinomas, surgery should be considered within <1 month; it is of crucial importance in bladder cancer and should be <1 month for a TURBT in cases of non-muscle-invasive bladder cancer and <1 month for a radical cystectomy in cases of muscle-invasive bladder cancer; it is important in invasive UTUC and should be <1 month for a radical nephroureterectomy; it is not crucial in cases of low-risk prostate cancer. In any other case, radical prostatectomy should be considered within <2 months; it is important in testicular cancer and should be fewer than 10 days for an orchiectomy. CONCLUSION: Prolonged surgical wait times have an impact on the overall quality of life and anxiety of the patient. Extending the wait time beyond a given threshold can also have a negative impact on the patient's clinical outcomes, but this threshold differs between urological neoplasms.

The surgical approach can be determined from the pathological specimen obtained after open or robot-assisted laparoscopic radical prostatectomy.

PURPOSE: To assess the surgical approach using the pathological specimen obtained after open radical prostatectomy (ORP) or robot-assisted radical prostatectomy (RALRP). METHODS: A prospective study has been performed in patients who underwent either ORP or RALRP for localized prostate cancer. Two dedicated uro-pathologists, blinded to the surgeons and the operating rooms' schedules, analyzed the pathological specimens according to the Stanford protocol. Both pathologists also determined the surgical approach used based on several criteria pertaining to the pathological specimen. RESULTS: Overall, 117 patients with a median age of 63 years were included. The main characteristics (i.e., Gleason score, pTNM stage, preoperative PSA and margin) were comparable in both groups (p > 0.05). Pathologists 1 and 2 were able to significantly assess the surgical procedure from the pathological specimen provided (in 76.1 and 69.2 % of cases, respectively). Pathologist 1 had a better performance than pathologist 2 (AUC 0.75, IC 95 % [0.67-0.83] vs. AUC = 0.68 IC 95 % [0.59-0.77]) (p = 0.017). The κ index of the inter-observer agreement was satisfactory (0.76). In a univariate analysis, the criteria linked to the pathologist's assessment were as follows: macroscopic integrity of the specimen (p = 0.04), presence of periprostatic fat (p = 0.04), width of periprostatic tissue (p < 0.001) and nerve-sparing status (p < 0.001). CONCLUSION: It was possible to determine the surgical procedure from the analysis of the specimen obtained after a radical prostatectomy. In view of these data and from this perspective, one could infer that there are indeed oncological differences between the robotic and open approaches to radical prostatectomy.

Comparison of oncologic outcomes after radical prostatectomy in men diagnosed with prostate cancer with PSA levels below and above 4 ng/mL.

PURPOSE: To assess whether the PSA level (threshold 4 ng/mL) is a prognostic factor in biochemical recurrence-free survival in men with prostate cancer (PCa) with an initial PSA level <10 ng/mL who underwent robotic-assisted laparoscopic radical prostatectomy (RARLP). METHODS: We prospectively recruited data for consecutive patients treated by RARLP for PCa with an initial PSA level below 10 ng/mL between 2003 and 2011 at our institution. We divided the population into two groups: patients with a PSA level below 4 ng/mL (G1; n = 53) and patients with a PSA level between 4 and 10 ng/mL (G2; n = 371). Biochemical recurrence was defined as a single increase in PSA greater than 0.2 ng/mL after surgery. Multivariate analysis was used to assess prognostic factors of recurrence-free survival. RESULTS: Overall, 424 patients were included, and the median age was 62 (58-67) years. The median PSA was 5.8 ng/mL (4.8-7.7 ng/mL). Overall, 6 patients from G1 and 34 patients from G2 experienced a biochemical recurrence. Overall, the 5-year recurrence-free survival rate was 86.6 %. The PSA level at diagnosis (under or over 4 ng/mL) was not significantly linked to recurrence-free survival (HR = 0.59, p = 0.25). However, positive margins and a Gleason score >7 on the specimen were significantly linked to recurrence-free survival with respective hazard ratios of 4.30 (p < 0.0001) and 6.18 (p < 0.0001), respectively. CONCLUSION: A PSA level <4 ng/mL alone appears to be obsolete as a cut-off to define a population of men likely to have indolent disease.

Secondary chemoprevention of localized prostate cancer by short-term androgen deprivation to select indolent tumors suitable for active surveillance: a prospective pilot phase II study.

