Robotic-assisted vs. open ureteral reimplantation: a multicentre comparison.

PURPOSE: Open ureteral reimplantation is considered the standard surgical approach to treat distal ureteral strictures or injuries. These procedures are increasingly performed in a minimally invasive and robotic-assisted manner. Notably, no series comparing perioperative outcomes and safety of the open vs. robotic approach are available so far. METHODS: In this retrospective multi-center study, we compared data from 51 robotic ureteral reimplantations (RUR) with 79 open ureteral reimplantations (OUR). Both cohorts were comparatively assessed using different baseline characteristics and perioperative outcomes. Moreover, a multivariate logistic regression for independent predictors was performed. RESULTS: Surgery time, length of hospital stay and dwell time of bladder catheter were shorter in the robotic cohort, whereas estimated blood loss, postoperative blood transfusion rate and postoperative complications were lower than in the open cohort. In the multivariate linear regression analysis, robotic approach was an independent predictor for a shorter operation time (coefficient - 0.254, 95% confidence interval [CI] - 0.342 to - 0.166; p < 0.001), a lower estimated blood loss (coefficient - 0.390, 95% CI - 0.549 to - 0.231, p < 0.001) and a shorter length of hospital stay (coefficient - 0.455, 95% CI - 0.552 to - 0.358, p < 0.001). Moreover, robotic surgery was an independent predictor for a shorter dwell time of bladder catheter (coefficient - 0.210, 95% CI - 0.278 to - 0.142, p < 0.001). CONCLUSION: RUR represents a safe alternative to OUR, with a shorter operative time, decreased blood loss and length of hospital stay. Prospective research are needed to further define the extent of the advantages of the robotic approach over open surgery.

Impact of Blood Loss on Renal Function and Interaction with Ischemia Duration after Nephron-Sparing Surgery.

OBJECTIVES: Nephron-sparing surgery (NSS) exposes the kidney to ischemia-reperfusion injury. Blood loss and hypotension are also associated with kidney injury. We aimed to test the hypothesis that, during NSS, both ischemia duration and blood loss significantly affect postoperative renal function and that their effects interact. METHODS: Consecutive patients undergoing NSS were enrolled. The primary endpoint was renal function expressed as the absolute delta between preoperative and postoperative peak creatinine. We developed a generalized linear model with the ischemia duration and absolute hemoglobin difference as independent variables, their interaction term, and the RENAL score. The model was than expanded to include a history of hypertension (as a proxy for hypotension susceptibility) and related interaction terms. Further, we described the perioperative and mid-term oncological outcomes. RESULTS: A total of 478 patients underwent NSS, and 209 (43.7%) required ischemia for a mean of 10.9 min (SD 8). Both the ischemia duration (partial eta 0.842, p = 0.006) and hemoglobin difference (partial eta 0.933, p = 0.029) significantly affected postoperative renal function, albeit without evidence of a significant interaction (p = 0.525). The RENAL score also significantly influenced postoperative renal function (p = 0.023). After the addition of a previous history of hypertension, the effects persisted, with a significant interaction between blood loss and a history of hypertension (p = 0.02). CONCLUSIONS: Ischemia duration and blood loss had a similar impact on postoperative renal function, albeit without potentiating each other. While the surgical technique and ischemia minimization remain crucial to postoperative kidney function, increased awareness of conscious hemodynamic management appears warranted.

Expression of programmed death ligand-1 (PD-L1) in metastatic and postchemotherapy viable testicular germ cell tumors.