PURPOSE: To investigate the impact of 3-month androgen deprivation therapy (st-ADT) a secondary chemoprevention of indolent-localized prostate cancer (PCa). METHODS: A prospective phase II study enrolled men over 4 years with low-risk PCa and the following characteristics: PSA < 10 ng/mL, Gleason score of 6 (3 + 3) or less, three positive cores or less, and tumor stage T2a or less. Patients received a single sub-cutaneous injection of 22.5 mg of leuprolide acetate with Atrigel 3-month depot associated with a daily oral intake of bicalutamide 50 mg/day during 15 days around the injection. Follow-up included PSA and bioavailable testosterone blood tests every 3 months and yearly surveillance biopsies. Primary end point was the presence of PCa on biopsy at last follow-up. Secondary end points were detailed pathological features and adverse events. RESULTS: Overall, 98 men were included and 45 of them (45.9 %) had a negative biopsy after a median follow-up of 13 months [11-19.5]. Of the 53 patients with positive biopsy, 17 had pathologic progression because of upgraded Gleason score (11 patients), four or more positive cores (three patients) or both (three patients). The only significant predictive factor biopsy outcome was the number of positive cores at diagnosis. CONCLUSIONS: Secondary chemoprevention by st-ADT for localized PCa could be useful to pinpoint indolent tumors suitable for AS. Indeed, after st-ADT nearly one patient out of two had negative biopsies and 17 % had pathological progression. This is an innovative option to consider as an alternative to current AS protocols contingent upon confirmation in subsequent studies.

Charlson score as a single pertinent criterion to select candidates for active surveillance among patients with small renal masses.

PURPOSE: The aim of the study was to assess the outcome after nephron-sparing surgery (NSS) of patients with small renal masses (SRMs) who would have been eligible for active surveillance (AS). METHODS: Data were collected retrospectively for 758 patients who underwent NSS over a 5-year period. Outcomes were assessed in two groups of patients who were eligible for AS according to different criteria. Group 1 criteria were as follows: age >75 years, renal mass ≤4 cm, significant comorbidities [Charlson Comorbidity Index (CCI) >2]. Group 2 criteria were as follows: any SRM ≤ 4 cm regardless of age, severe comorbidities with a 10-year mortality risk >50 % (CCI > 4). The two groups were not compared statistically because some patients were included in both. RESULTS: Fifty-five patients (7.3 %) were included in Group 1 and 62 (8.2 %) in Group 2. There was a significant proportion of benign tumours in Group 1 (N = 6; 11 %) and Group 2 (N = 6; 10 %). Six (11 %) positive margins were observed in Group 1 and 8 (13 %) in Group 2. The 2- and 5-year recurrence-free survival rates were 100 and 77.4 %, respectively, in Group 1, and 88.5 and 79.6 % in Group 2. The 2- and 5-year overall survival rates were 100 and 74.7 % in Group 1, and 96.7 and 78.1 % in Group 2. CONCLUSIONS: The majority of patients with SRMs who would have been eligible for AS had no recurrence after initial tumour removal. In these patients, a CCI > 4 appeared to be a pertinent criterion to identify those patients less likely to benefit from immediate surgery.

Location, extent, and multifocality of positive surgical margins for biochemical recurrence prediction after radical prostatectomy.

PURPOSE: To study the prognostic value of extent, number, and location of positive surgical margins (PSM). METHODS: A total of 1,504 consecutive adjuvant treatment naive and node-negative radical prostatectomy men were included in a prospective database including extent, number, and location of PSM. Mean follow-up was 33 months. Endpoint was biochemical progression-free (bPFS) survival. The impact of margin status and characteristics was assessed in time-dependent analyses using Cox regression and Kaplan-Meier methods. RESULTS: PSM was reported in 26.7 % of patients. The predominant PSM locations were apex and posterior locations. Median PSM length was 4.0 mm. The 2-year bPFS was 73.7 % in PSM patients as compared to 93.0 % in NSM patients (p < 0.001). The rate and extent of PSM increased significantly with pathologic stage (p < 0.001). The extent of PSM length was linearly correlated with bPFS (p = 0.017, coefficient: -0.122). In univariable analysis, extent and number of PSM were significantly linked to outcomes. None of PSM subclassifications significantly influenced the bPFS rates in the subgroup of pT2 disease patients. Conversely, stratification by PSM location (apex vs. other locations, p = 0.008), by PSM number (p = 0.006), and by PSM length (p < 0.001) showed significant differences in pT3-4 cancer patients. In that subgroup, PSM length also added to bPFS prediction using PSM status only in multivariable models (p = 0.005). CONCLUSIONS: PSM subclassifications do not improve the biochemical recurrence prediction in organ-confined disease. In non-organ-confined disease, PSM length (≥3 mm), multifocality (≥3 sites), and apical location are significantly linked to poorer outcomes and could justify a more aggressive adjuvant treatment approach.

Current role of image-guided robotic radiosurgery (Cyberknife(®) ) for prostate cancer treatment.

OBJECTIVES: To describe the most recent data from phase I and II clinical trials of stereotactic body radiation therapy (SBRT) using image-guided robotic radiosurgery, specifically the Cyberknife(®) (Accuracy Incorporated, Sunnyvale, CA, USA). To better determine thecurrent role of this type of radiosurgery in prostate cancer (PCa) management. MATERIALS AND METHODS: Current clinical trials and relevant retrospective studies were identified from the literature, clinical trial databases, websites and conference abstracts. The indications, technical aspects, efficacy and toxicity of SBRT using the Cyberknife(®) system were summarized. RESULTS: The Cyberknife(®) system is an experimental treatment mostly used for localized PCa in stage cT1/T2a-b N0 M0 with a Gleason score ≤ 7 and PSA level ≤ 20 ng/mL. Hypofractionated radiation therapy was delivered in five fractions of 7-7.25 Gy for a total dose of 35-36.25 Gy. After treatment, the median PSA levelfell from 4.9-8.3 ng/mL to 0.1-1.6 ng/mL at a median follow-up of 4-60 months. The biochemical progression-free survival rates ranged from 78.3 to 100%. Acute and late toxicities were mostly grade 1/2 rectal or urinary complications. Few grade 3 and no grade 4 toxicities occurred during follow-up; however, erectile dysfunction and testes toxicity were also reported. CONCLUSIONS: The use of the Cyberknife(®) system is limited mainly by its pretreatment and maintenance costs. Despite encouraging preliminary results, longer-term follow-up and randomized controlled phase III clinical trials are necessary before the Cyberknife(®) system becomes a standard treatment method.

A systematic review of the tools available for predicting survival and managing patients with urothelial carcinomas of the bladder and of the upper tract in a curative setting.

OBJECTIVES: To identify the predictive tools which have emerged recently in the field of urothelial carcinomas. MATERIALS AND METHODS: We performed a thorough MEDLINE literature review using a combination of the following keywords: urothelial carcinoma, transitional cell carcinoma, bladder, renal pelvis, ureter, predictive tools, predictive models and nomograms. We found 117 articles, but only the relevant reports were selected. RESULTS: The majority of available tools are prediction models, particularly nomograms. These models combine good performance accuracy with ease of use. They appear to be more accurate than risk grouping or tree modeling and are more suitable for clinicians than artificial intelligence. The most recent nomograms have been designed to be used in daily clinical practice and are even available as computer or smartphone applications. They focus on pathological outcomes or more frequently on survival statistics or recurrence risk after surgery. They provide an accurate prediction of disease evolution and may help clinicians to choose the most appropriate treatment option. However, these prediction tools still need to be validated and regularly utilized. CONCLUSION: Predictive tools represent very helpful clinical decision-making aids but need to be validated in larger populations.

Genetic polymorphisms on 8q24.1 and 4p16.3 are not linked with urothelial carcinoma of the bladder in contrast to their association with aggressive upper urinary tract tumours.

PURPOSE: Bladder urothelial carcinoma (bladder-UC) displays distinct genotypic differences compared to upper tract UC (UTUC). We recently reported specific 8q24 SNP variants confer susceptibility to UTUC and aggressive disease features. Herein, we evaluate a bladder-UC cohort to see whether similar polymorphisms are linked similarly same way with disease risk and aggressiveness. METHODS: 231 bladder-UC patients and 261 benign controls were matched for gender, age, ethnicity and smoking habits. We retrospectively retrieved information on tumour stage, grade, size, multiplicity, carcinoma in situ and tumour number. DNA was extracted from paraffin-embedded primary bladder-UC samples and blood of benign controls. Genotyping of rs9642880[T] (8q24.1) and rs798766[T] (4p16.3) was performed using commercially available Taqman(®) assays and the ABI™ 7000 Sequence Detector. RESULTS: Using a case-control analysis, bladder-UC risk was increased in individuals carrying the T/T genotype of rs9642880 [OR = 1.72 (95 % CI 1.1-2.8); p = 0.028] and rs798766 [OR = 1.84 (95 % CI 0.9-2.3); p = 0.01]. When analysing parameters of bladder-UC aggressiveness, the T/T genotypes for rs9642880 and rs798766 were not found to be associated with either grade [OR = 0.89 (95 % CI 0.52-1.32; p = 0.68) and OR = 0.95 (95 % CI 0.58-1.48; p = 0.61), respectively] or pathological stage [OR = 0.79 (95 % CI 0.42-1.48; p = 0.46) and OR = 0.90 (95 % CI 0.49-1.61; p = 0.72), respectively]. SNP variability of rs9642880[T] and rs798766[T] is associated with an increased risk of bladder-UC but we did not find an association with disease aggressiveness as we did previously for UTUC. CONCLUSIONS: This is further evidence of the distinct genetic differences that exist between bladder-UC and UTUC, and it is not possible to extrapolate results of genetic studies between these two urothelial disease entities.