INTRODUCTION: Chemotherapy for testicular germ cell tumors (GCT) is highly effective, with few patients who do not respond. Clinical studies to evaluated novel treatments are challenging given the rarity of these patients. Therefore, we sought to evaluate PD-L1 staining on metastatic and postchemotherapy viable testicular GCTs as a surrogate for potential benefit for immunotherapy targeting the PD-1/PD-L1 axis. METHODS: Ethics research committee approval for this retrospective study was obtained by four participating institutions (CHU de Québec, St. Joseph's Health Care, Halifax Health Science Centre, Johannes Gutenberg University). Patients with viable metastatic testicular GCTs pathology samples were included. Patients with pure teratoma were excluded. PD-L1 staining with the 22C3 clone was evaluated on samples with >100 viable tumor cells using the combined positive score (CPS). RESULTS: From 51 patients identified at participating institutions, 24 postchemotherapy and 18 chemotherapy-naive metastatic samples were available for PD-L1 staining, with 9 matched prechemotherapy samples and 7 matched orchiectomy pathology samples, respectively. The median CPS score was 55.6 (IQR 16-100) for all metastatic samples, 44.9 (IQR 13-100) for postchemotherapy metastatic samples, and 68.8 (IQR 38-100) for chemotherapy-naïve metastatic samples, with the median number of viable tumor cells at 545, 500, and 550, respectively. Differences were not significant between chemotherapy-naïve and postchemotherapy samples (P = 0.07), though among non-seminoma GCT metastatic samples, CPS scores were significantly lower postchemotherapy (P = 0.02). Significant differences among postchemotherapy metastatic tumors were also seen according to predominant subtype, with lower CPS scores for predominant yolk sac and higher values for predominant seminoma and choriocarcinoma. In 7 patients with matched specimens pre- and postchemotherapy, a significant increase in CPS was observed for seminoma (26.7 vs. 81.7, P = 0.045), but not nonseminoma GCTs. Comparing all chemotherapy naïve-samples, PD-L1 expression was higher in metastatic samples versus testicular samples (mean CPS 68.8 vs. 39.8, P = 0.02). This was also seen in matched chemotherapy-naïve samples (mean CPS 77.9 vs. 33.1, P = 0.01). CONCLUSION: Our results suggest that most patients with refractory GCTs postchemotherapy will not benefit from PD-1/PD-L1 immunotherapy. However, the high PD-L1 expression in patients with predominant or pure seminoma post-chemotherapy suggests this may represent a subgroup for whom further trials may be considered.

Global change of surgical and oncological clinical practice in urology during early COVID-19 pandemic.

OBJECTIVES: While the coronavirus disease 2019 (COVID-19) pandemic captures healthcare resources worldwide, data on the impact of prioritization strategies in urology during pandemic are absent. We aimed to quantitatively assess the global change in surgical and oncological clinical practice in the early COVID-19 pandemic. METHODS: In this cross-sectional observational study, we designed a 12-item online survey on the global effects of the COVID-19 pandemic on clinical practice in urology. Demographic survey data, change of clinical practice, current performance of procedures, and current commencement of treatment for 5 conditions in medical urological oncology were evaluated. RESULTS: 235 urologists from 44 countries responded. Out of them, 93% indicated a change of clinical practice due to COVID-19. In a 4-tiered surgery down-escalation scheme, 44% reported to make first cancellations, 23% secondary cancellations, 20% last cancellations and 13% emergency cases only. Oncological surgeries had low cancellation rates (%): transurethral resection of bladder tumor (27%), radical cystectomy (21-24%), nephroureterectomy (21%), radical nephrectomy (18%), and radical orchiectomy (8%). (Neo)adjuvant/palliative treatment is currently not started by more than half of the urologists. COVID-19 high-risk-countries had higher total cancellation rates for non-oncological procedures (78% vs. 68%, p = 0.01) and were performing oncological treatment for metastatic diseases at a lower rate (35% vs. 48%, p = 0.02). CONCLUSION: The COVID-19 pandemic has affected clinical practice of 93% of urologists worldwide. The impact of implementing surgical prioritization protocols with moderate cancellation rates for oncological surgeries and delay or reduction in (neo)adjuvant/palliative treatment will have to be evaluated after the pandemic.

Inhibition of GLI2 with antisense-oligonucleotides: A potential therapy for the treatment of bladder cancer.