Quantitative RT-PCR analysis of PSA and prostate-specific membrane antigen mRNA to detect circulating tumor cells improves recurrence-free survival nomogram prediction after radical prostatectomy.

BACKGROUND: Circulating tumor cell (CTC) analysis is a potential new biomarker in prostate cancer. We hypothesize that quantitative detection of CTCs in patients pre- and post-radical prostatectomy (RP) using quantitative TaqMan® fluorogenic RT-PCR will improve the accuracy of the Kattan nomogram to predict the probability of recurrence-free survival (RFS) post-RP. METHODS: Ninty-two patients who underwent RP between 2004 and 2009 had venous blood samples taken pre- (Day - 1) and post-operatively (Day + 7). We performed quantitative Taqman® RT-PCR to detect circulating prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) mRNA. We calculated both the logarithmic ratio of Day + 7/Day - 1 for PSA (PSAr) and PSMA (PSMAr) expression (log(Day+7/Day-1) ) and the Kattan nomogram predicted probability of disease recurrence for each patient. We then analyzed how the AUC-ROC analysis for the Kattan nomogram prediction alone (K) compared to the addition of the PSAr and PSMAr in predicting 5-year RFS. RESULTS: The mean age (years), PSA (ng/ml), and follow-up (mo) was 65.1, 9.13, and 72, respectively. The AUCs for K, PSAr + K, and PSMAr + K were 0.752 (95%CI 0.620-0.860), 0.830 (95%CI 0.740-0.911), and 0.837 (95%CI 0.613-0.923), respectively (P = 0.03). The Kattan 5-year PSA RFS was 75%. The actual 5-year PSA RFS survival rate was 77%. CONCLUSIONS: Data from modern quantitative RT-PCR to detect circulating prostate-derived PSA and PSM mRNA pre- and post-RP improves the accuracy of the Kattan nomogram to predict biochemical recurrence.

Genetic variability in 8q24 confers susceptibility to urothelial carcinoma of the upper urinary tract and is linked with patterns of disease aggressiveness at diagnosis.

PURPOSE: Upper urinary tract urothelial carcinoma is rare. Evidence shows that it behaves differently from urothelial bladder tumors. A polymorphism located at the T allele of rs9642880 on chromosome 8q24 is linked to an enhanced risk of bladder tumors. We explored the association of this polymorphism with susceptibility to upper urinary tract urothelial carcinoma. MATERIALS AND METHODS: We genotyped the constitutional DNA of 261 patients with upper urinary tract urothelial carcinoma and 261 healthy controls matched for age, gender, smoking habit and ethnicity. Polymorphisms at rs9642880 on chromosome 8q24 were determined using the 5' nuclease polymerase chain reaction method with specific primers and probes. Frequencies were compared between cases and controls. Genotypes were in Hardy-Weinberg equilibrium for cases and controls. RESULTS: Mean patient age was 68.7 years. The T/T genotype resulted in a significantly higher risk of upper urinary tract urothelial carcinoma (OR 1.72, 95% CI 1.1-2.8, p = 0.028). Using single polytomous regression analysis the T/T genotype was also associated with aggressive tumors when stratified by stage (p = 0.003), or grade G2 (p = 0.04) or G3 (p = 0.01). CONCLUSIONS: Our results strongly suggest that the T/T rs9642880 genotype is a risk factor for upper urinary tract urothelial carcinoma, as previously shown for bladder tumors. In contrast to bladder carcinoma, for upper urinary tract urothelial carcinoma the T/T genotype is associated with aggressiveness.

Persistently elevated prostate-specific antigen at six weeks after radical prostatectomy helps in early identification of patients who are likely to recur.