The sonic hedgehog (SHH) signaling pathway plays an integral role in the maintenance and progression of bladder cancer (BCa) and SHH inhibition may be an efficacious strategy for BCa treatment. We assessed an in-house human BCa tissue microarray and found that the SHH transcription factors, GLI1 and GLI2, were increased in disease progression. A panel of BCa cell lines show that two invasive lines, UM-UC-3 and 253J-BV, both express these transcription factors but UM-UC-3 produces more SHH ligand and is less responsive in viability to pathway stimulation by recombinant human SHH or smoothened agonist, and less responsive to inhibitors including the smoothened inhibitors cyclopamine and SANT-1. In contrast, 253J-BV was highly responsive to these manipulations. We utilized a GLI1 and GLI2 antisense oligonucleotide (ASO) to bypass pathway mechanics and target the transcription factors directly. UM-UC-3 decreased in viability due to both ASOs but 253J-BV was only affected by GLI2 ASO. We utilized the murine intravesical orthotopic human BCa (mio-hBC) model for the establishment of noninvasive BCa and treated tumors with GLI2 ASO. Tumor size, growth rate, and GLI2 messenger RNA and protein expression were decreased. These results suggest that GLI2 ASO may be a promising new targeted therapy for BCa.

Risk-adjusted proposal for >60 months follow up after surgical treatment of organ-confined renal cell carcinoma according to life expectancy.

OBJECTIVES: To determine the long-term oncological outcome of organ-confined (

Selective Inhibition of the Lactate Transporter MCT4 Reduces Growth of Invasive Bladder Cancer.

The significance of lactate transporters has been recognized in various cancer types, but their role in urothelial carcinoma remains mostly unknown. The aim of this study was to investigate the functional importance of the monocarboxylate transporter (MCT) 4 in preclinical models of urothelial carcinoma and to assess its relevance in patient tumors. The association of MCT4 expression with molecular subtypes and outcome was determined in The Cancer Genome Atlas (TCGA) cohort and two independent cohorts of patients with urothelial carcinoma. Silencing of MCT4 was performed using siRNAs in urothelial carcinoma cell lines. Effects of MCT4 inhibition on cell growth, apoptosis, and production of reactive oxygen species (ROS) were assessed. Moreover, effects on lactate efflux were determined. The in vivo effects of MCT4 silencing were assessed in an orthotopic xenograft model. MCT4 expression was higher in the basal subtype. Decreased MCT4 methylation and increased RNA and protein expression were associated with worse overall survival (OS). Inhibition of MCT4 led to a reduction in cell growth, induction of apoptosis, and an increased synthesis of ROS. MCT4 inhibition resulted in intracellular accumulation of lactate. In vivo, stable knockdown of MCT4 reduced tumor growth. The expression of MCT4 in urothelial carcinoma is associated with features of aggressive tumor biology and portends a poor prognosis. Inhibition of MCT4 results in decreased tumor growth in vitro and in vivo Targeting lactate metabolism via MCT4 therefore provides a promising therapeutic approach for invasive urothelial carcinoma, especially in the basal subtype.

Docetaxel-rechallenge in castration-resistant prostate cancer: defining clinical factors for successful treatment response and improvement in overall survival.

PURPOSE: The purpose of the study was to define clinical factors for successful treatment response and re-exposure to docetaxel in metastatic castration-resistant prostate cancer (mCRPC). METHODS: An mCRPC database of patients receiving first-line docetaxel and rechallenge courses was established. Several clinical factors were evaluated for prediction of treatment response. Multivariate cox-regression analysis was used to define pre-treatment and treatment factors for survival. RESULTS: Between 2005 and 2013, 94 patients with mCRPC were treated with docetaxel. Full data set and follow-up were available for 62 patients. Median follow-up was 84 m [interquartile range (IQR) 64-104 m]. Median biochemical progression-free survival (bPFS) and overall survival under docetaxel were 9 m (IQR 5-16 m) and 20 m (IQR 16-26 m), respectively. Partial PSA-response at first docetaxel-sequence (n = 62), rechallenge (n = 32), and third-sequence (n = 22) docetaxel was 48.4%, 31.6%, and 34.8%, respectively. Time from start of primary androgen deprivation to CRPC > 47 m was the only independent pre-treatment parameter to predict improved overall survival (Hazard Ratio 0.48, p = 0.015). Interestingly, there was a strong trend for improved overall survival in patients with high Gleason Score (Hazard Ratio 0.58; p = 0.08). Partial PSA-response at docetaxel-rechallenge (Hazard Ratio 0.31; p = 0.008) and treatment-free interval > 3 m (Hazard Ratio 3.49; p = 0.014) were the only independent predictive factors under taxane treatment for overall survival. CONCLUSION: Despite novel hormonal drugs, docetaxel still plays an important role in the treatment of mCRPC. Patients with partial-PSA-response at rechallenge or a treatment-free interval > 3 m benefit most from docetaxel re-exposure.

The role of netrin-1 in metastatic renal cell carcinoma treated with sunitinib.

INTRODUCTION: Clear-cell renal cell carcinoma (ccRCC) is the sixth most common malignancy in men in North America. Since ccRCC is a malignancy dependent on neovascularization, current first line systemic therapies like sunitinib, target the formation of new vessels allowing nutrient deprivation and cell death. However, recent studies have shown that patients develop resistance after approximately 1 year of treatment and show disease progression while on therapy. Therefore, we propose to identify the protein(s) responsible for increased migration with the aim of developing a new therapy that will target the identified protein and potentially slow down the progression of the disease. MATERIAL AND METHODS: Human renal cancer cell lines (Caki-1, Caki-2, ACHN) were treated with increasing doses of sunitinib to develop a sunitinib-conditioned renal cell carcinoma cell line. mRNA microarray and qPCR were performed to compare the differences in gene expression between Caki-1 sunitinib-conditioned and non-conditioned cells. NTN1 was assessed in our in vivo sunitinib-conditioned mouse model using immunostaining. xCELLigence and scratch assays were used to evaluate migration and MTS was used to evaluate cell viability. RESULTS: Human renal cell carcinoma sunitinib-conditioned cell lines showed upregulation of netrin-1 in microarray and q-PCR. Increased migration was demonstrated in Caki-1 sunitinib-conditioned cells when compared to the non-treated ones as well as, increased endothelial cell migration. Silencing of netrin-1 in sunitinib-conditioned Caki-1 cells did not demonstrate a significant reduction in cell migration. CONCLUSION: Netrin-1 is highly upregulated in renal cell carcinoma treated with sunitinib, but has no influence on cell viability or cell migration in metastatic RCC.

In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself.

BACKGROUND: Loss of PTEN is involved in tumor progression of several tumor entities including renal cell carcinoma (RCC). During the translation process PTEN generates a number of splice variants, including PTEN-Δ. We analyzed the impact of PTEN-Δ in RCC progression. METHODS: In specimens of RCC patients the expression of PTEN-Δ and PTEN was quantified. The PTEN expressing RCC cell line A498 and the PTEN deficient 786-O cell line were stably transfected with the PTEN-Δ or PTEN transcript. In Caki-1 cells that highly express PTEN-Δ, this isoform was knocked down by siRNA. Cell migration, adhesion, apoptosis and signaling pathways activities were consequently analyzed in vitro. RESULTS: Patients with a higher PTEN-Δ expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-Δ expression correlated with the PTEN expression. PTEN-Δ as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-Δ, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-Δ and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-Δ. In a phospho-kinase array and Western blot analyses a consequently reduced activity of AKT, p38 and JNK could be shown. CONCLUSIONS: We could show that the PTEN splice variant PTEN-Δ acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-Δ in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC.

Calcium-sensing receptor (CaSR) promotes development of bone metastasis in renal cell carcinoma.