OBJECTIVE: To determine the prognostic factors of biochemical recurrence in patients who failed to achieve an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP) for prostate cancer. MATERIALS AND METHODS: We reviewed data on 240 men who underwent RP as first-line treatment and who had a PSA assay available at 6 weeks after surgery. Persistent detectable PSA was defined as a PSA level ≥ 0.1 ng/ml at 6 weeks after surgery. RESULTS: Overall, 83 men presented persistently elevated PSA after RP and 81 had a biochemical recurrence. Median follow-up was 44 months. In univariate analysis, these factors were associated with biochemical recurrence: preoperative PSA level (P < 0.0001), biopsy and pathologic Gleason score (P < 0.001), capsular involvement (P = 0.0001), positive surgical margins (P < 0.0001), pathological stage ≥ T3 (P = 0.0001), and detectable post-operative PSA ≥ 0.1 ng/ml (P = 0.0001). In a multivariate analysis, only the detectable post-operative PSA level ≥ 0.1 ng/mL (P = 0.001), positive surgical margins (P = 0.002), and pathological stage ≥ T3 (P < 0.001) were significant. The individual, five-year, PSA-free survival rate for men with post-operative PSA <0.1 ng/ml and ≥ 0.1 ng/ml were 59 and 42%, respectively (P < 0.001). CONCLUSIONS: A majority of patients who failed to achieve an undetectable PSA after surgery had a subsequent biochemical recurrence in the outcome. A systematic PSA assay 6 weeks after RP could be useful to early identify patients who are likely to recur.

Low-intensity extracorporeal shock wave therapy for Peyronie's disease: a single-center experience.

The aim of this article is to assess the outcomes of a low-intensity extracorporeal shock wave therapy (LiESWT) protocol for the treatment of Peyronie's disease (PD). Patients treated for PD were prospectively recorded, and data were retrospectively reviewed. Age, characteristics of fibrous plaques, concomitant treatments, International Index of Erectile Function (IIEF-5), Lue score, and pain score on Likert scale were collected. Patients in acute phase of PD and an angulation of <40° were included. The protocol consisted of 6 weekly sessions of 4000 pulses each, applied from different directions, with a maximal power of 20 W and 8 Hz frequency. We included 39 patients (median age: 56.8 years, interquartile range [IQR]: 35.8-62.2 years). The median number of sessions received per patient was 7.2. After treatment, the median Lue score decreased from 6.8 initially to 3.3 (P = 0.003), the median Likert pain score dropped from 1.8 to 0.7 (P = 0.004), the median plaque size was reduced from 2 cm to 1.2 cm (P = 0.08), and the median penile curvature diminished from 31° to 17° (P = 0.07). On univariate and multivariate analysis, the only predictors of success were younger age (odds ratio [OR] = 0.95, P = 0.03 and OR = 0.91, P = 0.04, respectively) and concomitant use of phosphodiesterase-5 inhibitors (PDE5i; OR = 0.92, P = 0.02 and OR = 0.93, P = 0.01, respectively). LiESWT had a favorable impact on Lue score and notably penile pain, curvature, plaque size, and erectile function in patients treated for PD during the early inflammatory phase, with no side effects. Younger age and concomitant use of PDE5i were the only success predictors.

Oncologic outcomes and survival in pT0 tumors after radical cystectomy in patients without neoadjuvant chemotherapy: results from a large multicentre collaborative study.

PURPOSE: To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens. METHODS: A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival. RESULTS: Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence (P = 0.03 and P = 0.005, respectively) and specific mortality (P = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years. CONCLUSIONS: Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.

Tissue expression of IL16 in prostate cancer and its association with recurrence after radical prostatectomy.

BACKGROUND: Genetic polymorphism located within the IL16 gene has been reported to be associated with aggressive prostate cancer (PCa). Our aim was to establish whether the tissue expression of IL16 is a prognostic factor of survival in PCa. METHODS: The files of patients who underwent radical prostatectomy (RP) between 1995 and 2001 were reviewed. The cases were selected and classified according to the D'Amico classification for risk of recurrence (intermediate or high). The value of IL16 and its receptor CCR5 (chemokine (C-C motif) receptor 5) expression levels were determined as witness of aggressiveness patterns and markers of biological relapse in patients with PCa treated by RP. A tissue microarray of 304 cases was constructed. IL16 and CCR5 expression levels were characterized by immunohistochemistry. RESULTS: IL16 expression was correlated with high Gleason score (i.e., >7) (P < 0.01). It was not significant for CCR5. IL16 and CCR5 were not associated with prostate-specific antigen (PSA) or capsular extension of the disease. The accurate prediction of disease outcome, using stratification of cases, according to negative margins and D'Amico classification was significantly enhanced by status of IL16 expression (P ≤ 0.01). In univariate analyses, Gleason score, PSA level, stage and loss of IL16 expression were related to better biological-free survival (P < 0.05) but not CCR5. In a multivariate analysis, IL16 expression, Gleason score, and tumor stage were independent factors for biochemical-free survival (P = 0.001). CONCLUSIONS: IL16 appears to be a useful prognostic factor in PCa. Its expression in PCa tissue was correlated to tumor aggressiveness and biochemical relapse of the disease.