Bone metastasis is an important prognostic factor in renal cell carcinoma (RCC). The calcium-sensing receptor (CaSR) has been associated with bone metastasis in several different malignancies. We analyzed the impact of CaSR in bone metastasis in RCC in vitro and in vivo. The RCC cell line 786-O was stably transfected with the CaSR gene and treated with calcium alone or in combination with the CaSR antagonist NPS2143. Afterwards migration, adhesion, proliferation and prominent signaling molecules were analyzed. Calcium treated CaSR-transfected 768-O cells showed an increased adhesion to endothelial cells and the extracellular matrix components fibronectin and collagen I, but not to collagen IV. The chemotactic cell migration and proliferation was also induced by calcium. The activity of SHC, AKT, ERK, P90RSK and JNK were enhanced after calcium treatment of CaSR-transfected cells. These effects were abolished by NPS2143. Development of bone metastasis was evaluated in vivo in a mouse model. Intracardiac injection of CaSR-transfected 768-O cells showed an increased rate of bone metastasis. The results indicate CaSR as an important component in the mechanism of bone metastasis in RCC. Therefore, targeting CaSR might be beneficial in patients with bone metastatic RCC with a high CaSR expression.

The impact of time to metastasis on overall survival in patients with prostate cancer.

PURPOSE: Time to metastasis is often used as a surrogate parameter of treatment success in clinical trials for prostate cancer. However, it has not been shown that there is a clear correlation between time to metastasis and overall survival. Our objective was to evaluate the impact of time to metastasis on OS in patients with prostate cancer. METHODS: Between 2008 and 2015, 269 patients with mPCa were included in this retrospective study with a median follow-up of 7.1 years. Patients were divided into three groups: (1) Presentation with metastasis within three months of initial diagnosis (de-novo-M); (2) patients free of metastasis initially but developed metastasis more than 6 months prior to castration resistance (CSPC-M); (3) patients who developed metastasis within 6 months of becoming castration resistant or after (CRPC-M). RESULTS: There was a significant decrease in OS when metastases were present at diagnosis (median 6.39 years) compared to CRPC-M (19.07) and CSPC-M (18.19 years). De-novo-M and CSPC-M showed a longer OS from occurrence of metastasis to death when compared to CRPC-M, although reaching CRPC earlier. There was no difference in OS between the groups once castration resistance was reached. Time from initial diagnosis to metastasis and to CRPC was correlated with OS and remained important prognosticators in multivariate Cox-regression (p < 0.01 for both). CONCLUSIONS: Time from diagnosis to CRPC (all patients) and time to metastasis (for CRPC-M and CSPC-M patients) are significant prognosticators of overall survival and are therefore valid surrogates in a study setting. Therefore, time to CRPC should be prolonged as long as possible.

Development of a murine intravesical orthotopic human bladder cancer (mio-hBC) model.

We have developed a murine intravesical orthotopic human bladder cancer (mio-hBC) model for the establishment of superficial urothelial cell carcinomas. In this model we catheterize female atyhmic nude mice and pre-treat the bladder with poly-L-lysine for 15 minutes, followed by intravesical instillation of luciferase-transfected human UM-UC-3 cells. Cancer cells are quantified by bioluminescent imaging which has been validated by small animal ultrasound. Poly-L-lysine pre-treatment increased engraftment rate (84.4%) and resulted in faster growing tumors than trypsin pre-treatment. In addition, tumors respond through a decrease in growth and increase in apoptosis to chemotherapy with mitomycin C. Previous intravesical models utilized KU7 cells which have been later determined to be of non-bladder origin. They display markers consistent with HeLa cells, requiring a need for a true intravesical bladder model. Efficient engraftment and rapid superficial growth patterning of the human bladder tumor differentiate this in vivo orthotopic model from previous bladder models.

A prospective randomized pilot study evaluating an ERAS protocol versus a standard protocol for patients treated with radical cystectomy and urinary diversion for bladder cancer.

PURPOSE: There is a lack of evidence demonstrating the benefits of using enhanced recovery after surgery protocols (ERAS). Here, we propose to use a randomized clinical pilot study to demonstrate the benefits and feasibility of implementing ERAS versus standard protocols (SP) in patients undergoing radical cystectomy (RC) and urinary diversion. METHODS: 27 consecutive patients undergoing RC were included in the study. 12 patients were prospectively randomized to follow an ERAS protocol and 15 patients followed an SP. Duration of hospital stay, time to first flatulence and bowel movement, complications and 30 day readmission rates, as well as subjective outcomes such as postoperative pain, nausea, bowel symptoms, quality of life (QoL), and patient experience and satisfaction were evaluated. RESULTS: Patients following ERAS had a significantly shorter: hospital stay, time to flatulence, and time to bowel movement than patients following SP. No major complications were reported. Only one patient in the ERAS group was readmitted for bowel obstruction, and no patients were readmitted in the SP group. Patients under ERAS reported lower postoperative pain scores. Mean Functional Assessment of Cancer Therapy Bladder Cancer score decreased and mean Expanded Prostate Cancer Index Composite, bowel symptom score increased in the SP group at the time of discharge compared to prior to surgery. CONCLUSIONS: This study shows the feasibility of a randomized pilot study assessing ERAS compared to SP post RC. ERAS protocol provided evidence of significant benefits over SP with similar complication rates. This study suggests the need for a clinical trial of assessing ERAS protocols after RC.

Magnetically-actuated drug delivery device (MADDD) for minimally invasive treatment of prostate cancer: An in vivo animal pilot study.

BACKGROUND: The vast majority of prostate cancer presents clinically localized to the prostate without evidence of metastasis. Currently, there are several modalities available to treat this particular disease. Despite radical prostatectomy demonstrating a modest prostate cancer specific mortality benefit in the PIVOT trial, several novel modalities have emerged to treat localized prostate cancer in patients that are either not eligible for surgery or that prefer an alternative approach. METHODS: Athymic nude mice were subcutaneously inoculated with prostate cancer cells. The mice were divided into four cohorts, one cohort untreated, two cohorts received docetaxel (10 mg/kg) either subcutaneously (SC) or intravenously (IV) and the fourth cohort was treated using the magnetically-actuated docetaxel delivery device (MADDD), dispensing 1.5 µg of docetaxel per 30 min treatment session. Treatment in all three therapeutic arms (SC, IV, and MADDD) was administered once weekly for 6 weeks. Treatment efficacy was measured once a week according to tumor volume using ultrasound. In addition, calipers were used to assess tumor volume. RESULTS: Animals implanted with the device demonstrated no signs of distress or discomfort, neither local nor systemic symptoms of inflammation and infection. Using an independent sample t-test, the tumor growth rate of the treated tumors was significant when compared to the control. Post hoc Tukey HSD test results showed that the mean tumor growth rate of our device cohort was significantly lower than SC and control cohorts. Moreover, IV cohort showed slight reduction in mean tumor growth rates than the ones from the device cohort, however, there was no statistical significance in tumor growth rate between these two cohorts. Furthermore, immunohistochemistry demonstrated an increased cellular apoptosis in the MADDD treated tumors and a decreased proliferation when compared to the other cohorts. In addition, IV cohort showed increased treatment side effects (weight loss) when compared to the device cohort. Finally, MADDD showed minimal expression of CD45 comparable to the control cohort, suggesting no signs of chronic inflammation. CONCLUSIONS: In conclusion, this study showed for the first time that MADDD, clearly suppressed tumor growth in local prostate cancer tumors. This could potentially be a novel clinical treatment approach for localized prostate cancer.

Incidence, Risk Factors and Management of Symptomatic Lymphoceles after Radical Retropubic Prostatectomy.

INTRODUCTION: We investigated the incidence, clinical course and risk factors for symptomatic lymphoceles after radical retropubic prostatectomy with pelvic lymph node dissection. Moreover, we explored parameters for the failure of percutaneous lymphocele drainage. METHODS: The incidence of symptomatic lymphoceles in patients with prostate cancer who underwent radical retropubic prostatectomy with pelvic lymph node dissection in our department between 2008 and 2013 was investigated retrospectively. The occurrence of lymphoceles was correlated with several clinical and histopathological parameters. In addition, logistic regression analysis was performed to assess the value of independent variables with regard to the development of symptomatic lymphoceles and failure of percutaneous drainage. RESULTS: A total of 599 consecutive patients treated with radical retropubic prostatectomy with pelvic lymph node dissection were included in the study, of whom symptomatic lymphocele had developed in 5%. Median time to diagnosis of symptomatic lymphocele was 22.5 days. Median time of percutaneous drainage was 16 days. Overall 43% of patients required surgical unroofing. On multivariate analysis age greater than 67 years (OR 3.27, p=0.005) and removal of more than 10 lymph nodes (OR 2.57, p=0.018) were independent predictors for the development of symptomatic lymphoceles. A significantly increased risk of percutaneous drainage failure was observed in patients who had a body mass index greater than 27 kg/m2 (OR 7.0, p=0.03), followed by a trend for those with a drainage volume of more than 375 ml 24 hours after puncture (OR 3.89, p=0.12). CONCLUSIONS: Symptomatic lymphocele will develop in 1 of 20 patients after radical retropubic prostatectomy with pelvic lymph node dissection. The number of lymph nodes removed constitutes an independent risk factor. Percutaneous drainage failure is associated with high body mass index and high drainage volume within the first 24 hours after puncture.

Continent Anal Urinary Diversion in Classic Bladder Exstrophy: 45-Year Experience.

OBJECTIVE: To evaluate the long-term outcomes in patients with classic bladder exstrophy and continent anal urinary diversion (CAD) for continence, upper urinary tract status, secondary malignancies, and sexual function. PATIENTS AND METHODS: The medical records of 82 exstrophy patients having undergone CAD in our department between 1970 and 2015 were reviewed. Patients were invited for follow-up examinations and asked to complete validated questionnaires relating to sexual function. RESULTS: Thirty-two of 57 eligible patients with a median follow-up of 23.9 years were included in the study. Ninety-seven percent of patients were fully continent during daytime. Upper urinary tract and renal function remained stable in 75% and 87%, respectively. Five patients developed secondary malignancies originating from the rectal reservoir. Forty-one percent received prophylactic alkaline substitution. Sexual function as measured by the Female Sexual Function Index and the International Index on Erectile Function was negatively affected in all domains in both genders. Eighty-six percent of patients had a stable relationship and 35% were married. Five women conceived a total of 6 healthy children. Paternity rate was 40%. CONCLUSION: CAD constitutes an effective treatment option with acceptable long-term outcomes in exstrophy patients in whom all attempts at restoring the lower urinary tract have failed. Long-term follow-up of the upper urinary tract, assessment of acid-base balance, and endoscopy of the rectosigmoid reservoir are paramount for the safety of this type of management. Evaluation of sexual dysfunction should be an active part of follow-up.

Effect of contrast media on urinary cytopathology specimens.

INTRODUCTION: Urological dogma dictates that washings collected from the urinary tract for cytological assessment must be performed without interference from contrast agents that may alter cellular integrity and diagnostic interpretation. In practice, the initial contrast used to outline the upper tracts is commonly discarded with subsequent saline washings sent for cytology. We hypothesize that contrast washings do not affect the morphology of urothelial carcinoma cells or the integrity of cytology interpretation. METHODS: Samples obtained from (1) human bladder cell lines; (2) urine from a human xenograft bladder cancer model using UC-3 cells; and (3) patients with urothelial carcinoma were subjected to various experimental solutions (water, saline, urine, and dilutions of contrast media) for different exposure times. After exposure to various different solutions, samples underwent cytological analysis to assess morphologic and degenerative changes. RESULTS: No cytological differences were seen when cells were exposed to ionic, hyperosmolar, or non-ionic low-osmolar contrast agents for any exposures up to five minutes. Cells exposed to mixtures of contrast agents and urine also demonstrated no evidence of degenerative change. Cells exposed to water for greater than one minute demonstrated significant hydropic degeneration impacting cytological interpretation. At 40 minutes or later, all reagents caused severe degeneration when evaluating urine samples from the mouse bladder cancer model and from patients undergoing urothelial carcinoma. CONCLUSIONS: Commonly used contrast agents have no effect on urinary cytology up to five minutes. Contrast washings of the urinary tract should not be discarded and can be sent for cytological diagnosis if fixed within this time period.

Differences in Overall and Cancer-specific Survival of Patients Presenting With Chromophobe Versus Clear Cell Renal Cell Carcinoma: A Propensity Score Matched Analysis.

OBJECTIVES: To investigate prognostic parameters for the oncological outcome of patients treated for chromophobe renal cell carcinoma (chRCC) in comparison with patients treated for clear cell RCC (ccRCC) using propensity score matching for survival analysis. METHODS: From 1969 to 2009, we identified 1010 from 3567 patients with RCC. Survival was analyzed using Kaplan-Meier estimate for histological subtypes including 109 chRCC and 901 ccRCC. Uni- and multivariate Cox regression was used to analyze prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Propensity score matching was performed to adjust for differences in patient characteristics among histological subgroups. RESULTS: The median follow-up was 61 months (range 0-289). chRCC showed longer OS (5 year, 90.1%; 10 year, 74.2%; 15 year, 61.4%) and CSS (94.2%, 89.7%, 89.7%) compared with ccRCC (OS 75.7%, 54.9%, 46.1% and CSS 84.7%, 75.4%, 72.2%; P = .002). Multivariate Cox regression revealed histology as a significant prognostic factor. Propensity score matching showed a difference in 72.4% (OS) and 87.2% (CSS) of matching attempts confirming the significant impact of histology. Univariate Cox regression showed nephron sparing surgery, no metastasis and no symptoms at presentation, age <65, eosinophilic features, low American Society of Anesthesiologists score, and Charlson Comorbidity Index to be beneficial for CSS. Only age at surgery, metastasis at presentation, and American Society of Anesthesiologists and Charlson Comorbidity Index scores were significant factors for OS in chRCC patients. CONCLUSION: ChRCC appears to have a favorable outcome compared with ccRCC. Even after adjustment for differences in characteristics known to have an influence on survival by propensity score matching, histology remains a significant prognostic factor.

R.E.N.A.L. Score Outperforms PADUA Score, C-Index and DAP Score for Outcome Prediction of Nephron Sparing Surgery in a Selected Cohort.

PURPOSE: Several nephrometry scores have been proposed to predict perioperative outcomes in renal surgery. We evaluated which nephrometry score correlates best with the MIC (margin, ischemia and complications) score and quantitative perioperative outcomes in nephron sparing surgery. MATERIALS AND METHODS: Data on 188 patients undergoing nephron sparing surgery were retrospectively investigated for patient, operative and tumor characteristics. Nephrometry scores, including R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, hilar tumor touching the main renal artery or vein and location relative to polar lines), PADUA (preoperative aspects and dimensions used for an anatomical), C-index (concordance index) and DAP (diameter-axial-polar), were measured on preoperative computerized tomography or magnetic resonance imaging and coded continuously and categorically. Parameters pertaining to tumor margin, ischemia and complications were recorded as binary scores and classified as MIC achievement. Operative time, estimated blood loss, warm ischemia time and hospital stay were recorded as quantitative perioperative outcomes. RESULTS: The R.E.N.A.L. score correlated best with MIC and quantitative perioperative outcomes. The continuously coded R.E.N.A.L. score was predictive of MIC on univariate analysis (OR 0.75, 95% CI 0.58-0.97, p = 0.03) and it had the best predictive value on multivariate logistic regression analysis (OR 0.31, 95% CI 0.18-0.82, p = 0.03). The C-index but not the PADUA or the DAP score was predictive of MIC on univariate and multivariate logistic regression analysis. MIC achievement rates were significantly higher for low than for high complexity tumors as assessed by categorically coded R.E.N.A.L. score, C-index and DAP scores. Continuously coded R.E.N.A.L. and PADUA scores positively correlated with operative time, warm ischemia time and hospital stay. The C-index and the DAP score correlated with warm ischemia time. CONCLUSIONS: Of 4 nephrometry scores the R.E.N.A.L. score correlated best with MIC achievement and quantitative perioperative outcomes of nephron sparing surgery.